Proceedings surgery 2015 - ANZCVSoldwebsite.anzcvs.org.au/surgery_assets/Science... · standard...

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Australian and New Zealand College of Veterinary Scientists

Surgery Chapter

Scientific Presentations 2015

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Table of Contents

Page 3 3D Printed Titanium Prostheses J Bray 5 Extremity STS – metronomics vs cut small J Bray 10 Should we offer Metastatectomies J Liptak 12 Limb Salvage for non-radial Osteosarcoma J Liptak 17 Apocrine Gland Anal Sac Adenocarcinomas J Liptak 21 Sentinel Lymph Nodes J Liptak 22 Challenging Maxillectomy cases – Triumphs and Failures J Liptak 30 Mandibulectomies – How much is too much J Liptak 36 Collaborative Comparative Oncology Research – One Cancer Concept R Straw 38 The relevance of surgical margins R Straw 41 How to amputate for Hip cancer – Hemipelvectomy R Straw 44 Precancerous solar induced nasal lesions – can we avoid Nosectomy? R Straw 53 Extremity Soft Tissue Sarcoma Radiation R Straw 56 Use of Pleural Ports in Veterinary Surgery M Thomson 58 Orbitectomy in the Dog M Thomson 61 Surviving Gastroduodenostomy in the Dog (75% of the time) M Thomson 64 Platipump C Kuntz 66 Brain Surgery – Cerebrum, Cerebellum, Pituitary C Kuntz 69 Gastrointestinal Biopsy Techniques C Kuntz 74 Extremity Soft Tissue Sarcoma – Wide Local Excision C Kuntz 77 Incisional vs Excisional biopsy and staging S Ryan 81 The treatment of Malignant Pericardial Effusions S Ryan 83 Adrenalectomy: Midline vs Retroperitoneal vs Laproscopic S Ryan 86 Principles of Eyelid Tumour surgery – How to cut them out S Jacobi 92 Surgery of the Globe: Enucleation and Evisceration with intraocular silicone prosthesis C Hardman 95 New Strategies – metronomics, immunotherapy, EBC46 P Bennett 97 Role of Chenotherapy postop – anal sac, spleen, MCT, OSA P Bennett 99 Bone marrow transplantation in Australia S Nguyen 101 Splenectomy after rupture – is it ethical? S Nguyen 103 The hunt for metastatic disease: Use of imaging for staging cancer and M Milne Oncological surgical planning specifically of the thorax 109 Screening for Abdominal neoplasia: A comparison of modalities & techniques M Frances 116 Optimising image quality for CT/MRI in surgical practice: a radiologist’s tips Z Lenard 120 Spinal neoplasia – myelography vs advanced imaging: What do we know and where can we go? C Beck 125 Is Hyperadrenocorticism a surgical disease? An internist perspective D Church 131 Thyroid cancer – surgery vs radioactive iodine L Lacorcia 137 Endoscopic diagnosis of gastric and duodenal neoplasia: How to maximize returns J Dandrieux 143 Pre and Postop radiotherapy – Which patients benefit? E Gumpell 148 A dental perspective on oral tumour management. A Caiafa 150 Femoral nerve entrapment in a dog with diffuse idiopathic skeletal hyperostosis A Lai 151 The effect of intramedullary pin size and plate working length on plate strain in T Pearson Locking compression plate-rod constructs 152 Negative pressure wound therapy using portable. Single-use device for free skin grafts A Miller On the distal extremity in 7 dogs 153 Ozonated water is inferior to alcohol for disinfecting hands C Appelgrein 154 Locking plates vs compression plates for ilial wing fractures in dogs G Dodds 155 A retrospective review of perioperative antimicrobial cycling in Veterinary Orthopaedic surgery E Hoffman 156 Quantitative histological evaluation of the soft palate in dogs affected by K Crosse Brachycephalic obstructive airway syndrome 157 The use of combination vinblastine and toceranib phosphate (Palladia) for treatment J Olsen of Grade II and III mast cell tumours in dogs 158 Outcomes of cellophane banding with no attenuation for treatment of extrahepatic K Leidreiter portosystemic shunts in dogs 159 Comparison of peri-operative wound parameters in cats undergoing flank vs midline ovariectomy M Swaffield 160 Computed tomography findings and outcomes after surgery for dermoid sinuses: A case series C Appelgrein 161 Effect of cassette open time on strength of multi-use polydioxanone and comparison O Schaaf to single-use polydioxanone

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3D-PRINTED TITANIUM PROSTHESES

Jonathan Bray MVSc MSc(ClinOnc) MANZCVS DiplECVS Associate Professor, Companion Animal Clinical Studies

Head of Companion Animal Group IVABS, Massey University, Palmerston North, New Zealand

[email protected]

Osteosarcoma is the most common primary bone tumour in dogs. Large and giant breed dogs, including the Rottweiler, Great Dane, greyhound and deerhounds, are particularly at risk of developing osteosarcoma of the skeleton. Traditionally, surgical management of the affected bone has involved amputation. However, amputation may not be a viable option for some dogs, either as a result of their physical size and weight or due to concomitant musculoskeletal or neurological disease. In these cases, limb-sparing techniques have been developed to provide a viable curative intent treatment. Reported techniques include autografting (after pasteurisation or irradiation of the tumour), allograft, distraction osteogenesis, manus translation, ulna rollover, vascularised fibular grafts or the use of metal endoprosthetics. Stereotactic radiosurgery has also been reported to provide good clinical results in selected cases. The earliest method for limb-sparing involved replacement of the cancerous segment of bone with a similar sized and shaped length of bone harvested from a cadaver (cortical allograft). Whilst allograft replacement of the distal radius provided good clinical function, it was limited by the immunogeneity of the implant, which lead to rejection in more than 50% of cases. This high complication rate, and the difficult logistics of sourcing sterile cadaveric bone, stimulated the interest for a wholly synthetic implant that is available ‘off-the-shelf’ and suited for a range of patient sizes. The use of synthetic prostheses is well–developed in human oncologic surgery, with a variety of implants available for limb salvage of various bones. Complications of prosthetic replacement include mechanical failure of the prosthesis (8-29%), and soft tissue infection (26%). In general, excellent clinical results are reported. The advantage of a metal prosthetic is a bone bank is not necessary, and the surgical planning and performance are much easier. A veterinary-specific stainless steel endoprosthetic is available in the US. Dogs tolerate this technique very well, but complication rates are high with significant infection or implant failure developing in more than 50% of patients. Given that 50% of dogs with bone cancer will succumb to metastatic disease within a year of treatment, this high complication rate erodes the enormous benefits that limb-sparing surgery can otherwise provide these patients for their remaining lifetime. Stainless steel is a poor choice for managing large skeletal defects due to its relative rigidity, its poor integration with host tissues, and its propensity to retain a large bacterial biofilm burden on its surface. To overcome these complications, future success with endoprosthetics will likely involve the use of osteophilic materials that allow for bony ingrowth and soft tissue attachment. These properties allow integration of the implant with local tissues and greatly improve the strength, longevity and durability of the endoprosthetic construct. Titanium and its alloys are rapidly becoming materials of choice for biomedical implants due to many favourable properties. The advent of computer aided design and 3D printing technologies using titanium powder allows creation of an implant that is uniquely designed to fit a specific patient. A crucial design element of the titanium implant is a porous scaffold that enables vascular and cellular

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ingrowth into the implant, such that new bone tissue will ultimately form on the implant surface. This potential for complete integration of the implant into the host tissues (a process known as osseointegration) is a ‘holy grail’ for human biomedical implants; integration mimimises the potential for infection and implant failure, which can be devastating for the patient. However, the precise geometry and architecture of the scaffold structure to support osseointegration along a length of a large defect remains unknown. Massey University VTH has access to some extraordinary resources, including engineering expertise at Axia Design (Napier, NZ) and the New Zealand Titanium Technologies and Powder Metallurgy Platform. This has enabled us to create unique titanium implants for managing bone cancer affecting the lower jaw (mandible) and forelimb (radius) in dogs. Using information from a CT scan of the affected bone, CAD-design software is used to create an implant specific to that patient. The final design solution is then converted to suitable data files for 3D reconstruction using a Selective Laser Melting (SLM) instrument at TiDA (Tauranga, NZ). Th turn-around time from patient presentation to impant creation is short (a few days), and the implant cost is competitive with existing options. To date, implants have been implanted with good outcome in five dogs afflicted with bone cancer. The implant can be uniquely tailiored to the individual characteristics of the patient, allowing surgery to be accomplished with ease. Excellent clinical function was achieved in each case. Infection developed in one dog (distal radius), but was successfully managed with antibiotics. Selected references: 1. Hollister SJ, Murphy WL. Scaffold translation: barriers between concept and clinic. Tissue Eng Part B Rev. 2011;17(6):459-74. doi: 10.1089/ten.TEB.2011.0251. 2. Liptak JM, Dernell WS, Ehrhart N, Lafferty MH, Monteith GJ, Withrow SJ. Cortical allograft and endoprosthesis for limb-sparing surgery in dogs with distal radial osteosarcoma: a prospective clinical comparison of two different limb-sparing techniques. Vet Surg. 2006;35(6):518-33. 3. Verran J, Whitehead K. Factors affecting microbial adhesion to stainless steel and other materials used in medical devices. Int J Artif Organs. 2005;28(11):1138-45. 4. Liu Y, Lim J, Teoh SH. Review: development of clinically relevant scaffolds for vascularised bone tissue engineering. Biotechnol Adv. 2013;31(5):688-705. doi: 10.1016/j.biotechadv.2012.10.003. 5. Van der Stok J, Van der Jagt OP, Amin Yavari S, et al. Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects. J Orthop Res. 2013;31(5):792-9. doi: 10.1002/jor.22293. 6. Razi H1, Checa S, Schaser KD, Duda GN. Shaping scaffold structures in rapid manufacturing implants: a modeling approach toward mechano-biologically optimized configurations for large bone defect. J Biomed Mater Res B Appl Biomater. 2012 Oct;100(7):1736-45. doi: 10.1002/jbm.b.32740.

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EXTREMITY STS - METRONOMICS VS CUT SMALL

Jonathan Bray MVSc MSc(ClinOnc) MANZCVS DiplECVS Associate Professor, Companion Animal Clinical Studies

Head of Companion Animal Group IVABS, Massey University, Palmerston North, New Zealand

Preventing local recurrence following surgical resection is the characteristic challenge in the management of STSs. Local recurrence of tumour can develop in between 17-75% of all patients, with recurrence consistently associated with reduced overall survival for the dog. In veterinary medicine, surgery remains the most effective single-modality strategy in the management of STS, but controversy exists as to how surgery is best employed. Historically, standard recommendations for resection of STS have prescribed wide local excision of the tumor en bloc with measured margins of 2- to 3-cm of normal tissue laterally and one clean fascial plane deep to the tumor.[1, 2] Some authors have argued that even more radical tissue removal would lead to further improvements in local tumor control.[3] Recently, several authors have challenged the requirement for wide surgical excision margins, [4-7] with some studies suggesting the extent of resection performed did not influence the disease-free interval or overall survival.[6, 7] Caution is required before recalibrating surgical margin recommendations for sarcoma resection based on these recent studies. Considerable selection bias exists in these different study populations, with varying proportions of tumour grade included which is very influential on outcome.[8] For this reason, it is unsurprising that surgical outcomes are better in those studies with a higher proportion of low-grade tumours,[4, 6, 7, 9] compared to those studies with more high-grade tumours.[10-12] There are currently no diagnostic tests that can reliably predict the amount of surgical margin required for a particular tumour, leading to a mismatch between treatment and disease: some dogs are overtreated for their disease, resulting in large wound reconstructions or amputation when smaller surgical margins would have been effective. Other dogs are undertreated, and inappropriately conservative resections may result in inadequate tumour control. Treatment strategies need to take account the behavioural characteristics of each individual tumor. It remains a concern that unplanned resection of the STS - with the operating surgeon having performed no prior diagnostic investigations to alert them to the malignant potential of the mass – remain common. In recent studies by the author, a diagnosis of STS was obtained in less than 20% of cases prior to surgery, and fewer than 10% of patients were operated with the surgical margins recommended in most textbooks for this tumour type.[6, 7] There is no simple answer to the question posed by the title of this lecture – it certainly isn’t a question of “either/or”. STS are a complex tumour type, and many uncertainties surround their biology. As a consequence, I don’t believe there is a single generic solution that can be applied for every STS. To explain some of these controversies, I would like to propose some questions of my own: ARE WE ALL TALKING ABOUT THE SAME DISEASE?

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STS are a heterogenous group of tumours with variations in histopathology, molecular signature, histological grade, and primary site. Because of this variability, different outcomes are likely for different individuals exposed to the same quantity of surgery. As an example, McSporran highlighted the importance of tumour grade on patient outcome after surgery. After marginal excision, he found that only 7% (3/41) of low-grade tumors recurred, compared with 34% (14/41) and 75% (3/4) for intermediate and high grade tumors, respectively. There is a bias for lower-grade tumours to be managed in first opinion practice.[6, 7] In one study, the majority (66%) of tumors were classified as low grade, with just 27.1% intermediate and 6.3% high-grade lesions. This contrasts with 36% intermediate and 22% high grade tumours in a referral population.[10] This bias towards more low-grade tumors in first opinion practice is also supported by analysis of pathology submissions to a UK commercial laboratory during a 3-year period, during which time 87% of canine soft tissue sarcomas were classified as low grade, with smaller numbers of intermediate (8%) and high grade (3%) tumors. The impact of this bias is important, but is rarely acknowledged. However, I think we would agree that the prognosis and treatment strategy for a 2 cm well-circumscribed mobile STS would be very different to an 8cm STS with a necrotic centre, which has suddenly developed. IS THE PSEUDOCAPSULE A BARRIER OR NOT? There is increasing evidence that the structure and composition of the pseudocapsule may prove vital in determining the outcome following surgical resection. For many low-grade lesions, the compressed fibrous zone may actually provide an effective barrier against tumor growth and infiltration. However, higher grade lesions will expand faster than the fibrous capsule can form, leading to disruption and localized infiltration of the peritumoral tissue by sarcoma cells, creating a reactive zone that surrounds the tumour by a variable distance. This “reactive zone” represents an important interface between the tumor and the host tissue, and is an area of new and evolving neoplastic activity. It is reasoned that if the plane of surgical excision passes through this area, there is a higher likelihood for tumor recurrence to occur.[13, 14] This may be because the microenvironment of the remaining tumour bed is ‘tumour permissive’, but may also be because microscopic clusters of tumour cells have migrated beyond this area. WHAT IS A MARGIN? The issue of “how much resection is enough” has been a hotly debated topic in human STS for decades. For tumours on the extremity, the impact of an increasing resection width may be the difference between achieving simple closure, or the need for advanced tissue reconstruction, amputation or euthanasia. Evidence from human and veterinary papers tend to support the notion that resections based solely on width are unlikely to lead to demonstrably improve cure rates sufficient to justify the increased morbidity such a resection would bring. However, inappropriate conservative margins may be equally detrimental to patient outcomes. In human oncologic surgery, the issue of ‘how much to resect’ has been largely circumvented by the routine inclusion of radiotherapy (adjuvant or neoadjuvant) into the context of ‘standard treatment’ for soft tissue sarcoma. However, some of the ‘historical’ observations from the human literature may retain some relevance for veterinary patients, where radiotherapy is less commonly used. 1. Measured “width only”

a. Dickinson et al (2006) showed the probability of survival increased with an increasing width of the margin (P = 0.002), but there was no significant difference in

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survival rates for those with uncontaminated margins of up to 19 mm (P = 0.122). There was no survival difference between those patients with margins of 1-9mm and those with margins of 10-19mm. In this study, the nature of the margin was not defined, just the overall width.

b. Other authors have described levels of tumour recurrence (~10%) despite clean histological margins of between 2.5-4cm.[15]

2. Tissue Barriers a. The Japanese Orthopaedic Association defined a curative margin as a resection

margin that was greater than 5cm beyond the reactive zone. (Kawaguchi et al, 1995). However, attempts were made to account for the effects of various tissue barriers that may impact on tumour infiltration. A thick barrier was a physically strong membranous tissue such as joint capsule, iliotibial band, etc and converted to an equivalent of 3cm of normal tissue. A thin barrier was a weaker membranous tissue of muscle, fascia, periosteum in adults, epineurium, etc and was equivalent to 2cm of normal tissue.

3. Anatomical compartments a. Enneking (1980) recognised that soft tissue sarcoma will respect fascial boundaries

and preferentially expand within the structure of origin along the path of least resistance.[16] By acknowledging this growth characteristic, Enneking proposed a classification for planning resection of human musculoskeletal tumours that was based on the gross extent of the tumour and divided sections of the body into distinct anatomical spaces he termed “compartments”.[17] This system was validated in several clinical trials, with demonstration of significantly improved patient survival times and reduced tumour recurrence in patients undergoing compartmental tumour excision compared to those undergoing conventional wide margin excision.[17-21] In a series of 471 patients, Azzarelli (1993) reported a significant improvement in local disease control in patients treated with compartmental surgery compared to those treated with wide excision (p < 0.001). [22] When a compartmental strategy was applied to the management of tongue tumours, a significant increase in survival and a 25% increase in locoregional control was achieved over standard wide excision.

(LARGE) SARCOMA SURGERY IS DIFFICULT – SHOULD EVERYONE BE DOING IT? Resection of large STSs requires a detailed anatomic knowledge of the affected tissues, combined with a sound understanding of oncologic principles, surgical and para-surgical skills. Extensive resections are complicated even for experienced surgeons, so it is naïve to assume that surgeons inexperienced with these techniques will achieve equitable results. Monteiro et al (2011) showed a significant difference in the risk of an incomplete excision when the tumor was excised by a surgical resident compared with a specialist surgeon (OR 1.22: P = 0.012).[23] Similar variances are identified in human medicine, prompting demands for STS to only be operated by trained surgeons in dedicated centres.[24] While there may be obstacles to creating a similar system in veterinary medicine, this philosophy does highlight the complexity surrounding the management of STS, particularly if they are large or biologically aggressive. CONCLUSION There is no ‘one solution’ that will suffice in the management of STS. Currently, our tendency is to “overtreat” as this (probably) provides the best outcome for the majority of patients. However, some patients will suffer needlessly as a result of this strategy. In the future, predicting the potential biologic behaviour of a tumour should enable better stratification of treatment options. This may include the use of single or multiple modalities, or even accepting a palliative strategy

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is best. At this time, considerable deficiencies remain in our ability to accurately determine the optimal surgical dose and prognosis for an individual patient with a sarcoma, but several indicators exist that may alert the surgeon to the invasive potential of an individual tumour, including the palpable characteristics of the tumour, tumour size, tumour mobility and histological grade.[7, 8, 25] it is important the clinician understands that a spectrum of disease aggression occurs within the sarcoma grouping, and knows how and when to amend their treatment plan accordingly. 1. Dernell, W.S., et al., Principles of treatment for soft tissue sarcoma. Clin Tech Small

Anim Pract, 1998. 13(1): p. 59-64. 2. Ehrhart, N., Soft-tissue sarcomas in dogs: a review. J Am Anim Hosp Assoc, 2005.

41(4): p. 241-6. 3. Phelps, H., et al., Radical excision with five-centimeter margins for treatment of feline

injection-site sarcomas: 91 cases (1998-2002). Vet Surg, 2011. 239: p. 97-106. 4. Banks, T., et al., Soft tissue sarcomas in dogs: a study correlating optimal surgical

margin with tumour grade. Australian Veterinary Practitioner, 2004. 34: p. 158-163. 5. Cavanaugh, R., et al. Local recurrence rate of canine soft-tissue sarcomas of the distal

limbs treated by marginal excision alone. . in Proceedings of the 27th Annual Conference of the Veterinary Cancer Society. 2007. Fort Lauderdale, Florida.

6. Bray, J., et al., Soft Tissue Sarcoma Managed in First Opinion Practice: Outcome in 350 cases. Veterinary Surgery, 2014. 43(7): p. 774-82.

7. Chase, D., et al., Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases. Journal of Small Animal Practice, 2009. 50(11): p. 568-74.

8. McSporran, K.D., Histologic grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas. Vet Pathol, 2009. 46(5): p. 928-33.

9. Stefanello, D., et al., Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996-2006). Veterinary Surgery, 2008. 37(5): p. 461-5.

10. Kuntz, C.A., et al., Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). J Am Vet Med Assoc, 1997. 211(9): p. 1147-51.

11. Bostock, D.E. and M.T. Dye, Prognosis after surgical excision of canine fibrous connective tissue sarcomas. Vet Pathol, 1980. 17(5): p. 581-8.

12. Heller, D., et al., A retrospective study of 87 cases of canine soft tissue sarcoma, 1986-2001. Intern J Appl Res Vet Med 2005. 3(2): p. 81-87.

13. Kind, M., N. Stock, and J.M. Coindre, Histology and imaging of soft tissue sarcomas. Eur J Radiol, 2009. 72(1): p. 6-15.

14. White, L.M., et al., Histologic assessment of peritumoral edema in soft tissue sarcoma. Int J Radiat Oncol Biol Phys, 2005. 61(5): p. 1439-45.

15. Sampo, M., et al., Impact of the smallest surgical margin on local control in soft tissue sarcoma. British Journal of Surgery, 2008. 95(2): p. 237-243.

16. Enneking, W.F., S.S. Spanier, and M.M. Malawer, The effect of the Anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer, 1981. 47(5): p. 1005-22.

17. Enneking, W.F., S.S. Spanier, and M.A. Goodman, A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res, 1980(153): p. 106-20.

18. Enneking, W.F., S.S. Spanier, and M.A. Goodman, A system for the surgical staging of musculoskeletal sarcoma. . Clin Orthop Relat Res, 2003(415): p. 4-18.

19. Enneking, W.F., History of orthopedic oncology in the United States: progress from the past, prospects for the future. Cancer Treat Res, 2009. 152: p. 529-71.

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20. Fisher, C.G., et al., Surgical management of primary bone tumors of the spine: validation of an approach to enhance cure and reduce local recurrence. Spine (Phila Pa 1976), 2011. 36(10): p. 830-6.

21. Calabrese, L., et al., Compartmental surgery in tongue tumours: description of a new surgical technique. Acta Otorhinolaryngol Ital, 2009. 29(5): p. 259-64.

22. Azzarelli, A., Surgery in soft tissue sarcomas. Eur J Cancer, 1993. 29A(4): p. 618-23. 23. Monteiro, B., S. Boston, and G. Monteith, Factors influencing complete tumor excision

of mast cell tumors and soft tissue sarcomas: a retrospective study in 100 dogs. Can Vet J, 2011. 52(11): p. 1209-14.

24. Gustafson, P., K.E. Dreinhofer, and A. Rydholm, Soft tissue sarcoma should be treated at a tumor center. A comparison of quality of surgery in 375 patients. Acta Orthop Scand, 1994. 65(1): p. 47-50.

25. Dennis, M.M., et al., Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs. Vet Pathol, 2011. 48(1): p. 73-84.

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SHOULD WE OFFER METASTATECTOMIES?

Dr. Julius M. Liptak, BVSc, MVetClinStud, FACVSc, DACVS, DECVS ACVS Founding Fellow in Surgical Oncology

Alta Vista Animal Hospital, Ottawa, Ontario, Canada

The role of metastatectomy is largely unknown in veterinary oncology. In human oncology, metastatectomy is performed in specific circumstances using well-defined criteria. Similar guidelines and criteria have been published for pulmonary metastatectomy in dogs with metastatic appendicular osteosarcoma, but not other tumors metastatic to the lungs and not other metastatic sites. Metastatectomy is rarely performed in cats, dogs and humans because the presence of metastasis is associated with advanced disease, an aggressive biological behaviour, and the likelihood of further metastatic lesions developing in the near future. Quality of life, palliation of clinical signs, improvement in prognosis, and costs of metastatectomy also need to be evaluated when considering whether further treatment is indicated. In humans, metastatectomy is most commonly performed in patients with liver metastasis from colorectal cancer. Initially, the criteria for liver metastatectomy was less than four sites of metastasis, tumor-free margins of a minimum of 1cm was possible with surgery, and no evidence of metastasis elsewhere; however, this has since been refined to achievable tumor-free margins and preservation of sufficient liver tissue to maintain hepatic function. Using either criteria, reported 5-year overall survival rates with liver metastatectomy are 30-40% compared to less than 10% with chemotherapy. Metastatectomy has not been reported in cats or dogs with liver metastases; however, palliative embolization or chemoembolization may provide some benefit. Pulmonary metastatectomy is performed most commonly for colorectal carcinoma lung metastasis. Unlike the criteria established in dogs, the criteria for people are the metastatic lesions should be resectable and there should be sufficient pulmonary functional reserves following metastatectomy. In dogs with metastatic appendicular osteosarcoma, the criteria for pulmonary metastatectomy include primary tumor control for greater than 300 days, less than three metastatic lesions, and a doubling time of the metastatic nodules of less than 40 days. Pulmonary metastatectomy can also be performed for palliative reasons in dogs with hypertrophic osteopathy secondary to pulmonary metastasis regardless of the progression-free interval or doubling time, however the number of lesions should still be small and resectable without affecting respiratory function. The role of lymphadenectomy in the management of patients with nodal metastasis is controversial. There are two prevailing theories of lymphadenectomy. The Halsted theory is that lymphadenectomy is both a clinical staging and a therapeutic procedure which provides evidence of whether the cancer has metastasized to the lymph nodes, but also provides a survival advantage if there is nodal metastasis. The Cady-Fisher theory is that lymphadenectomy is necessary for clinical staging, but does not provide any therapeutic benefit because lymph nodes do not provide a barrier to further metastasis. In veterinary medicine, lymphadenectomy is known to provide a survival benefit in dogs with cutaneous mast cell tumors metastatic to the sentinel lymph node and dogs with apocrine gland anal sac adenocarcinoma metastatic to the sublumbar lymph nodes; however, the role of lymphadenectomy is unknown in other cancer

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types which commonly metastasize to the lymph nodes, such as malignant melanoma, mammary carcinoma, and histiocytic sarcoma.

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LIMB-SALVAGE FOR NON-RADIAL OSTEOSARCOMA



Limb-sparing surgery is most commonly performed for dogs with primary bone tumours of the distal radius because of the ability to resect the tumour with adequate margins and reconstruct the bony column with arthrodesis of the carpal joint with resultant good to excellent limb function. However, because of the metaphyseal location of the vast majority of primary bone tumours in dogs, limb-sparing surgery is infrequently performed for tumours in other locations because of poor postoperative orthopedic function following arthrodesis of joints such as the shoulder, hock and stifle. However, limb salvage for proximal tibial, distal femoral, and proximal femoral tumours may become more common as total stifle and total hip replacement techniques are adapted for oncologic surgery with concomitant joint preservation. Ablative limb-sparing surgery is also possible for tumours in locations where removal of part or all of the involved bone does not resultant in significant mobility issues postoperatively, such as the digits, ulna, scapula, and for some pelvic sites. Good limb-spare candidates should have firm tumours with a definable soft tissue compartment, minimal extension into adjacent soft tissues, no evidence of a pathologic fracture, and less than 50% of the length of the bone involved. Furthermore, they should have no evidence of pyoderma and have good cardiac, renal and bone marrow function. Dogs with ill-defined and edematous adjacent soft tissue are less ideal candidates, particularly those with 360° involvement. Pathologic fracture is a relative contraindication for limb-sparing surgery, particularly if minimally displaced, because the dispersement of tumour cells into the surrounding tissues may increase the risk of local tumour recurrence. However, this has not been confirmed and the role of local chemotherapy and/or adjunctive radiation therapy in minimizing the risk of local tumour recurrence needs to be defined. Preoperative Margin Assessment Primary appendicular bone tumours are usually confined to the tumour pseudocapsule and a marginal excision is usually adequate to completely dissect the tumour away from the surrounding skin. Other soft tissue, such as muscle bellies and tendons, should be resected with 2-3 cm margins if possible. Bone should be excised with a minimum of 3 cm margins. The extent of tumour involvement in the bone can be assessed by survey radiographs, nuclear scintigraphy, CT or MRI scans. There is discrepancy in the literature whether radiography underestimates or overestimates the proximal extent of distal radial osteosarcoma (OSA) lesions in dogs. Nuclear scintigraphy overestimates the degree of tumour involvement by up to 14%. Computed tomography scans also overestimate the intramedullary extent of tumours by up to 27%. MRI is useful for determining the intramedullary extent of tumours on T1-weighted images, and overestimate this involvement by only 3%, and soft tissue involvement with contra-enhanced images. Overestimation of the proximal extent of the tumour may decrease the risk of incomplete excision, but it also may incorrectly exclude a dog as a suitable candidate for limb-sparing surgery if the extent of tumour involvement exceeds 50% of the length of the bone.

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Appendicular Sites Other Than The Distal Radius Stereotactic Radiosurgery Despite previously being thought to be a radiation-resistant tumour, some reports detail significant tumour necrosis in OSA after radiation therapy. These reports have served as the basis for investigating radiation therapy for curative-intent purposes. Until recently, no curative-intent radiation therapy strategies existed for dogs with appendicular OSA. Since 2004, investigative curative-intent radiation therapy for canine OSA has been described with either curative-intent full-course fractionated external beam protocol, single megadose radiation therapy as part of an intraoperative extracorporeal irradiation limb-sparing procedure, and as part of a stereotactic radiosurgery (SRS) protocol. Conventional radiation therapy relies on the use of fractionated protocols to minimize damage to surrounding healthy tissues. Conversely, SRS uses multiple, non-coplanar beams of radiation that are stereotactically focused on the target to deliver the entire radiation dose in a single treatment. Stereotactic radiosurgery minimizes damage to healthy surrounding tissues by relying on the extreme accuracy of radiation delivery to a tumour and a steep dose gradient between the tumour and the surrounding normal tissues. The major benefits of this technique over fractionated protocols include fewer anaesthetic episodes and a greater biologic effect on tumour cells. Stereotactic radiosurgery has been reported in human and veterinary patients for the treatment of intracranial abnormalities, but only one report exists describing the use of SRS for the treatment of appendicular OSA. In that report, pretreatment preparation involved placement of a targeting array and contrast-enhanced CT images. In the first OSA cases treated with SRS, treatment plans were initially designed to surround the entire contrast-enhanced region with the 20 Gy isodose line. Since these early cases, a better understanding of the extent of radiation doses that can be tolerated by the surrounding tissues (i.e., skin) has resulted in the use of increased doses such that the periphery of the lesion is covered with the 30-35 Gy isodose line and the center receives approximately 60 Gy. This plan is suitable for proximal humeral tumours, but the proximity of the skin to the outer surface of the bone in the distal radius location makes safe delivery of these doses possible only when the diseased tissue is mostly confined to the intramedullary portion of the bone. Following localization via the targeting array and infrared camera system, the area of interest is positioned under the isocenter of the linear accelerator and radiation therapy is performed (6 MV). Immediately following treatment, the localizing array, biteplate and associated pins are removed and the dog recovered from anesthesia. Carboplatin (300 mg/m2) is infused intravenously over 20 minutes immediately after completing SRS to potentiate the antitumour effects of radiation and to treat micrometastatic disease. Adjunctive chemotherapy (single agent carboplatin or alternating doxorubicin and carboplatin) is continued for treatment of micrometastatic disease. An additional advantage of SRS is that it can be applied to almost any bone. Dogs have been treated with lesions in the distal radius, proximal and distal ulna, proximal humerus, proximal and distal tibia, proximal and distal femur, and skull. Subjectively, tumour-associated swelling and lameness improve in most cases within 2-3 weeks of treatment. Skin-related effects include alopecia, desquamation, leukotrichia, and hyperpigmentation. Skin desquamation is typically observed 3-4 weeks after therapy and resolves over the following 4 weeks. Because the size and shape of the tumour are different with every case, the amount and distribution of radiation delivered is customized for each patient. Case selection is important for the success of SRS because the success rate for long-term control is determined by the size and extent of the lesion.

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Smaller lesions with minimal bone lysis and contained within the bone cortices allow greater coverage without injuring the skin. Pathologic fracture can occur following SRS because there is minimal bone regeneration following irradiation and radiation affects the vascularity of bone and results in the bone becoming more brittle. For these reasons, smaller lesions with minimal bone lysis are less likely to develop post-treatment pathological fractures. In contrast, larger lesions with an extensive outer soft tissue component are more difficult to treat effectively with SRS. Preoperative bone biopsy is not recommended since several treated cases have developed pathologic fractures through bone biopsy tracts approximately 6 months following SRS. If SRS is being considered as a treatment option, then fine-needle aspiration rather than needle core biopsy is recommended for diagnostic purposes. Intraoperative Extracoporeal Radiation Intraoperative extracorporeal radiation has been used for limb-sparing surgery in a small number of dogs with appendicular OSA. This technique involves an osteotomy above or below the tumour (depending on the anatomic site of the tumour) and dissection of normal tissues from the tumour bone segment while preserving the adjacent joint capsule and supporting ligamentous structures (e.g. collateral ligaments). The neurovascular bundle, muscle, skin are held away from the affected bone and the tumour-containing bone segment is rotated approximately 90° out of the wound bed. The bone tumour segment is then irradiated with a single dose of 70 Gy. Collimation of the beam is performed so that approximately 1 cm of bone at the osteotomy site is spared to allow healing of the osteotomy site following internal fixation with either a bone plate, interlocking nail or combination of the two. The advantage of this technique is that an arthrodesis of the adjacent joint is not typically necessary (which is the major limiting factor to the success of limb-sparing in sites other than the distal radius and ulna). Of the initial 14 cases reported, limb function was good in the immediate postoperative period; however, 50% of dogs required revision within 5-9 months of surgery, including four limb amputations. Additionally, local recurrence and infection were reported in four dogs each. In situ radiation of distal femur and any tibial tumour can be performed without osteotomy. In distal radial cases, collapse of the subchondral bone and subsequent implant failure has been observed. Thus transcarpal plating to the third metacarpal bone is recommended to span the subchondral bone of the distal radius and prevent collapse. Further evaluation, as well as technique modification, is required before this procedure can be recommended. Proximal Femur Limb-sparing surgery of a proximal femoral OSA has been described. Following tumour resection according to oncologic principles, the proximal femoral diaphysis was reconstructed with a cortical allograft and the hip joint with a custom femoral stem and standard acetabular cup. The challenge with these reconstructions is the availability of customized femoral stems and reconstruction of the tendinous insertions on the proximal femur. Scapulectomy Subtotal (or partial) or total scapulectomy are recommended for the surgical treatment of non-metastatic scapular tumours. Limb amputation is an alternative to scapulectomy, but scapulectomy is preferred because limb function can be preserved. Scapulectomy is performed through a lateral approach to the scapular spine. If a biopsy has been performed, then the biopsy tract should be excised en bloc with the bone tumour and all involved soft tissues. The trapezius and omotransversarius muscles are dissected close to their origins on the scapula, as are the acromial and spinous heads of the deltoideus muscle, but greater margins may be required depending on the location of the tumour. The scapula is retracted laterally to permit deep

15

dissection of the serratus ventralis muscle from the medial surface of the scapula. The brachial plexus and axillary artery and vein should be preserved during deep dissection. If required, the suprascapular and subscapular nerves are identified, infused with 0.2-0.5 ml of bupivicaine, and then transacted. For subtotal scapulectomy, the infraspinatus, supraspinatus, and subscapularis muscles are tranescted at the level of the planned osteotomy. For total scapulectomy, the coracobrachialis, teres minor, infraspinatus, supraspinatus, and subscapularis tendons are then transected from their insertions on the humerus. The teres major and long head of the triceps muscles are incised from their insertions on the caudal scapula. For subtotal scapulectomy, an osteotomy is performed at or proximal to the scapular neck to preserve the glenoid cavity and origin of the biceps tendon. The osteotomy should be performed a minimum of 3 cm from the distal aspect of the tumour, as determined by bone scintigraphy or CT scans. For total scapulectomy, the glenohumeral joint capsule is incised and disarticulated. The scapula is then removed with the attached infraspinatus, supraspinatus, and supscapularis muscles. For dogs treated with total scapulectomy, limb function may be improved by tenodesis of the biceps tendon to the proximal humerus with either bone screws or mattress sutures to the remaining joint capsule. Following partial scapulectomy, the omotransversarius, trapezius, serratus ventralis and rhomboideus muscles can be attached to the distal scapula with nonabsorbable suture material through predrilled holes on the edge of the scapula segment. Alternatively, the supraspinatus, infraspinatus, deltoid and long head of the triceps can be sutured to the serratus ventralis, omotransversarius and trapezius muscles without direct attachment to the scapular segment. This is done so that the muscles cover the scapular segment and minimize dorsal displacement of the scapula during weight bearing on the limb. A closed-suction drain can be used in the subcutaneous space, but is rarely indicated because seroma formation is an uncommon postoperative complication. The subcutaneous tissue and skin are closed routinely. Following total scapulectomy, the triceps muscle is sutured over the humeral head to the deltoid, omotransversarius and trapezius muscles. The trapezius muscle is sutured to the serratus ventralis muscle. The subcutaneous tissue and skin are closed routinely. The postoperative outcome following scapulectomy is dependent on whether a subtotal or total scapulectomy has been performed and body weight. Analgesia and physiotherapy are important to maximize postoperative recovery and ameliorate lameness following both subtotal and total scapulectomy. Limb use is often good to excellent for dogs treated with subtotal scapulectomy because the scapulohumeral joint is stabilized by preservation of the acromial head of the deltoid muscle and distal portions of the infraspinatus and supraspinatus muscles, and the range of motion of the scapula is maintained by the brachiocephalicus and latissimus dorsi muscles. At 14 days postoperatively, weight has a significant impact on limb use with limb use better in lighter dogs. Postoperative limb use is less predictable following total scapulectomy and recovery times are subjectively longer in comparison to subtotal scapulectomy, but one study showed no difference in limb use between dogs treated with partial versus total scapulectomy. If possible, total scapulectomy should only be performed in cases where the tumour involves the distal scapula or where adequate surgical margins cannot be attained without excision of the glenoid. The prognosis for dogs with scapular tumours is dependent on the tumour type. The median survival time for dogs with scapular OSA is 246 days, while survival times greater than 2 years have been reported for dogs with scapular CSA. Scapular OSA has a similar biologic behavior to appendicular OSA with a high metastatic rate and hence adjuvant chemotherapy is recommended.

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Ulnectomy Limb-sparing surgery of the ulna can also be performed successfully, provided the tumour is located in the mid-to-distal part of the bone. Ulnectomy can be performed without subsequent reconstruction of the ulna. Care is taken not to score the radius during ulnar osteotomy as radial fractures have resulted from such scoring. For very distal tumours, it is sometimes necessary to remove the entire styloid process. Despite disruption of the lateral collateral ligament, stabilization is typically not required following resection of the styloid process. If the proximal ulnar osteotomy must be performed proximal to the interosseous ligament, then stabilization of the remaining proximal ulna to the radius is necessary to prevent distraction of the proximal ulna by the triceps muscles during ambulation. This is typically achieved by placing cortical bone screws from the ulna to the radius in a caudal-to-cranial direction or, alternatively, cerclage wires can be used. In one study of 30 dogs with ulnar OSA, the median survival time was 463 days following either ulnectomy or limb amputation. Dogs with telangiectatic OSA were 7-times more likely to die as a result of their disease than other OSA histologic subtypes. Digit Amputation and Partial Foot Amputation Amputation of one or two digits can be performed with minimal impact on limb function, even if the two weight-bearing third and fourth digits are amputated. In one study of 11 dogs treated with partial foot amputation, lameness was noted postoperatively in all dogs, but resolved in eight dogs after a median of 37 days.

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APOCRINE GLAND ANAL SAC ADENOCARCINOMAS



Apocrine gland anal sac adenocarcinoma (AGASAC) accounts for 2% of all skin tumors in dogs and is commonly associated with paraneoplastic hypercalcemia and regional lymph node metastasis. Paraneoplastic hypercalcemia is common with up to 90% of dogs with AGASAC presenting with either symptomatic or asymptomatic hypercalcemia. Hypercalcemia of malignancy, or pseudohyperparathyroidism, is caused by the production of parathyroid hormone-related protein by tumor cells in either the primary tumor or metastatic lymph nodes. Hypercalcemia resolves following surgical resection of the primary tumor and metastatic lesions, if present, and hypercalcemia recurs in dogs that develop either local tumor recurrence or metastatic disease postoperatively. Metastasis is very common in dogs with AGASAC. At the time of diagnosis, 47%-72% of dogs have metastasis to the sublumbar lymph nodes and a further 7%-9% have metastasis to the lungs and other sites such as the spleen, bone, pancreas, heart, and mediastinum. Clinical Signs The two major presentations for dogs with AGASAC are local effects caused by the tumor and/or enlarged metastatic sublumbar lymph nodes and hypercalcemia. The size of AGASACs varies widely from non-palpable to very large, although most AGASACs are palpable. When small to moderate-sized, these masses correlate with the normal position of the anal sacs at 4-5 o'clock on the right side and 7-8 o'clock on the left side. For larger masses, the entire perineal space can be occupied by the AGASAC. These masses may be visible to the owner, but more commonly dogs present because either the anal sac mass ± enlarged metastatic sublumbar lymph nodes cause constipation, tenesmus, and a change in fecal shape (usually flattened or ribbon-like). Other dogs will present because of clinical signs associated with hypercalcemia, such as polyuria, polydipsia, and urinary incontinence. Rarely, dogs will present with pain, lameness, or neurologic disease due to regional bone metastasis or direct extension into the lumbar vertebrae from metastatic sublumbar lymph nodes.

Diagnosis Physical and rectal examinations are essential to identify the side of the anal sac mass and to palpate enlarged sublumbar lymph nodes. Bilateral AGASACs are very rare, but they have been reported and hence both anal sacs should be carefully palpated. An aspirate of the anal sac mass can be performed to confirm the diagnosis of AGASAC and differentiate AGASAC from non-neoplastic anal sac diseases such as anal sacculitis and anal sac abscesses. Carcinoma is readily diagnosed in the majority of dogs with AGASAC. Incisional biopsy is rarely required for diagnosis and delays definitive treatment. Blood tests include hematology, serum biochemistry, calcium levels, and possibly parathyroid hormone and parathyroid hormone-related protein assays. Although total calcium levels can be used for the diagnosis of hypercalcemia, ionized calcium levels are preferred because they

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represent the physiologically active component of calcium balance. Hypercalcemia is defined as a total serum calcium level > 3.8 mmol/L or an ionized calcium level > 1.5 mmol/L, however these are laboratory-dependent. Furthermore, dogs with hypercalcemia may have biochemical evidence of renal failure including elevated creatinine, urea, and phosphorus. Parathyroid hormone and parathyroid hormone-related protein assays may be required in dogs with hypercalcemia but no evidence of an anal sac mass or other causes of hypercalcemia, such as lymphosarcoma, primary or secondary hyperparathyroidism, vitamin D toxicity, and hypoadrenocorticism. Dogs with paraneoplastic hypercalcemia will have increased levels of parathyroid hormone-related protein and normal parathyroid hormone concentrations. Clinical Staging Clinical staging involves assessment of local tumor size and evaluating for the presence of metastatic disease. `Three-view thoracic radiographs are recommended for evaluation of pulmonary metastasis. Surgery Surgery is recommended for the treatment of dogs with either non-metastatic AGASAC or AGASAC with metastasis to the sublumbar lymph nodes. Severe hypercalcemia is uncommon in dogs with AGASAC but, if present, aggressive medical management may be required prior to surgery. This includes the administration of prednisone, calcium-free intravenous fluids (i.e., isotonic saline) to reverse hypercalcemia-induced extracellular fluid volume contraction, and calciuretic loop diuretics (i.e., furosemide) to increase the rate of renal calcium excretion following volume expansion. Anal Sacculectomy For resection of AGASAC, dogs should be positioned in sternal recumbency with the tail reflected dorsally. The rectum should be manually emptied of feces, but enemas are not recommended because they liquefy intestinal contents and increase risk of spillage during surgery. The risk of spillage is further reduced by inserting gauze swabs or tampons into the rectum. A purse-string suture can also be used, but this may interfere with surgical resection. The use of antibiotics is controversial and is dependent on the surgeon. A pararectal surgical approach is used to resect the AGASAC. The affected anal sac and mass are excised by a closed anal sacculectomy technique. An open technique is not recommended because of the risk of contaminating the surgical site and increasing the risk of local tumor recurrence. Marginal resection is recommended because the perineal space contains no structures amenable to achieving wide resection. Both the external anal sphincter and caudal rectal nerve should be identified and preserved if possible. The tumor rarely involves the rectum, but if partial rectal resection is planned then the owner should be warned about the risk of fecal incontinence if greater than 50% of the anal sphincter is resected. The surgical complication rate following resection of the anal sac mass, sublumbar lymph nodes, or both is 10%. These complications include intraoperative hemorrhage, infection, fecal or urinary incontinence, hypocalcemia, tenesmus, and perianal fistula formation. Lymphadenectomy Resection of metastatic sublumbar lymph nodes is indicated in dogs with sublumbar node metastasis and hypercalcemia or tenesmus. In dogs with hypercalcemia, both the anal sac mass and metastatic sublumbar lymph nodes need to be resected to achieve resolution of

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hypercalcemia because the cells responsible for production of the parathyroid-related hormone are present in all tumor sites, both the primary tumor and metastatic lymph nodes. The sublumbar lymph nodes are resected through a caudal midline ventral celiotomy. Despite descriptions in anatomy textbooks, the sublumbar lymph nodes are not restricted to the medial iliac and hypogastric lymph nodes but actually consist of a lymphatic bed from which a number of enlarged lymph nodes can arise, including the internal and external iliac lymph nodes and medial and lateral sacral lymph nodes. These lymph nodes are often located at the terminal aorta between the branches the external iliac and median sacral arteries. The caudodorsal abdominal cavity should be carefully palpated to identify all enlarged lymph nodes. Lymph node resection can be difficult because of poor visibility, limited access, and the proximity of vascular structures. Sublumbar lymph nodes can be resected in the majority of cases, but resectability cannot be determined preoperatively and large sublumbar nodes do not preclude resection. Some metastatic lymph nodes are cystic and can easily rupture during attempted dissection. Omentalization of a ruptured cystic sublumbar lymph node has been described in one dog. Tumor seeding and carcinomatosis are rarely observed in dogs with ruptured metastatic lymph nodes. Fatal hemorrhage is reported in approximately 5% of dogs during sublumbar lymph node resection. Some surgeons are reluctant to perform sublumbar lymph node resection because of unfamiliarity with the anatomy or reluctance because of the complexity of the anatomical structures in the caudal abdomen. However, intraoperative problems are rarely encountered with review of the anatomy and a careful dissection technique. Furthermore, in one retrospective study, excision of metastatic sublumbar lymph nodes significantly improved survival times. These authors also suggested that metastatic lymph nodes less than 4.5cm in diameter should be surgically excised, but dogs with metastatic lymph nodes larger than 4.5cm in diameter should be treated with chemotherapy and their response monitored. I personally prefer to surgically excise all metastatic lymph nodes regardless of size or number. Radiation Therapy Radiation therapy has a number of potential roles in the treatment of dogs with AGASAC. Intraoperative radiation therapy has been used to irradiate the sublumbar lymph node bed to minimize the risk of further metastatic lesions developing. Because of the risk of local tumor recurrence and sublumbar lymph node metastasis, full-course external beam radiation therapy of the perianal and pelvic regions has been recommended for all dogs following surgery. Radiation therapy can also be used for inoperable or recurrent AGASAC and inoperable metastatic sublumbar lymph nodes. The major disadvantage of full-course fractionated external beam radiation is the radiation field contains many radiation-sensitive organs, such as the colon and bladder, resulting in debilitating acute radiation effects such as colitis, proctatitis, bladder fibrosis, and urinary incontinence. Chemotherapy Adjunctive chemotherapy is recommended because of the high metastatic rate in dogs with AGASAC. However, it should not be used as the only treatment because of a significantly decreased median survival time. A number of different chemotherapy protocols have been described, but none are superior to surgery alone. These protocols include platinum drugs, anthracyclines such as doxorubicin and mitoxantrone, non-steroidal anti-inflammatory drugs, and dual-agent therapy with alternating carboplatin and doxorubicin. Tyrosine kinase inhibitors such as Palladia have been shown to have objective responses in approximately 25% of dogs with measurable AGASAC.

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Prognosis The prognosis for treated dogs with non-metastatic AGASAC and AGASAC metastatic to the sublumbar lymph nodes is good, with an overall median survival time of 479-544 days. Local tumor recurrence is observed in 25%-50% of dogs following surgical resection with a median disease-free interval of 10 months. Prognostic factors in dogs with AGASAC include tumor size, hypercalcemia, untreated nodal metastasis, lung metastasis, and treatment. The median survival time for dogs with tumors ≥ 10 cm2 is 292 days and significantly worse than the median survival time of 584 days for dogs with smaller tumors. In another study, dogs with tumors > 2.5cm diameter had a significantly worse prognosis with a median survival time of 722 days compared to 1,205 days for dogs with tumors < 2.5cm diameter, however this was not evident in the prospective arm of their study. The median survival time for dogs with hypercalcemia is 256 days and significantly worse than the median survival time of 584 days for dogs with no hypercalcemia. The median survival time for dogs with lung metastasis is 219 days and significantly worse than the median survival time of 584 days for dogs with no lung metastasis. In a recent study, the presence of sublumbar lymph node metastasis was associated with a significantly worse prognosis, but extirpation of metastatic nodes resulted in a significantly better outcome which highlights the important of surgical excision of metastatic sublumbar lymph nodes in dogs with AGASAC. Finally, the median survival time for dogs with AGASAC is significantly worse if surgery is not incorporated into the treatment regimen (402 days) or dogs are treated with chemotherapy alone (212 days). Although not statistically significantly, the following median survival times and 1- and 2-year survival rates were reported for treated AGASAC: Surgery Surgery and

Chemotherapy Surgery, Radiation and Chemotherapy

Median survival time 500 days 540 days 742-956 days 1-year survival rate 65% 69% 80% 2-year survival rate 29% 38% 56% From these results, the best results are achieved with a combination of surgery and postoperative radiation and perhaps chemotherapy.

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SENTINEL LYMPH NODES



Lymph node status is important in the clinical staging of cats and dogs with cancer. The sentinel lymph node (SLN) is a significant concept in surgical oncology. The SLN concept is based on the theory that the metastatic process occurs in an orderly progression within the lymphatic system with tumor cells draining into a specific lymph node (i.e., SLN) in a regional lymphatic field before draining into other regional lymph nodes. The SLN has an important role as a filter and barrier for disseminating tumor cells. Conceptually, distant metastasis should not be present if the SLN does not have evidence of a tumor burden, but distant metastasis is possible if the SLN is positive for tumor cells. Hence, the status of the SLN node may reflect the status of the entire regional lymphatic bed. Sentinel lymph nodes are successfully identified in over 95% of women with breast cancer and 97% of patients with gastric cancer and this is predictive of the status of the remainder of the regional lymph node bed in > 85% and 99% of cases, respectively. The SLN is not specific for tumor type or location, but is individual and changes from patient to patient. In people, identification of the SLN is important in the diagnosis of lymph node metastasis, early identification of patients requiring additional therapeutic options to manage metastatic disease (such as lymph node dissection and adjuvant chemotherapy or radiation therapy), and establishing a prognosis. Sentinel lymph nodes can be identified using a number of techniques, including contrast-enhanced ultrasonography, lymphoscintigraphy, pertitumoral injection of blue dye, and intraoperative cytology or histopathology. Despite the importance of SLNs in numerous types of cancer in human oncology (including head and neck cancer, breast cancer, cutaneous melanoma, gastric carcinoma, colon cancer, and genitourinary cancers), this concept has not been widely tested or accepted in veterinary medicine. The importance of identification of the SLN is highlighted by studies of oral tumors in cats and dogs, and cutaneous mast cell tumors in dogs. In one study of 100 dogs with oral melanoma, 40% of dogs with normal sized lymph nodes had metastasis and 49% of dogs with enlarged lymph nodes did not have metastasis. Similarly, lymph node metastasis has been identified in grossly normal lymph nodes in animals with tumors which have a high risk of nodal metastasis, such as cats with mammary carcinomas and dogs mast cell tumors and apocrine gland anal sac adenocarcinomas. Furthermore, in animals with oral tumors, the regional lymph nodes include the mandibular, parotid, and medial retropharyngeal lymph nodes; however, the parotid and medial retropharyngeal lymph nodes are not externally palpable. Only 55% of 31 cats and dogs with oral tumors and metastasis to the regional lymph nodes had metastasis to the mandibular lymph nodes, meaning that metastasis would have been missed in 45% of animals if these nodes had not been extirpated. In a study of dogs with cutaneous mast cell tumors, 8/19 dogs had sentinel nodes different to the regional lymph node. The acceptance of SLN mapping would revolutionize oncologic practice in animals by permitting the early identification of animals at risk of nodal metastasis and hence the need for additional therapies.

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CHALLENGING MAXILLECTOMY CASES – TRIUMPHS AND FAILURES



Canine Oral Tumors Oral cancer accounts for 6% of all canine cancers and is the fourth most common cancer overall. The most common malignant oral tumors in dogs are, in descending order:

§ Malignant melanoma § Squamous cell carcinoma § Fibrosarcoma § Osteosarcoma

Other malignant oral tumors in dogs include chondrosarcoma, anaplastic sarcoma, multilobular osteochondrosarcoma, intraosseous carcinoma, myxosarcoma, hemangiosarcoma, lymphosarcoma, mast cell tumor, and transmissible venereal tumor. Benign tumors also occur relatively frequently, including acanthomatous ameloblastoma and peripheral fibrosing odentomas. Feline Oral Tumors Oral tumors account for 3%-10% of all cancers in cats. Unlike dogs, over 90% of feline oral tumors are malignant. Squamous cell carcinoma is the most common oropharyngeal cancer in cats, followed by fibrosarcoma, which accounts for 13% of feline oral tumors.

DIAGNOSIS Oral cancers have wide ranges of biologic behavior and therapeutic options, hence a knowledge of tumor type is important prior to definitive therapy. A short general anesthesia is usually required for careful palpation, regional radiographs, and a biopsy. A large incisional biopsy is required for diagnosis. Cytologic touch or aspiration preparations of oral tumors are usually not rewarding because most oral tumors are associated with a high degree of necrosis and inflammation. Dogs with exophytic or ulcerated masses will generally tolerate a deep wedge or core punch biopsy without general anesthesia. Because oral cancers are often infected, inflamed, or necrotic, and it is important to obtain a large specimen. Electrocautery may distort the specimen and should only be used for hemostasis after collection of the biopsy. Large samples of healthy tissue at the edge and center of the lesion will increase the diagnostic yield, but care must be taken not to contaminate normal tissue, which cannot be removed with surgery or included in the radiation field. Biopsies should always be performed from within the oral cavity and not through the lip to avoid seeding tumor cells in normal skin and compromising curative-intent surgical resection.

CLINICAL STAGING

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Local Tumor Regional radiographs or advanced imaging are recommended for local staging of oral tumors which are palpably fixed to underlying bone. Bone invasion can often be more extensive than is apparent on external palpation, and thus is important for planning of surgical margins. Regional radiographs include open mouth, intraoral, oblique lateral, and ventrodorsal or dorsoventral projections. Bone lysis is not radiographically evident until > 40% of the cortex is destroyed by the neoplastic process. Apparently normal radiographs do not exclude the possibility of bone invasion. Computed tomography is preferred to magnetic resonance imaging for local staging of oral tumors because it is very sensitive for the detection of bone involvement. Computed tomography is recommended for caudal mandibular (Fig. 1) and all maxillary tumors (Fig. 2) to more accurately assess the degree of bone invasion and possible tumor extension into the nasal cavity, caudal pharynx, or orbit.

Fig. 1. A CT scan of a dog with an osteoma of the mandibular

ramus. Advanced imaging provides better delineation of bone

involvement in all oral tumors, particularly maxillary and

caudal mandibular tumors. This imaging provides superior

information for planning of the surgical approach and resection

margins.

Fig. 2.

A CT

scan

of a dog with a fibrosarcoma of the caudal maxilla. In this dog, the CT scan shows the tumor

extending to the midline of the hard palate, the nasal septum, and more than 50% of the

ipsilateral maxilla and infraorbital bone. There is also a soft tissue component resulting in lateral

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and dorsal displacement of the eye. This extent of tumor involvement could not have been

determined with either palpation or regional radiographs.

Regional Lymph Node Metastasis Regional lymph nodes should be carefully palpated for enlargement or asymmetry. However, lymph node size is not an accurate predictor of metastasis. In one study of 100 dogs with oral melanoma, 30% of dogs with normal sized lymph nodes had metastasis and 40% of dogs with enlarged lymph nodes did not have metastasis. The regional lymph nodes include the mandibular, parotid, and medial retropharyngeal lymph nodes, but the parotid and medial retropharyngeal lymph nodes are not palpable. Furthermore, only 55% of 31 cats and dogs with metastasis to the regional lymph nodes had metastasis to the mandibular lymph node. Lymphoscintigraphy or contrast-enhanced ultrasonography can be used to detect the sentinel lymph nodes and guide lymph node aspirates. Lymph node aspirates should be performed in all animals with oral tumors, regardless of the size or degree of fixation of the lymph nodes. En bloc resection of the regional lymph nodes has been described and, although the therapeutic benefit of this approach is unknown, it may provide valuable staging information.

Distant Metastasis Three-view thoracic radiographs are recommended for evaluation of pulmonary metastasis. The most common tumors to metastasize to the lungs are oral malignant melanoma and squamous cell carcinoma of the caudal oral, pharyngeal, and tonsillar area. MAXILLECTOMY Maxillectomy techniques include unilateral and bilateral rostral maxillectomy, hemimaxillectomy, caudal maxillectomy, and radical maxillectomy.

Depending on the location of the tumor, maxillectomy procedures may involve resection of part or all of the incisive, maxillary, zygomatic, lacrimal, and orbital bones, and hard palate. As mentioned above, advanced imaging is an important preoperative diagnostic modality to determine the extent of the tumor and plan surgical margins. There is a moderate risk of blood

5

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loss during hemi- and caudal maxillectomies because of the large resections, numerous foramina and blood vessels (Fig. 5), and exposure of the nasal cavity. Cross-matching or blood typing are recommended prior to maxillectomies in case a blood transfusion is required. Maxillectomies are closed with a full-thickness labial mucosal-submucosal flap using one or two layers. Two-layer closures are recommended for animals receiving adjuvant chemotherapy or radiation therapy. A two-layer closure consists of a deep layer of simple interrupted sutures through predrilled holes in the bony hard palate and a superficial layer apposing the palatal mucosa to the labial mucosa (Fig. 6). The palatal mucosa can be undermined by 2-3 mm to assist in tissue apposition.

Unilateral Rostral Maxillectomy Unilateral rostral maxillectomy is recommended for resection of benign tumors or squamous cell carcinoma of the rostral maxilla that do not cross the midline and are rostral to the second premolar tooth.

Fig. 6. A two-layer closure following maxillectomy for tumor resection. The palatal mucosa (C) is reflected 2-3 mm and holes are drilled into the palatine bone (B). The deep layer consists of simple interrupted sutures from the submucosa of the mucosal flap (A) through the predrilled palatal holes. The superficial layer consists of simple interrupted or continuous sutures opposing the labial mucosa to the mucoperiosteum of the hard palate. (From Bojrab (ed). Current Techniques in Small Animal Surgery (4th edn), 1998.)

The animal is positioned in lateral recumbency. The labial and gingival mucosa rostral and lateral to the mass are excised with 1 cm margins. The incision is continued through the hard palate medial and caudal to the lesion. An oscillating bone saw or osteotome is used to perform osteotomies over previous mucosal incisions. Curved bone margins will reduce tension and improve apposition and healing compared to square margins. The resected segment of bone is removed en bloc by severing soft tissue attachments. Hemorrhage from the hard palate incision, branches of the major palatine artery, and nasal cavity is usually brisk and should be controlled with digital pressure, cautery, or ligation. Turbinectomy should be performed if there is evidence of tumor invasion or iatrogenic trauma. The defect is closed as described above. Bilateral Rostral Maxillectomy Bilateral rostral maxillectomy is recommended for resection of benign tumors or squamous cell carcinoma of the rostral maxilla that crosses the midline and are rostral to the second premolar tooth. Bilateral rostral maxillectomy can be combined with resection of the nasal planum and premaxilla for more invasive tumors and tumors of the nasal planum.

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The animal is positioned in either ventral or dorsal recumbency. The dissection technique and closure are the same as described above. Hemimaxillectomy Hemimaxillectomy is recommended for the resection of lateral and caudal maxillary tumors that do not cross the palatine midline. This involves removal of the oral mucosa, teeth, and segments of the incisive, maxillary, palatine, and zygomatic bones. The extent of surgery is determined by the size and location of the tumor, degree of soft tissue involvement, and expected biologic behaviour of the tumor. Caudal maxillectomies can be combined with resection of the inferior orbit, zygomatic arch, and vertical mandibular ramus depending on the extent of the tumor. Hemimaxillectomies are performed through either intraoral or combined intraoral and dorsal skin approaches. The intraoral approach is recommended for tumors confined to the alveolar margin. The mucosal incision is started at the labial-gingival margin dorsal to the middle incisors and continued laterally and caudally to the level of the second molar tooth. The medial incision is started at the central incisors and extended through the midline of the hard palate and continued caudally to the level of the second molar. The mucosal and palatal incisions are joined caudally with an incision caudal to the second molar tooth at the junction of the hard and soft palates. The terminal branches of the maxillary artery (i.e., infraorbital, sphenopalatine, and minor palatine arteries) are identified and ligated at the caudal aspect of the surgical field. An oscillating bone saw or osteotome is used to perform osteotomies through the incisive, palatine, and maxillary bones. The resected segment of bone is removed en bloc by severing soft tissue attachments. Hemorrhage from the hard palate incision, branches of the major palatine artery, and nasal cavity is usually brisk and should be controlled with digital pressure, cautery, or ligation. Turbinectomy should be performed if there is evidence of tumor invasion or iatrogenic trauma. The defect is closed as described above (Fig. 7).

Fig. 7. Hemimaxillectomy. A. The dotted line indicates the mucosal incision. B. The labial mucosa-submucosa is undermined with Metzenbaum scissors to create a lip-margin based labial flap for closure of the hemimaxillectomy. C. Simple interrupted or continuous sutures are used to close the mucosal flap over the defect. (From Bojrab (ed). Current Techniques in Small Animal Surgery (4th edn), 1998.)

A combined dorsal and ventral approach to the maxilla is recommended for large lateral or dorsal maxillary masses as a bipedicled tissue flap over the lateral aspect of the maxilla can be

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retracted dorsally or ventrally to provide excellent exposure for the dorsal osteotomy. A dorsal incision is made immediately lateral to the dorsal midline of the nasal cavity and continued caudally and ventrally to the eye and along the zygomatic arch. The skin incision is continued through the subcutaneous tissue, between the paired levator nasolabialis muscles, and to the bone. The ventral aspect of the globe and the masseter muscle are separated from the dorsal and ventral aspects of the zygomatic arch, respectively, with blunt and sharp dissection. The dorsal osteotomy is prepared with subperiosteal elevation of periosteum and soft tissue from the resection site. The intraoral approach, maxillectomy, and closure are performed as described above. Caudal Maxillectomy via a Combined Intraoral-Dorsolateral Skin Approach Caudal maxillectomy via an a combined intraoral and dorsolateral approach was first described by Lascelles et al (2003) and is an excellent approach for tumors of the mid-to-caudal maxilla and inferior orbit which either arise or extend dorsolaterally and/or caudally to the alveolar margin. The combined approach provides better exposure, and thus improved ability to achieve hemostasis and completely excise the tumor, compared to the intraoral approach for more extensive caudal maxillary tumors. A CT scan is recommended for tumors of the caudal maxilla and orbit to determine the extent of the tumor, determine whether the tumor is resectable, and to plan the surgical approach. In some cases, particularly those with more extensive involvement of the orbit, enucleation may be required to improve exposure and likelihood of achieving complete excision of the tumor.

Dogs are positioned in lateral recumbency with the mouth held open using a gag. The pharynx should be packed with gauze sponges to minimize the risk of aspirating blood and lavage fluid. The dorsolateral skin incision is created first with an incision lateral to midline of the dorsal aspect of the nasal cavity and extending caudally and ventrally to the eye along the zygomatic bone. This incision is continued through the subcutaneous tissue, between the paired levator nasolabialis muscles, and down to bone. Caudally, the ventral aspect of the globe is separated from the dorsal zygoma with a combination of sharp and blunt dissection leaving the conjunctival sac intact, while the masseter muscle is elevated from the ventral aspect of the zygomatic arch using a combination of sharp and blunt dissection. The most common complication of the combined approach for caudal maxillectomy is blood loss from the maxillary artery. The maxillary artery should be ligated early in the procedure, if possible, to prevent this complication. The maxillary and palatine arteries are exposed deep within the orbit by carefully retracting the globe dorsally and ligated with either suture material or metallic clips. Exposure may be limited and can be improved by resecting the zygomatic arch rostral to the orbital ligament, however this is often difficult and ligation of the maxillary artery is frequently completed at the end of the procedure when the bone segment is freed. The tumor should be excised with appropriate margins depending on whether it is benign or malignant. The dorsal margins are prepared by reflecting the periosteum and associated soft tissues with a periosteal elevator. A second incision is made in the buccal musosa dorsal to the gingiva and with appropriate margins through an intraoral approach. The mucosal incision is continued down to the bone and undermined with periosteal elevators and scissors to connect the mucosal and dorsal skin incisions and create a bipedicle flap. The infraorbital artery and vein, which will be encountered during this dissection along with the infraorbital nerve, should be individually ligated. The facial vein should also be ligated at the most dorsocaudal aspect of the incision, but the facial vein should be preserved at the level of the dorsal nasal tributary if possible to facilitate venous drainage from the muzzle.

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The bipedicle flap can be retracted dorsally and ventrally to allow visualization of the lateral aspect of the maxilla and improve exposure for tumor excision. The dorsal and rostral maxillary osteotomies are performed at appropriate margins from the tumor with an oscillating saw, pneumatic burr or osteotome. An incision is then made through the mucoperiosteum of the hard palate medial to the alveolar margin or as dictated by the margins of the tumor. The major palatine artery or its branches may be transected during this incision and bleeding from these vessels can be controlled with either digital pressure, cautery or ligation. The mucoperiosteum is elevated with a periosteal elevator to preserve the soft tissues which will be used later for reconstruction of the defect. An osteotomy is performed in the palatine bone from the ventral aspect of the rostral maxillary osteotomy and extending caudally to the planned caudal extent of the excision. Finally, the caudal osteotomy is completed such that it connects the caudal aspects of the dorsal maxillary and palatine osteotomies. Both the palatine and caudal osteotomies can be performed with either an oscillating saw or osteotome and mallet. If the caudal osteotomy involves the inferior orbit, then this is preferably performed with an osteotome and mallet with the osteotome started at the junction between the inferior orbit and caudal maxilla, caudal to the molar teeth, and directed rostrally to connect the lateral maxillary and palatine osteotomies. The maxillary artery courses deeply through the caudoventral aspect of the inferior orbit. If the maxillary artery has not been previously ligated, then it should be ligated with either suture material or metallic clips at this stage. Following completion of the osteotomies, the free bone segment should be gently elevated and removed. Bleeding from the surgical site is then controlled with either suture or metallic clip ligation or cautery for vessels; and a combination of tamponade and ice-cold saline or 0.05% oxymetazoline spray for bleeding from the turbinates because cautery is rarely successful for turbinate bleeding. The intraoral incision is closed first. This is best approached from a dorsal direction through the bipedicle flap. The degree of tension on the lip should be assessed prior to closure. To minimize tension and to prevent the lip being drawn medially resulting in a poor cosmetic result, particularly following extensive resection of the hard palate, a labial mucosal-submucosal flap may be required. The flap is sutured into position with a two-layer closure. If this closure is performed through the dorsal skin incision, then the labial mucosa and mucoperiosteum of the hard palate are opposed using a simple interrupted or continuous suture pattern. The thick fibrovascular free edge of the lip is sutured to pre-drilled holes in the bone of the hard palate. If this closure is performed through an intraoral approach, which tends to be more awkward, then the lip submucosa to palatine bone closure is performed first followed by the mucosa-mucoperiosteum closure. Finally, the dorsolateral skin incision is closed routinely. No attempt is made to close the dead space between the oral and lateral nasal incisions. Drains are not required, as the surgical site opens into the nasal cavity and drainage occurs via the nasal orifice. The cosmetic appearance is usually very good to excellent, especially if the globe can be preserved. Functional outcome is usually excellent in both cats and dogs. The most common complications include transient epistaxis, dehiscence of the intraoral wound with subsequent oronasal fistula, epiphora, nasal discharge (serous to purulent), surgical swelling, and paradoxical motion of the skin overlying the resected maxillary bone. Radical Maxillectomy Radical maxillectomy has been described for the surgical resection of large rostral maxillofacial tumors in cats and dogs. The level of maxillectomy was originally described as being rostral to

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the canine tooth, but radical maxillectomy has since been reported as far caudal as the third premolar tooth. The technique is similar to bilateral rostral maxillectomy but includes resection of the nasal planum and skin to the same level as the maxillectomy (Fig. 8). The skin and lips are closed to the maxillary and palatine bone in two layers as described above (Fig. 9). These procedures are associated with good to excellent tumor control, good functional results, and challenging but acceptable cosmetic appearance.

Fig. 8. The skin and maxillary and palatine bones are

resected at the same level.

Fig. 9. The skin and lips are closed in two layers as described in Fig. 6. (From Kirpensteijn et al, Vet Surg, 1993.)

Complications associated with maxillectomy procedures include transient epistaxis for 1-3 days postoperatively, oronasal fistula following wound dehiscence, mucosal ulceration because of trauma from the ipsilateral mandibular tooth, cosmetic appearance (for rostral maxillectomies in particular), and less commonly epiphora, sneezing, and nasal discharge.

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MANDIBULECTOMIES – HOW MUCH IS TOO MUCH?



Canine Oral Tumors Oral cancer accounts for 6% of all canine cancers and is the fourth most common cancer overall. The most common malignant oral tumors in dogs are, in descending order:

§ Malignant melanoma § Squamous cell carcinoma § Fibrosarcoma § Osteosarcoma

Other malignant oral tumors in dogs include chondrosarcoma, anaplastic sarcoma, multilobular osteochondrosarcoma, intraosseous carcinoma, myxosarcoma, hemangiosarcoma, lymphosarcoma, mast cell tumor, and transmissible venereal tumor. Benign tumors also occur relatively frequently, including acanthomatous ameloblastoma and peripheral fibrosing odentomas. Feline Oral Tumors Oral tumors account for 3%-10% of all cancers in cats. Unlike dogs, over 90% of feline oral tumors are malignant. Squamous cell carcinoma is the most common oropharyngeal cancer in cats, followed by fibrosarcoma, which accounts for 13% of feline oral tumors.

DIAGNOSIS Oral cancers have wide ranges of biologic behavior and therapeutic options, hence a knowledge of tumor type is important prior to definitive therapy. A short general anesthesia is usually required for careful palpation, regional radiographs, and a biopsy. A large incisional biopsy is required for diagnosis. Cytologic touch or aspiration preparations of oral tumors are usually not rewarding because most oral tumors are associated with a high degree of necrosis and inflammation. Dogs with exophytic or ulcerated masses will generally tolerate a deep wedge or core punch biopsy without general anesthesia. Because oral cancers are often infected, inflamed, or necrotic, and it is important to obtain a large specimen. Electrocautery may distort the specimen and should only be used for hemostasis after collection of the biopsy. Large samples of healthy tissue at the edge and center of the lesion will increase the diagnostic yield, but care must be taken not to contaminate normal tissue, which cannot be removed with surgery or included in the radiation field. Biopsies should always be performed from within the oral cavity and not through the lip to avoid seeding tumor cells in normal skin and compromising curative-intent surgical resection.

CLINICAL STAGING

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Local Tumor Regional radiographs or advanced imaging are recommended for local staging of oral tumors which are palpably fixed to underlying bone. Bone invasion can often be more extensive than is apparent on external palpation, and thus is important for planning of surgical margins. Regional radiographs include open mouth, intraoral, oblique lateral, and ventrodorsal or dorsoventral projections. Bone lysis is not radiographically evident until > 40% of the cortex is destroyed by the neoplastic process. Apparently normal radiographs do not exclude the possibility of bone invasion. Computed tomography is preferred to magnetic resonance imaging for local staging of oral tumors because it is very sensitive for the detection of bone involvement. Computed tomography is recommended for caudal mandibular (Fig. 1) and all maxillary tumors to more accurately assess the degree of bone invasion and possible tumor extension into the nasal cavity, caudal pharynx, or orbit.

Fig. 1. A CT scan of a dog with an osteoma of the mandibular

ramus. Advanced imaging provides better delineation of bone

involvement in all oral tumors, particularly maxillary and

caudal mandibular tumors. This imaging provides superior

information for planning of the surgical approach and resection

margins.

Regional Lymph Node Metastasis Regional lymph nodes should be carefully palpated for enlargement or asymmetry. However, lymph node size is not an accurate predictor of metastasis. In one study of 100 dogs with oral melanoma, 30% of dogs with normal sized lymph nodes had metastasis and 40% of dogs with enlarged lymph nodes did not have metastasis. The regional lymph nodes include the mandibular, parotid, and medial retropharyngeal lymph nodes, but the parotid and medial retropharyngeal lymph nodes are not palpable. Furthermore, only 55% of 31 cats and dogs with metastasis to the regional lymph nodes had metastasis to the mandibular lymph node. Lymphoscintigraphy or contrast-enhanced ultrasonography can be used to detect the sentinel lymph nodes and guide lymph node aspirates. Lymph node aspirates should be performed in all animals with oral tumors, regardless of the size or degree of fixation of the lymph nodes. En bloc resection of the regional lymph nodes has been described and, although the therapeutic benefit of this approach is unknown, it may provide valuable staging information.

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Distant Metastasis Three-view thoracic radiographs are recommended for evaluation of pulmonary metastasis. The most common tumors to metastasize to the lungs are oral malignant melanoma and squamous cell carcinoma of the caudal oral, pharyngeal, and tonsillar area.

MANDIBULECTOMY Surgery and radiation therapy are the most common modalities used for the treatment of the local oral tumor. Surgical resection is preferred for the majority of oral tumors in cats and dogs because it is more economical, fast, and curative than other available treatment options. The type of surgery depends on tumor type and location. Radical surgeries such as mandibulectomy, maxillectomy, and orbitectomy are well tolerated by cats and dogs with good postoperative function and acceptable cosmetic appearance. Orbitectomy will be discussed in the lecture on axial bone tumors. These procedures are indicated for all oral tumors, particularly lesions with extensive bone invasion or poor sensitivity to radiation therapy. Oral tumors other than fibromatous and ossifying epulides have some underlying bone involvement and surgical resection should include a minimum of 1 cm bone margins to increase the rate of local tumor control. If possible, surgical margins greater than 2 cm should be attempted in cats with oral squamous cell carcinoma because of high local recurrence rates. Reconstruction following bony resection has been described but is rarely necessary. Rostral and segmental resections may be sufficient for benign tumors and rostral squamous cell carcinoma in dogs. More radical resections resections, including hemimandibulectomy, hemimaxillectomy, orbitectomy, and radical maxillectomy, are necessary for more aggressive tumors, especially fibrosarcomas, and malignant tumors with a more caudal location. Although these large resections carry some morbidity, owner satisfaction with the cosmetic and functional outcomes are in excess of 85%. Cosmetic appearance is usually very good following most mandibulectomy and maxillectomy procedures, but can be challenging with aggressive bilateral rostral mandibulectomies and radical maxillectomies. Blood loss and hypotension are the most common intraoperative complications, particularly during caudal or aggressive maxillectomy procedures. Postoperative complications include incisional dehiscence, epistaxis, increased salivation, mandibular drift and malocclusion, and difficulty prehending food, particularly after bilateral rostral mandibulectomy caudal to the second premolar teeth. Enteral feeding tubes are not usually required following oral surgery in dogs, but are recommended for cats treated with any type of mandibulectomy as eating can be difficult for 2-4 months following surgery. Local disease control is the goal of treatment for most animals with oral tumors. Regional lymph node resection has been described in cats and dogs and, although it adds to clinical staging information, its effectiveness in controlling local and metastatic disease is unknown. Unilateral Rostral Mandibulectomy Unilateral rostral mandibulectomy is recommended for resection of benign tumors, such as acanthomatous epulis, or squamous cell carcinoma of the rostral mandible that do not cross the midline and are rostral to the second premolar tooth.

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The animal is positioned in lateral recumbency with affected side facing dorsally. The labial mucosa is incised with 1 cm minimum margins around the gross mass. Dissection is continued around the mandibular body to the caudal extent of the mandibular symphysis or osteotomy site. The sublingual and mandibular salivary gland ducts open under body of tongue at sublingual caruncle and should be preserved. The rostral osteotomy should be eccentric (i.e., between the contralateral incisors or canine and incisors) to ensure complete resection of the mandibular symphysis (Fig. 2). The caudal osteotomy should be tapered at the occlusional margin to minimize wound tension. The mucosa is closed with monofilament absorbable suture material in a simple interrupted or continuous pattern. Bilateral Rostral Mandibulectomy Bilateral rostral mandibulectomy is recommended for resection of benign tumors or squamous cell carcinoma of the rostral mandible that crosses the midline and are rostral to the second premolar tooth, although aggressive procedures rostral to the fourth premolar tooth bilaterally have been described. The animal can be positioned in either dorsal, lateral, or sternal recumbency. Dorsal recumbency provides superior exposure for dissection and osteotomy, while ventral recumbency provides superior exposure for more difficult wound closures. The dissection technique is similar to described above. The mandibular body is transected in a caudodorsal to rostroventral direction to allow apposition of mucosa over mandible without tension. Mandibular stabilization is not necessary, but bone screws, bone graft, or pins have been reported for mandibular stabilization following mandibulectomy. Redundant skin may need to be removed before closure by excising V-shaped wedges rostrally or laterally. The rostral soft tissue ridge (or dam) can help maintain saliva in mouth. The defect is closed by suturing the labial mucosa to the sublingual mucosa using monofilament absorbable suture material in a simple interrupted or simple continuous pattern. Complications following unilateral and bilateral rostral mandibulectomies include tongue drooping, hypersalivation and excessive drooling, mandibular shortening, and cheilitis. Segmental Mandibulectomy Segmental mandibulectomy is recommended for benign tumors and low-grade malignant tumors of the mid-horizontal mandible which do not penetrate cortical bone. Contraindications include tumors with penetration of the mandibular canal and malignant tumors as extension along the mandibular artery, vein, and nerve is common. The dogs is positioned in lateral recumbency. The labial and lingual mucosa are incised with 1 cm margins around the gross tumor and then dissection is continued around the mandibular body until fully exposed. Rostral and caudal osteotomies are performed a minimum of 2 cm from the tumor. The defect is closed by suturing the labial mucosa to the lingual mucosa with monofilament absorbable suture material in a simple interrupted or continuous pattern (Fig. 3).

Fig. 3. Segmental horizontal mandibulectomy. A. The dotted line indicates the proposed area to be excised. The osteotomies should be tapered away from the lesion on the occusal surface to minimize suture line tension.

2

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B. Simple interrupted or continuous closure of the labial to lingual mucosa. (From Bojrab (ed). Current Techniques in Small Animal Surgery (4th edn), 1998.) Hemimandibulectomy Hemimandibulectomy is recommended for high-grade tumors with extensive involvement of the horizontal ramus or invasion into the medullary canal. The animals is positioned in lateral recumbency. The commissure of the lips can be incised full thickness to the rostral aspect of the vertical ramus to improve exposure. If done, branches of facial artery and vein will need to be ligated and the parotid salivary duct is preserved. The labial and buccal mucosa are incised with 1 cm margins around the gross mass and extended caudally to the vertical ramus. The mandibular and sublingual salivary ducts are identified and ligated. The genioglossus, geniohyoideus, and mylohyoideus are transected from the medial aspect of the mandible. The sublingual mucosa is incised to free the lateral border of the tongue. The mandibular symphysis is separated to allow free lateral movement of the hemimandible and enhance exposure and visualization for caudal dissection. Subtotal mandibulectomy can be performed at the rostral edge of the masseter muscle insertion on the mandible for rostral tumors with bone marrow involvement resulting in preservation of the vertical ramus and temporomandibular joint. For total mandibulectomy, the masseter muscle is dissected from the ventrolateral surface and ventral margin of ramus, the digastricus muscle is dissected from the insertion on the caudoventral border of the horizontal mandible, and the pterygoid muscles are dissected from its insertion on the medial aspect of the caudoventral surface of the angle of the mandible. The temporomandibular joint capsule is incised laterally and medially and luxated, and then the temporalis muscle is dissected from its insertion on the coronoid process of the mandible. Identification and ligation of the mandibular alveolar artery and vein as it courses over the lateral surface of the medial pterygoid muscle before it enters the mandibular foramen (ventromedial and rostral to the border between the angular and coronoid processes of the mandible) is important to minimize the risk of intraoperative hemorrhage. The resultant defect is closed in three layers with the deep layer consisting of apposition of the pterygoid, masseter and temporalis muscles, then closure of the submucosa followed by the mucosa. Monofilament absorbable suture material is used in a simple continuous pattern if there is minimal tension or a simple interrupted pattern if there is tension. The lip commissure can be advanced rostrally to the level of the canine or first premolar tooth to prevent hanging of tongue. Postoperative complications include ranula formation because of transection of the salivary ducts during tumor excision, wound dehiscence because of excessive tension, hypersalivation, mandibular drift towards the resected side with resultant malocclusion, and prehension and mastication difficulties. Vertical Ramus Mandibulectomy Mandibulectomy of the vertical ramus is recommended for benign and low-grade malignant tumors confined to the vertical ramus. The temporomandibular joint can be preserved or excised. Vertical ramus mandibulectomy can be combined with inferior orbitectomy for tumors with more extensive soft tissue involvement. The animal is positioned in lateral recumbency. A curved skin incision is performed over the ventral aspect of the zygomatic arch. The temporalis and masseter muscles are subperiosteally elevated off the dorsal and ventral aspects of the zygomatic arch, respectively. The infraorbital artery, vein, and nerve course along medial aspect of zygomatic arch and should be preserved.

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The rostral and caudal osteotomies of the zygomatic arch are performed with either an oscillating saw or Gigli wire, but not an osteotome because this tends to shatter the brittle bone of the zygomatic arch. The masseter muscle is elevated from the ventrolateral surface and ventral margin of the ramus. The temporalis muscle is elevated from its rostromedial insertion on the coronoid process of the mandible. The mandibular alveolar artery and vein should be identified and preserved as it courses over the lateral surface of the medial pterygoid muscle before entering the mandibular foramen if the temporomandibular joint is preserved. But the mandibular alveolar artery and vein should be ligated and transected if the temporomandibular joint is excised as the medial pterygoid muscle is elevated from the ventromedial aspect of the mandibular angle. The resultant defect is closed in three layers: the fascia of the temporalis and masseter muscles are opposed and then the subcutaneous tissue and skin are closed.

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COLLABORATIVE COMPARATIVE ONCOLOGY RESEARCH - ONE CANCER CONCEPT

Rodney C. Straw BVSc, M(A)ANZCVS, DACVS, ACVS Founding Fellow Surgical Oncology

Brisbane Veterinary Specialist Centre & the Australian Animal Cancer Foundation Albany Creek, Queensland, Australia

In July 1986 I joined the Comparative Oncology Unit, as it was called then, at Colorado State University in the USA. My primary job was as a surgeon in the National Cancer Institute funded Program of Projects utilising spontaneous animal cancer models to investigate novel ways to treat cancer and to better understand cancer mechanisms. It was a collaborative program between Colorado State University, North Carolina State University and Duke Medical School. Comparative oncology is the study of naturally developing cancers in animals as models for human disease. My role was in many aspects of osteosarcoma management and limb preservation. This was my career “eureka moment”: the coming together of medical, surgical and radiation veterinary oncologists, physicists, statisticians, human physicians, basic scientists of various disciplines and a whole body of support staff all investigating cancer occurring spontaneously in pet animals owned by members of the general public. I realised that spontaneous cancers in dogs and cats are an underused group of naturally occurring malignancies that share many features with human cancers such as osteosarcoma, prostate and breast cancers, non-Hodgkin's lymphoma, melanoma, soft tissue sarcoma, head and neck carcinoma, and virally induced lymphomas. Intellect, skills and many areas of expertise combined. Enormous gains were made. The power of the One Cancer Concept has still not been maximised. Many have recognised the significance of this and the One Health Initiative epitomises the concept with this mission statement: “Recognizing that human health (including mental health via the human-animal bond phenomenon), animal health, and ecosystem health are inextricably linked, One Health seeks to promote, improve, and defend the health and well-being of all species by enhancing cooperation and collaboration between physicians, veterinarians, other scientific health and environmental professionals and by promoting strengths in leadership and management to achieve these goals.”1

In 2003, the National Cancer Institute's Center for Cancer Research (CCR) launched the Comparative Oncology Program (COP)2 to help researchers better understand the biology of cancer and to improve the assessment of novel treatments for humans by treating pet animals-primarily cats and dogs-with naturally occurring cancer, giving these animals the benefit of cutting-edge research and therapeutics. There are no Australian institutions involved until now. I would like to see veterinarians and others in Australia make contribution within the One Cancer concept. At the end of 2014, it was my privileged to be a co-investigator in a team lead by David Reutens, the director of the Centre for Advanced Imaging. We applied for applying for a grant offered by the Australian Cancer Research Foundation. The basis of the proposal was to purchase a digital hybrid PET-CT scanner to fill a critical gap in the group’s imaging capabilities in large animal and human PET, and to provide a unique platform in Australia to harness the power of PET and Comparative Oncology. The ACRF recognised the strength of the One Cancer concept and awarded $2.5M to the project allowing the first Comparative Oncology program in Australia to be established, bringing together cancer researchers and veterinary oncologists from UQ’s School of Veterinary Science and from the Brisbane Veterinary Specialist Centre.3

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What makes the spontaneous cancers in dogs and cats so interesting for comparative investigation? Although mouse models have yielded important insights into cancer biology, many novel anti-cancer agents that are effective in mice fail in humans. This is presumably because mouse models used in cancer drug development do not adequately represent important biological features, such as recurrence and metastasis, which play an important role in patient outcome. Naturally occurring cancers in companion animals such as dogs share clinical and biological similarities to human cancers that are difficult to replicate in other model systems. The purpose of Comparative Oncology is to make use of these cancers as models to bridge the gap between conventional preclinical models and human trials, facilitating clinical translation of new cancer drugs, devices, techniques, and imaging procedures. The prevalence of cancer in companion animals, its rapid progression and early metastatic failure allow rapid completion of trials. Ethical constraints prevent novel agents from being used before conventional therapies in human cancer trials whereas novel agents can often be studied ab initio in companion animals because methods of treatment are yet to be established. Companion animals also allow efficacy studies in the setting of minimal residual disease. Furthermore, the relatively large size of dogs is an advantage for surgical procedures and imaging studies like PET where limited spatial resolution restricts the information that can be obtained in smaller species. The cancers planned for investigation initially by our Comparative Oncology program are osteosarcoma, glial tumours, prostate cancer and melanoma. As the program develops, veterinarians throughout Australia and New Zealand will be called on to help with recruitment of cases and to become part of our Collaborative Comparative Oncology Research – One Cancer Concept. References:

1. http://www.onehealthinitiative.com/ 2. https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home 3. https://acrf.com.au/cancer-research-grants/cancer-research-projects/university-of-

queensland-centre-for-advanced-imaging-2014/

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THE RELEVANCE OF SURGICAL MARGINS Rodney C. Straw BVSc, M(A)ANZCVS, DACVS, ACVS Founding Fellow Surgical

Oncology Brisbane Veterinary Specialist Centre & the Australian Animal Cancer Foundation

Albany Creek, Queensland, Australia

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. Oncologists rely on accurate histopathology to form the cornerstone and foundation of patient management. The pathology report provides critical information that ultimately guides clinicians’ decisions in determining optimal management of the cancer patient. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. Because there was no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. I was on this committee. The consensus guidelines produced were subsequently reviewed and endorsed by the World Small Animal Veterinary Association. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Transfer of information begins with sample submission where communication is provided both verbally on the submission form and nonverbally via tissue demarcation. This information significantly affects gross specimen tissue trimming, which ultimately determines the areas evaluated microscopically by the pathologist. Other information provided, including signalment, anatomic location, lesion description, and lesion progression, may affect the histopathological diagnosis and prognostic information. In addition to providing the most accurate diagnosis possible, the report should furnish the clinician with parameters that may predict biological behaviour when applicable, such as tumour grade, mitotic index, assessment of vascular invasion, and a detailed margin description. These parameters are important for the oncologist to make informed decisions but are often not reported, possibly because of inappropriate sample submission or simply omission by the pathologist. Surgical margins may, at times, be the most important parameter for the clinician. Accurate margin evaluation can only be provided on samples that have been submitted and trimmed accordingly. The method by which sections are trimmed for margin evaluation should be provided. This can be achieved verbally or with an annotated image of the gross specimen. An image allows the pathologist to easily identify and describe areas of incomplete resection to the client. Microscopic evaluation of margins should include (1) a description of the neoplastic cells closest to the margin (e.g., peripheral cells of an overt mass, infiltrative nests beyond the mass), (2) an accurate and objective measurement (via stage or ocular micrometre) of the distance from the tissue edge to the closest neoplastic cell (this parameter is limited to nontangential sections), and (3) the tissue constituents (e.g., adipose tissue, dense connective tissue) and tissue quality (e.g., viable, necrotic, inflamed) composing the margin, since different tissue types provide variable barriers against invasion or infiltration of neoplastic cells. Assuming appropriate sample submission and trimming, as discussed previously, a pathologist should be able to clearly determine which slides and/or colours of surgical ink represent which respective margins so they can reliably provide the above parameters. Measurements can be reported in micrometres, millimetres, or centimetres but should remain consistent for all margins reported for that specimen. Reports of this information should be concise yet detailed and accurate, such as

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‘‘random, rare, nests of neoplastic cells are within 3 mm of the deep margin which consists of normal adipose tissue (2.5 mm) and panniculus muscle (0.5 mm)’’ followed by ‘‘in the plane of section of the tissue examined.’’ Vague or ambiguous terms, such as clean, dirty, close, and narrow, should be avoided because they are subjective and introduce inter-pathologist variability. When surgical excision is extensive and no neoplastic cells are present in the nontangential margin sections, the margin measurement can be reported as ‘‘at least x,’’ where x constitutes the entire length/distance of the examined tissue. In 1980, Drs Enneking, Spanier and Goodman published work describing a system for the surgical staging of musculoskeletal sarcoma that has been used ever since in many surgical oncology settings. Operative margins in their paper are defined as intralesional, marginal, wide, and radical, and relate the surgical margin to the lesions, its reactive zone, and anatomic compartment. The system defines prognostically significant progressive stages of risk which also have surgical implications. When the system was linked to clearly defined surgical procedures, it permitted appropriate evaluation and comparison of the new treatment protocols designed to replace standard surgical treatment. However, there is a move to consider a different way of evaluating margins to determine the accuracy of surgery. The venerable Enneking, Goodman and Spanier system is, perhaps, losing relevance and any “clean but close” nomenclature is too imprecise for systematic use. Adopting a modified system used by colorectal surgeons warrants consideration: Proposed Modified Residual Tumour (R) Classification: RX Presence of residual tumour cannot be assessed R0 > 1 mm No residual tumour, minimal distance between tumour and resection margin; margin > or equal to1 mm. The margin is clean. We shouldn’t need any further treatment but we will need surveillance. R0 is where you are happy with the magnitude of the margin R1 < or equal to 1 mm No residual tumour, minimal distance between tumour and resection margin; margin < or equal to 1 mm. This can be a grossly negative margin. You leave the operating room believing your margin to be negative. But the pathologist sees tumor abutting ink. So any microscopically positive margin, at any location in the specimen is R1. There is no wiggle room, no gray area – it is simply a tumor cell abutting ink. R2 (Incomplete excision/Grossly positive margin. R2 is identified in surgery. You either have tumor spillage, inadvertently enter the tumor, or have a margin that you can tell grossly is positive.)

As a consequence of this classification, recommendations can be more definitive. Discussion on this subject recently by members of the Veterinary Society of Surgical Oncology (VSSO) fostered these thoughts. It is R0 where you are happy with the magnitude of the margin and so the margin is “clean” and you can tell your client “we shouldn’t need any further treatment but we will need surveillance”. R1 is where you deem it to be too close for comfort and your discussion goes more like “Although the margin is clean, I’m afraid this is a nasty tumor. I’m going to recommend some adjuvant treatment” or “We thought the margin would be clean but the pathologist sees an area under the microscope where the margin is dirty. We need to do some radiation.” (Email communication April 2015: William C. Eward DVM, MD, Assistant Professor of Orthopaedic Surgery, Section of Orthopaedic Oncology, Duke Cancer Institute, Duke University, Durham, NC, USA, and others in VSSO)

An example of the importance of the R1 margin is in soft tissue sarcoma (STS). Bacon et al retrospectively evaluated 41 dogs that had undergone recent incomplete excision (R1) of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University. Median follow-up time was 816 days. Local recurrence of tumour

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developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs. Healthy tissue margins of 0.5 to 3.5 cm were achieved at re-excision (R0). Residual tumour was identified in 9 of 41 (22%) resected scars. In conclusion, after incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow (R1). A long-term favourable prognosis is achievable without radiation therapy or amputation. The presence of residual tumour in resected scar tissue should not be used to predict local recurrence. The clinical significance of margin status is determined by the clinician managing the case. The decision is based on accurate pathology and margin evaluation and a firm understanding of the tumour type, grade and stage. Therefore, ultimate decision on case management lies with the clinician. A proposal to prospectively test the residual disease classification of margins in the STS setting is in planning stages with VSSO. References:

Vet Pathol. 2011 Jan;48(1):19-31. Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsyspecimens in veterinary surgical pathology. Kamstock DA, Ehrhart EJ, Getzy DM, Bacon NJ, Rassnick KM, Moroff SD, Liu SM, Straw RC, McKnight CA, Amorim RL, Bienzle D, Cassali GD, Cullen JM,Dennis MM, Esplin DG, Foster RA, Goldschmidt MH, Gruber AD, Hellmén E, Howerth EW, Labelle P, Lenz SD, Lipscomb TP, Locke E, McGill LD, Miller MA,Mouser PJ, O'Toole D, Pool RR, Powers BE, Ramos-‐Vara JA, Roccabianca P, Ross AD, Sailasuta A, Sarli G, Scase TJ, Schulman FY, Shoieb AM, Singh K,Sledge D, Smedley RC, Smith KC, Spangler WL, Steficek B, Stromberg PC, Valli VE, Yager J, Kiupel M; American College of Veterinary Pathologists' Oncology Committee.

Clin Orthop Relat Res. 1980 Nov-Dec;(153):106-20. A system for the surgical staging of musculoskeletal sarcoma. Enneking WF, Spanier SS, Goodman MA.

J Am Vet Med Assoc. 2007 Feb 15;230(4):548-54. Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999-2004). Bacon NJ, Dernell WS, Ehrhart N, Powers BE, Withrow SJ.

Cancer. 2009 Aug 1;115(15):3483-8. doi: 10.1002/cncr.24320. A uniform residual tumor (R) classification: integration of the R classification and the circumferential margin status. Wittekind C1, Compton C, Quirke P, Nagtegaal I, Merkel S, Hermanek P, Sobin LH.

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HOW TO AMPUTATE FOR HIP CANCER - HEMIPELVECTOMY Rodney C. Straw BVSc, M(A)ANZCVS, DACVS, ACVS Founding Fellow Surgical



Angus Jenson, Jasper Lieberman and Wolfie Van Horn were the first three dogs for which I was involved in performing hemipelvectomy as part of their treatment for cancer (chondrosarcoma, fibrosarcoma and chondrosarcoma respectively) back in the early 1980’s. How is it that over thirty years later the memory is so vivid and these names pop up at just the mention of “hemipelvectomy”? Because on a scale of one to ten, hemipelvectomy is pretty close to a ten with respect to degree of “aggressiveness” of surgery dose. Add this to being a first-of-its-kind surgery in those days, as we were all trail blazing surgical oncology techniques in animals then. These memories are indelibly welded and concreted into the neurological pathways of my recall. The task given to me today is to describe how these surgeries are done for those with intrepid surgical souls. In 1992, with Steve Withrow (SJW) and Barb Powers, I published the first series of hemipelvectomy cases in the veterinary literature. This paper represented our first eleven patients at Colorado State University. Since then there have been other reports and a technique overview by Kramer et al in 2008. The procedure is not as infrequently considered or performed as it was in the early 80’s. However, it must be said, that surgical oncology is not a collection of techniques and surgeries performed by way of recipes or charts. To paraphrase the sagacious SJW, a surgical oncologist is not a slashing technologist; rather a surgical oncologist is a thinking biologist. Just because hemipelvectomy is a procedure well described, it may not be the procedure best prescribed. Consider the tumour type, patent selection, your support team, facilities, equipment, anaesthesia, analgesics, circulatory support, medicines available and aftercare available before travelling this road. Lastly and also importantly is having good communication with the pet’s human family so they have full understanding of what is to be accomplished with what risks. The obvious reason for removing some pelvis is when there is a primary bone cancer in the proximal femur. To ensure appropriate proximal margins it is usually necessary to perform an en bloc partial hemipelvectomy in conjunction with pelvic limb amputation. I like to call these acetabulectomies. Although osteosarcoma is often reported to not “cross joints” this may be true in radiographic descriptive terms but histologically, tumours of the proximal femur may involve peri-articular soft tissues, the joint capsule or ligament of the head of the femur or of these. Acetabulectomies are relatively straightforward and really represent an upsized amputation. Instead of incising through the coxofemoral joint, which is the way I do my hind limb amputations in dogs and cats, the acetabulum is removed with osteotomies through the ilium, ischium and pubis. Besides tumours affecting the proximal femur, reasons for hemipelvectomy also include tumours affecting pelvic segments, lumbar transverse processes, sacrum and caudal vertebrae. These are generally sarcomas including sciatic nerve tumours and feline injection site sarcomas. A full understanding of the biology of these tumours and the stage and grade of disease is imperative. Hemipelvectomy has also been described in the management of trauma induced pelvic malunions.

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Besides accurate screening for the presence of metastatic cancer and lymph node involvement a key to staging is the imaging of the primary site. This requires advanced imaging. Computed tomography (CT) is generally suitable for planning the surgery. Good quality magnetic resonance imaging (MRI) is ideal scrutinising the soft tissue in detail. Margin planning takes experience and as a guide we aim for 20 mm lateral margins and at least one fascial plane deep. Wider margins are considered necessary for high-grade tumours and there are those who recommend 50mm margins for feline injection site sarcomas. We use the CT scanner for staging the lungs at the same time the contrast enhanced pelvic study is performed. The patient’s minimum data base clinical pathology should include a complete blood count (CBC) with particular reference to the red cell indices. Matched fresh whole blood or packed cells should be available in any case. A serum biochemistry panel should include at a minimum liver and renal enzymes, differential protein evaluation and electrolytes as a base line. I also like to have a full urinalysis or at least a urine specific gravity. During preparation and anaesthesia consideration should be given to performing epidural administration of morphine and long acting local anaesthetic. Pre-emptive pain relief is critical. A careful plan for a preoperative, intraoperative and postoperative pain management protocol is imperative. Consultation with a specialist anaesthesiologist is recommended. Once the patient has had a wide area clipped and prepared for surgery and the urethra is catheterised. Some place a syringe case in the rectum to help delineate this structure ding surgery. I place a purse-string suture in the anus. Use first generation, intravenous, cephalosporin antibiotics at the appropriate dose rate starting soon after anaesthesia induction then every two hours until the animal in in the recovery ward then further one or two doses are given eight hours apart. I do not use postoperative antibiotics unless infections occur then antibiotics are used judiciously generally also guided by culture and sensitivity results. An excellent, three-dimensional knowledge of the regional anatomy is imperative. Hemipelvectomy may be categorised a total hemipelvectomy, mid-to-cranial partial hemipelvectomy, mid to caudal hemipelvectomy and caudal partial or internal hemipelvectomy. If the weight-bearing segment is to be removed, generally the limb is amputated at the same time. Also if essential neurovascular bundles are involved this also dictates that amputation is performed concurrently. I usually perform these surgeries with the animal in lateral recumbence with the ipsilateral pelvic limb hung for complete incorporation into the surgical field. Placing in slight oblique orientation with the dorsal surface upper most helps if laminectomy is needed. The skin incision is made after careful planning with reconstruction in mind. All biopsy tracts and any skin and soft tissue in close proximity to the tumour (20 mm margins) are excised with the specimen. Preserve all viable skin remote from, and not involved with tumour. Often the entire medial skin and muscle can be preserved for reconstruction. Care is taken to preserve blood supply to tissue to be used in reconstruction. The tumour gradually excised from ventral, caudal and dorsolateral approaches. Sometimes axial pattern skin flaps can be used to reconstruct. Castration and scrotal ablation is recommended for male dogs to avoid scrotal haematoma and oedema postoperatively. Tumours encroaching passed the midline (especially the dorsal midline) offer special problems and may indeed not be able to be removed with the prescribed potentially curative margins. A rethink of the plan may be necessary for such patients.

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The surgery is well detailed in the musculoskeletal system chapter in the Veterinary Society of Surgical Oncology textbook edited by Kudnig and Séquin, Veterinary Surgical Oncology. This is an excellent reference source for these and other complex cancer surgeries. Post operatively the urinary catheter and closed suction drains are left in place for two to three days and sometimes longer. Penrose drains are not used in these patients in our hospital. Analgesia is maintained with continuous rate infusions gradually weaning to rely on transdermal systems and oral medications after a few days. Pain soaker catheters may be placed prior to wound closure to permit the delivery of local anaesthetics in the first few post operative days. Non-steroidal anti-inflammatory drugs are often helpful when possible. Wounds, drains and soaker catheters are covered with sterile adherent dressings and carefully monitored. Animals are likely to need help to rise and need encouragement to walk on non-slick surfaces for the first few days especially to support the medial thigh muscle function. Surprisingly, given the extent of the resection in many of these patients, the cosmetic outcome and function is excellent. Complications are also surprisingly few. To the surprise of many, perineal hernia has not been our experience in any case of hemipelvectomy. References: Straw RC, Withrow SJ, Powers BE. 1992. Partial or total hemipelvectomy in the management of sarcomas in nine dogs and two cats. Vet Surgery 21:183-188. Kramer A, Walsh P, Séquin B. 2008. Hemipelvectomy in dogs and cats: Technique overview, variations and description. Vet Surg 37:413-419. Liptak JM, Dernell WS, Farese JP, Worley DR. Musculoskeletal system in Veterinary Surgical Oncology Kudnig ST & Séquin B. (eds) 491-568. Wiley & Sons 2012

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PRECANCEROUS, SOLAR INDUCED NASAL LESIONS – HOW CAN WE PREVENT NOSECTOMY?

Rodney C. Straw BVSc, M(A)ANZCVS, DACVS, ACVS Founding Fellow Surgical Oncology

Brisbane Veterinary Specialist Centre & the Australian Animal Cancer Foundation Albany Creek, Queensland, Australia

The solar induced cancers we battle most frequently in cats and dogs are squamous cell carcinoma (SCC) and cutaneous haemangiosarcoma (cHSA). Many cats love to lounge in the warmth of a sun soaked window ledge and those cats with little or no skin pigment are at greatest risk of developing cancer as a result. This discussion focuses on the planum nasale of such cats. So, how bad can it be for the white cat luxuriously lounging in the sun? Solar radiation represents an essential requirement for life, not only by spending the thermal energy for photosynthesis in plants, which provides our atmosphere with oxygen, but also by facilitating the cutaneous synthesis of vitamin D in vertebrates and many other organisms. It is well known that cats have to obtain an adequate source of vitamin D, in order to develop and maintain a healthy mineralized skeleton and in order to be protected against cancer and a broad variety of other diseases. On the other hand, solar UV radiation can be assumed to be the most relevant environmental carcinogen causing SCC and cHSA skin cancer with alarming incidences particularly in Australia. During the last decades, epidemiological studies and experimental animal models, including genetically engineered mice, the Xiphophorus hybrid fish, the South American opossum and human skin xenografts, have further elucidated the multi-step process of UV-induced carcinogenesis. It has to be emphasized that, in contrast to intermittent, short-term high-dose solar UV-exposure, more chronic less intense exposure (which is recommended by many experts in the field to obtain a sufficient vitamin D status) has not been found to be a risk factor for the development of solar induced cancer and in fact has been found in several studies to be protective. Interestingly, several independent lines of investigation have demonstrated convincing evidence that vitamin D, its analogues or both may be effective in the prevention and treatment of melanoma. The p53 tumour suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. P53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific ‘signature' mutations that can result in oncogenic transformation. Repair of UV induced DNA damage is of key importance to UV-induced skin carcinogenesis. Specific signal transduction pathways that regulate cell cycling, differentiation and apoptosis are found to be corrupted in skin cancers. Mutations in genes coding for proteins in these pathways lead to persistent disturbances that are passed along to daughter cells. Point mutations in the P53 gene from SCC patients (and likely to such cats as well) are unambiguously attributable to solar UV radiation. Solar UVB radiation is most effective in causing these point mutations. Other forms of UV-induced genetic changes (e.g., deletions) may, however, contribute to skin carcinogenesis with different wavelength dependencies. So, how do we avoid nosectomy in our cats with precancerous, solar induced nasal lesions? I used to recommend my clients take their cats with such lesions and move to Denmark. Since my travels to Scandinavia, I thought this was an area on the planet with very little sunlight and away

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from the hole in the ozone layer. Here I presumed the precancerous lesions may repair once the offending UV irradiation was minimised. My research, however tells me otherwise. Strictly, all places on Earth receive virtually the same amount of sunlight in a calendar year. However if you are looking for the place on earth where, due to cloud cover, fog and so on, there is less sunlight at the earth’s surface then it is hard to beat Macquarie Island where there is only 856 hours per year of unfiltered sun. But what about the ozone layer? The stratospheric ozone layer absorbs most of the harmful ultraviolet B (UVB) radiation (shortwave UV rays measuring 280-315 nanometers, or nm) emitted by the sun. But what happens when the ozone layer is threatened? That's what happened in the 1970s and 1980s. Concerns regarding the ozone layer began in 1970 with Paul Crutzen's study suggesting that nitrogen oxides could act as catalysts to destroy ozone. Then, Harold Johnston suggested that nitrogen oxides from stratospheric supersonic transport aircraft (such as the Concorde) might deplete the ozone layer by 3 to 23 percent. Next, Richard Stolarski and Ralph Cicerone identified a chlorine reaction that could do the same. And in 1974, Mario Molina and F. Sherwood Rowland suggested that CFCs (chlorofluorocarbons, certain inert gaseous compounds) could also accumulate in the atmosphere, releasing chlorine into the stratosphere that could deplete ozone; CFCs were widely used in spray cans, as refrigerants, and as industrial cleaning and drying agents. All of these experts' concerns proved prescient in 1985, when Joe Farman, Brian Gardiner, and Jon Shanklin published a paper describing the serious decline in ozone over Antarctica, the so-called Antarctic ozone hole. The more damage there is to the ozone layer, the more UVB rays that reach our cats’ noses. Therefore, ozone loss is a serious health threat. In 1987, the international community responded to the ozone crisis with the Montreal Protocol. This treaty limited production and consumption of ozone-depleting substances, allowing for changes to the agreement as scientific understanding evolved. Since 1987, the Protocol has been updated seven times, and CFC production is now globally banned.

Now, more than 25 years after the Montreal Protocol was negotiated, CFC levels are finally declining in our atmosphere. It was first recognized in 1995 that CFC levels were no longer increasing in the troposphere, the portion of the atmosphere below the stratosphere. By 2000, satellite observations showed that chlorine levels in the stratosphere had stabilized, and today they are gradually decreasing. Change is slow because CFCs have very long lifetimes in our atmosphere; for example, CFC-12, a.k.a. Freon-12, will require 100 years to decrease to about one third of its current amount.

Between 1980 and 1995, ozone declined about four percent over the mid-latitudes of the Northern Hemisphere. But today, combined ground and satellite observation shows that ozone is only about three percent below the levels seen in the 1960s and 70s. This means that the ozone layer may be repairing itself. However, the Antarctic ozone hole hasn't gone away. Each year severe ozone losses between August and September culminate in a broad region of stratospheric air, at an altitude of 12 miles that has nearly zero ozone. Over the past 15 years, the ozone-hole area has grown to about 25 million square kilometers (9.7 million square miles) in spring - an area larger than the continent of North America. In Antarctica during the dark winter months, special types of clouds called polar stratospheric clouds (PSCs) are formed in the extremely cold stratospheric air (less than 109 degrees F). These PSCs convert stable chlorine molecular species into radical forms that can destroy ozone molecules while regenerating themselves (a catalytic cycle). As the sun rises over Antarctica in the southern hemisphere spring, the sunlight provides the energy necessary for the ozone destruction. This results in accelerated destruction of the ozone layer in the Antarctic spring period compared to other regions further to the north. In addition, a 'polar vortex' wind pattern keeps ozone from elsewhere from filling in the depleted

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section, leaving the vast hole to develop during the spring period. Fortunately, the size of the hole is not likely to increase further because chlorine and bromine compounds are no longer increasing. The same processes that have caused the ozone hole over the Antarctic have similarly affected the region over the North Pole. While less stable stratospheric weather patterns limit ozone destruction over the Arctic, early spring Arctic ozone levels are typically 10 percent lower than levels seen in the 1970s.

Reduced stratospheric ozone leads to increases in surface ultraviolet (UV) radiation. UV light is divided into three bands: UVC (100-280 nanometers), UVB, and UVA. UVC is the most dangerous, but is mostly absorbed by oxygen and ozone molecules in the stratosphere and does not reach the earth's surface. When UV radiation passes through the earth's atmosphere, some of it collides with other molecules and particles, causing it to bounce around and change direction. This scattered UV radiation can increase sunburn risk even when you are in the shade. UVB is partly scattered back to space by the atmosphere and absorbed by ozone, limiting how much reaches the earth throughout the year, while UVA is absorbed less by ozone and scattered less by the atmosphere; thus a larger percentage of UVA reaches the earth year-round. UVB strikes the earth more intensely during summer months when the sun is higher in the sky, so that the radiation travels on a shorter path through the atmosphere. Ozone and clouds are the most important factors in limiting UVB penetration. How much UV reaches the earth's surface depends on the amount of ozone overhead, clouds, small particles or aerosols, and pollution. Measuring long-term changes in UV penetration is quite difficult. First, the amount of ozone overhead varies daily because of weather patterns, and to a lesser extent, due to ozone destruction by CFCs. Secondly, cloud systems change rapidly, and can cause the amount of surface UV to change by 10 to 50 percent (occasionally more) within minutes: While thick, uniform cloud layers allow little UV to arrive at the earth's surface, side reflections from tall, puffy clouds can actually enhance penetration of UV radiation by a few percent when compared with clear skies. As much as 80 percent of UV Radiation can pass through thin clouds that appear to block the sun, so that you can sunburn even on an apparently cloudy day. Since 1979, we have been able to estimate this large variation in UV levels on the ground by using satellites that measure ozone and cloud amounts over the entire earth, and then calculating the UV penetration to the ground. The calculations are validated by ground-based instruments.

Because of ozone depletion, by the mid-1990s average clear sky erythemal (skin reddening/sunburn-inducing) radiation had increased by about seven percent from levels in the 1970s at middle latitudes. This has fallen off somewhat and is now only about four percent higher than in the 1970s. Overall, the news is good: The Montreal Protocol has had a dramatic impact in reducing ozone-depleting substances. The ozone layer is no longer declining, and there are signs of improvement. The Montreal Protocol has also helped to slow dangerous climatic changes such as global warming by reducing CFCs and other ozone depleting substances, powerful greenhouse gases that prevent infrared radiation from escaping the atmosphere, reflecting it back towards earth and thus causing the earth to warm. While the Kyoto Agreement on greenhouse gases would have reduced carbon dioxide (CO2) emissions by two billion tons by 2010, the Montreal Protocol's reduction of ozone-depleting substances already reduced greenhouse gases emissions by the equivalent of more than 10 billion tons of CO2 at the end of 2008.

When can we expect ozone levels to return to those seen in the 1970s? With CFC production curtailed, scientists have estimated release rates of existing CFC stocks to project future levels. These projections are fed into complex computer models of the chemistry, radiation, and

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dynamics of our atmosphere. The models project that ozone levels in the northern mid-latitudes will recover by about 2050, while polar levels (the Antarctic ozone hole) will recover by approximately 2065. A future epidemic of UV-related skin cancers may have been avoided.

What might have happened if we had done nothing about CFCs? In the 1970s, prior to discovery of the ozone problem, CFC production was increasing 7-10 percent per year. Using the same computer models that predict the future recovery, we estimated that CFC emissions would have increased by three percent per year after 1974. By 2060, the levels of stratospheric chlorine would have been 16 times above 1980 levels. Average global ozone levels would have decreased by two thirds. The UV index in the northern mid-latitudes would have increased to a value near 30 for midsummer noon conditions. The average mid-summer UV index value now is about 10 in these regions. Typically, it takes about 15 minutes for a fair-skinned person to develop perceptible sunburn in mid-summer. In this theoretical world ("world avoided") it would have taken less than five minutes to develop a perceptible burn. But thanks to guidance by scientists and prompt intervention by policy makers, industry leaders, and diplomats around the world, CFC-related ozone depletion did not become an environmental catastrophe. The process was not easy, but we now know that the price for doing nothing would have been very high.

OK, that is the climate and sun exposure issue, what if the client is reluctant to take their cat to Macquarie Island to live? As if that is really going to help anyway – really. Can we treat the precancerous lesions? We treat people with these skin lesions, can we use the same products in cats? Let’s first look at the current recommendations for people.

Current treatments for precancerous lesions in people (Actinic Keratoses or AKs) involve topical and destructive modalities. The most commonly used topical agents to treat AKs are 5-FU, imiquimod (Aldara), and diclofenac (Solaraze). 5-FU is a chemotherapeutic agent that inhibits both RNA and DNA synthesis and targets dividing cells. AKs have a higher proportion of dividing cells than adjacent epidermis. 5-FU has significant side effects, including prominent inflammation, ulceration, and even scarring; use of 5-FU is associated with a demonstrably lower quality of life for patients, and thus has many negative features as a first-line topical agent. Use of 5-FU in cats is usually fatal since cats will ingest the substance which causes serious CNS toxicity.

Imiquimod, a TLR7 agonist, acts through an immune-mediated mechanism that produces prominent inflammation leading to elimination of AKs. This inflammation resembles psoriasis in its intensity and at the molecular level, and has been associated with induction of autoimmune reactions such as alopecia areata and vitiligo. Another common topical agent to treat AKs is diclofenac, a topical non-steroidal anti-inflammatory compound with an unclear mechanism of action on AKs. Recent studies using diclofenac and imiquimod showed therapeutic weaknesses associated with poor clearance rates and significant irritation. Overall, the most common topical agents used to treat AKs have significant negative features, including irritation, decreased quality of life, and limited efficacy. These data indicate a potential benefit to developing topical treatments that target pathophysiology of AKs without inducing skin irritation.

Recent innovations in medicine have resulted from the application of small molecules that correct signalling deficits in human neoplasia. Systemic administration of small molecules that can enhance p53 function, such as CP-31398, can inhibit UVB-induced carcinogenesis in mice. Imatinib (Gleevec) and related compounds have been useful in treating neoplasia associated with increased tyrosine kinase activity, including chronic myelogenous leukaemia and gastrointestinal stromal tumours with c-Kit mutations. It is important to note that imitinib is very similar to

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toceranib (Palladia) which can be used in cats. The systemic application of small molecules to target kinases driving neoplasia or to activate anti-oncogenic signalling pathways could be used to treat AKs and cSCC in humans; identifying skin-permeable small molecules that target these pathways essential for lesion formation would be a first step. The murine models of skin cancer and xenografted genetically engineered human skin are screening tools for identifying potential topical agents that may be useful in treating AKs and cSCCs in humans. I wonder if we are missing something here. What about using dogs and cats with SCC as models for human disease? Translational cancer research is the way – one cancer.

What do veterinarians do for cats with solar associated planum nasale lesions? In 1996 Théon et al performed work to develop a slow-release carboplatin formulation for intratumoural administration to cats. This preliminary study was to analyse pharmacokinetic effects of purified sesame oil in the carboplatin formulation for intratumoural administration, and a second study was performed to evaluate the efficacy and toxicosis of intratumoural administration of carboplatin in purified sesame oil. Twenty three cats with squamous cell carcinomas of the nasal plane were used in the study. Eight cats with advanced-stage tumours were submitted to intratumoural administration of 100 mg of carboplatin/m2 of body surface area, with or without purified sesame oil, using a two-period, cross-over design. Fifteen additional cats were treated by intratumoural administration of carboplatin in purified sesame oil. Four weekly intratumoural chemotherapy injections of carboplatin in purified sesame oil at a dosage of 1.5 mg/cm3 of tissue were given. Purified sesame oil in the formulation significantly reduced systemic exposure to carboplatin and drug leakage from the sites of injection. Cumulative effects of repeated intratumoural administrations on plasma concentrations of carboplatin were not observed. Systemic toxicosis was not observed, and local toxicosis was minimal. Healing of ulcerated lesions was not compromised. Rates of complete clinical tumour clearance and complete response were 67 and 73.3%, respectively. Product-limit estimates of mean progression-free survival times was 16 +/- 3.3 months. The 1-year progression-free survival rate was 55.1 +/- 13%. Local recurrence was observed in 7 cats; 4 had marginal tumour recurrence, and 3 had in-field and marginal tumour recurrence. They concluded that intratumoural carboplatin chemotherapy is safe and effective for cats with squamous cell carcinoma of the nasal plane. Future studies to improve treatment efficacy could include evaluation of increased dose-intensity as well as combination of this modality with radiotherapy. These studies were not reported and although at the time, the authors concluded that intratumoural administration of carboplatin in a water-sesame-oil emulsion was found to be a practical and effective new treatment for facial squamous cell carcinomas in cats, the technique has not gained a lot of favour over the years. The work place health and safety issues are considerable. In 1997 the medical records of 61 cats were reviewed for a retrospective study at Colorado State University. Typical presentation was an older (median age, 12 years) cat with an erythematous, crusty, and erosive lesion. Methods of treatment included surgery, radiation, and cryotherapy. Disease-free interval and survival time were calculated for each case and grouped according to lesion location and treatment type. All treatments were found to be effective, with surgery resulting in the longest disease-free interval (median, 594 days). In 2001 a group treated superficial squamous cell carcinoma of the nasal planum, pinna and eyelid in cats by photodynamic therapy, using topical 5-aminolaevulinic acid cream, with subsequent exposure to red light of wavelength 635 nm, supplied by a light-emitting diode source. A total of 13 squamous cell carcinomas were treated, including 10 nasal planum lesions, two pinnal lesions and one eyelid lesion. After a single treatment, complete responses were seen in nine out of 10 nasal planum lesions, one out of two pinnal lesions and the eyelid lesion. The overall complete response rate for lesions managed with a single photodynamic therapy treatment was 85 per cent. Seven of the 11 lesions (63.6 per cent) showing a complete response

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subsequently recurred; the time to recurrence ranged from 19 to 56 weeks (median 21 weeks, mean 26.7 weeks). In 2009 a Brazilian group looked at photodynamic therapy (PDT) using a haematoporphyrin derivative (Photogem, General Physics Institute and clustes Ltda) as photosensitiser and light emitting diodes (LEDs) as the light source was evaluated in 12 cats with cutaneous squamous cell carcinoma. Lesions were illuminated with LEDs, (300 J/cm for 30 min) 24 h after the administration of the photosensitiser. Clinical responses were classified as complete disappearance of the tumour with total re-epithelialization; partial response (a reduction greater than 50%); and no response (less than 50% reduction). Tumours localized to the pinna treated with one (n = 3) or two (n =4) applications of PDT yielded no response. Highly invasive tumours of the nose and nasal planum also showed no response, after two treatments (n = 2). A combination of PDT and surgery was performed in three cases. Two cats showed partial response and one complete response with one application of therapy 30 days after nasal surgery. Small and non-infiltrative lesions (n = 3) of the nasal planum showed a PR with one application (n = 2) and a CR with two applications (n = 1). This study shows that PDT using Photogem and LEDs can provide local control of low-grade feline squamous cell carcinoma. Recently a group in New Zealand evaluated curettage and diathermy as a treatment for actinic dysplasia and superficial squamous cell carcinoma of the feline nasal planum. Thirty-four cats clinically assessed to have actinic dysplasia and superficial squamous cell carcinoma involving less than 50% of the nasal planum were treated with a three-cycle curettage and diathermy procedure. Degree of dysplasia, response to treatment, adverse effects, owner perceptions, time to recurrence and proportion disease free at 1  year were evaluated. Lesions ranged from actinic keratoses to invasive squamous cell carcinoma. A complete response to treatment was obtained in all cats. The median follow-up time was 18  ·  2 (IQR: 12  ·  0-22  ·  8) months. Two cats had a clinical recurrence of lesions at 161 and 192  days after treatment. The probability of remaining disease free after 12  months was 0  ·  94 (95% CI: 0  ·  85-1  ·  0). Median time to recurrence was not reached. The procedure was well tolerated with a good cosmetic outcome and no significant post-operative complications. The authors’ summarised that their study suggests curettage and diathermy is an effective treatment for feline actinic dysplasia and for superficial squamous cell carcinoma involving less than 50% of the nasal planum. Curettage and diathermy appeared to be an easily mastered technique, requiring minimal equipment. In 2009, Italian investigators published a preliminary study reports on the management of SCC in cats combining the local administration of bleomycin (plus hyaluronidase for a more uniform distribution) with permeabilising biphasic electric pulses. Nine cats with SCC graded T(2)-T(4) were treated over a 5 year period, and each cat received two sessions of electrochemotherapy (ECT) 1 week apart. The side effects of this treatment were minimal and limited to mild erythema of the nose. Seven of the cats (77.7%) had a complete response lasting up to 3 years. ECT seems to be a safe and effective option for the treatment of feline sun-induced squamous cell carcinomas and warrants further investigation. In 2008, Peters-Kennedy et al described an apparent clinical resolution of pinnal actinic keratoses and squamous cell carcinoma in a cat using topical imiquimod 5% cream while Gill et al in 2009 reported the use of imiquimod 5% cream (Aldara) in twelve cats with multicentric squamous cell carcinoma in situ. They concluded that Imiquimod 5% cream, which is an immune response modifier that has been reported as a successful treatment for Bowen's disease in humans, appears to be well tolerated in the majority of cats, and further studies are warranted to further examine its usefulness in cats with this disease. Another group evaluated strontium Sr 90 for the treatment of superficial squamous cell carcinoma of the nasal planum in 49 cats between 1990 and 2006. Information including FIV infection status, diagnosis of SCC vs SCC in situ (i.e., evidence that the tumour did or did not penetrate the epidermal basement membrane, respectively), (90)Sr dose and number of probe

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applications, treatment-related response and complications, and recurrence of SCC and new lesion development was obtained from medical records. The relationships of these variables with calculated progression-free and overall survival times were assessed. Of 49 cats that underwent (90)Sr plesiotherapy (median dose, 128 Gy), 48 (98%) had a response to treatment and 43 (88%) had a complete response. Median progression-free and overall survival times were 1,710 and 3,076 days, respectively. Treatment complications were infrequent (4 [8%] cats) and mild. Following treatment, the SCC recurrence rate was 20% (10/49 cats); 16 (33%) cats developed new lesions in other locations. Overall survival time was significantly longer for cats with a complete response to treatment than for those with a partial response. None of the other variables evaluated had a significant effect on progression-free or overall survival time. The authors concluded that treatment of cats with SCC of the nasal planum with a single fraction of (90)Sr appeared to be effective and well tolerated. Initial response to treatment was predictive of overall survival time. The group at the Animal Health trust in Suffolk also looked at strontium Sr 90. They reported the responses of 15 cats with histologically (n=14) or cytologically (n=1) confirmed nasal squamous cell carcinoma treated with (90)Strontium plesiotherapy which were reviewed retrospectively. Cats were treated such that a total dose of 50Gy was delivered at a depth of 2mm, administered in five fractions over a 10-day period. Of the cats, 11 were stage T(2), three were T(is) and one had only a cytological diagnosis precluding staging. Eleven of the cats achieved complete response (no visible lesion after 6-8 weeks) following the first cycle of therapy, and two cats with partial response achieved complete response with a second cycle of therapy. The remaining two cats achieved partial response following therapy, but further intervention was declined. Euthanasia was performed in these two cats because of progressive disease after 81 and 142 days. Of the 85% of cats that achieved a complete response, there was no recurrence of disease during a follow-up period of 134-2,043 days (median 652 days). In addition to prolonged disease-free survivals, (90)Strontium therapy produced excellent cosmetic results from the owners' perspective. These results demonstrate that superficial squamous cell carcinoma of the feline nasal planum responds excellently to (90)Strontium plesiotherapy, and this form of therapy may offer advantages over other alternatives currently available. Readers are advised to consider the radiation health issues with this treatment regime and need to ensure they comply with regulations such as the Queensland licence requirements which can be found at www.health.qld.gov.au/radiationhealth/documents/30255.pdf. As well as a good response to plesiotherapy, SCC of the nasal planum in cats also responds to external beam radiation therapy. In 1995 Theon et al reported on ninety cats that were irradiated for treatment of squamous cell carcinoma of the nasal planum. The 1- and 5-year progression-free survival rates were 60.1 +/- 5.5% and 10.3 +/- 6.2%, respectively. Analysis of progression-free survival times revealed that clinical stage and tumour proliferative fraction (estimated by the use of a proliferating cell nuclear-antigen immunohistochemical method) had significant prognostic value. Conversely, coat colour, presence of multiple facial carcinomas, histologic grade, and feline immunodeficiency virus infection status were not found to have prognostic value. Acute radiation reactions were mild and self-limiting. Severe chronic radiation reactions were more frequent in cats infected with feline immunodeficiency virus. Results of the study indicated that cats with squamous cell carcinoma of the nasal plane benefit from radiotherapy and that treatment might be improved by increasing the radiation dose as well as altering the dose-fractionation scheme. Coarse fractionation does not seem to be as good. A Brazilian group in 2010 reported a study to evaluate the efficacy of a hypofractionated radiation protocol for feline facial squamous cell carcinoma (SCC). Twenty-five histologically confirmed SCCs in 15 cats were treated with four fractions of 7.6-10Gy each, with 1 week intervals. The equipment used was a linear accelerator Clinac 2100 delivering electron beam of 4 or 6MeV, and a bolus of 5 or 10mm was used in all lesions. Of the lesions, 44% were staged as T4, 16% as T3, 8% as T2 and 32% as T1. Of the irradiated lesions, 40% had complete response, 12% had partial response

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and 48% had no response (NR) to the treatment. For T1 tumors, 62.5% had complete remission. Mean overall survival time was 224 days. Owners requested euthanasia of cats having NR to the treatment. Mean disease free time was 271 days. Side effects observed were skin erythema, epilation, ulceration and conjunctivitis, which were graded according to Veterinary Radiation Therapy Oncology Group (VRTOG) toxicity criteria. Response rates found in this study (52%) were lower when compared to other protocols, probably due to technique differences, such as fractionation schedule, bolus thickness and energy penetration depth. However, the hypofractionated radiation protocol was considered safe for feline facial SCC. A Swiss paper in 2001 of fifteen cats were treated for squamous cell carcinoma of the nasal planum using proton beam radiation. The protocol used was accelerated with eight equal fractions given on four consecutive days, with a minimum of six hours between fractions. Total dose of radiation delivered was escalated with nine cats receiving 40.4 CGE (60Co Gy equivalent), and three cats each receiving 42.4 and 44.8 CGE. Complete response to the protocol was 60% (9/15), partial response was 33% (5 of 15), and no response was seen in 6.6% (1 of 15). Tumour control rate at one year was 64% and no cat had tumour recurrence after one year. Median survival was 946 days (+/- 516 days). Side effects were minimal with no severe reactions noted in the early or late period. This protocol offers an effective treatment for squamous cell carcinoma of the feline nasal planum with minimal side effects and may be adaptable to conventional radiation sources particularly when the field size is very small. Our (BVSC + The Animal Hospital) results with an eighteen daily fractionation protocol with electron beam irradiation for advanced SCC of the nasal planum in cats generally very well tolerated with long progression free survival data (median survival not reached). In summary, treatment with nosectomy (or nasal planectomy) can be avoided by cats with solar induced, precancerous SCC if they are moved to Macquarie Island or locations with similarly gloomy climates away from the ozone holes, have cryosurgery, minimal resection or curettage and diathermy, plesiotherapy, photodynamic therapy, electrochemotherapy, possibly imiquimod or intralesional carboplatin and sesame oil. There are many ways these cats have been managed. Unfortunately the cats I see generally have failed these procedures or are not presented until very late in the course of the disease with advanced stage tumours (T3 or worse). Some of these cats cannot be helped but wide resection with nasal planectomy is effective in 80% and, for those with very advanced local disease, a combination of surgery and curative intent radiation or radiation alone can be very effective for good moderate to long term control. Suggested reading: J Am Anim Hosp Assoc. 1997 Jul-Aug;33(4):329-32. Feline cutaneous squamous cell carcinoma of the nasal planum and the pinnae: 61 cases. Lana SE(1), Ogilvie GK, Withrow SJ, Straw RC, Rogers KS. J Feline Med Surg. 2013 May;15(5):401-7. Cutaneous squamous cell carcinoma in the cat: current understanding and treatment approaches. Murphy S. Vet Dermatol. 2009 Jun;20(3):174-8. 2009 Apr 3. Hematoporphyrin-based photodynamic therapy for cutaneous squamous cell carcinoma in cats. Ferreira I(1), Rahal SC, Rocha NS, Gouveia AH, Corrêa TP, Carvalho YK, Bagnato VS. J Small Anim Pract. 2001 Apr;42(4):164-9. Photodynamic therapy of feline superficial squamous cell carcinoma using topical 5-aminolaevulinic acid. Stell AJ(1), Dobson JM, Langmack K. N Z Vet J. 2009. Detection of two different papillomaviruses within a feline cutaneous squamous cell carcinoma: case report and review of the literature. Munday JS(1), Dunowska M, De Grey S. Small Anim Pract. 2013 Feb;54(2):92-8. Curettage and diathermy: a treatment for feline nasal planum actinic dysplasia and superficial squamous cell carcinoma. Jarrett RH(1), Norman EJ, Gibson IR, Jarrett P. Vet J. 2009 Jan;179(1):117-20.

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Electrochemotherapy for the treatment of squamous cell carcinoma in cats: a preliminary report.Spugnini EP(1), Vincenzi B, Citro G, Tonini G, Dotsinsky I, Mudrov N, Baldi A. Vet Comp Oncol. 2008 Mar;6(1):55-64. Use of imiquimod 5% cream (Aldara) in cats with multicentric squamous cell carcinoma in situ: 12 cases (2002-2005). Gill VL(1), Bergman PJ, Baer KE, Craft D, Leung C. J Feline Med Surg. 2008 Dec;10(6):593-9. Apparent clinical resolution of pinnal actinic keratoses and squamous cell carcinoma in a cat using topical imiquimod 5% cream. Peters-Kennedy J(1), Scott DW, Miller WH Jr. Am J Vet Res. 1996 Feb;57(2):205-10. Intratumoral administration of carboplatin for treatment of squamous cell carcinomas of the nasal plane in cats. Théon AP(1), VanVechten MK, Madewell BR. J Am Vet Med Assoc. 2007 Sep 1;231(5):736-41. Evaluation of strontium Sr 90 for the treatment of superficial squamous cell carcinoma of the nasal planum in cats: 49 cases (1990-2006). Hammond GM(1), Gordon IK, Theon AP, Kent MS. Clin Tech Small Anim Pract. 2007 May;22(2):42-5. Squamous cell carcinoma of the nasal planum in cats and dogs. Thomson M J Feline Med Surg. 2014 Apr;16(4):291-9. Electrochemotherapy with intravenous bleomycin injection: an observational study in superficial squamous cell carcinoma in cats. Tozon N(1), Pavlin D, Sersa G, Dolinsek T, Cemazar M. J Feline Med Surg. 2010 Apr;12(4):306-13. Radiation therapy for feline cutaneous squamous cell carcinoma using a hypofractionated protocol. Cunha SC(1), Carvalho LA, Canary PC, Reisner M, Corgozinho KB, Souza HJ, Ferreira AM. J Feline Med Surg. 2006 Jun;8(3):169-76. A retrospective study of (90)Strontium plesiotherapy for feline squamous cell carcinoma of the nasal planum. Goodfellow M(1), Hayes A, Murphy S, Brearley M. Vet Surg. 2008 Jul;37(5):438-43. Clinical study of cryosurgery efficacy in the treatment of skin and subcutaneous tumors in dogs and cats. De Queiroz GF(1), Matera JM, Zaidan Dagli ML. J Am Vet Med Assoc. 1995 Apr 1;206(7):991-6. Prognostic factors associated with radiotherapy of squamous cell carcinoma of the nasal plane in cats. Théon AP(1), Madewell BR, Shearn VI, Moulton JE. J Vet Intern Med. 2008 Nov-Dec;22(6):1385-9. Photodynamic therapy of superficial nasal planum squamous cell carcinomas in cats: 55 cases. Bexfield NH(1), Stell AJ, Gear RN, Dobson JM. J Vet Intern Med. 2007 Jul-Aug;21(4):770-5. Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy. Buchholz J(1), Wergin M, Walt H, Gräfe S, Bley CR, Kaser-Hotz B. Vet Radiol Ultrasound. 2001 Nov-Dec;42(6):569-75. Proton irradiation of feline nasal planum squamous cell carcinomas using an accelerated protocol.

Fidel JL(1), Egger E, Blattmann H, Oberhänsli F, Kaser-Hotz B. Adv Exp Med Biol. 2014;810:390-405.

Sunlight, vitamin D and malignant melanoma: an update. Reichrath J, Reichrath S. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma Vladimir Ratushny, Michael D. Gober, Ryan Hick, Todd W. Ridky, and John T. Seykora J Clin Invest. 2012;122(2):464-472.

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EXTREMITY SOFT TISSUE SARCOMA RADIATION Rodney C. Straw BVSc, M(A)ANZCVS, DACVS, ACVS Founding Fellow Surgical



Soft tissue sarcomas (STS) represent a heterogeneous group of tumours, which are classified based on similar pathologic appearance and clinical behaviour. STS originate from mesenchymal tissues and comprise approximately 15% of all skin and subcutaneous tumours in the dog. Tumours that are classified as STS include such tumours as fibrosarcoma, perivascular wall tumours (including haemangiopericytoma), liposarcoma, myxosarcoma, peripheral nerve sheath tumours (schwannoma, neurofibrosarcoma), rhabdomyosarcoma, leiomyosarcoma, malignant mesenchymoma, and malignant fibrous histiocytoma, among others. These tumours tend to appear as pseudoencapsulated soft-to-firm tumours but, despite their localised clinical appearance, are locally invasive and have poorly defined histologic margins and infiltrate through and along fascial planes. Local tumour control is the most important consideration in the management of soft tissue sarcomas. Surgery alone is curative if the tumour can be removed completely. However, treatment decisions become problematical when these tumours occur in the distal extremities. In 1976, Dr Ed Gillette published work describing radiotherapy for spontaneous fibrous and connective tissue in animals paving the way for the use of this modality. Later he was involved in showing that radiation can be, at least partially effective with good local control achieved with radiation alone for one year at doses with a low probability for serious complications. Through dose escalation studies, he and his co-workers found that control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. However, at two years, control rates had decreased to 33% even at the dose of 50 Gy. He also estimated the dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions Then he mused that higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia were needed for longer-term control. The effectiveness of wide surgical excision has been documented. Charles Kuntz published in 1997 a study where 75 dogs with soft tissue sarcomas had wide surgical resection. On the basis of a low local recurrence rate (15%) and high median survival time (1,416 days), wide excision of tumour margins or radical surgery appeared to be a very effective means for managing soft-tissue sarcomas of the trunk and extremities. Analysis of histologic characteristics for prognosis supported use of preoperative biopsy. A conclusion was that surgical margins should be evaluated, and early use of aggressive surgery is indicated in the management of soft-tissue sarcomas in dogs. This understanding remains today.

However, I am disturbed by recent literature seemingly indicating that a more relaxed approach to the surgical management of STS in dogs is appropriate given that the retrospective information presented in this literature downplays the seriousness of the biological behaviour of this group of tumours. This information is flawed and I urge all who treat animals with these cancers to consider the large body of work supporting wide resection or combined modality treatment rather than to treat these animals with minimal resections alone. Using surgery alone with a minimal margin approach provokes catastrophe. Recurrence will be your hallmark and failure the outcome.

Charles Kuntz will describe, in his companion presentation, his experience with wide resection and delayed secondary healing for soft tissue sarcomas of the antebrachium. His group has

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published on this and demonstrated very good local control and survival outcomes underscoring the need for treatment of a wide area around measurable clinical disease.

For tumours not located in the antebrachium and for those in “tight” compartments of the extremities where the deep margins cannot be wide without limb amputation, a combination of surgery and radiation becomes an attractive alternative. As Dr Ed Gillette suggested in 1976, surgery combined with radiation may produce better local control over radiation at tolerable doses alone.

When these tumours occur in locations where wide resection is not possible (i.e. distal extremities) adjunctive radiation therapy (RT) after marginal resection is a viable option for permanent control. In a study of 34 dogs with incompletely excised soft tissue sarcomas in 2000 were treated post operatively with a total tumour radiation dose ranging from 42 to 57 Gy given in 3- to 4.2-Gy daily fractions on a Monday through Friday schedule. Overall median survival was 1,851 days. Median time to local recurrence was greater than 798 days. Soft-tissue sarcoma tumours at oral sites had a statistically significant lower median survival (540 days) as compared to other tumour sites (2,270 days). Radiotherapy is a useful adjuvant therapy for incompletely excised soft-tissue sarcomas with an expectation for long-term patient survival. Another similar study also in 2000 showed a five-year survival of 75%. RT can be utilised preoperatively or postoperatively. Preoperative radiation therapy is not commonly utilised due to increased wound complications post-surgery. As shown by Dr Gillette twenty years ago, as a single modality, RT is generally considered palliative for STS with control defined as a slowly regressing or stable-in-size tumour mass for a median of twelve months.

We often see quite old dogs with soft tissue sarcomas of the extremities or in compartments not amenable to wide resection. Owners of these dogs are often reluctant to treat with our curative postoperative radiation protocol of 19 daily fractions to a total dose of 54 Gy after marginal resection usually due to financial reasons but also because of concerns about the acute effects of radiation and the need for daily general anaesthesia. For these dogs we designed a protocol of five weekly 6 to 8 Gy fractions after marginal resection. The protocol is very cost effective with very few acute effects making it a suitable protocol especially for old dogs that are not expected to live long enough to risk late effects of this large dose per fraction protocol. Recently we published our results from 48 consecutively treated cases. The median progression free survival was 698 days. The local failure-free probability at 1 and 3 years was 81 and 73%. The one and three year tumour-specific overall survival was 81 and 61%. Long-term local tumour control was achieved in the majority of dogs. This protocol is reasonable to prescribe in older patients or when financial limitations exist.

References:

J Natl Cancer Inst. 1976 Feb;56(2):365-8. Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals. Hilmas DE, Gillette EL. J Am Vet Med Assoc. 1989 Jan 1;194(1):60-3. Radiotherapy of soft tissue sarcomas in dogs. McChesney SL, Withrow SJ, Gillette EL, Powers BE, Dewhirst MW. J Am Vet Med Assoc. 2000 Jul 15;217(2):205-10. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. McKnight JA, Mauldin GN, McEntee MC, Meleo KA, Patnaik AK.

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J Vet Intern Med. 2000 Nov-Dec;14(6):578-82. Postoperative radiotherapy for canine soft tissue sarcoma. Forrest LJ, Chun R, Adams WM, Cooley AJ, Vail DM. J Am Vet Med Assoc. 1997 Nov 1;211(9):1147-51. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). Kuntz CA, Dernell WS, Powers BE, Devitt C, Straw RC, Withrow SJ. Vet Comp Oncol. 2014 Nov 13. Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma. Kung MB, Poirier VJ, Dennis MM, Vail DM, Straw RC.

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USE OF PLEURAL PORTS IN VETERINARY SURGERY

Maurine Thomson, B.V.Sc, FANZCVS. Veterinary Oncology Specialists. Underwood, Brisbane

Chronic pleural effusion results in tachypnoea, dyspnoea and can lead to fibrosing pleuritis. Where elimination of the inciting cause is not possible, palliation can be achieved via repeat thoracocentesis or surgical shunting techniques. The potential complications of repeat thoracocentesis include iatrogenic lung trauma or infection and animals require heavy sedation or anaesthesia. Surgical shunting techniques include pleuroperitoneal shunting, pleurovenous shunting, and omentalization of the pleural space. Pleuroperitoneal shunts have had limited success because of complications with obstruction, inefficient pumps, and irritation at the implant site. Pleurovenous shunts have similar complications plus the possibility of thrombosis. Thoracic omentalization has been described in dogs and cats for the successful palliation of thoracic effusions, and requires surgical exposure of both the thoracic and abdominal cavity, and the possibility of creating a diaphragmatic hernia.

The use of modified vascular access ports for the management of chronic pleural effusions has been described in dogs and cats. PleuralPort (Norfolk Vet Products) is a commercially available device designed specifically for thoracic drainage. It is available in 2 sizes (7 and 9 French) and comprises a fenestrated radio-opaque silicone tube that is placed in the thorax, and a drainage hub that is placed in a subcutaneous pocket outside the thorax. The hub is identical to that used for vascular access ports, and is aspirated with a Huber needle. This allows for repeated puncture of the hub without compromising the seal. The advantages of the pleuralPort include being minimally invasive to place, relatively inexpensive to place, and reduced risk of incidental infection or removal by the animal. The owners can drain the thorax at home. Intracavitary chemotherapy can also be administered via the tube also.

A Brooks et al Use of the PleuralPort device for management of pleural effusion in 6 Dogs and Four Cats. . Vet Surg 2011. Placed 1 tube in 1 hemithorax between 7th and 10th ribs, advanced til all fenestrations within thorax. The nonfenestrated tubing then tunnelled subcutaneously and a 6-8cm dorsoventral skin incision made over the caudal thorax in dogs or caudal abdominal epaxial muscles in the cats. The hub was sutured to fascia of the latissimus dorsi or epaxial musculature with 5 simple interrupted sutures. The tubing was then connected to the hub and covered with the small blue sleeve which stops kinking. Typically 9 F in dogs and 7F in cats. Post op radiographs are taken to check the position of the tube.

Causes of the effusions were 9 with chylous and 1 with idiopathic. When placed percutaneously, mean surgical time was 30 minutes, and median hospital stay was 24 hours. Immediate post op radiographs showed some coiling of the tubes in all patients; this was most obvious in the cats. No significant migration of the hub occurred in any animal. Post op complications occurred in 4 animals, 1 cat with fibrosing pleuritis developed pneumothorax after post placement and was euthanased, port obstruction occurred in 3 at day 46, one at day 1, and day 11 (post mortem showed blocked with fibrin clot) in 2 dogs. Median duration of port function was 20 days (range 1-391), median duration of implantation was 391 days (range 6-723 days) 5 of 10 remained in

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place >362 days with no local or systemic effect, so very inert. So they don’t need to be removed if no longer being drained. Biggest complication was obstruction in 3 of 11, so possibly flushing after each use might be needed. Manufacturer recommends flushing with heparin (100 IU/ml), but this was not performed in this study.

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ORBITECTOMY IN THE DOG


Malignant neoplasia of the orbit, zygomatic arch or extension from the caudal maxilla, vertical ramus or frontal sinus may require orbitectomy. Both total and partial orbitectomy techniques have been described (O’brien 1996). It can be further referred to as Superior orbitectomy, which involves removal of the caudodorsal part of the maxillary bone and the dorsal and medial parts of the frontal bone, inferior refers to the removal of the caudoventral maxillary bone, the lacrimal and zygomatic bones, and the ventral part of the palatine bone, and total. The eye is usually preserved with superior or inferior orbitectomies, but removal of the eye is required when a total is performed. If disease extends to the temporal or sphenoid bones, complete resection is not possible. The surgical technique will depend on the type/location of the tumour. Minimum margins of 1-2 cm are normally required. Advanced imaging such as CT or MRI is needed to really determine extent of disease, along with biopsy and staging. Having skull specimens is extremely helpful and a thorough knowledge of the anatomy is mandatory. Total orbitectomy with eye removal (Not for the faint hearted, bleeding you can see, haemorrhage you can hear!) The aim is to perform an osteotomy of the maxilla laterally which is continuous with the frontal bone dorsally, the ventral maxilla intraorally, the frontal bone medial to the eye which is continuous into the lateral aspect of the palatine bone, and completed by osteotomy of the zygomatic bone. The patient is placed in lateral recumbency. A gauze bandage is packed into the pharynx after all tubing is inserted. Tape all connections to tracheal tube in place to prevent disconnection as the head is moved. Know the starting PCV. Small dogs may require blood transfusion (sometimes also large dogs) The initial skin incision is performed over the laterodorsal aspect of the maxilla from the level of the infraorbital foramen rostrally, around the eye, and caudally along zygomatic arch as determined by tumour extent (Lascelles , Thomson 2003 JAAHA: Combined dorsolateral and intraoral approach to maxilla). Any existing biopsy tract must be removed, so normally skin incision goes around biopsy site with 1cm margins. The skin and s/c are elevated rostrally from the caudal maxilla. Dorsally the soft tissue is retracted medially, and laterally to identify the osteotomy sites in the frontal bone, then laterally to identify frontal and zygomatic bones. The soft tissue of the maxilla is transected more deeply to the level of the bone along dorsal maxilla and frontal bone. The levator nasalabialis m is elevated over the maxilla and the frontalis and interscutularis m over the frontal bones. The angularis oculi vein is encountered medial to the eye and ligated. An intraoral approach is combined with the lateral maxillary from level of infraorbital foramen to the caudal aspect of the maxilla. This incision is continuous with the dorsal incision, allowing a bipedicled flap of skin, and underlying musculature to be elevated from the entire lateral maxilla. A periosteal elevator is useful for mobilizing this tissue. The infraorbital vessels and N are transected as the exit the infraorbital foramen. Another incision is made in the oral mucosa medial to the dental arcade in the hard palate, the same distance as the lateral mucosal incision. This completes the lateral and dorsal approach. The frontalis and retractor anguli muscles overlying the lateral orbital ligament are incised, and the attachment of the Masseter M on cranial aspect of zygomatic arch is transected and retracted ventrally. The osteotomy of the zygomatic arch is usually performed just caudal to the thick

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orbital ligament. An incision is made in the periosteum, ant the osteotomy performed with an oscillating saw. I use a Hohman retractor to separate musculature medially to zygomatic arch during this cut. The temporalis muscle is retracted from the frontal bone at the site of the proposed osteotomy. Medial to the eye the pterygoid Muscle is elevated from the lateral aspect of palatine bone. This part of the dissection needs to be done meticulously so as not to damage the major vessels at the ventromedial portion of the orbit. If identified they can be ligated (maxillary A, and pterygoid, palatine and ophthalmic plexi). Otherwise they are ligated after all osteotomies are complete. The remaining osteotomies are now performed with an oscillating saw, leaving the medial cut in the orbit to last, as profuse haemorrhage is encountered and normally can only be stopped after the bone of the orbit is removed. First osteotomy is normally the lateral maxilla and dorsal aspect of the frontal bone. The rostral extent is typically in front of carnassial, pending breed and tumour extent. The next osteotomy is intraoral one medial to the teeth. It extends rostrally to join up with the lateral maxilla cut, and caudal extent of the maxilla. Medial osteotomy is last and hardest. Begin caudodorsally, just caudal to zygomatic process of the frontal bone, and then aim towards the caudal maxilla (avoiding optic canal, orbital fissure and rostral and caudal alar foramens of the sphenoid bone. It is safer to use an osteotomy and mallet for this after cutting through frontal bone. Remaining soft tissues are incised, and the orbit is gently pulled out of the skull. Gentle traction is needed to avoid damage to the optic chiasm. The caudal N of the eye is transected (optic, oculomotor, trochlear, and abducent, with branches of trigeminal and facial). Any remaining arteries are ligated (haemoclips or ligasure easiest). Closure requires re-establishing separate oral and nasal cavities. A buccal flap is elevated and used to attach to the mucoperiosteum in 2 layers ( I use continuous 2-0 or 3-0 monosyn/PDS in s/c and 4-0 vicryl in the mucosa). Undermine the buccal flap to prevent excessive pulled in appearance of caudal maxilla. I don't predrill holes in maxilla. The muscles within orbitectomy area are opposed as possible, dead space remains and is unavoidable. S/C and skin closed routinely. The nasal cavity and sinuses will be continuous with the orbitectomy. Superior orbitectomy Differs mostly from total orbitectomy in that there is no oral approach. There is only one skin incision performed on the dorsal aspect of the maxilla and frontal bone. The dorsal osteotomy involves the frontal bone and caudal maxilla, but dorsal to infraorbital foramen, and lateral to the rim of the orbit, and the medial cut is not as ventral as a total orbitectomy Inferior orbitectomy This requires an intraoral approach, and the dorsolateral osteotomy in the maxilla is just rostral to the orbital rim at the level of the lacrimal bone . The osteotomy medial to the eye begins at the level of the lacrimal bone, aiming the caudal aspect of the maxillary osteotomy towards medial aspect of the molars. The zygomatic arch is cut where required. Closure requires re-establishing the nasal and oral cavities with a buccal mucosal flap. Post operative management. Maintain intravenous fluids till eating and drinking (normally 24-48 hours). A feeding tube can be placed at surgery but rarely ever required. Pain management is extremely important and necessary for the successful outcome of these patients. We use local bupivacaine blocks, CRI fentanyl (2-5 ųg/kg/hr), fentanyl patch. At home with fentanyl patch and oral NSAIDS., tramadol 4mg/kg PO Cosmetic appearance often swollen and bruised post op. (look like they have been in a boxing ring I tell the owners). When nasal cavity is entered you may have initial movement of the skin as they breathe. Bleeding from the nose immediately post op. Dehiscence may be a problem if

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tension, or not a lot of mucosal tissue for closure. Animals can have a more sunken appearance depending on amount of tissue resected. Generally functional and cosmetic outcomes are very good. Prognosis effectively determined by tumour type and surgical margins. In 1 paper survival times >456 days for 24 dogs and 6 cats treated for sarcomas and carcinomas. References Lascelles BD, Thomson Mj, Dernell WS et al 2003. Combined dorsolateral and intraoral approach for the resection of tumours of the maxilla in the dog. JAAHA 39:294-305 O’Brien MG, Withrow SJ, Straw RC et al 1996, Total and partial orbitectomy for the treatment of periorbital tumours in 24 dogs and 6 cats. Vet Surgery 25:471-479 Lascelles BD and Davidson M. Eyelids, eye and orbit . Veterinary Surgical Oncology 2012. Ed Kudnig S T and Sequin B,. Wiley-Blacwell Publishing, Chapter 12, page 396- 403

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SURVIVING GASTRODUODENOSTOMY IN THE DOG (75% of the time)


Gastroduodenostomy is an infrequently performed surgical procedure for neoplasia, chronic gastritis, and perforated ulcers. Gastric neoplasia requires complete staging for a successful outcome. Ultrasound is usually the first diagnostic tool, to assess gastric wall thickening and other intra-abdominal metastatic disease. Generally correlation between findings with U/S and definitive histopathology is inconsistent, though extension of the disease beyond the mucosa is consistent with carcinoma. Overall the degree of thickening of the wall, presence of lymphadenopathy, or ulceration or echogenicity was not useful in predicting tumour type. U/S guided FNA is frequently used as the first step in a diagnosis, though only diagnostic in about 50% of cases (particularly for lymphoma). CT is extremely useful for identifying extent of disease, and endoscopic or laparoscopic biopsies frequently diagnostic. Laparoscopic exploration is extremely useful to identify extent of disease and allow biopsy of liver and lymph nodes. Entrap cytology can be very useful also. Relevant anatomy 4 regions are Fundus, body, antrum and pylorus. Gastric blood flow is from celiac A, which originates from aorta just cranial to the cranial mesenteric A. Right and left gastric A arise from the celiac and supply the lesser curvature, right and left gastroepiploic arise from branches of the celiac and supply the greater curvature. 80% of the blood flow is to the mucosa, with 20% to the serosa, muscularis and submucosa. Essential anatomic structures in the region of the gastric pylorus are bile duct, which empties into the major duodenal papilla 2-3cm aboral to the pylorus in dog and cat. If it is transected it will require biliary diversion, i.e. cholecystoduodenostomy. The portal vein must be preserved at al costs, or death from fatal portal hypertension occurs. Preservation of the hepatic A is also required. General principles of gastric surgery are gentle tissue handling, moistening of tissues to reduce inflammation and adhesions, and at the pylorus single layer sutures are used to avoid luminal narrowing. Generally 3-0 to 4-0 PDS, Maxon or monocryl sutures. Billroth 1 (pylorectomy and gastroduodenostomy) Care is taken with the biliary duct, pancreatic duct, hepatic A and portal vein. Wide margins are not possible in this region; ideally 1-2cm beyond gross evidence of the tumour is required. The antral and pyloric regions are mobilized by transecting the gastrohepatic ligaments and paraduodenal peritoneum. This allows greater gastric mobility and better exposure of the dorsal aspect of the stomach. Branches of the gastric and gastroepiploic vessels supplying the region are ligated (clips, cautery). Stay sutures are placed 1-2cm oral and aboral from the transection site, atraumatic clamps are placed oral and aboral to the tumour, and the tissue transected. Try and leave 1cm of duodenum near the duodenal papilla to minimize bile duct obstruction from oedema. Due to obvious discrepancy in the duodenum vs gastrostomy sites, the gastrostomy is partially closed with 1 or 2 layer closure with 3-0-4-0 mason or PDS, ensuring the gastric submucosa (holding layer) is included. Alignment is very important to minimize narrowing the gastroduodenostomy site. I personally suture the dorsal aspect, i.e. furtherest away, with a combination of simple and continuous 4-0 sutures. The Y junction with the stomach is very important to make leak proof. Place bite 2-3 mm apart, 2-3m from incised edge. An end to side

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anastomoses can also be performed with the stomach, by completely suturing the gastrostomy or stapling with a TA and then over sewing. Then creating a new incision for the gastroduodenostomy. Post operative care These dogs need extremely close monitoring and post op care. They are frequently debilitated from chronic GI disease. Very close attention during surgery for hypotension or hypoglycaemia. If anemic require blood products. Feeding tubes required as needed. Provision of nutritional support is vital in animals recovering from gastric surgery. Ideally oral feeding with an easily digestible, low-fat high carbohydrate diet is begun 12-24 hours post op. This aids in preservation of the mucosal barrier and stimulates healing through mucosal nutrition. Generally GI protectants such as histamine blockers or proton pump inhibitors are used to reduce gastric acidity. Promotility drugs such as metoclopramide are used to reduce ileus and nausea. Opioids are used for pain relief (I prefer fentanyl CRI). The centrally acting anti emetics maropitant and ondansetron are used also if needed. Movement aids gastrointestinal mobility and should be encouraged early. Billroth II This is gastroduodenostomy or gastrojejunostomy that requires removal of the duodenal papilla and rerouting of the biliary tract via cholecystoduodenostomy or jejunostomy. Complications of Billroth I Partial gastrectomy can cause loss of reserve capacity, depending on the amount removed. Generally readily tolerate resection of 50%, and increased reserve occurs over few weeks/months. Limited data exists on complications in dogs in the literature, but include dehiscence, stenosis, pancreatitis and functional problems. In humans extent of resection is always associated with increased problems. Vomiting is a frequent problem post Billroth I and II, associated with rapid passage of acidic stomach contents into the duodenum, and reflux of bile and pancreatic secretions into the stomach causing gastritis. Billroth II is associated with poor quality of life post operatively and should only be performed after thorough explanation to the owner, i.e. your dog with vomit till it dies. Roux-en-Y may have better outcomes, but generally loss of body weight and chronic vomiting are features of aggressive GI surgery in dogs. Other reported problems include hypotension, hypoglycaemia, aspiration pneumonia and pancreatitis. Prognosis. Adenocarcinoma is the most common malignant neoplasia, with short survival times reported post operatively (1-3 months). It is generally considered that chemotherapy is not effective for gastric carcinomas. Leiomyosarcoma are the next reported malignancy, and can potentially have much longer ST. Many of these tumours have now been reclassified as gastrointestinal stromal tumours (GISTs). GISTs express CD-117 (Kit) and expect a better survival time post op when treated with Palladia. GIST survival time about 1 year vs 8 months for leiomyosarcomas. Evaluation of Risk Factors for Morbidity and Mortality after

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Pylorectomy and Gastroduodenostomy in Dogs JASON EISELE, DVM , JANET KOVAK MC CLARAN, DVM, Diplomate ACVS JEFFREY J. RUNGE, DVM , DAVID E. HOLT, BVSc, Diplomate ACVS , WILLIAM T. CULP, VMD, Diplomate ACVS , SERENA LIU, DVM, MS, Diplomate ACVP , FENELLA LONG, BVSc, Dip. ACVP , and PHILIP J. BERGMAN, DVM, MS, PhD Diplomate ACVIM (Oncology) Veterinary Surgery 39:261–267, 2010 24 Dogs from AMC and Penn, pylorectomy and gastroduodenostomy performed through a ventral midline incision. Gastroduodenal anastomoses performed in a single layer closure using 3-0 to 4-0 in either 2 simple continuous or interrupted sutures. Dorsal surface opposed first. Modifications included stapling stomach and end to side anastomoses for duodenum and stomach. Biliary diversion by cholecystoeneterostomy as needed. J, G or GT tubes placed at surgeon’s discretion. Most common clinical signs were vomiting, anorexia and weight loss. (Range 2-180 days). Preop weight loss was negative indicator for survival (MST 33 days). 1 had chest mets, 8 had abdominal mets (33%). Presence of metastatic disease was not associated with shorter ST. 6 dogs had endoscopic biopsies, 4 matched final histopath. Mean surgical time was 208 minutes!. 6 dogs (25%) died/euthanasia within 14 days of surgery. 8 of 24 needed blood products, 3 of 24 developed pancreatitis, 3 developed aspiration pneumonia, septic peritonitis in 2 (leaked and both survived). 13 dogs had malignant neoplastic, 7 adenocarcinoma, 2 plasma cell tumours, 1 each poorly differentiated carcinoma, GIST, lymphoma, sarcoma. 1 had leiomyoma, and 1 adenoma. 8 completely resected, 5 not. Incomplete margins ST 33 day’s vs complete with 578 days. 6 had inflammatory disease. Dogs with malignant disease had overall ST 33 days vs >1659 d without. Overall preop weight loss and malignant disease were only factors associated with shorter ST. U/S was accurate for detecting metastases in most cases. Ideally preop biopsy as poor survival times for malignant disease. Preop hypoalbuminaemia was not associated with poorer outcomes, but small number of cases.

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PLATIPUMP

Dr. Charles A. Kuntz, DVM, MS, Diplomate of the American College of Veterinary Surgeons, Registered Specialist of Small Animal Surgery, ACVS Founding Fellow -

Surgical Oncology Southpaws Specialty Surgery for Animals, Moorabbin VIC Australia

Historical development Cisplatin-impregnated open-cell polylactic acid (Opla-pt) sponges were developed at Colorado State University as an alternative to conventional chemotherapy in animals with osteosarcoma. A single implantation of a sponge was associated with a median survival time which was equivalent to intravenous chemotherapy with fewer side-effects. Opla-Pt has also been used as a radiation sensitiser in dogs having radiation therapy for nasal carcinoma, and has been implanted into wounds created by the marginal excision of soft tissue sarcomas with results equivalent to the use of radiation therapy. The efficacy of platinum-based chemotherapy is proportional to the area under the curve (AUC) of serum levels while side effects are related to peak serum levels. Opla-Pt sponges have an AUC which is 7-22 times greater than that achieved with a single equivalent IV dose of cisplatin. The peak serum levels are significantly lower than those achieved with IV doses resulting in fewer side effects. Despite great clinical success, investment by a commercial company to help fund FDA approval could not be secured and the progress in the development of this technology stalled. In an attempt to emulate the benefits of Opla-Pt, an elastomer pump was found which could release a known volume of fluid over a period of 3, 5 or 7 days. We decided to use carboplatin instead of cisplatin because of equivalent efficacy with less gastrointestinal and renal toxicity. The platinum compounds are not vesicants and have been injected subcutaneously in previous publications with no local side-effects. We initially treated 5 patients with osteosarcoma with amputation and subQ Platipump infusion. Once those 5 patients had succumbed to their tumours, we analysed the data and found that survival times were similar to what was observed with IV carboplatin. We have since published its use in 17 patients having had amputation for osteosarcoma with a median survival time of 365 days. Side effects included neutropenia in proportions similar to that seen with IV carboplatin and infection of the subQ site. Potential advantages: 1. Completion of the amputation and chemotherapy protocol in only one week, allowing the

patient to enjoy a longer period of good quality life without the need for repeated vet visits and chemotherapy injections.

2. Lower cost. At our practice, a single infusion of carboplatin over 4 days costs about $2600 compared with about $4000 for 4 IV carboplatin injections

3. Side effects have included mild gastrointestinal signs (which may or may not be related to the chemotherapy infusion), infection of the infusion site (which may provide a survival benefit in patients with osteosarcoma) and neutropenia (about 20% of patients with about 5% requiring hospitalisation). We have had no deaths in the period surrounding the infusion of carboplatin in over 100 patients.

Future directions:

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1. We are currently preparing a manuscript on its use in 45 patients having had amputation for osteosarcoma (median survival time equivalent to IV carboplatin).

2. We are currently preparing a manuscript on it use in 17 patients having had palliative radiation therapy for appendicular osteosarcoma with a median survival time of 11 months.

3. We have used it as a radiation sensitiser in 6 patients with nasal adenocarcinoma. These patients had a marginal surgery and postoperative orthovoltage radiation therapy. Our median survival time is 26 months. We have not yet analysed data to determine if it offers any increase in efficacy over surgery and radiation therapy alone.

4. We have used it in 3 patients with marginally excised soft tissue sarcomas with no wound complications. In previous studies using Opla-Pt in the same setting the majority of patients had severe wound complications. We have had no recurrences, but obviously numbers are too small to allow any conclusions about its efficacy.

5. We have done double infusions 3 weeks apart in a small number of patients with no evidence of toxicity. While none of these patients have developed metastasis, they are recent and no conclusions can be made about efficacy.

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BRAIN SURGERY – CEREBRUM, CEREBELLUM, PITUITARY



Brain tumour surgery in animals lags behind its human analogue by decades. Human brains are large and fairly uniform in size. In one human neurosurgical textbook, there are 52 different approaches to the brain. Human blood products are readily available. Specialist anaesthetists are present for every surgery. Critical care facilities are present on site. Healthcare is universally accessible in Australia. Financial constraints are basically irrelevant. Caseload is large and there is a huge incentive to be successful in management in central neurological conditions. Factors that contribute to lag in veterinary brain surgery include small patient and brain size, difficulty in neurolocalisation of normal brain structures within the cortex, limited access to surgical navigation, relative paucity of training programs, and the need for brain surgery programs to be financially viable. Limitations aside, the science of veterinary brain surgery is advancing rapidly. Our patients don’t need the degree of mental acuity required by humans giving us more of a margin for error. Advanced imaging is now readily available. There is a plethora of second hand equipment available on eBay and other auction sites. Pet insurance is being taken up to a greater degree and advanced training programs are becoming more widely available. Perioperative critical care is progressing rapidly. Now can be viewed as a sort of “Golden Age” for aspiring veterinary brain surgeons. Definitions: Intra-axial - lesions within the brain parenchyma. Example: Glioblastoma, astrocytoma Extra-axial - lesions outside the brain parenchyma. Example: meningioma, pituitary macroadenoma Intra-ventricular - lesions within the fluid-filled cavities of the brain. Example: choroid plexus tumour Cytological malignancy - morphological assessment of anaplasia Biological malignancy - likelihood that the tumour will kill the animal Causes of dysfunction with brain tumours: Infiltration of normal tissue, compression of adjacent structures, disruption of cerebral circulation, local necrosis, obstructive hydrocephalus, increased intracranial pressure, cerebral oedema and brain herniation. Slow tumour growth allows the surrounding tissues to adapt. These patients can have vague signs. Patients may have rapid progression when compensatory mechanisms are exhausted. Imaging Radiographs generally do not provide much insight into the diagnosis of brain tumours with the exception of skull tumours which are compressing the brain parenchyma. Magnetic resonance imaging (MRI) is considered the gold standard imaging modality for brain tumours. MRI allows detection of the primary tumour, oedema, cyst formation, vascular changes, haemorrhage and necrosis. It also allows better definition of anatomical relationships of the tumour and

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surrounding structures. The downsides of MRI include greater relative cost of equipment and siting, longer scan time, difficulty in interpretation and artefacts created by metal in the patient. MRI is capable of detecting nearly all brain lesions. Computed tomography (CT) is more readily available, has a lower cost of purchase, siting and maintenance of equipment, has greater versatility for imaging other structures, greater speed and has the ability to perform pulmonary metastasis checks. CT is capable of detecting the majority of brain lesions but does not provide the level of detail which can be achieved with MRI. Presurgical biopsy If surgical excision is planned for extra-axial brain lesions, pre-surgical biopsies are not routinely performed. With CT and/or MRI histological diagnosis can be made with a reasonable degree of certainty. If surgery is not possible or will be difficult, a pre-surgical biopsy can be performed. Generally, this requires specialised equipment in the form of a surgical navigator or stereotactic biopsy device. There are commercially available surgical navigators dedicated to the veterinary market and human devices can be modified as well. New units are prohibitively expensive for most general and speciality practices. Second-hand units can be purchased through auction websites. Using specialised instruments, these devices allow three-dimensional navigation of the brain in real-time. Approaches It is important that the jugular veins not be compressed with positioning because this can cause an increase in intracranial pressure. Human “duraguard” drill/routers are challenging to use in dogs because of the thickness and irregularity of the canine skull. My preference is to use a rotary laminectomy drill with a 3-4 mm burr. I prefer to drill to the point that the residual bone is extremely thin and the rest is removed using a sharp dental pick. The bone is removed and in most cases is not replaced. The dura mater is incised using a blade and then durotomy scissors. Haemostasis is achieved using bipolar cautery, bone wax, gelatin foam and/or collagen. If the dura is not adhered to the tumour, then it should be preserved and replaced. Intraoperative ultrasound can help with visualising intra-axial lesions during surgery. Upon closure, we are not particularly concerned with sealing the dura. CSF leakage is a major concern in humans but does not appear to be a big issue in animals. If the ventricle is encountered, then the dura must be replaced and sealed or pneumocephalus can occur which can result in significant neurological deficits and can be life-threatening. Frontal muscle fascia can be used as a dural substitute. When possible, temporal muscle should be pulled over the defect to provide some protection to the brain. Approaches Lateral rostrotentorial - This approach allows exposure of the lateral parietal, temporal and occipital cortices. Radical rostrotentorial - This is an extension of the lateral rostrotentorial approach into the ipsilateral frontal sinus. It allows exposure of the rostral cortex and olfactory lobe. Suboccipital - The approach allows exposure of the caudal cerebellum, the caudal medulla oblongata and the cranial cervical spinal cord.

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Bilateral rostrotenteorial (dorsal) - Allows exposure of the dorsal olfactory, frontal, parietal, temporal and occipital cortices. Transsphenoidal - Allows exposure of the pituitary. Transorbital - Allows exposure of the piriform and olfactory lobes. Equipment 1. Stereotactic biopsies - use three-dimensional geometry derived from sectional imaging to

allow biopsy of deep structures in the brain. These may be framed or frameless. 2. Surgical navigators - use sectional imaging and fiducial markers to allow 3d spatial

localisation within the brain in real-time for biopsy or excision of brain lesions. 3. Retractors - Layla brain retractors mount to the table and allow retraction of the cerebral

cortex accurately and gently. 4. Biopolar electrocautery 5. Encephaloscopy-assisted brain tumour surgery. This technique involves the use of rigid

telescopes to help identify residual tumour after excision of the main tumour mass. It is associated with the longest median survival time ever reported with brain tumour excision in animals.

Alternatives to surgery 1. Stereotactic radiosurgery 2. Proton beam therapy 3. Chemotherapy 4. Cryosurgery

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GASTROINTESTINAL BIOPSY TECHNIQUES



Gastrointestinal (GI) biopsies can provide information which cannot be gained from any other method. That being said, the need for biopsies has decreased through appropriate use of therapeutic trials. The need for full-thickness surgical biopsies has been further reduced through the use of endoscopy. When indicated, implementation of proper biopsy technique and sample preparation greatly enhances the quality and amount of information gained. Generally, the decision to perform a biopsy is based on the presence of clinical signs attributable to the GI system which cannot be attributed to other body systems. These include chronic vomiting, weight loss, GI blood loss, gastroduodenal reflux or evidence of small intestinal diarrhoea. GI biopsy is probably the last step in making a diagnosis after other less-invasive tests have been exhausted unless there is evidence of obstruction, severe haemorrhage or perforation. The more clinically ill the patient is (ie severe weight loss, poor body condition score, hypoalbuminaemia, anorexia, ultrasonic evidence of infiltrative disease) the more likely therapeutic trials should be skipped and biopsies should be performed. Patients of appropriate age which have clinical signs attributable to inflammatory bowel disease (IBD) should have therapeutic trials prior to biopsies. These include empirical treatment for Giardia and endoparasites, supplementation with cobalamin and folate, dietary trials, antibiotic trails, corticosteroids or other immunosuppressive medications. When therapeutic trials have been unsuccessful, abdominal imaging (ultrasound or CT) should be performed to try to identify lesions which may not be accessible endoscopically, including lesions in the liver, spleen, lymph nodes, lower duodenum, jejunum, pancreas and/or kidneys. If clinical signs are attributable to the upper gastrointestinal tract, and abdominal imaging has eliminated lesions which may not be accessed, endoscopy with biopsies is generally preferred to full-thickness surgical biopsies. Endoscopy is contraindicated if there is evidence of GI perforation characterised by free abdominal air or peritonitis. Gastrointestinal Biopsies General comments about gastrointestinal biopsies 1. It is not always appropriate to biopsy every patient with chronic gastrointestinal disease 2. Biopsies are probably not appropriate for patients with upper gastrointestinal clinical signs of

less than 3 weeks duration. 3. There can be great inter-observer variation in histologic findings between pathologists 4. Duodenal biopsies (compared with other GI sites) are often the most telling in dogs with

chronic vomiting or small-bowel diarrhoea. 5. Biopsies of the ileum are generally recommended because they add significantly to the

complete diagnosis of the patient even if lower intestinal signs are absent. 6. GI lymphoma is often localised in the ileocecal junction.

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7. Ileal biopsies allow diagnosis of tumours and protein-losing enteropathy which may be missed on duodenal and colonic biopsies.

8. In most patients, duodenal and ileal biopsies are required, and must be of excellent quality. 9. Expectations from gastrointestinal biopsies

A. Differentiate mycotic enteritis from lymphoma or IBD B. Differentiate moderate IBD from lymphoma C. Differentiate eosinophilic enteritis from lymphoma D. Immunophenotyping can help differentiate IBD from lymphoma E. Cannot expect to be able to accurately assess the severity of IBD or determine which

patients will respond to therapy. Endoscopic Biopsies General comments about endoscopic biopsies 1. Smaller biopsy forceps (less than 2.5 mm) should not be used 2. Accuracy of endoscopic biopsies are highly operator dependent 3. Samples must include mucosa and submucosa 4. GI lymphoma appears to be primarily a submucosal disease; biopsies which only get the

villous tips will likely miss the diagnosis 5. The quality of endoscopic ileal biopsies are often superior to duodenal biopsies because the

mucosa of the ileum is thinner, allowing more reliable inclusion of the submucosa 6. 7-8 samples from each location should be taken 7. Good biopsy samples should be pale and preferably white, long pieces of tissue, with solid

rather than gelatinous consistency 8. As quality increases, the required number of samples decreases 9. The quality of endoscopic biopsies greatly influences the pathologists ability to diagnose

gastrointestinal disease 10. It may be challenging in some areas of the GI tract to obtain samples which are deep enough

because it can be difficult to orient the scope perpendicular to the mucosa 11. Some anatomical sites (duodenum, ileum) can be difficult to access by inexperienced

clinicians 12. Submucosa can be difficult to access in dogs greater than 35 kg 13. Properly performed biopsies eliminate the need for surgical biopsies in 95% of cases where

the endoscope can reach the lesion 14. If the duodenum or ileum cannot be entered, the biopsy forceps should be blindly advanced

into the duodenum or ileum and multiple samples collected 15. One of the samples can be assessed cytologically using squash preparation for eosinophilic

enteritis, adenocarcinoma, lymphoma, inflammatory cells or spirochetes. 16. Submission of endoscopic samples

A. When samples are collected, they should be handled carefully to minimise artefacts and distortion.

B. Tissue should be removed using a 25 gauge needle C. Samples should be submitted in cassettes, not free-floating in formalin. D. Tissue samples should be oriented luminal side away from the sponge in the cassette. E. Cassettes are placed in 10% buffered formalin F. Different locations are placed in different labelled vials G. Small tissue samples should not be allowed to dry out

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H. When endoscopic samples are submitted, the pathologist should report on the number and quality of samples to help the clinician to determine if technical modifications should be made to improve biopsy procedure

Advantages of endoscopic biopsies include: 1. Endoscopy is minimally invasive 2. Multiple biopsy samples can easily be collected 3. Morbidity and mortality from endoscopically collected gastrointestinal biopsies are very low

with fewer complications than open surgical biopsies 4. Endoscopy allows visualisation of mucosal lesions prior to biopsy which can increase the

diagnostic yield 5. Microbiological samples can be simultaneously collected 6. Ulcerations are easily visualised 7. Endoscopy allows photographic documentation of findings 8. Endoscopic biopsy allows detection of Helicobacter pylori 9. Endoscopy allows detection of gastric mucosal hypertrophy and duodenal polyps 10. Endoscopic appearance is better correlated with outcome in pets with IBD than histological

diagnosis 11. Endoscopy procedures are generally shorter, less stressful and less expensive than surgical

biopsy procedures Disadvantages of endoscopic biopsies include: 1. Preparation of the gastrointestinal tract is absolutely required. Only fasting is required for the

upper GI whereas fasting, enemas and ingestion of electrolyte solutions are required for colonoscopy

2. Functional disease cannot be diagnosed and luminal diameter cannot be determined 3. Generally not able to diagnose dietary responsive enteropathy, antibiotic responsive

diarrhoea or GI motility disorders 4. Only mucosal and intraluminal diseases can be detected 5. Distal duodenal and jejunal lesions cannot be detected in most patients 6. Diffuse disease processes may be missed if only the stomach and duodenum are sampled 7. Biopsy size is limited 8. Not appropriate if perforation is suspected 9. Gastric distention may reduce venous blood return an induce vagal bradycardia 10. Can be easy to collect inadequate samples Open Surgical Full-thickness Biopsies Open biopsies should be reserved for the following circumstances: 1. Abdominal imaging suggests that lesions exist outside what is accessible via a scope 2. There is evidence of perforation 3. There is evidence of obstruction 4. The clinician lacks skill and expertise to enter and sample the duodenum and ileum 5. The results of endoscopy/biopsy inadequately explain the clinical picture

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6. Cats with evidence of chronic gastrointestinal disease. One study in cats (Evans, 2006) showed that while endoscopic biopsies were adequate to diagnose gastric lymphoma, full-thickness biopsies were required to diagnose intestinal lymphoma. Lymphoma would have been missed in 9/11 cats if full-thickness intestinal biopsies had not been performed. It is not clear if the addition of ileal biopsies would have increased the diagnostic accuracy of endoscopic biopsies. Less than half of the cats with lymphoma had gastric lymphoma.

General considerations of surgical biopsies: 1. Stay sutures help immobilise the intestine for sample collection and intestinal suturing 2. Additional suture may be used in the proposed sample site to help elevate and retract it 3. The organ should be packed off prior to biopsy procedure to prevent spillage of intestinal

contents 4. Omentalisation reduces postoperative leakage and should always be performed 5. Early postoperative feeding accelerates intestinal healing and reduces leakage and sepsis in

humans 6. Consider alimentation during procedure 7. The entire abdomen should be evaluated visually from the cardia of the stomach to the

terminal colon 8. Samples should be obtained from any grossly abnormal areas and from the stomach,

duodenum, jejunum, ileum, mesenteric lymph nodes and liver (and pancreas in cats) 9. The stomach is generally closed in a two layer pattern 10. Intestine is generally closed in a single layer using a simple continuous pattern Advantages of an open biopsy 1. A single biopsy in each of the following: stomach, duodenum, jejunum and ileum is usually

sufficient 2. Open full-thickness biopsies are larger samples 3. The entire abdomen can be explored and biopsies performed 4. Risk is low (but not insignificant) 5. Surgical biopsies can be curative for focal disease 6. No specialised equipment is required 7. Ileal biopsies which are so important in diagnosing the cause of gastrointestinal signs can be

easily acquired Disadvantages of open full-thickness surgical biopsies 1. Cannot see mucosal lesions when deciding on location of biopsy 2. As many as 12% of patients have been reported to have intestinal dehiscence and leakage

following full-thickness biopsy procedures (Shales CJ 2005). There were no risk factors identified.

3. Grossly abnormal areas can have disruption of the suture-holding submucosal layer which can make risk of biopsy higher

4. Inexperienced surgeons have significantly longer surgical times Risk factors for leakage of intestinal biopsy procedures

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1. Surgical technique 2. Hypoproteinaemia 3. Uraemia 4. Infection 5. Corticosteroid administration 6. Systemic disease 7. Malnutrition 8. Weight loss 9. Preexisting peritonitis Colonic biopsies The primary indication for colonic endoscopy/biopsy is chronic large bowel disease unresponsive to appropriate dietary, antibacterial or anthelmintic therapies. Also includes patients that have haematochezia are losing weight or are hypoalbuminaemic (possible protein losing enteropathy). Colonic endoscopy requires fairly involved preparation. Rigid biopsy forceps can be used to obtain excellent biopsy samples including submucosal lesions. Endoscopy generally obviates the need for surgical biopsies as most of the required information can be acquired with rigid endoscope and flexible biopsies of the ileum. Flexible biopsy instruments can obtain mucosal samples but not submucosal samples of the colon. While the risk with surgical and endoscopic biopsies is relatively low, if the colon is severely ulcerated, biopsies should be taken with care because perforation may occur. There is a great deal of disparity between results of ileal and colonic biopsies. Therefore, ileal biopsies are required particularly in dogs with large-bowel diarrhoea and in cats with vomiting and diarrhoea. Generally, if the primary clinical signs are related to large-bowel disease, then endoscopic biopsies can be performed obviating the need for full-thickness surgical biopsies. If there is an indication for surgical abdominal exploration, then ileal and colonic full-thickness biopsies can be performed. In the author’s opinion, there is not a high risk with colonic biopsy as long as there are no preexisting risk factors. There is, however, little advantage to full-thickness ileal and colonic biopsies over endoscopic biopsies if endoscopic biopsies can be reliably performed. Laparoscopy Laparoscopy can be used to fully explore most of the abdomen. Biopsies from all abdominal organs can be performed. Gastrointestinal biopsies are performed by making a small abdominal incision and exteriorising the gastrointestinal organ to be sampled. Laparoscopy is generally limited by the availability of equipment and expertise. When preparing for laparoscopic surgery, the entire abdomen should be clipped and prepared in the event that the procedure needs to be converted to an open laparotomy.

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EXTREMITY STS – WIDE LOCAL EXCISION



Introduction: Local recurrence is a major cause of treatment failure and death in patients having cancer surgery. Causes of local recurrence include residual cancer cells at the surgery site, the presence of “skip lesions” around the primary tumour, tumour specific characteristics and wide-spread environmental effects to the region (solar induced squamous cell carcinomas). Adjuvant treatment in the form of second surgery, radiation therapy, and metronomic chemotherapy have been shown to significantly reduce recurrence in patients who have incomplete excisions. Prediction of local recurrence allows prognostication and determination of the need for adjuvant treatment. Predictors of local recurrence include extent of surgery, surgeons perception of completeness of surgical margins, histological interpretation of completeness of surgical margins and tumour characteristics. Local recurrence: Local recurrence can occur following cancer surgery. Local recurrence has been repeatedly shown to predict early death in animals having surgical excision of soft tissue sarcomas. Cells can exist beyond the palpable and visible extent of the tumour. The distance that these cells exist beyond the palpable and visible extent of the tumour edge is variable. Removal of all of these invisible and unpalpable tumour cells reduces the incidence of tumour recurrence. A practical method of detecting tumour cells in the bed following excision does not exist in veterinary medicine although these methods are currently being developed in human medicine. Cancer surgeons typically take a cuff of normal-appearing tissue surrounding all visible and palpable tumour in attempt to completely surround these tumour cells and reduce the incidence of cancer recurrence. Generally, the recommendation has been made to remove 2-3 cm margins and one fascial plane deep with all cancer surgery. Recent recommendations: There have been recent publications which have advocated less aggressive surgery for soft tissue sarcomas may be adequate for control of soft tissue sarcomas. Bray (2009) reported on 104 soft tissue sarcomas operated in primary access practice. Only 10% were removed with wide margins and none had adjuvant therapy. In this paper, they reported 27.9% recurrence and 21.7% tumour related death. The conclusion of this paper was “Many spindle cell tumours managed in first opinion practice exhibit a low-grade biological behaviour and may respond well to more conservative surgery than current recommendations advise…” In a later publication by the same author, 350 STS’s were operated in primary care practice with 5.4% operated with wide margins. A 20.8% recurrence rate was reported with 30% tumour-related death. The conclusion of this paper was “Wide resection margins are not the primary determinant of outcome for all soft tissue sarcomas.”

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I suggest that the reader consider the following scenario: You are sitting across the desk from a human surgical oncologist who is considering operating on your family member. He or she reports that his or her recurrence rate is around 20% and there is a 1 in 4 chance that your loved-one will die a tumour related death. Would that be acceptable? I would think not. Options which provide very good local control of soft tissue sarcomas include wide local excision alone and marginal excision with adjuvant radiation therapy or metronomic chemotherapy. With respect to wide local excision of antebrachial soft tissue sarcomas, we operated on 31 dogs with STS’s on the extremities. All patients were operated with wide surgical margins including 2 cm in all directions and one fascial plane deep. All wounds were left to heal by second intention. In this study, we achieved complete surgical margins in ALL patients and had 100% local tumour control at the end of the study. One patient suffered recurrence and was reoperated with wide margins. It remained tumour free 4 years after its last surgery. 29 of 31 wounds healed completely with the remaining 2 requiring skin grafts. This is the lowest recurrence rate ever published in the veterinary literature for dogs with soft tissue sarcomas. Margin determination: The presence of tumour cells right at the edge of the excised sample is assumed to mean that tumour cells were left in the tumour bed. Histological detection of residual tumour cells at the edge of the excised tumour sample is the intent of margin determination. The completeness of surgical margins is highly predictive of local recurrence in dogs with soft tissue sarcomas in the majority of studies. Generally, the studies which have not confirmed this finding, have had low recurrence rates overall making establishing statistical significance difficult. Adjuvant therapy: Radiation therapy has been shown to be very effective in preventing recurrence of soft tissue sarcomas following incomplete excision. Local recurrence predicts early death for soft tissue sarcomas so prevention of local recurrence will improve survival. Radiation therapy is not innocuous. If it were, then it would be administered in all patients having had cancer surgery. Radiation therapy has negative factors including cost, inconvenience, requirement for repeated anaesthetics and side effects. The decision to administer adjuvant therapy depends on many factors. The most commonly used parameter to decide on the use of adjuvant therapy is the completeness of surgical margins. This is reasonable with soft tissue sarcomas where incomplete margins have almost universally predicted recurrence and subsequent death in many studies. Other parameters which may be helpful include the surgeons perception of the completeness of margins at the time of surgery, the grade, invasiveness and size of the tumour and owner’s wishes to prevent local recurrence at all costs. The advantages of planned wide local excision/second intention healing alone over marginal excision with adjuvant therapy include: 1 Single anaesthetic event in most cases compared with 15-20x for surgery and radiation

therapy

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2 Cost - $4500 including bandage changes compared with $9000 for surgery and radiation therapy

3 Lack of early and late radiation side effects 4 Availability - No need for specialised equipment or expertise 5 Near 100% local tumour control compared with about 80-85% for marginal surgery with

radiation therapy The antebrachium offers a unique anatomic opportunity for wide local excision because of the presence of the antebrachial fascia which provides a barrier to deep tumour penetration in many cases. Clearly, in anatomical areas where wide local excision is not possible, radiation therapy offers an excellent choice for long-term local control of soft tissue sarcomas which cannot be completely excised. Selected surgical references (radiation references are not provided and will be provided by Dr. Rod Straw): 1 Stefanello D, Morello E. Marginal excision of low-grade spindle cell sarcoma of canine

extremities: 35 dogs (1996-2006). Veterinary Surgery 2008;37:461–465. 2 Bacon NJ, Dernell WS, Ehrhart N, et al. Evaluation of primary re-excision after recent

inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999-2004). J Am Vet Med Assoc 2007;230:548–554.

3 Baker Gabby M, Hunt GB, France MP. Soft tissue sarcomas and mast cell tumours in dogs; clinical behaviour and response to surgery. Aust Vet J 2003;81:732–738.

4 Dernell WS, Withrow SJ, Kuntz CA, et al. Principles of treatment for soft tissue sarcoma. Clin Tech Small Anim Pract 1998;13:59–64.

5 Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). J Am Vet Med Assoc 1997;211:1147–1151.

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INCISIONAL VS EXCISIONAL BIOPSY & STAGING

Dr. Stewart Ryan, BVSc(Hons), MS, MANZCVS, Diplomate ACVS, Founding Fellow ACVS (Surgical Oncology)

The University of Melbourne, Werribee, Victoria, Australia

The approach to any patient with suspected cancer should be systematic and thorough. This lecture will describe a clinical approach to diagnosing and staging cancer in companion animals. Three questions should be asked and answered during the diagnostic approach to a suspected cancer: 1. What is it?

Classification and naming: § Is the mass neoplastic or non-neoplastic? (e.g. inflammatory lesion)

§ If it is neoplastic, what is the cell of origin?(e.g. epithelial, mesenchymal or round cell)

2. How bad is it?

Determine expected behavior: § Is the mass benign or potentially malignant? (using cytology and/or histopathology)

§ If malignant, can a ‘grade’ be obtained for the tumour? (using histopathology)

3. Where is it?

Determining the spread of cancer (clinical ‘stage’): § What is the likely metastatic pattern? (e.g. lymphatic or haematologic)

§ What imaging modalities and which regions should be imaged?

Once these questions have been answered, the prognosis and optimal treatment pathway can be determined based on knowledge of tumor type, grade, clinical stage and known expected biologic behavior of a particular tumour. Diagnostic modalities The diagnostic approach to any patient with suspected cancer will involve multiple modalities and examines the animal as a whole, not just focusing on the identified mass or masses. Diagnosis will typically start with a thorough history taking, physical examination and clinical assessment. If the suspected cancer is externally palpable, then the location, firmness and adherence to underlying structures should be assessed by palpation. Clinical pathology data in the form of serum biochemistry and haematology +/- urinalysis should be collected as appropriate to the initial presentation. Diagnostic imaging techniques including radiography, ultrasonography or advanced imaging modalities (CT/MRI) may be required to assess cancers whose deep borders extend beyond external palpation or which are located internally. When a mass is first detected it is important to determine if neoplasia is present or not (causes of non-neoplastic masses include inflammation, cysts and haematomas). If neoplasia is confirmed, the next step is to identify the type of cells present (the cell of origin) and whether they are likely to be benign or malignant. If malignant, the grade (histologic behavior) and stage (size and spread) of the cancer should be determined. To answer these questions a cytological or histopathological diagnosis is required. This may involve collection of a fine needle aspirate (FNA) for cytology or an incisional or excisional

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biopsy for histopathology. The use of appropriate techniques for collection and processing of cytology and histopathology samples is important to maximize diagnostic yield. Fine needle aspirate (FNA) technique Obtaining a fine needle aspirate (FNA) for cytologic evaluation is an appropriate first diagnostic step when evaluating a mass (external or internal). The procedure is quick, easy, minimally invasive and inexpensive. The area to be aspirated should be cleaned of any large debris but clipping and cleaning the area is usually not required for skin masses. Performing a sterile preparation of the area is recommended if sampling internal structures. The equipment used includes:

§ 22 gauge needle (smaller may lyse cells)

§ 5 or 10 ml syringe (smaller 3 ml syringes can be used but reduce vacuum yield)

§ Clean microscope slides

§ Quick stain (e.g. Diff-Quik) and microscope (for in-house evaluation)

There are two techniques that can be used to obtain a FNA: aspirational (using a syringe to apply vacuum pressure) or non-aspirational (needle only). With both techniques, once the needle is placed into the mass it should not be drawn out of the skin until the sample is obtained. The needle should be moved up and down (but not sideways) and within multiple planes of the mass to try and obtain the best representative sample. No more than 4-5 movements of the needle should be used to help avoid iatrogenic haemorrhage. When using the true aspiration technique, follow these steps: 1) Break the seal of the syringe by pulling back on the plunger. Return the plunger so that no air is contained within the syringe. 2) Attach the needle to the syringe. 3) Insert the needle and syringe into the mass. 4) Pull back on the plunger to create and maintain vacuum pressure. 5) Redirect the needle (4-5 times) without exiting the mass. 6) Before exiting the mass, release the vacuum pressure. This may feel counterintuitive but is essential to avoid movement of the sample into the barrel of the syringe. Next you must transfer the material within the needle to a slide. If you have used the true aspiration technique, remove the syringe from the needle and fill the syringe with 2-3ml of air. If you used the needle only technique, obtain a syringe and fill it with a similar amount of air. Re-attach the syringe to the needle and position to the needle towards one end of a slide with the bevel facing down (onto the slide). Depress the syringe rapidly and the sample should exit the needle onto the slide. Even if only a small amount of material is obtained, all slides should be smeared to prevent large clumps of cells that cannot be evaluated by the pathologist. To gently smear the sample, a second clean glass slide is placed on top of the sample in either perpendicular or parallel orientation with only light pressure. The two slides are then slid apart. You now have two slides that can be evaluated in-house or submitted to the laboratory for evaluation. Samples should be air-dried before staining. Samples sent to the laboratory should be dry and unstained (however if you have a stained slide then please send this also – as it may be the diagnostic slide!). § Avoid exposure to formalin fixative (liquid and fumes) as this can alter cell staining and evaluation of

morphology. Cytology samples should be packaged and sent separately from histopathology samples.

§ Although cytology is quick, easy, minimally invasive and inexpensive, it does have limitations when compared to histopathology:

o Only a small proportion of the mass is evaluated (diagnosis may be missed)

o Masses may be poorly exfoliative (especially mesenchymal tumours)

o Cytology samples lack architecture (cannot evaluate for invasiveness or metastasis)

§ To improve diagnostic power, multiple aspiration attempts should be performed, especially with multiple masses or generalised lymphadenopathy (with 4-5 slides per site being ideal). Ensure accurate labelling of the sample and a complete history to allow full interpretation by the pathologist.

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1. Surgical Biopsy:

Surgical biopsy of a neoplasm should be considered when findings of cytology are equivocal, there is confirmation or concern for a malignant neoplasm based on cytology findings, if it has been requested by the owner or the animal is undergoing anaesthesia for another procedure. Once the decision has been made to biopsy, you must decide what type of biopsy to perform: An incisional biopsy should be considered when: • Results of FNA cytology are non-diagnostic or equivocal

• The type of treatment would be altered by tumour type or grade

• The extent of treatment would be altered by tumour type or grade

• Major or reconstructive surgery is required.

• The owner’s willingness to pursue therapy would be altered by knowledge of tumour type or grade.

• Complete removal of the mass is not possible, an organ exhibits diffuse changes or the ultimate goal is diagnosis only.

Incisional biopsies can be obtained via needle techniques (Tru-cut/Biopty), surgical wedges or skin punch biopsies. Ideally a biopsy at the junction of tumour and normal tissue is preferred, provided that this does not compromise definitive excision. The incisional biopsy tract must be planned so that it is removed at the definitive surgical procedure. Similar principles apply for sampling of bony lesions, except that the central region of the lesion is the preferred location to obtain the biopsy. The type of primary bone tumour can significantly affect the prognosis and median survival times. Jamshidi biopsy needles represent an efficient way of collecting tissue from bone for the purposes of biopsy. 4-5 core biopsy samples should be collected through a single cortical access hole by redirecting the biopsy needle within the marrow cavity. Biopsy needle tracts must be placed with care and are considered contaminated and so must be removed with any definitive surgery. Fluoroscopic guidance may increase accuracy of diagnosis but is not essential. An excisional biopsy should be performed when definitive treatment will not be altered by knowledge of tumour type or grade (e.g. for a benign mass, a splenic mass requiring splenectomy) or if the risk or morbidity of a second surgery is too great (e.g. brain or spinal neoplasia). Excisional biopsies should not be performed if the optimal treatment pathway for definitive therapy could be compromised. Definitive surgical resection with appropriate surgical margins should be used for the first curative intent surgical procedure when possible. Inflamed or ulcerated tissue should be avoided when obtaining an incisional biopsy as inflammation and ulceration can distort tissue architecture and cause a degree of cellular atypia. Masses should not be removed with electrocautery as this will also cause tissue damage and obscure surgical margins. Any time a surgical biopsy is performed, the tissue should be submitted for histopathology. Biopsy tissue should be placed in a container with formalin at a ratio of one part tissue to ten parts formalin. If tissue must be cut in to smaller pieces, the goal should be as few pieces as possible and information on proper tissue orientation should be relayed to the pathologist. Tissue should not be greater than 1cm in diameter to allow penetration of formalin before autolysis. Masses can be sliced without complete sectioning to achieve this (bread loafing); however, do not be over zealous and do not slice the margins. If you are submitting incisional biopsies, multiple biopsies are helpful and tissue cores should be at least 5mm long. Tissue should be submitted in a secure container with a screw lid. Communication with the pathologist is very important, so that as much information as possible can be used to make the final cytological or histopathological diagnosis and provide useful comments. All samples should be labelled with the animal’s name and client’s last name, the tissue or anatomic site and the date of sampling. Containers should be labelled on the jar as well as the lid just in case the two become separated. Patient signalment details (breed, sex, neuter status, age) should be included with the submission form. A thorough history including location, duration and appearance of lesion, any change

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in appearance over time, previous medical problems and results of clinical pathology tests should be included. The more information you can provide to the pathologist, the better they will be able to make appropriate interpretations. When you receive either a cytology or histopathology report, make sure to read the comments as well as the interpretation or diagnosis. The comment section will include suggestions for further diagnostics, staging recommendations and margin evaluation. Whether or not a mass was completely excised will be included in the comments. If the final interpretation or diagnosis does not fit with the case presentation, call the pathologist to discuss your concerns. Re-cuts or second opinions can also be requested. It is important to remember histopathology still only allows for a small portion of tissue submitted to be evaluated and everyone’s ultimate goal is appropriate treatment of the patient. Clinical tumour staging: Once a cytological or histopathological diagnosis of cancer is established, clinical staging to determine the extent of disease should be pursued. Draining lymph nodes, abdominal organs (especially liver, spleen), and the lungs should be evaluated for signs of metastasis. These findings along with tumour type and grade (behaviour) and the animal’s clinical presentation will help with determining prognosis and the most appropriate treatment options. Although staging can be performed at the outset, for practical and financial reasons, staging is often performed after a surgical biopsy procedure. If biopsy results indicate malignancy, then staging is warranted. Knowledge of the tumour type and likely metastatic behaviour allows staging to be targeted more appropriately. The staging information obtained will modify the prognosis and guide further treatment. A number of staging systems exist. A practically useful one is TNM, referring to tumour (T) node (N) and metastasis (M) allowing comparisons of treatment efficacy between animals for the purposes of prognostication. Conclusion: Fine needle aspiration and surgical biopsy are diagnostic techniques that form the basis of a rational approach to any mass lesion. The cytology and/or histopathology results will determine if a mass is cancer or not and, if it is, information on the type and behaviour (tumour grade) as well as the extent of cancer (clinical stage) will be known. Utilising a combination of the initial clinical findings, the results of cytology and/or histopathology, additional diagnostic tests (including imaging) and knowledge of expected biological behaviour of different cancer types, a realistic prognosis and recommendation on an optimal treatment pathway and alternative treatment options can be made, so the owner can make an informed treatment decision for their pet.

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TREATMENT OF MALIGNANT PERICARDIAL EFFUSIONS - OPEN OR THORASCOPIC APPROACH

Dr. Stewart Ryan, BVSc(Hons), MS, MANZCVS, Diplomate ACVS, Founding Fellow ACVS (Surgical Oncology)

The University of Melbourne, Werribee, Victoria, Australia

Pericardial effusion result from neoplastic or non-neoplastic diseases. The pericardial effusion can be classified as a transudate (e.g. right- sided heart failure, hypoproteinaemia, incarceration of liver lobe in pericardial cavity, PPDH, increased vascular permeability), an exudate (e.g. infectious pericarditis (FIP), or bacterial) or most commonly haemorrhagic (e.g. idiopathic (most common), neoplastic (right atrial HSA, heart base tumour, mesothelioma or anticoagulant toxicity). Dogs with pericardial effusion present with a classic triad of clinical signs: muffled heart sounds, rapid weak arterial pulse and distended systemic veins. Cardiac tamponade occurs when the intrapericardial pressure equals or exceeds right ventricular diastolic filling pressures, leading to a decreased cardiac output. Pericardiocentesis is indicated for initial stabilisation to relieve clinical signs of cardiac tamponade and provide fluid samples for diagnostic evaluation with fluid analysis and cytology. In approximately 50% of idiopathic pericardial effusion cases, a single pericardiocentesis is curative. Recurrence of pericardial effusion will occur in the other 50% of idiopathic cases and in almost neoplastic effusion cases. The site for pericardiocentesis is the middle to caudal region of the right 4th, 5th or 6th intercostal spaces at the level of the costochondral junction. The patient can be either in a standing position or in or left lateral recumbency. A large bore needle (12-14G for a large dog) attached to extension tube and 3-way stopcock is used for the procedure. A pop should be felt as the needle passes through the pericardium. The right-sided approach is used to avoid inadvertent laceration of the left extramural coronary artery and also the presence of a larger cardiac notch in the right lung lobes. The heart rhythm should be monitored with an ECG during pericardiocentesis to detect any VPC's that may occur if the needle touches the heart. TREATMENT

Percutaneous balloon pericardiotomy (PBP) is a reported technique that can be done in a minimally invasive manner under fluoroscopic guidance to make a small hole in the pericardium. [1, 2] A percutaneous right 5th intercostal space approach is made with a 16G catheter introduced into the pericardial sac for pericardiocentesis. Under fluoroscopic visualisation and ECG monitoring, a guide wire is introduced through the needle and a balloon-dilating catheter is placed over the wire so that the balloon is positioned across the pericardium. The balloon is inflated to create a hole in the pericardial sac. The technique is described as applicable for palliative therapy of cardiac tamponade in cases of neoplastic pericardial effusion in which survival time is expected to be limited or for clients with financial constraints that limit the option of an open or thoracoscopic surgery for pericardiectomy. The main disadvantages of this technique include the inability to obtain a tissue biopsy specimen and the possible recurrence of pericardial effusion due to closure of the pericardial window.

Subtotal pericardiectomy is recommended as a curative definitive treatment of idiopathic pericardial effusion and a palliative treatment of malignant pericardial effusion by preventing recurrent cardiac tamponade as pericardial fluid can drain into the pleural space where it is more readily absorbed. Open surgical approaches for subtotal pericardiectomy include median sternotomy or right or left lateral intercostal thoracotomy. The advantages of open thoracotomy include complete removal of the pericardium below the level of the phrenic nerve, accurate

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identification of masses arising from the right atrium, and the ability to excise the right auricular appendage when the mass is isolated to that part of the heart. A median sternotomy approach has the advantage of allowing complete exploration of the thoracic cavity and better visualisation of both sides and phrenic nerves. A right 5th intercostal thoracotomy is appropriate if right atrial haemangiosarcoma is suspected and the right atrial appendage will be biopsied or removed.

Electrosurgery techniques are recommended for cutting the pericardium as it can be quite vascular. Thoracoscopic pericardiectomy has the advantage of decreased morbidity compared to open thoracotomy which is important especially when neoplastic effusion is suspected or confirmed and expected survival time is limited. A potential disadvantage of thoracoscopic pericardiectomy includes the inability to visualize the entire right atrium. After exploration of the thoracic cavity, a pericardial window is made rather than a complete subtotal pericardiectomy. The pericardial window needs to be sufficient size to avoid closure of the pericardial window by healing (as can occur with the balloon pericardiotomy technique) leading to recurrence of clinical signs and not large enough to allow herniation of the heart through the pericardial window. A 3cm x 3cm or 4 x 4cm pericardial window has been recommended. The pericardial window id made on the cranial surface of the heart towards the apex. The patient is positioned in dorsal recumbency. A trans diaphragmatic subxiphoid portal for the telescope is placed with instrument ports placed at the right 4th and 7th intercostal spaces. The thoracoscopic pericardiectomy technique does not require one-lung ventilation. [3, 4] Resection of a right atrial mass can also be achieved via thoracoscopy. [5] Outcome:

Case et al. (2013) reported on the outcome evaluation of a thoracoscopic pericardial window procedure or subtotal pericardiectomy via thoracotomy for the treatment of pericardial effusion in 58 dogs with pericardial effusion. Dogs with idiopathic pericardial effusion treated with a subtotal pericardiectomy via thoracotomy had a significantly longer DFI and MST, compared with dogs treated by the thoracoscopic pericardial window procedure. This difference in outcome may be related to inaccuracy of the initial diagnosis or ineffectiveness of the pericardial window to palliate the signs of idiopathic pericardial effusion long term. However, for dogs with neoplastic pericardial effusion, DFI and MST were not significantly different between dogs treated with either surgical technique. 1. Sidley, J.A., et al., Percutaneous balloon pericardiotomy as a treatment for recurrent pericardial

effusion in 6 dogs. J Vet Intern Med, 2002. 16(5): p. 541-6. 2. Cobb, M.A., et al., Percutaneous balloon pericardiotomy for the management of malignant

pericardial effusion in two dogs. J Small Anim Pract, 1996. 37(11): p. 549-51. 3. Dupre, G.P., J.P. Corlouer, and B. Bouvy, Thoracoscopic pericardectomy performed without

pulmonary exclusion in 9 dogs. Vet Surg, 2001. 30(1): p. 21-7. 4. Case, J.B., et al., Outcome evaluation of a thoracoscopic pericardial window procedure or

subtotal pericardectomy via thoracotomy for the treatment of pericardial effusion in dogs. J Am Vet Med Assoc, 2013. 242(4): p. 493-8.

5. Crumbaker, D.M., M.B. Rooney, and J.B. Case, Thoracoscopic subtotal pericardiectomy and right atrial mass resection in a dog. J Am Vet Med Assoc, 2010. 237(5): p. 551-4.

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ADRENALECTOMY: MIDLINE VS RETROPERITONEAL VS LAPAROSCOPIC Dr. Stewart Ryan, BVSc(Hons), MS, MANZCVS, Diplomate ACVS, Founding Fellow

ACVS (Surgical Oncology) The University of Melbourne, Werribee, Victoria, Australia

Adrenalectomy is indicated for removal of adrenal neoplasia (adrenocortical carcinoma, adenoma or pheochromocytoma) or in some cases for management of pituitary dependent hyperadrenocorticism.

Functional adrenocortical tumours (most commonly adrenocortical carcinomas) cause adrenal dependent hyperadrenocorticism. Adrenalectomy is the treatment of choice for dogs with cortisol-secreting adrenocortical tumours. Medical management is indicated for patients where there is metastatic disease and for clients that do not want to pursue surgery.

Pheochromocytomas are tumours that originate from the chromaffin cells of the adrenal gland that can produce catecholamines. They most often arise from the adrenal medulla but can occur at extra-adrenal sites. They can be solitary or bilateral, benign or malignant, functional or non-functional. Catecholamine release may be initiated by tumour blood flow, direct pressure or various chemicals and drugs. Clinical effects of catecholamine release are tachycardia and hypertension. Pheochromocytomas have a high incidence of invasion into the caudal vena cava. Pheochromocytomas are locally invasive in 39% of affected dogs and produced metastases in 13% of the cases. Common sites for metastases included regional lymph nodes, liver, lung, kidney, spleen, and bone. A high frequency (54%) of concurrent neoplasia, including endocrine neoplasia, is seen in pheochromocytoma cases. Peri-operative management for adrenal tumours:

The perioperative management for cortisol producing tumours and catecholamine producing tumours is important and differ for each tumour type. For cortisol producing tumours, hypocortisolameia, which can be life threatening, can occur during and after adrenalectomy. This is a result of suppression of the pituitary-adrenal axis and atrophy of the contralateral adrenal gland. Supplementation with a glucocorticoid is recommended to avoid this situation. Treatment with dexamethasone (0.1mg/kg IV q12 hrs.) started before surgery then prednisolone (0.5-1.0mg/kg q 12hrs) once eating after surgery, gradually tapered over 4-6 weeks for adrenocortical tumors. Normal cortisol levels are usually present by 3-9 weeks after unilateral adrenalectomy. Medical management for pheochromocytomas pre-operatively will inhibit the effects of catecholamines and minimize hypertension and expand plasma volume by decreasing vasoconstriction and catecholamine release during surgery. Pre-operative treatment with phenoxybenzamine, an alpha adrenergic blocker, (0.6 - 2.5mg/kg q12hrs PO) for 2-4 weeks prior to surgery has been shown to significantly decrease mortality rate compared with untreated dogs (13 versus 48%, respectively). [1] Drugs that can potentiate the effects of catecholamines (e.g. atropine, phenothiazines and halothane) should be avoided. Cardiac arrhythmias or severe tachycardia that is persistent despite alpha adrenergic blockade can be treated with beta blockers (propranolol). Beta blockers should never be used in the absence of established alpha blockade. Intraoperative hypertension can be managed with nitroprusside (vasodilator) or phentolamine (alpha adrenergic blocker). Hypotension can occur after removal of the tumour as an effect of chronic vasoconstriction and decreased plasma volume.

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After bilateral adrenalectomy, patients should be maintained on the lowest prednisone dose once a day and also treated with a mineralocorticoid (DOCP 2.2 mg/kg IM or SC every 25 days or fludrocortisone 0.02mg/kg PO SID). Mineralocorticoid supplementation should start before surgery. Surgical considerations A complete abdominal exploration should be done to evaluate the retroperitoneal area, sympathetic chain surrounding the aorta, local LNs, caudal vena cava for metastasis. Care should be taken to avoid the ureters and blood supply to kidney. If the renal vessel are involved with the mass or are damaged during surgery, then nephrectomy may need to be done as part of the procedure. The phrenicoabdominal vein is ligated and divided between sutures or vascular clips. The use of vessel sealing devices and electrocoagulation provides good haemostasis control and surgical field visualisation. There are a number of surgical approaches for adrenalectomy: 1. The retroperitoneal approach for adrenalectomy was described by Johnston in 1977 [2],

however this approach was not widely adopted by many surgeons. One potential advantage of this approach is decreased risk of damage to the pancreas and pancreatic blood supply. 2. A midline laparotomy allows complete exploration of the abdominal cavity. The ventral

midline approach can be combined with a paracostal extension to aid visualisation of right adrenal masses. The adrenals are quite deep I the surgical field and visualisation of the right adrenal gland can be difficult. Most surgeons use this approach due to the familiarity. 3. A paracostal approach has been described for adrenalectomy and for thoracic duct

ligation and cysterna chyli ablation. 4. An intercostal approach between the 12th and 13th ribs has been described for right

adrenalectomy in dogs [3] and offers superior exposure of the right adrenal gland compared to the ventral midline and paracostal approaches as the right adrenal gland is more cranially located than the left adrenal gland.

5. Laparoscopic adrenalectomy can be done for adrenal tumours without invasion of the caudal vena cava. [4, 5] The dog is positioned in lateral recumbency with the unaffected side down and affected side uppermost. Three 5-mm portals (1 laparoscopic portal and 2 instrument portals) are placed in the paralumbar fossa. A fourth instrumental portal (5-12 mm) is placed above the kidney. After dissection and haemostatic control of the phrenicoabdominal vein, the adrenal gland is carefully dissected using a vessel sealing device or laparoscopic instruments. A retrieval bag or part of a surgical glove finger should be used to remove the adrenal gland from the abdomen removed through the 12-mm trocar site with laparoscopic procedures to avoid the risk of portal site tumour seeding. Mayhew, P. D., et al. (2014) reported that with careful patient selection, laparoscopic adrenalectomy was associated with a low complication rate and low conversion rate for resection of adrenocortical masses that did not invade the vena cava or other surrounding organs as well as shorter surgical and hospitalization times, compared with open adrenalectomy. Naan, E. C., et al. (2013) described an innovative approach to laparoscopic adrenalectomy for treatment of unilateral adrenal gland tumours in dogs in which dogs are positioned in sternal recumbency

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with the abdomen suspended by two cushions to facilitate gravitational displacement of the abdominal viscera. This positioning improves access to, and visibility of, the adrenal gland for laparoscopic removal compared to the lateral recumbency position. Adrenal glands not involving the caudal vena cava in affected dogs were successfully removed laparoscopically.

Caudal vena caval invasion Three types of tumor thrombi are described: those confined to the phrenicoabdominal vein and not entering the caudal vena cava, local caval thrombus confined to the prehepatic caudal vena cava and extensive caval thrombus extending to the intrahepatic section of the caudal vena cava. Thrombi enter the caudal vena cava either via the phrenicoabdominal vein producing a stalked caval thrombus or by local invasion through the wall of the caudal vena cava. Diagnosis of caudal caval invasion can be made prior to surgery by ultrasonography [6, 7] or computer tomography (CT). The vascular pattern and contrast-enhancement characteristics of adrenal gland tumours by means of contrast-enhanced ultrasonography may be useful in assessment of malignancy and tumour type. If caudal vena cava tumour thrombosis is present, temporary occlusion of the cava using Rummel tourniquets followed by venotomy and temporary partial caval occlusion with Satinsky forceps can be used to remove the tumour thrombus. Outcome Barrera, J. S., et al. (2013) reported that risk factors for poor short-term survival in 86 dogs that underwent adrenalectomy for treatment of adrenal gland tumours were vena caval invasion, extent of invasion, pheochromocytoma, intraoperative transfusion, and postoperative factors including disseminated intravascular coagulation, pancreatitis, hypotension, hypoxemia, and renal failure. [8] Multivariate analysis revealed that extensive invasion was the most important risk factor. Regardless of extent of invasion or tumour type, long-term survival was possible. Dogs with very large tumours or acute adrenal haemorrhage may have a more guarded prognosis. [9] Massari, F., et al. (2011) reported the outcome of adrenalectomy in 52 dogs with adrenal gland tumours. Dogs with an adrenal gland tumour with major axis length greater than 5cm, documented metastasis, or vein thrombosis had a poorer prognosis. [10] Metastasis was more frequent in dogs with adenocarcinoma and vein thrombosis when tumours were greater than 5cm in length. 1. Herrera, M.A., et al., Predictive factors and the effect of phenoxybenzamine on outcome in dogs

undergoing adrenalectomy for pheochromocytoma. J Vet Intern Med, 2008. 22(6): p. 1333-9. 2. Johnston, D.E., Adrenalectomy via retroperitoneal approach in dogs. Journal of the American Veterinary

Medical Association, 1977. 170(10, I): p. 1092-1095. 3. Andrade, N., et al., Intercostal approach for right adrenalectomy in dogs. Vet Surg, 2014. 43(2): p. 99-

104. 4. Pelaez, M.J., B.M. Bouvy, and G.P. Dupre, Laparoscopic adrenalectomy for treatment of unilateral

adrenocortical carcinomas: Technique, complications, and results in seven dogs. Veterinary Surgery, 2008. 37(5): p. 444-453.

5. Mayhew, P.D., et al., Comparison of perioperative morbidity and mortality rates in dogs with noninvasive adrenocortical masses undergoing laparoscopic versus open adrenalectomy. J Am Vet Med Assoc, 2014. 245(9): p. 1028-35.

6. Pey, P., et al., Use of contrast-enhanced ultrasonography to characterize adrenal gland tumors in dogs. Am J Vet Res, 2014. 75(10): p. 886-92.

7. Davis, M.K., R.A. Schochet, and R. Wrigley, Ultrasonographic identification of vascular invasion by adrenal tumors in dogs. Vet Radiol Ultrasound, 2012. 53(4): p. 442-5.

8. Barrera, J.S., et al., Evaluation of risk factors for outcome associated with adrenal gland tumors with or without invasion of the caudal vena cava and treated via adrenalectomy in dogs: 86 cases (1993-2009). J Am Vet Med Assoc, 2013. 242(12): p. 1715-21.

9. Lang, J.M., et al., Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). J Am Anim Hosp Assoc, 2011. 47(6): p. 428-35.

10. Massari, F., et al., Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc, 2011. 239(2): p. 216-21.

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PRINCIPLES OF EYELID TUMOUR SURGERY _ HOW TO CUT THEM OUT

Susan Jacobi, Dr.med.vet., DVM, MS, Diplomate ACVO

Veterinary Specialist Services 104 Eastlake Street

Carrara, QLD 4211, Australia

Eyelid neoplasia is commonly seen in our domestic animals. Especially dog eyelids can exhibit a large number of different neoplasms that are in most cases benign and minimally invasive. Therefore they do often respond to fairly conservative surgical procedures. The type of surgical procedure depends on the size and site of the eyelid mass. Eyelid neoplasia is best removed early, when the resultant defect is smallest. Removal of larger masses will result in more extensive defects that require greater reconstruction.

Depending on the laxity of the lids, eyelid masses involving up to 25 % of the lid length may be excised as a full-thickness wedge shaped either as a V or a four sided house-shaped defect. Recommended is a margin of at least one meibomian gland or 1mm beyond the tumor. Depending on the size, closure is done by one or two layers. 6-0 to 8-0 absorbable suture material can be used for the deeper tarsoconjunctival layer, which can be apposed by simple, continuous sutures, with the knots buried. The eyelid margin is apposed with a figure-of-8 or U-figure using 5-0 to 6-0 absorbable or non-absorbable suture material. The perfect apposition of the lid margin is of great importance as scar formation needs to be prevented to avoid corneal irritation later on. Fig 1, Fig 2

Fig 1

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Fig 2

Both cryotherapy and carbon dioxide laser therapy have also been reported for uncomplicated, canine lid tumors. A diode laser can be used to remove pigmented lesions.

Reconstructive blepharoplasty includes different surgeries to restore the lids with resulting extensive defects. The basic blepharoplastic procedures include sliding skin and pedicle grafts, tarsoconjunctival grafts, and full thickness eyelid grafts. By choosing the best technique it is important to note that the upper lid is larger and more mobile than the lower lid and is the most important lid to cover the cornea and in the blink reflex. Trichiasis is to be avoided to ensure corneal health.

Two complex cases of surgical removal of mast cell tumors with following lid reconstruction are presented here.

The first case presented with a grade 2 MCT at the lateral lower lid of the left eye. The tumor was removed including 2cm margins and the defect was reconstructed via a rotational mucocutaneous subdermal plexus flap using the dog’s upper lip. This surgical technique was chosen for reconstruction of a functional lower lid avoiding postsurgical trichiasis. Fig 3-7

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Fig 3

Fig 4

Fig 5

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Fig 6

Fig 7

In the second case a recurrent large grade 2 MCT was removed from the medial canthal area with 2 cm margins. Removal of the underlying periost and additional bone from the frontal bone and the maxilla was also performed. The medial one-half of the upper and lower eyelids and the medial canthus were reconstructed using an axial pattern flap based on the cutaneous branch of the superficial temporal artery. The bulbar conjunctiva of the nictitans was preserved and the third eyelid was sutured to the medial flap edge, thus creating a conjunctival lining to the deep aspect of the flap, protecting corneal epithelium. Fig 8-11

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Fig 8

Fig 9

Fig 10

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Fig 11

Krehbiel JD, and Langham RF. Eyelid neoplasms in dogs. Am J Vet Res, 36:115, 1975

Roberts SM, Severin GA, and Lavach JD. Prevalence and treatment of palpebral neoplasms in the dog: 200 cases (1975-1983). J Am Vet Med Assoc, 189:1355, 1986

Gelatt KN and Blogg JR. Blepharopastic procedures in small animals. J Am Anim Hosp Assoc 1969; 5: 67-78

Gwin RM. Selected blepharoplastic procedures of the canine eyelid. Compendium on Continuing Education 1980; 2: 267-272

Hamilton HL, Whitley RD, McLaughlin SA, Swaim SF. Basic blepharoplasty techniques. Compendium on Continuing Education 1999; 21: 946-953

Bussieres M, Krohne SG, Stiles J, Townsend WM. The use of carbon dioxide laser for the ablation of meibomian gland adenomas in dogs. J Am Anim Hosp Assoc 2005; 41: 227-234

Pavletic MM, Nafe LA, Confer AW. (1982) Mucocutaneous subdermal plexus flap from the lip for lower eyelid restoration in a dog. J Am Vet Med Assoc 1982; 180:921-926

Holmberg DL. Cryosurgical treatment of canine eyelid tumors. Vet Clin N Am Sm Anim Pract 1980; 10: 831-836

Jacobi S, Stanley BJ, Petersen-Jones S, Dervisis N, Dominguez PA. Use of an axial pattern flap and nictitans to reconstruct medial eyelids and canthus in a dog. Vet Ophthalmol 2008 Nov-Dec; 11 (6):395-400

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SURGERY OF THE GLOBE: ENUCLEATION AND EVISCERATION WITH INTRAOCULAR SILICONE PROSTHESIS

Chloë Hardman FANZCVSc(Ophthalmology) BVSc(Hons) MVS

Animal Eye Care, Melbourne, Australia

ENUCLEATION

The indications for enucleation include generally relate to pain or intraocular neoplasia

-‐ Glaucoma – sustained increased intraocular pressure unresponsive to therapy resulting in pain

-‐ Extensive trauma to the globe with such severe damage to intraocular tissues either without the possibility of repair, or without the possibility of return of vision

-‐ Severe uveitis that has resulted in severe damage to intraocular tissues and chronic pain -‐ Severe globe proptosis with marked trauma to extraocular muscles +/- optic nerve -‐ Intraocular tumours confined to the globe -‐ Phthisis bulbi = globe shrinkage that has resulted in pain due to entropion, conjunctivitis

+ /- keratitis

-‐ Severe painful dry eye unresponsive to treatment when no parotid duct transfer is possible or if blindness is already present

The most common approaches are transconjunctival and transpalpebral. The globe, eyelid margins, third eyelid, conjunctiva and lacrimal gland are excised. Extreme care must be taken with enucleation in cats to minimise traction on the globe as excessive traction on the globe may damage the opposite optic nerve at the optic chiasm.

Transpalpebral approach is obviously the most suitable when concerns are related to infection of neoplastic. I personally use this approach for all my enucleations as I find it faster and an easier method to successfully remove the entire conjunctiva. Specific enucleation scissors with a 90 degree curve make the surgery easier as the allow severing of the optic nerve with minimal traction on the globe. A silicone implant may be implanted into the orbit to reduce the postoperative sinking of skin into the orbital recess. An alternative to this is placing nylon sutures from orbital rim to orbital rim to act as a scaffold to prevent sinking.

Exenteration is the complete removal of all of the orbital tissues. Indications include orbital neoplasia, medically non-responsive orbital infections, and extensive intraocular neoplasia that has extended into the orbit. Surgery is very similar to transpalpebral enucleation except that the surgical dissection is along the orbital walls, external to the extraocular muscles. This procedure results in more haemorrhage.

Antibiotic treatment should only be needed when intraocular infection was present, or in older animals especially cats with dental disease to reduce the risk of a tooth root infection extending into the orbit.

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Histopathology by an pathologist experienced with ophthalmic tissues is highly recommended. We send all our samples to Dr Christina McCowan of ASAP Pathology in Melbourne. The eyelids must be excised from the globe but can be left on at one attachment point for orientation. Globes must be fixed in a suitable volume of formalin – approximately 250ml for a small animal globe.

Complications following eye removal are rare. A procedure is described whereby the third eyelid is sutured across the orbit to reduce sinking of the skin into the orbital recess. In some patients, this has resulted in leakage of lacrimal secretions through an opening along the initial incision. Follow up surgery is required to remove the third eyelid and lacrimal gland if it was left in situ. Infections will result if swabs are left in the orbit or as previously mentioned if tooth root infections are present. Nerve pain at the severed end of the optic nerve only occurs rarely. Some cases respond to gabapentin however unresponsive cases can be frustrating to treat and may require treatment with nerve deadening agents.

EVISCERATION WITH INTRAOCULAR SILICON PROSTHESIS (ISP)

ISP is often considered a cosmetic procedure because of the better cosmetic result achieved, however I generally prefer this technique as it is a far less traumatic surgery. In this procedure, the sclera is incised and globe contents removed, compared to enucleation where the eyelids, extraocular muscles and optic nerve are all cut.

The indications for ISP are generally the same with the exception of intraocular neoplasia. We treat virtually all our buphthalmic and blind glaucomatous globes with ISP surgery. Case selection is of extreme importance as not all painful globes are suitable candidates for ISP.

The contra-indications for ISP include:

-‐ Severe corneal disease including deep corneal ulceration -‐ Severe dry eye that is poorly or non-responsive to therapy -‐ Intraocular neoplasia -‐ Granulomatous scleritis

Equipment required includes a Carter sphere holder and implanter and a range of black silicon prosthesis from 15mm to 22mm in diameter. Silicone prostheses have been found to be non-painful, non-toxic, non-antigenic, easily implanted and similar to the normal eye in appearance. Selection of sphere size is by measuring the normal globe’s corneal diameter in mm and adding 2mm i.e. if the corneal diameter is 17mm, the size prosthesis selected will be 19mm. Some examples are an American Cocker Spaniel is usually 19mm prosthesis, a Jack Russell or Maltese 18mm and a Golden Retriever 20mm. The buphthalmic globe will reduce in size over the following 1-3 months to the sphere size.

The surgical procedure involves placing a speculum, incising the conjunctiva and sclera 6-10mm back from the limbus, eviscerating the contents of the globe, suturing the sclera then conjunctiva with 6/0 vicryl, and placing temporary tarsorrhaphy sutures with 4/0 nylon. The reason for the TT sutures is to protect the cornea during the post-operative period during a period

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of reduced trigeminal nerve function resulting in reduced corneal sensation, reduced blink, and exposure keratitis leading to superficial corneal ulceration. We leave the TT sutures in for 4 weeks. Post-operative treatment includes topical antibiotic ointment TID, oral carprofen and oral tramadol for analgesia.

ISP surgery sounds easy and can be successful for the experienced surgeon; however disadvantages include cost involved with equipment needed as the prostheses are expensive and a large range of sizes is required. In an ophthalmology practice, this equipment is used regularly, however in a general practice, suitable cases may only present once to twice a year. Furthermore there are multiple traps for inexperienced clinicians. One example is cases that are predisposed to entropion may develop entropion postoperatively when the buphthalmic globe shrinks down to the sphere size. This is a complication seen in Shar Pei dogs. Further surgery will be required if additional surgery is not performed at the initial ISP surgery.

References

Handbook of small animal ophthalmic surgery. Vol 1: extraocular procedures. Gelatt KN, Gelatt JP 1994

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NEW STRATEGIES – METRONOMICS, IMMUNOTHERAPY, EBC46 Peter Bennett BVSc FANZCVS DACVIM

University of Sydney, Camperdown, NSW, Australia There are many newer therapies that are being used more widely in veterinary medicine. How they work, the benefits and outcomes are still being examined. There is promise and also caution as we explore the appropriate use of these options. There is evidence of efficacy, but this is mainly anecdote. There is some knowledge of toxicities, but long term adverse effects are still unknown for many of these options. Metronomic Chemotherapy: The work of Drs Folkman and Kerbel in the late 70s and early 80s showed that inhibition of angiogenesis was a useful tool in the management of solid tumours. The initial compounds that were used (angiostatin and endostatin) were effective in controlling xenograft tumours in rodent models, but were very expensive. Kerbel’s laboratory then showed that daily chemotherapy had an effect on angiogenesis and this was then further explored. The rationale behind targeting the vasculature was that the endothelium is relatively genetically stable, hence less likely to develop resistance mutations, and that the majority of the body’s endothelium was relatively long lived, but not the disorganised and abnormal vasculature found in tumours. Further work has shown that the effects are not only related to angiogenesis. We are giving cytotoxic chemotherapy so there is some cell killing. More important might be the effects on the immune system. In cancers there is often increased numbers of T regulator cells present that dampen the body’s immune response to a tumour. The use of metronomic chemotherapy has been shown to decrease the number of these cells and this in turn will increase the body’s immune system attack on the cancer cells. There are effects on other cells such as circulating endothelial progenitor cells and host immune cells which can be used by the cancer to proliferate and survive. There has been little work on efficacy of this approach and the ideal drug or drug combination has not been established. The majority of veterinary investigation has been with cyclophosphamide, but other drugs including chlorambucil and Lomustine have been tried. There are some limited studies that have shown that there is a reduction in the risk of regrowth or delaying the regrowth in soft tissue sarcomas with questionable margins and also in dogs with haemangiosarcoma. Large prospective randomised and blinded studies have not been performed. But there is a lot of anecdote of efficacy. Toxicity has been low with a low incidence of gastroenteritis or myelosuppression. Sterile haemorrhagic cystitis has been seen in patients receiving cyclophosphamide. Marrow stem cell suppression might be an issue with prolonged use. Immunotherapy: The idea of utilising the host immune system to manage and control cancer is not new and has been tried for years. Some successes have been seen, particularly with the more antigenic tumours such as melanomas, but the responses are variable and difficult to predict. There have been a wide number of strategies used to enhance the immune response. Many early failures arose from failure of recognition of the immune suppression induced by the cancer cells and the role of the host immune cells in driving some cancers. In many cases a single approach might not be ideal. Early trials used very simple vaccines and these included whole cell lysates or inactivated cells. In veterinary medicine one version of this approach was to crush papillomas on patients to elicit an immune reaction. But this does not work in all cases. One reason is that when cells are killed or lysed, there can be loss of external antigens and exposure of internal antigens. The immune system cannot recognise internal antigens, only surface antigens in living cells.

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The immune suppression can be overcome to a degree if a strong immune response is formed directed at a specific tumour antigen. An example of this is Merial’s melanoma vaccine, Oncept. This vaccine utilises human tyrosinase as a DNA plasmid vaccine to generate a response against the tyrosinase in the melanoma cells. There have not been any prospective, randomised blinded studies to show efficacy, but tumour responses in individual patients show that there can be efficacy. Currently it is hard to know the full extent of the benefit in patients with high grade melanoma. Some of the lack of information has been driven by the licensing requirements. Drugs are required to show safety and efficacy. Biologicals, which include the vaccines, are often only required to show safety prior to being available commercially. The use of monoclonal antibodies against surface antigens is widely used in human lymphoma and has made a large difference in outcome. Recently there is limited use of canine versions for B and T cell lymphoma that are currently under evaluation with benefit reported in the early studies. There are a large number of other approaches. Metronomic chemotherapy is an example of immunotherapy through its effects on T regulator cells. Host immune cells that infiltrate cancers can initially target the cancer cells, but with time they can undergo changes that will lead them to enhance tumour growth and survival. There are now evaluations of methods to modify or remove these cells to control cancers. These have ranged from the use of chemotherapy or other drugs to target the tumour infiltrating cells or using cytokine therapy. The use of intratumoural cytokine therapy has shown some success, but not in all cases. Inflammation and systemic inflammatory responses can be limiting with some of these approaches. Ex vivo activation of immune cells has been investigated with the major group being dendritic cell vaccines. The patient’s own cells are collected and grown up in vitro and exposed to their autologous antigens. Once primed to attack the cancer cells these are then reinfused into the patient with some very good responses. This approach is difficult and costly so some veterinary groups have been developing a similar approach using lymphocytes which are also antigen presenting cells. The preliminary data on this approach has been promising. There are a number of autologous vaccines that are currently in use. Modified cells and cell lysates have been tried. There is now a commercial autologous vaccine available that uses modified tumour proteins. EBC46: This is a product that was extracted from a Queensland tropical rainforest plant. There is limited published data on its use and safety in dogs and cats. There is one study in rodent models published. This agent appears to cause tumour necrosis through protein kinase C pathways and altered vasculature within the tumour. The drug is used either topically or intralesionally. The reactions reported appear similar to bloodroot (also known as black salve) that has been used for years. There are anecdotal reports of effective treatment of superficial tumours in dogs and cats. The overall response rate and rate of adverse events is not known. In people there has been concern about failure for local cure and excessive scar tissue formation after the use of bloodroot. It is not known if this is a risk with EBC46. The local reaction that occurs can be very painful and this has been found in some patients treated with EBC46.

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ROLE OF CHEMOTHERAPY POSTOP – ANAL SAC, SPLEEN, MCT, OSA Peter Bennett BVSc FANZCVS DACVIM

University of Sydney, Camperdown, NSW, Australia Adjunctive chemotherapy is regularly recommended for all of the diseases listed. The degree of benefit is variable and better documented for some more than others. There is better defined optimal drug choices in some compared to others also. The risk to benefit ratio, the individual patient tolerance and the owners willingness to undertake treatment are all considerations in making the recommendation for adjunctive chemotherapy. Anal Sac Carcinoma: Anal sac carcinoma is an uncommon tumour in dogs and rare in cats. There are limited studies looking at the benefit of adjunctive chemotherapy and outcome and all reported to date have been retrospective. Retrospective studies will often have a strong bias as the more aggressive tumours based on either histology or clinical assessment will have a stronger recommendation than less aggressive disease. When dogs with gross tumour are treated with chemotherapy there is about a 30% response rate. So we know that anal sac carcinoma cells can respond to chemotherapy. In studies of adjunctive therapy there has usually been no statistical difference in outcome between those receiving chemotherapy or not. In some studies those receiving chemotherapy have lived longer, while in others they have a shorter median survival. In most studies a mixture of patients who have had surgery to reduce their disease to microscopic levels and those with some visible disease have been combined in both groups. A variety of drugs have been used and reported, including cisplatin, carboplatin, doxorubicin, mitoxantrone and melphalan. In more recent times there are anecdotal reports of the use of metronomic chemotherapy and tyrosine kinase inhibitors. Anal sac carcinoma can behave as a locoregional disease with the primary tumour and regional lymphadenopathy being the only disease present for long periods of time. For this reason there is benefit in local treatment with surgery being the best option or combining this with radiation therapy. Good responses have been seen. Why should adjunctive chemotherapy be considered after surgery? Not all patients are candidates for radiation therapy, or the clients are not willing to pursue this option. Complete resection of anal sac tumours cannot be guaranteed. The close proximity to the anal sphincter and the lack of a fascial plane between the anal sac and the pelvic canal make complete resection uncertain in all cases. In patients with nodal disease, the close proximity to the pelvis and great vessels also precludes wide resection. We know that the many diseases the use of chemotherapy can delay local recurrence and this might be the case with anal sac carcinoma. We do not know for certain without a prospective study using appropriately staged and matched patients. We also have to consider the risk of distant disease that occurs in a reasonable percentage of patients. Chemotherapy can also be utilised when surgery cannot reduce the amount of disease to microscopic amounts. In these latter patients monitoring of tumour response can be used to guide ongoing treatment. Splenic tumours: There is more evidence for the use of adjuvant chemotherapy in splenic tumours and anal sac carcinoma. We know that in dogs about 2/3 of patients with a splenic mass will have a malignancy and about 2/3 of these are haemangiosarcoma. There are many studies that have shown a survival benefit in patients with haemangiosarcoma if treated with adjunctive chemotherapy compared to surgery alone. Survival medians of 1.5 to 3 months are usually reported with surgery alone, compared to medians of 6 to 9 months if adjunctive chemotherapy is used. Doxorubicin or doxorubicin combinations (such as VAC) have been used most often, but metronomic chemotherapy has also been suggested to have benefit. There is debate about

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whether combining doxorubicin with metronomic chemotherapy, either concurrently or sequentially, will improve their outlook. Another tumour where there is reasonable evidence that adjunctive chemotherapy is of benefit is lymphoma. Benefit is not seen for all variants of lymphoma. High grade disease will have a longer median survival if chemotherapy is given. Surgery is not often used for patients with lymphoma, but some present with isolated splenic disease and a cavitated lesion, so it is diagnosed after the event. In other patients, splenic rupture leads to an emergency splenectomy. But we see low grade and indolent lymphoma in the spleen such as marginal zone lymphoma. In these patients there is not known benefit for adjuvant therapy. Histiocytic sarcoma of the spleen is uncommon and is an aggressive disease. While not backed by good studies, the use of adjuvant Lomustine will likely improve the patient’s outcome, though median survival of less than 6 months is likely. There is little evidence of the use of adjunctive chemotherapy for other splenic tumours. High grade stromal tumours and other soft tissue sarcomas might benefit, but there are no studies. High grade fibrohistiocytic nodules might be misdiagnosed other diseases which are where previous reports of some benefit may have arisen as recent work has diagnosed some of these as haemangiosarcoma or lymphoma. Other diseases such as mast cell tumour or other specific tumours might benefit. Mast Cell Tumour: Adjunctive chemotherapy for mast cell tumours is a recognised practice. In most cases it has been used to manage the risk of systemic spread from high grade tumours, but it has been used to manage incompletely removed lower grade tumours when repeat surgery or radiation are not options. The main debates regarding mast cell tumours have arisen in the variation seen in grading and the choice of therapies. There are currently two grading schemes, Patnaik and Kuipel. Neither is perfect and there is variation between pathologists on the grades reported. The use of c-kit mutation status and possibly c-kit immunohistochemical staining patterns might help further define the grades, this has yet to be universally accepted. There are patients seen where the biological behaviour of the tumour does not match the pathology and in these patients this should be the overriding factor in deciding on the use of adjuvant therapy. In terms of choice of treatment we have the cytotoxic drugs vinblastine and Lomustine that have been used. In more recent years we have the development and release of the tyrosine kinase inhibitors toceranib and masitinib. Both options can be very effective and there is much individual choice as to which is used first or if they should be used in combination. This is an area where studies need to be performed. Osteosarcoma: This is the most common primary bone tumour seen in dogs and cats. In the dog this is a very aggressive disease with the majority of patients having microscopic metastatic disease present at the time of diagnosis. About 10% of patients will have visible metastatic disease. Control of the local tumour with surgery will lead to a median survival of around 5 months increasing to between 12 and 18 months if adjuvant chemotherapy is used. The range in outcomes is dependent on the histological grade of the tumour and the pre-operative serum ALP level. There are some patients where the use of chemotherapy can help when visible metastatic disease develops. In some patients surgery can be used and while not studies have been done in dogs, the use of additional adjunctive chemotherapy has been recommended. In some patients chemotherapy alone can lead to tumour remission, though this is not common.

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BONE MARROW TRANSPLANTATION IN AUSTRALIA

Dr. Sandra Nguyen Dip. ACVIM (Onc) and Dr. Angela Frimberger Dip. ACVIM (Onc) Autologous bone marrow transplantation is a documented treatment for canine lymphoma1,2,3

and can be achieved via peripheral blood haematopoietic cell transplantation (PBHCT) or bone marrow harvest and reinfusion. The remission duration and overall survival is increased with these protocols. In Australia a dose intensified combination chemotherapy protocol, involving a high dose of cyclophosphamide, followed by an autologous bone marrow transplant, is available. The patient The canine patient must weigh greater than 15kg, have B cell lymphoma and be fully staged to document that lymphoma has not infiltrated the bone marrow (i.e. normal bone marrow cytology prior to starting chemotherapy). Concurrent disease is considered on a case-by-case basis. More recently we have offered this procedure to patients with osteosarcoma, utilising high dose carboplatin. The procedure Patients with lymphoma are started on a course of chemotherapy. The first treatment is a standard dose of cyclophosphamide, to ensure that the patient’s lymphoma is sensitive to that drug in an attempt to reduce the risk of relapse after the transplantation. After the initial dose, cyclophosphamide is only used again as a high dose to ensure resistance is not selected for. Once the patient is in complete remission, plasma is harvested from the patient and frozen (usually around week 7) with the red cells re-infused to the patient that day. Prior to marrow harvest the patient G-CSF is administered twice daily for 1 week by the owner. At harvest, the bone marrow is harvested under general anaesthesia from the proximal humeri and cryopreserved in heparinized tissue culture medium, the patient’s plasma and DMSO. The marrow is again tested for infiltration of lymphoma. Two weeks later the patient receives a single intravenous dose of cyclophosphamide at 500mg/m2, with frusemide and mesna. Two days later the cryopreserved bone marrow is administered intravenously. Patients are given prophylactic antibiotics from the day of high dose chemotherapy, and continued until the bone marrow recovers. Toxicity This procedure is incredibly well tolerated, with patients only required to be in hospital for one night, and to date only one hospitalisation due to sepsis has occurred, which responded to standard supportive care and the patient was discharged in 48 hours. There has been no treatment-related mortality. The neutrophil nadir occurs on day 9 after high dose chemotherapy and the neutrophil count is usually normalized in approximately 2 weeks after treatment. This is contrast to the PSHCT procedure, which provides similar long-term disease control outcomes but involves total body irradiation, at least 2 weeks in isolation, and a treatment-related mortality rate of 12 - 13%. Ongoing work We continue to offer this treatment for dogs with lymphoma as a now-established clinical treatment option. We plan to expand the treatment for those with osteosarcoma, using high dose carboplatin; and mast cell disease, using high dose vinblastine, as well as for cats with lymphoma.

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References 1. Frimberger AE, Moore AS, Rassnick KM, Cotter SM, O'Sullivan JL, Quesenberry PJ. A combination chemotherapy protocol with dose intensification and autologous bone marrow transplant (VELCAP-HDC) for canine lymphoma. J Vet Intern Med. 2006 Mar-Apr;20(2):355-64. 2. Willcox JL, Pruitt A, Suter SE. Autologous peripheral blood hematopoietic cell transplantation in dogs with B-cell lymphoma. J Vet Intern Med. 2012 Sep-Oct;26(5):1155-63. 3. Warry EE, Willcox JL, Suter SE. Autologous peripheral blood hematopoietic cell transplantation in dogs with T-cell lymphoma. J Vet Intern Med. 2014 Mar-Apr;28(2):529-37.

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SPLENECTOMY AFTER RUPTURE – IS IT ETHICAL? Sandra M. Nguyen BVSc (Hons I) Dip. ACVIM (Onc)

Ethics

1. Pertaining to or dealing with morals or the principles of morality: pertaining to the right and wrong in conduct.

2. Being in accordance with the rules or standards for right conduct or practice, especially the standards of a profession.

Overview To decide whether or not splenectomy after rupture is ethical we first need to know what the potential outcomes of the procedure are. Certainly we know that the likely outcome of doing nothing is death, which in itself poses an ethical question of whether or not to assist that death. Once we know the potential ramifications of surgery vs. not, we then need to communicate these options to the patient’s caregiver, our client, in a way that enables them to make the most appropriate decision for them and their situation. Splenic rupture and disease In a large study of 539 dogs with splenic masses that underwent surgery, the perioperative mortality rate was 7.6%1, and in another of 83 dogs the mortality rate was16%6, therefore splenectomy results in a good surgical outcome. In broad terms, approximately 2/3 of the splenic masses will be neoplastic, while 1/3 will be benign disease. Of the cancers, approximately 2/3 will be haemangiosarcoma and 1/3 will be a different neoplasia2. Unfortunately it is difficult to predict prior to histopathology what the splenic mass is going to be. Anecdotally, the larger the mass the more likely it is to be benign, and this has been shown in a series of 65 dogs with splenic masses that underwent surgery2. Cytology may be useful in identifying round cell tumours such as lymphoma if there is the luxury of time before the splenectomy. Bleeding from metastatic disease is one of the more common reasons for perioperative mortality, and again metastatic disease can be challenging to predict prior to surgical exploration1,3. Conversely, if the bleeding is confined to the spleen, this is actually a positive predictor for survival6. Most of the time follow up chemotherapy is recommended for neoplastic splenic masses. The most common splenic neoplasia is haemangiosarcoma, and while surgery alone results in a median survival time of 19-86 days, with adjunctive chemotherapy this can be increased to about 200 days4. Dogs with advanced stage disease, if they survive the perioperative period, have an 86% response rate to chemotherapy and their survival time is no different to those with less disease at presentation5. There are some long-term responders, but the 1-year survival rate is about 10% even with chemotherapy. Neoplastic diseases with better outcomes include splenic sarcomas, fibrohistiocytic nodules and lymphoma; and indeed in some cases no follow up therapy is recommended, and the patient’s survival will not be impacted by the splenic neoplasia beyond surgical removal. It is important to remember that non-haemangiosarcoma neoplasia and non-neoplastic disease makes up about 50% of cases with splenic masses.

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Communication Ultimately it is the decision of the patient’s caregiver as to whether or not a splenectomy is performed, and the role of veterinarian is to present the treatment options and likely prognosis in this situation. We are often asked ‘What would you do if it was your dog?’ and this question should be answered with care, as the patient is not your dog, and what would work in your situation may not be appropriate for the client’s. You can also risk alienating the client should you communicate strong feelings in the opposite direction to theirs. Certainly while guiding them through the decision making process, and once a decision is made, you can validate their feelings with self-disclosure, but empathic responses during the discussion will assist them in making a decision that is best for them. When we know a disease is terminal and the patient is suffering, euthanasia is a very reasonable treatment option to offer, and for the patient’s family to consider. In an emergent situation this can be difficult for the client, especially if the decision is being made because of financial constraints. With an excellent peri-operative survival rate, splenectomy after rupture should be offered for our patients, which then can have the benefit if a diagnosis. References 1. Wendelburg KM, O'Toole TE, McCobb E, Price LL, Lyons JA, Berg J. Risk factors for perioperative death in dogs undergoing splenectomy for splenic masses: 539 cases (2001-2012). J Am Vet Med Assoc. 2014 Dec 15;245(12):1382-90. 2. Mallinckrodt MJ, Gottfried SD Mass-to-splenic volume ratio and splenic weight as a percentage of body weight in dogs with malignant and benign splenic masses: 65 cases (2007-2008). J Am Vet Med Assoc. 2011 Nov 15;239(10):1325-7 3. Ivancić M1, Long F, Seiler GS. Contrast harmonic ultrasonography of splenic masses and associated liver nodules in dogs. J Am Vet Med Assoc. 2009 Jan 1;234(1):88-94 4. Withrow and MacEwen’s Small Animal Clinical Oncology 5th Ed. Eds Withrow, Vail and Page 2013. 5. Alvarez FJ1, Hosoya K, Lara-Garcia A, Kisseberth W, Couto G. VAC protocol for treatment of dogs with stage III hemangiosarcoma. J Am Anim Hosp Assoc. 2013 Nov-Dec;49(6):370-7. 6. Lux CN1, Culp WT, Mayhew PD, Tong K, Rebhun RB, Kass PH. Perioperative outcome in dogs with hemoperitoneum: 83 cases (2005-2010). J Am Vet Med Assoc. 2013 May 15;242(10):1385-91.

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THE HUNT FOR METASTATIC DISEASE: USE OF IMAGING FOR STAGING CANCER AND ONCOLOGICAL SURGICAL

PLANNING, SPECIFICALLY OF THE THORAX

Dr Marjorie Milne BVSc(Hons) FANZCVS (Radiol) Veterinary Hospital, Faculty of Veterinary and Agricultural Sciences, University of

Melbourne, Werribee, VIC, Australia Role of diagnostic imaging in oncology identify primary and metastatic lesions monitor lesions facilitate diagnostic sampling assist surgical planning Imaging modalities Radiography Readily available, inexpensive, baseline screening test. Thoracic radiography is the mainstay to screen for pulmonary metastases. Abdominal radiography complements ultrasound and provides a global overview about

relative size and location of organs. Ultrasound Readily available, relatively inexpensive. Better characterisation of organs compared to radiography but poor specificity for disease

processes, and sampling of tissue still required for diagnosis. Highly user-dependent. In dogs over 25 kg, abdominal CT is able to detect more lesions and more clinically relevant

lesions than abdominal US and should be the preferred imaging modality in these larger patients. (Fields 2012)

Limited use in the thorax - heart, parts of mediastinum, thoracic wall, pleural effusions, peripheral pulmonary lesions.

Very easy to perform ultrasound guided sampling. Computed tomography More expensive, may require anaesthesia. Better soft tissue contrast compared to radiography. Elimination of superimposition can make interpretation easier. Larger field of view compared to ultrasound allows formation of a global overview,

particularly useful for large and complex lesions. Thoracic CT usually provides additional useful information compared to thoracic radiography,

and often leads to a change in diagnosis. (Prather 2005) Use of multiplanar reformations and 3-dimensional modeling improves speed of interpretation,

(Mang 2011, McMenamin 2015), accuracy (Berg 1998, Ferencik 2007), and diagnostic confidence (Chooi 2005).

More sensitive for bone loss, more sensitive for pulmonary change including identification of nodules (Nemanic 2006)

‘Whole body CT’ to screen for primary and metastatic neoplasia? increased radiation dose to patient

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decreased accuracy of interpretation with increased number of images to review (Andriole 2011, Lee 2013)

how to interpret the ‘incidentaloma’? sampling of tissue still required for diagnosis in some cases, scintigraphy (Oblak 2013) or PET/CT (Seiler 2015) may be more

appropriate CT-guided biopsy

Useful to target deep lesions or contrast-enhancing (‘viable’) tissue (Tidwell 1994). In a case series of CT-guided sampling of thoracic lesions in 30 cats and dogs,

complications of pneumothorax & pulmonary haemorrhage occurred in 43% of patients, but all complications were mild and clinically silent. (Zekas 2005)

A smaller case series of 14 dogs and cats with CT-guided sampling of lung lesions found that a clinical diagnosis was reached in all cases that had a biopsy, but only 80% of cases that had FNA. Although minor pneumothorax and bleeding were noted in some cases, no clinical signs were associated with these complications. (Yoshida 2007)

CT data often used for radiation therapy planning (may be fused to MRI data). Nuclear Scintigraphy Limited availability, produces planar (two-dimensional) images. Images physiologic processes. High sensitivity (depending on selection of appropriate radiopharmaceutical) but poor

specificity. Able to provide both functional and morphologic information, but has poor anatomic detail. Generally, animals must be hospitalised until radiation emission returns to safe levels. Magnetic Resonance Imaging Limited availability, relatively expensive. Excellent sensitivity for soft tissue lesions; often useful to identify tumour margins prior to

surgery or radiation therapy. May over-estimate tumour size due to adjacent inflammatory change. Variable quality of images (magnetic field strength, operator expertise, available coils). Studies can be time-consuming to acquire, requires general anaesthesia. Difficulties in imaging thorax:

aerated lung - deficiency of mobile protons (water) returns no signal air-soft tissue interface artefacts motion blur (respiratory, cardiac, pulsatile blood flow) may be partially mitigated using

techniques such as respiratory and cardiac gating. CT tends to be preferred over MRI for advanced imaging of the thorax. Future developments Improved use of thoracic CT More research needed!

Larger case series leading to better knowledge about characterising specific tumours based on CT appearance.

Better lesion characterisation using dynamic CT and three-phase CT Fusion of CT and ultrasound for ultrasound-guided sampling, based on CT images SPECT

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Single Photon Emission Computed Tomography Similar to Nuclear Scintigraphy, but rotating the detector about the patient generates a 3D

rendering of the structure of interest. More accurately depicts distribution of radiopharmaceutical, but still has poor anatomic detail. Described in dogs with neoplasia (Whittemore 2004), but also in the investigation of

myocardial perfusion and epilepsy in dogs. PET and PET/CT Positron emission tomography Often uses ‘FDG’: 2-deoxy-2-[18F]fluoro-D-glucose - relies on excessive glucose utilisation

by metabolically active tissue, including tumours and inflammation. Routinely used in human oncology for detection of cancer, staging and monitoring. Limited availability in veterinary medicine: largely experimental or small case series

(Lawrence 2010, Seiler 2015). Poor anatomic detail of PET is overcome by simultaneous acquisition of CT, and image fusion

of PET and CT data. Molecular imaging Tailored contrast agents or monoclonal antibodies, targeting specific molecules. Typically used in MRI or nuclear imaging (scintigraphy, SPECT, PET). Magnetic Resonance Spectroscopy (MRS) (Lynch 2014) available in some high-field strength

MRI units. Potential to allow specific tissue diagnosis. Screening for pulmonary metastases Thoracic radiography Commonly employed, but is not as sensitive as thoracic CT. Three-view thoracic radiographs are preferred over two-view.

dependent lung rapidly develops atelectasis and obscures lesions superimposition of mediastinal structures can obscure lesions eliminating one view from a three-view study would have changed the diagnosis in 12 to

15% of patients (Ober 2006) Ensure lungs are well inflated; if patient is anaesthetised, radiograph soon after induction and

use positive pressure ventilation to inflate the lungs. Do not use digitized thoracic radiographs - loss of image information means reduced ability to

detect pulmonary nodules. (Armbrust 2005) American College of Veterinary Radiology recommends interpretation of digital images be

based on the DICOM format rather than jpeg or other compressed files. Computed radiography and film-screen radiography performed similarly in ability to detect

pulmonary nodules. (Alexander 2012) Size limit for detection of soft-tissue pulmonary nodules on a radiograph is 5mm diameter,

with detection reliable at 7 - 9mm diameter. (Nemanic 2006) Metastatic disease may also have unstructured interstitial pattern, or alveolar pattern.

Computed tomography Preferred modality to screen for pulmonary metastases Technical aspects:

Multi-row detector CT machines preferred over single-row detector machines

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more rapid acquisition no respiratory motion artefact superior image quality sub-mm slice thickness, isovolumetric voxels MPRs without ‘stair-stepping’ artefact

General anaesthesia with breath-hold techniques provide superior lung inflation and lesion detection; if breath-hold cannot be safely performed, then induce apnoea.

If dependent atelectasis is present, flip the patient, inflate using positive pressure ventilation, and repeat the scan

Acquire both pre- and post-contrast images. Single-row detector machine:

for best results in detection of pulmonary nodules, use a narrow collimation (3 to 5mm), pitch of 2 and reconstruction interval of 1 (Joly 2009) consider high-resolution computed tomography (HRCT) protocols (Johnson 2004)

excellent spatial resolution but slow to acquire and usually cannot acquire through entire thorax, particularly useful for diffuse or interstitial lung disease

axial mode of acquisition tightly collimated beam high kVp and mA decreased field of view high spatial frequency reconstruction algorithm

Detection of pulmonary nodules:

Compared to thoracic radiography, thoracic CT is able to detect smaller nodules (lower limit of detection approx 1mm diameter), more pulmonary nodules, and detect nodules in a greater number of lung lobes (Nemanic 2006, Eberle 2011, Armbrust 2012, Alexander 2012).

NOT ALL NODULES ARE METASTASES! In humans, over 80% of pulmonary nodules identified in patients with extra-thoracic primary tumours were benign! (Chalmers 1991) Guidelines for how to deal with small pulmonary nodules identified on thoracic CT in dogs with neoplasia are lacking, but in humans a repeat CT scan is recommended to monitor nodules for resolution or increase in size.

Note that linear measurements of nodule or mass size are much less accurate than volume measurements, and volume measurements are recommended for follow-up CT studies. (Revel 2004)

Primary pulmonary neoplasia

Focal (mass or nodule) vs diffuse (ground-glass appearance) Concurrent tracheobronchial lymph node (TBLN) abnormalities suggest pulmonary

neoplasia; CT had a positive predictive value of 100% and negative predictive value of 89% for detection of abnormal TBLNs (Paoloni 2006), which appear enlarged (>12mm transverse maximum LN diameter) and heterogenous or ring-like contrast enhancement (Ballegeer 2010).

In cats: (Aarsvold 2015) occurs more often in the caudal lung lobes, with 49% in the right and 30% in the left caudal lung lobe. CT features of primary pulmonary neoplasia:

mass in contact with visceral pleura (96%) irregular margins (83%) but well-defined borders (79%)

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bronchial compression (74%) or bronchial invasion (19%) gas containing cavities (63%) mineralisation (56%)

In dogs: (Marolf 2011) 95% were solitary, located in both cranial and caudal lung lobes, in central or peripheral zones (rather than perihilar) CT features of primary pulmonary neoplasia:

solitary, well circumscribed, bronchocentric mass with internal air bronchograms narrowing and displacement of bronchi mineralisation (16%) tracheobronchial lymphadenopathy (21%) mild to moderate heterogeneous contrast enhancement (65%)

References Aarsvold S et al. Computed tomographic findings in 57 cats with primary pulmonary neoplasia. Vet Rad Ultrasound. 2015. 56(3):272-277 Alexander et al. A comparison of computed tomography, computed radiography and film-screen radiography for the detection of canine pulmonary nodules. Vet Rad Ultrasound 2012. 53(3):258-265 Andriole KP et al. Optimizing analysis, visualisation, and navigation of large image data sets: one 5000-section CT scan can ruin your whole day. Radiology. 2011. 259(2):346-362 Armbrust L et al. Comparison of digitized and direct viewed (analog) radiographic images for detection of pulmonary nodules. Vet Radiol Ultrasound. 2005. 46(5):361-367 Armbrust L et al. Comparison of three-view thoracic radiography and computed tomography for detection of pulmonary nodules in dogs with neoplasia. J Am Vet Med Assoc. 2012. 240:1088-1094 Ballegeer et al. Computed tomography characteristics of canine tracheobronchial lymph node metastases. Vet Rad Ultrasound. 2010. 51(4):397-403. Berg M et al. Assessment of renal artery stenosis with CT angiography: usefulness of multiplanar reformation, quantitative stenosis measurements, and densitometric analysis of renal parenchymal enhancement as adjuncts to MIP film reading. J Comp Assist Tomography. 1998. 22(4):533-540 Chalmers N and Best J. The significance of pulmonary nodules detected by CT but not chest radiographs in tumour staging. Clin Rad. 1991. 44(6):410-412 Chooi WK et al. Multislice computed tomography in staging lung cancer: the role of multiplanar image reconstruction. J Comp Assist Tomography. 2005. 29(3):357-360 Eberle N et al. Comparison of examination of thoracic radiographs and thoracic computed tomography in dogs with appendicular osteosarcoma. Vet Comp Oncology. 2010. 9(2):131-140 Ferencik M et al. Diagnostic accuracy of image postprocessing methods for the detection of coronary artery stenoses by using multidetector CT. Radiology. 2007. 243(3):696-702 Fields E et al. Comparison of abdominal computed tomography and abdominal ultrasound in sedated dogs. Vet Radiol Ultrasound. 2012. 53(5):513-517 Johnson V et al. Thoracic high-resolution computed tomography in the diagnosis of metastatic carcinoma. J Small Anim Pract. 2004. 45(3):134-143

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Joly et al. Comparison of single-slice computed tomography protocols for detection of pulmonary nodules in dogs. Vet Radiol Ultrasound. 2009. 50(3):279-284 Lawrence J et al. PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring: Fundamentals, early results and future perspectives. Vet Comp Onc. 2010. 8:163-187 Lee C et al. Cognitive and system factors contributing to diagnostic errors in radiology. Am J Roentgen. 2013. 201:611-617 Lynch K, Obrien R. 1H Magnetic resonance spectroscopy: A review of the current literature and its potential utility in veterinary oncology. Vet J. 2014. 200:240-247 Mcmenamin D et al. Visual search in abdominopelvic CT interpretation: accuracy and time efficiency between coronal MPR and axial images. Acad Radiol. 2015. 22(2):164-168 Mang T et al. Comparison of diagnostic accuracy and interpretation time for standard and an advanced 3D visualisation technique in CT colonography. Eur Radiol. 2011. 21:653-662 Marolf AJ et al. Computed Tomographic Appearance of Primary Lung Tumors in Dogs. Vet Rad Ultrasound. 2011. 52(2):168-172 Nemanic S et al. Comparison of thoracic radiographs and single breath-hold helical CT for detection of pulmonary nodules in dogs with metastatic neoplasia. J Vet Intern Med. 2006. 20:508-515 Ober Comparison of two- vs. three-view thoracic radiographic studies on conspicuity of structured interstitial patterns in dogs. Vet Rad Ultrasound. 2006. 47(6):542-545. Oblak M. et al. Comparison of concurrent imaging modalities for staging of dogs with appendicular primary bone tumours. Vet Comp Oncology. 2013. 13(1):28-39 Paoloni et al. Comparison of results of computed tomography and radiography with histopathologic findings in tracheobronchial lymph nodes in dogs with primary lung tumors: 14 cases (1999-2002). JAVMA. 2006. 228(11):1718-1722. Prather A et al. Use of radiography in combination with computed tomography for the assessment of noncardiac thoracic disease in the dog and cat. Vet Radiol Ultrasound. 2005. 46(2):114-121 Revel MP et al. Are two-dimensional CT measurements of small non-calcified pulmonary nodules reliable? Radiology. 2004. 231(2):453-458 Seiler S et al. Comparative oncology: evaluation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) for staging of dog with malignant tumours. PLoS ONE. 2015. 10(6) Tidwell A et al. Computed tomography-guided percutaneous biopsy in the dog and cat: description of technique and preliminary evaluation in 14 patients. Vet Radiol Ultrasound. 1994. 35(6):445-456 Whittemore J et al. Indium-111 labeled vitamin B12 imaging of ciliary adenoma with concurrent grade 2 soft tissue sarcoma of the leg in a Labrador Retriever. Vet Opthamol. 2004. 7(3):209-212 Yoshida et al. Computed tomography-guided needle biopsy of lung lesions in 14 cats and dogs. J Jap Vet Med Assoc. 2007. 60(3):211-215 Zekas L et al. Computed tomography-guided fine-needle aspirate and tissue-core biopsy of intrathoracic lesions in thirty dogs and cats. Vet Radiol Ultrasound. 2005. 46(3):200-204

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SCREENING FOR ABDOMINAL METASTATIC NEOPLASIA A comparison of modalities and techniques.

Dr Mika Frances BSc BVMS FANZCVS (Radiol)

Western Australian Veterinary Specialty and Emergency, Perth WA, Australia Goals

• Identifying and characterising the presence of nodules (metastatic or multicentric, eg with respect to round cell neoplasia) in the liver, spleen and other less common organs (kidneys, adrenal glands)

• Identifying lymphadenopathy • Finding a primary lesion when metastatic disease has been detected • Assessing the extent of/invasion by the primary tumour (screening for metastasis is

often combined with assessment of the primary lesion) • Assessing for the presence of concurrent disease in aged patients • Assessing for common concurrent tumours ie MENS. • Assessing function eg contralateral adrenal atrophy • Commonly combined with thoracic CT or radiograph to assess for the presence of

pulmonary metastatic lesions Tumour types and metastatic “destinations” to the abdomen

• Liver • Spleen • Lymph nodes • Bone • Others (spinal canal, renal, adrenal, peritoneum, muscle)

Metastasis to the liver – common primaries Spleen

Haemangiosarcoma Round cell neoplasia (lymphoma, histiocytic neoplasia, mast cell neoplasia) Non-angiomatous, non-lymphomatous sarcomas

Pancreas Adenocarcinomas Insulinoma Gastrinoma

GIT Gastric carcinoma Intestinal lymphoma, MCT, leiomyosarcoma

Metastasis to liver less common primaries • Cutaneous (HSA, MCT) • Peri-anal adenocarcinoma • Oral cavity eg rhabdomyosarcoma • Skeletal HSA • Adrenal tumours

o cortical carcinomas o Phaeochromocytomas

• Reproductive tumours

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o Mammary gland ovarian, testicular • Cardiac tumours eg chemodectomas Metastasis to the spleen Mast cell neoplasia - cutaneous Hepatic sarcomas eg HSA, Leiomyosarcoma, FSA Intestinal tumours Peri-anal ACA Cardiac HSA Oral cavity neoplasia Skeletal HSA Adrenal neoplasia – phaeochromocytoma Round cell neoplasia (lymphoma, histiocytic). Regional LN Many tumour types! Patterns of lymph node drainage – visceral, parietal and sternal nodes Metastasis to bone Carcinomas, commonly prostate, bladder, urethral, mammary OSA HSA Feline SCC Lymphoma, multiple myeloma Metastasis to other places Kidneys – HSA, histiocytic neoplasia, TCC, Spinal cord/canal – invasion from adjacent masses more common but mets from other sites do occur, including carcinomas of all types. Muscle - HSA, undifferentiated sarcomas, ACA, TCC, SCC, lymphoma. Identifying metastases Imaging identifies structural changes

Change in size and (generalised / focal / multifocal) Change in shape (eg increased short to long axis ratio of lymph nodes). Border definition Change in tissue character (eg hypo/hyperechoic on ultrasound, differential attenuation or enhancement characteristics on CT) – tumour vascularity.

Structural changes Structural changes are often non-specific, for example nodular hyperplasia can appear very similar to various forms of hepatic neoplasia. Therefore the presence of a nodule, mass or diffuse change are insufficiently specific findings to conclude that there is the presence of metastatic disease. In addition to interpreting the whole study together (eg are there changes in multiple organs, does this fit with what we know about the underlying tumour type and its common patterns of metastasis), we often focus on the latter of these three – changes in tissue character. Modalities at our disposal for screening for metastatic disease

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Radiographs – primarily changes in size and shape of organs, osseous changes, mineralisation. US – SSMEEL, tumour vascularity. CT – SSM, tissue attenuation characteristics, vascular phases (arterial, venous) with intravenous iodinated contrast media. MRI – SSM, tissue attenuation characteristics, vascularity, gadolinium and some organ specific contrast agents. Tissue character - tumour vascularity Much research has focussed on this as a method of increasing the specificity of our imaging techniques for detection of metastatic disease. Malignant angiogenesis occurs in a different manner to non-malignant angiogenesis.

Tumour vascularity – imaging applications US – characteristic vessel morphology may be detected with B-mode and Doppler imaging. CEUS - use of microbubble contrast agents to highlight arterial and parenchymal phases – not available clinically but may be in future, does allow an understanding of vascularity that can be applied to other modalities. CT – use of multiphase imaging (this involves using timed image acquisition, often with bolus tracking) to record both an arterial and venous/parenchymal phase of enhancement MRI – GAD and other liver-specific contrast agents (Superparamagnetic oxide is a tissue specific contrast used to image the liver in humans. Shortens T2 relaxation times. Taken up by RES (Kuppfer cells) which are lacking in many tumours therefore they don't enhance).

Imaging tools – appearance of metastatic disease Radiographs Eg prostatomegaly/reactive bony change, other osseous metastasis. Sublumbar lymphadenopathy Organomegaly US of abnormal lymph nodes Helena Nyman – multiple papers describing characteristics of neoplastic lymph nodes

• rounded (short to long axis ratio > 0.55 • hypoechoic (often with distal enhancement) • may be well defined • peripheral or mixed vascular pattern • disrupted/absent hilus.

Salwei VRU 2005 – 11 dogs lymphomatous nodes had displacement of the central hilar vessel, aberrant vessels, pericapsular vessels and subcapsular vessels.

Kinns VRU 2007 - 23 dogs and 18 cats - Sonographic heterogeneity significant association between heterogeneity and malignancy (including metastatic neoplasia and round cell neoplasia) in canine abdominal lymph nodes (P 1⁄4 0.024). In cats there was no significant association between heterogeneity and malignancy (P 1⁄4 0.537) – mainly lymphoma

Nyman VRU 2005 - 318 nodes 142 dogs Vascular flow indices Normal nodes and reactive nodes had a RI < 0.59 and PI < 0.7, mets were RI >0.79 and PI > 1.72.Nyman 2005 VRU (2004)

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Problem with this method is it requires Power Doppler which is motion sensitive Prieto 2009 VRU

US of abnormal Liver Warren-Smith JSAP 2012 – 371 dogs

• No statistically significant associations found between US appearance of hepatic nodules and histologic diagnosis, however metastatic nodules were most commonly hyperechoic and multifocal. Primary tumours were most commonly heterogeneous and were also often multifocal (HCC, HSA).

• Target lesions were associated with malignancy in 67% of cases. Kemp JVIM 2013 – 138 dogs

An unremarkable ultrasound was statistically associated with normal histopathology, however few cases of diffuse neoplasia in this study.

Guillot VRU 2009 – 70 dogs Sonographic detection of a hepatic mass > 3 cm, ascites, enlarged hepatic nodes an abnormal spleen correlated with malignancy (as assessed by cytology).

Nyman VRU 2004 - Vascular flow indices • Doppler perfusion indices – use calculation of total blood volume in the liver

– variable results from different authors and time-consuming. • Velocity of hepatic parenchymal blood flow – usually low velocity, AV

shunts that develop in tumours may exhibit higher velocity flow (70-700 cm/s) - little supporting evidence in the Veterinary literature in companion animals (rats and rabbits)

US of abnormal spleen Sharpley VRU 2012 – 31 dogs

• The presence of an aberrant or tortuous vessel within a mass was nearly significant (P 0.59) however there were no other patterns of vascularity which indicated malignancy.

• Peritoneal effusion was associated with malignancy. US of abnormal liver and spleen

Cucovillo VRU 2005 • Multiple target lesions in one organ PPV of malignancy 74%, two organs

PPV 81%. • A hypoechoic halo may be necrosis, tumour, compressed hepatocytes. • Bening conditions that were seen as target lesinos were nodular hyperplasia,

hepatitis, cirrhosis. Crabtree VRU 2010 – 28 dogs

Accuracy of US for lymphoma – good for normal spleen, poor for liver (false positives). Mottled spleen PPV of 100% for lymphoma. ** Care with high frequency transducers, this paper used 8 MHz.

Contrast enhanced ultrasound – improved visualisation of tumour vascularity Gas microbubbles in a shell Injected IV Multiple sized bubbles in one dose Vascular phase +/- a parenchymal phase Applications: 1. Vessel distribution 2. perfusion patterns (dynamic)

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3. Quantitative analysis of ROIs to provide a “vascularity index” 4. Time-intensity curves. Contrast enhanced US - applications There are limitations for the use CEUS in the liver in dogs and cats (unavailable in many areas) to characterize lesions . If this changes there is potential for TAC to be created which may enable quantification of wash in/out times with characteristic patterns as utilised in humans. Computed Tomography Liver • Primary and metastatic diseases have a variable appearance. • Dual phase CT may be of benefit to detect small liver lesions because lesions may only

enhance in the arterial phase or appear as low density lesions in the venous phase. • There is some variation in technique between studies, including the time of attaining the

arterial phase and categorization of hypo/hyper attenuation by number of HU (in particular the threshold is only +/- 10 HU in some cases which is less than that which can be assessed subjectively and is small enough to suggest a possible source of error depending on ROI assignment). Also there is a lack of statistical significance in some groups.

• General/common conclusions: § Primary tumours tend to be large irregular masses associated with anarchic

vascularisation. Adenomas may also be large. § Metastasis are frequently multiple rounded hypodense nodules. § Homogeneous patterns of enhancement may be seen with either metastatic nodules

or nodular hyperplasia however metastases are more commonly hypoattenuating in all phases.

§ Interestingly the number of masses was not significant in suggesting a tumour type in the largest study (Kutara)

Kutara VRU 2013, Fukushima VRU 2012, Taniura Hiroshima J Med Sci 2009, Irausquin Canadian Vet J in 2008, Vignoli VRU 2013 Muscle • useful for identification of muscle metastasis present in 2% of oncologic patients in one

study of 1201 dogs. • Haemangiosarcoma** - may be haemorrhagic – hyeprattenuating on pre-contrast study

(~70 HU) Osseous – ribs and vertebral bodies Spinal – variably visible depending on enhancement characteristics. MRI Liver • In normal contrast enhanced MRI there is little hepatic enhancement in the arterial phase.

Most primary hepatic tumours and some mets take over arterial supply and enhance avidly.

• During the portal phase, the liver enhances, because 75% of the blood flow to the liver comes from the portal vein.

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• During this phase, a decrease in lesion contrast exists for some types of HCC and hypervascular metastasis.

• Other characteristics commonly seen with metastasis are continuous peripheral rim enhancement (neoangiogensis) or possibly inflammatory infiltrate or oedema as the nodule grows.

• Hepatic regenerative nodules are reported to have a similar appearance to liver. • In one study (Clifford 2004 JVIM) MRI was accurate in differentiating benign from

malignant disease was 94%, with 100% sensitivity and 90% specificity. • Correctly diagnosed HCC in 5 cases. Spleen • Splenic metastatic nodules are described as being similar pre-con to benign nodules but

enhanced more post contrast with peripheral and heterogeneous patterns of enhancement. Clifford 2004 JVIM, Chang 2002 VRU, Pokorny VRU 2011.

Advantages and disadvantages of different modalities

Radiographs Cheap, easy to perform, available Limited information about internal structure of organs Ultrasound Advantages

No sedation, cheaper. Ability to assess vascularity without contrast. Primary advantage is ability to obtain samples under ultrasound guidance, beware cytology accuracy, consider trucut biopsy. Cytology has a role to identify normal, differentiate between round cell neoplasia which may present as multifocal nodules, and metastatic disease.

Disadvantages Assess fewer organs than other modalities (eg muscles, bone, spine) Less efficient for whole body screening (eg if also imaging thorax) Takes longer In some cases with large tumours/where closely compressed to other organs may be less able to determine organ of origin Contrast agents not readily available therefore to some degree more limited in terms of assessing tumour vascularity. Accuracy?

Advantages and disadvantages - CT Advantages

Rapid, global assessment of multiple organs and body systems including osseous and neurologic tissues Can screen additional areas eg thorax rapidly Some ability to characterise tumour type based on vascular patterns with multiphase imaging.

Disadvantages Requires GA, more expensive (particularly if response to chemotherapy is to be assessed, US more rapid for multiple repeat studies) Variation between institutions and across literature re technique, parameters, scan times, arterial/venous phases Few papers with large numbers correlated with cytology/histopathology findings.

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while CT guided sampling can be performed, US is more commonly utilised following CT

Advantages and disadvantages of MRI Advantages

No radiation Multiple phases Multiple tissues/body systems in one study Liver –specific agents promising

Disadvantages Cost, availability Need high field strength magnets for some of the faster series required for multi-phase imaging. Requires GA

Get some cells? - accuracy of cytology is not 100% Conclusions We don’t have all the answers yet, however we can address many of the indications for imaging. In many cases we are adding evidence to increase our index of suspicion for metastatic disease, identifying lesions for biopsy and identifying cases where there are no structural abnormalities (often indicative of normal organs). We may not be able to provide a definitive diagnosis as to the presence or absence of metastatic disease based on imaging findings alone. Radiographs, US and CT are useful and accessible modalities, if their limitations are understood. MRI with gadolinium reportedly has excellent sensitivity and specificity for characterizing liver masses and nodules in dogs, however there are practical limitations to this modality. Although Kuppfer-specific contrast agents (superparamagnetic oxide ) have been validated in normal beagles, this is not a technique in common use in Vet Medicine.Future larger studies may identify further associations between tumour vascularity as assessed by colour Doppler or contrast enhancement, and histopathologic findings.

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OPTIMISING IMAGE QUALITY FOR CT/MRI IN SURGICAL PRACTICE: A RADIOLOGIST’S TIPS

Zoè Lenard BVSc(Hons) FANZCVS(Radiology) Veterinary Imaging Centre, Perth Veterinary Specialists

Western Australia, Australia Veterinary practitioners frequently have access to advanced imaging modalities (CT and MRI) either in practice or at human referral institutions. CT and MRI provide high quality non-invasive imaging information. Failure to understand the basic physical principles of CT and MT will lead to poor technique, markedly reducing study quality and in some cases rendering studies non-diagnostic. An artifact occurs when the imaged tissue does not accurately represent anatomy. The aim of this presentation is to educate non-radiologist veterinarians about ways to position small animal patients and manipulate scanners to reduce artifacts and increase the diagnostic utility of CT and MRI studies. Of course, different radiologists have different preferences; there are multiple ways to bake the cake and eat it! This presentation reflects the author’s experiences and preferences for image optimisation. Post processing Post-processing allows a revision and reorganisation of data acquired in the scan into a variety of different formats and is heavily utilized CT. Post processing options are available for advanced MR studies but not used in routine studies. Beyond just changing the display characteristics of the digital image (i.e. altering the window and level), post processing allows the data to be displayed to highlight different tissues (like bone vs lung vs soft tissue) and different planes (multiplanar reformats – MPRs, e.g. dorsal and sagittal planes). Whilst post processing can correct a multitude of errors, it takes time (often much longer than the initial scan), considerable skill/expertise and expensive software that may not be available to veterinarians. It is far easier to spend a few minutes to ensure correct positioning of dogs and cats in the gantry than to waste time with post processing to re-create standard imaging planes afterwards. CT Image degradation: Factors that lead to image degradation in CT include respiratory motion, beam hardening, poor patient alignment and inappropriate choice of CT algorithm. Respiratory motion can severely degrade image quality in the thorax, abdomen and spine: this may be most obvious in sagittal MPRs. Motion artifacts are frustrating when assessing small but anatomical important structures like the spinal cord, pancreas or portal vein. Beam-hardening is the increase in energy of the beam as it travels through tissues related to the attenuation of the scanned tissue. Bones can induce beam-hardening creating a spider-web like artefact; this may obscure small soft tissue structures like the caudal fossa of the brain or around the elbow joints. Understanding optimal position to reduce the bones in the scan field (by extending the thoracic or pelvic limbs out of the way) is useful to improve image quality. Similarly anaesthetic monitoring equipment containing metal (like pulse oximetry probes and wires) can also induce beam hardening; these can be removed for the duration of the scan. Scan planning: Plan your scan in advance. Determine which regions will be scanned, whether IV contrast is required, and the order the scans need to be obtained. Long scan length may lead to issues with increased tube heat generation, necessitating a pause between scans or an adjustment in parameters (lowering kVp, mAs, increasing tube rotation time, altering pitch etc.) particularly in machines with “less slices”. This may result in scanning after the IV contrast “flush” and therefore difficulties in assessing whether contrast enhancement has occurred. Many machines will let you plan the entire scan series upfront to determine whether the whole series will run.

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Being cognisant of minimising radiation dose in human patients results in shorter scans and scanning only of the specific region of interest. Minimising radiation dose in animals is not necessary but scanning the entire body because you can is not ideal. The volume of information created by multidetector CT scans run to thousands of images necessitating increased PACS storage, issues with image transfer remotely and increasing the length of time to adequately review the study. Judicious scanning based on proper localisation is recommended for animal patients. Contrast use in CT: IV contrast is generally indicated in CT scanning when the lesion may affect soft tissues (inflammation, neoplasia) and can provide some degree of quantification of function in some organs, like the liver and kidneys. CT contrast is renotoxic and is contraindicated in dehydrated patients; renal insufficiency is not necessarily a contraindication providing the patient is well-hydrated. We prefer to run IV fluids for all CT patients receiving iodinated contrast to mitigate this risk. IV contrast is generally not indicated in scans of bony structures (like elbows, shoulders, tarsii) or the lungs (although it is useful for assessing mediastinal structures). To anaesthetise or not? A plethora of recently published studies promote conscious CT scanning of cats and small dogs instead of performing scans of anesthetised patients. Faster CT scanning with multidetector units has promoted conscious scanning. A proprietary product (VetMousetrapTM) has been developed for scanning conscious cats. Conscious scans are usually affected by motion artefact and require significant time, expertise and software for post processing in order to re-align appropriate anatomical planes. It is the author’s opinion that conscious scans are more useful when appropriately trained medical imaging technologists are available for post processing, and not as a general rule in veterinary medicine. The author has performed CT scans for dogs for elbow assessment and spinal fractures with heavy sedation, but prefers the safety of a short period of anesthesia (intubation and regulation of breathing) to conscious scanning. MRI Factors that lead to image degradation in MRI, specifically for head and spine scanning, include motion (patient, blood vessel motion), poor patient alignment, and inappropriate sequence choice. The complex physics involved in image acquisition makes this modality particularly prone to a range of artifacts (field inhomogeneities; susceptibility, gradient, coil, motion, chemical shift, partial volume and aliasing artifacts) which potentially destroy the ability to interpret the images. Even more concerning, some of these artifacts are subtle and not easily detected by the non-trained eye, resulting in false negative errors (failing to identify an abnormality, or misinterpreting an abnormality as insignificant) or false positive diagnoses (finding an abnormality that is not really there, or finding an abnormality and misinterpreting this as significant). The concept of a “plug and play” MRI (particularly a low-field one) which can be operated by someone with little technical knowledge is a dangerous one for our profession and may lead to a disservice to our clients. Get advice from an expert: an appropriately trained MR technician or a radiologist. For coil selection, generally select the smallest coil possible for the region of anatomy being scanned and site the region as close as possible to the coil. MRI contrast (gadolinium) tends to be safe in veterinary patients when used at the correct dose. Contrast is useful for most scans but may not provide significant additional information in MSK imaging and some spinal imaging. Obtaining post contrast scans can significantly increase the length of time of the scan. Radiologists Radiologists, especially those in practices that perform CT and MR scans, tend to have valuable experience in optimising image quality and determining whether artifacts are present. Consultation with a radiologist prior to performing a scan may provide you will important

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information for maximising image quality. Using radiologists for interpretation is recommended because radiologists have the appropriate software and experience to ensure that the best information is obtained from the scan. Further reading:

• Bushberg JT, Siebert JA, Leidholdt EM, Boone JM. The Essential Physics of Medical Imaging, 2nd Edn. Lippincott Williams and Wilkins, Philadelphia 2002.

• Bushong SC. Radiological sciences for technologists: physics, biology and protection, 5th edn. St Louis: Mosby, 1993.

• Oliveira, CR, Ranallo FN, Pijanowski GJ et al. The VetMousetrap: a device for computed tomographic imaging of the thorax in awake cats. Vet Radiol Ultrasound 52:41-2011.

• Oliveira CR, Mitchell MA, O’Brien RT. Thoracic computed tomography in feline patients without use of chemical restraint. Vet Radiol Ultrasound 52:368. 2011.

• Collins SP, Matheson JS, Hamor RE et al. Comparison of the diagnostic quality of computed tomography image of normal ocular and orbital structures acquired with and without the use of general anaesthesia in the cat. Vet Ophthal 16:352, 2013

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CT scanning for dogs and cats: Technique suggestions. Region to be scanned

Is IV contrast necessary?

Patient orientation

Optimal position

Breath-hold? Algorithm Notes

Head (face, brain, mandibles)

Yes Sternal recumbency, hard palate parallel to the table

Line sagittal crest and midline of nose straight along the midline of table. Remove forelimbs/feet from FOV (i.e. pull forelimbs caudally to lie next to thorax).

No Soft tissue, bone and brain windows

Volume rendering is helpful for facial fractures.

Neck (soft tissues)

Yes Sternal recumbency

Position neck straight with spine along the midline of the table. Remove forelimbs/feet from the FOV (pull forelimbs caudally).

No Soft tissue, bone

Thorax No for lungs, yes for mediastinal structures (e.g. lymph nodes) or body wall

Sternal recumbency, this will minimise respiratory atelectasis

Extend forelimbs forward and place next to head to reduce beam hardening. Extend pelvic limbs caudally away from body

Induce apnoea with hyperventilation Breath-hold or wait for induced apnoea

Lung and soft tissue window, perhaps bone (if evaluating ribs, spine)

If atelectasis is present and concerning, consider repeating the scan with the patient repositioned (dorsal or lateral recumbency)

Abdomen Yes Sternal recumbency

Extend pelvic limbs caudally to reduce beam hardening. Extend thoracic limbs cranially.

Induce apnoea with hyperventilation. Breath hold or wait for induced apnoea

Soft tissue window. Bone if evaluating spine.

Spine Not routinely, unless concerned about tumour/infection. Myelography may be useful. IV contrast will not be useful if administered after the myelogram.

Dorsal recumbency to minimise respiratory artefact affecting the spine and keep the spine straight. Small, radiographic V-troughs can be helpful

Align sagittal midline of spine along centre of table. Extend pelvic limbs away from the body for LS scans to reduce beam hardening artifact.

Induce apnoea with hyperventilation Breath-hold or wait for induced apnoea

Bone and soft tissue algorithms

Post myelogram CT allows for excellent definition of extradural and intradural lesions, and may allow detection of some intramedullary lesions.

Elbows/tarsii Not routinely Dorsal recumbency

Extend both elbows and tarsii away from body to reduce beam hardening artefact. Foam positioning pads are useful.

No Bone algorithm. Soft tissue algorithm for assessment of synovial effusion and volume reformats

Both elbow (or tarsal) joints are scanned concurrently in the same plane, but can be reformatted separately.

Pelvis Yes, if concerned about soft tissue disease, including LS disease. Myelography may be less useful, depending on patient size

Dorsal recumbency

Extend the pelvic limbs to reduce beam hardening

No Bone, soft tissue

Volume rendering is helpful for pelvic fractures.

Zoe Lenard 2015.

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SPINAL NEOPLASIA: MYELOGRAPHY vs ADVANCED IMAGING: WHAT DO WE KNOW AND WHERE CAN WE GO?

Cathy Beck BVSc(Hons) Dip Vet Clin Stud MVS FANZCVS(Radiology)

GradCertUniTeach Senior Lecturer in Diagnostic Imaging

Veterinary Hospital Faculty of Veterinary and Agricultural Sciences University of Melbourne

250 Princes Highway, Werribee, VIC 3030

Where do we go and what do we know? We firstly need to know what we are looking for: Spinal neoplasms can be categorised in a number of ways1. They can be classified based on their location relative to the dura mater. Those arising from an extradural location are extradural, within the dura but outside the spinal cord are intradural-extramedullary and those that arise from the spinal cord parenchyma are intradural. Tumours may expand and extend from one anatomic area to another, this is most commonly seen with peripheral nerve sheath tumours which may begin in the extradural location and extend into the intradural-extramurally space and then spinal cord1. Tumours may also be classified into primary (those from cells native to the spine, dura and other spinal tissues) or secondary in the form of metastatic disease1. Most extradural tumours are malignant neoplasms of the vertebral column arising from the vertebrae or the soft tissues surrounding or within the vertebral column. Intradural extramedullary tumours are mostly nerve sheath tumours and meningiomas. Intramedullary neoplasms are usually of glial cell origin such as astrocytomas or ependymomas2. Extradural tumours such as osteosarcoma and fibrosarcoma are the most common3 spinal neoplasms. Imaging: Myelography vs advanced imaging- it does depend on what you have available but cross sectional imaging (MRI, CT) is superior to radiography for imaging the spine. If you have access to MRI this is the preferred method for imaging the spine. You do however need to make sure you have a good technician to get the best images. You need to be aware of which sequences are appropriate and in most cases give IV contrast. CT is the next best option- usually combined with subarachnoid as well as IV contrast administration. Osseous lesions of the vertebra may be seen on radiology however radiology often underestimates the extent of the lesion. Vertebral lysis or new bone production may be seen radiographically. These changes need to be differentiated from discospondylitis and vertebral body osteomyelitis. Classically vertebral tumours do not cross the intervertebral disc space1 and following myelography there is evidence of extradural cord compression of the spinal cord overlying the vertebral body rather than the intervertebral disc space. Careful evaluation of the soft tissues surrounding

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the osseous lesion may reveal associated soft tissue swelling. Ensure that you use the functions of zoom and levelling and different filters to fully evaluate these lesions radiographically. Make sure you always have orthogonal projections and consider oblique projections for complete evaluation of lesions. Neoplasms arising from the soft tissues surrounding the spinal cord, including the nerves, are usually not seen radiographically. However as many peripheral nerve sheath tumours are slow growing they may enlarge the intervertebral foramen. This may be seen on lateral projections. Careful comparison of the size of the foramina should be part of your radiographic interpretation of the spine. Radiographic myelography was once the imaging of choice for evaluation of spinal cord lesions. (I do miss a good myelogram). Myelography is still used with CT to evaluate the spinal cord and subarachnoid space. CT is superior to radiology due to its cross sectional images, ability to reformat in any plane and superior contrast resolution. A study comparing myelography to CT concluded that lytic/proliferative osseous lesions were depicted more clearly on CT than radiographs4. Many of the traditional radiographic descriptive terms from the myelographic days remain important when describing changes seen on CT myelogram and MRI. In the case of extradural tumours one or both contrast columns will be displaced axially. With intradural-extramedullary lesions expansion of the subarachnoid space with the tumour forming a filling defect leads to the golf tee sign. Displacement of the contrast columns abaxially is classically seen with an intramedullary lesion. MRI is the preferred imaging method for imaging the spine5 due to its superior soft tissue resolution. CT examination of spinal tumours, other than osseous lesions, requires IV or subarachnoid contrast administration, or both. Whilst IV contrast administration is an important part of a complete MRI to evaluate spinal neoplasia subarachnoid contrast administration is not required due to the soft tissue resolution of MRI. A couple of older studies have stated that myelography was more useful in differentiating between intradural-extramedullary and intramedullary tumours than CT4 and MRI6. It may be that this statement is not so true with our more modern machines, image manipulation software and our understanding that we need to examine each plane (transverse, dorsal and sagittal) carefully. We do need however to acquire excellent images. With MRI some smaller machines with a small field of view may make identification of each vertebra difficult- use the localiser to help. An understanding of CT and MRI physics and sequences is essential to good image acquisition. Meningiomas are most commonly intradural-extramedullary lesions and are the most common primary intraspinal neoplasms in dogs7. They can however be extradural or intramedullary in location6. They are most commonly found in the cranial cervical and lumber regions7. In a review of canine meningiomas Petersen et al (2008) found that almost half of the patients in which radiography was performed had widening of the spinal canal noted on survey radiographs. Myelography was found to clearly define the location of the tumour longitudinally along the neuroaxis in 23/24 dogs. Prediction of location with respect to the dura was in agreement with surgery in 19/24 dogs. On pre contrast CT meningiomas may be iso to hyperattenuating relative to the spinal cord. A filling defect within the contrast column is seen following

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subarachnoid contrast administration- the golf tee sign. On CT examination following IV contrast administration there is typically contrast enhancement of the meningioma. In cases which had radiographic myelograms followed by CT the CT was no more successful than radiographic myelography at characterising tumour location with respect to the dura7. On MRI most meningiomas are iso-hyperintense to the spinal cord on T1W images but may some may be hypointense7, 8 Meningiomas are mild to markedly hyperintense to spinal cord on T2W images. In the study by Petersen et al (2008) 12/15 meningiomas were contrast enhancing with 3/4 having a dural tail sign. The dural tail is a strong linear enhancement of the meninges adjacent to the lesion. It has been shown to be due to vascular congestion in the dural mater because of packing of vessels with tumour cells at the point of tumour attachment and not necessarily because of tumour invasion9. There are no reviews of feline intraspinal meningiomas however their appearance on MRI is similar to dogs. CNS lymphoma may be extraparenchymal, intraparenchymal or both. In a study of 12 cases of CNS lymphoma 2 dogs and 2 cats are reported with spinal lymphoma. All lesions were hyperintense to white matter on T2W images and hypo-isointense to white matter on T1W images with the exception of one case of brain lymphoma in a dog which was hyperintense on T1W images. All lesions were contrast enhancing. The CT appearance of spinal lymphoma will be dependent on the origin of the lesion with respect to the dura. Peripheral nerve sheath tumours (PNST) can be extradural, intradural-extramedullary or invade into the parenchyma to become intradural lesions. Most PNST are axillary and are when intradural-extramedullary are a major differential diagnosis for meningiomas. A major finding with PNST is muscle atrophy so ensure that you evaluate the surrounding soft tissues. Detection of PNST on CT can be challenging as they are usually small and isoattenuating to the surrounding soft tissues2. In a study on the CT appearance of brachial plexus masses moderate rim enhancement and contrast enhancement was noted in 20/24 cases10. The masses may be linear and can invade the vertebral canal10 leading to widening of the intervertebral foramen. With MRI multiple sequences in multiple planes are required for complete evaluation of PNSTs11. In the retrospective study by Kraft et al (2007)10 they found that 8/18 had diffuse thickening of the brachial plexus nerves, 6 of which extended into the vertebral canal. The other 10/18 had a nodule or mass in the axilla, 3 of which extended into the vertebral canal. The majority of tumours were hyperintense to muscle on T2W images and isointense on T1W images. 8/18 had only minimal to mild contrast enhancement, 13/18 heterogeneous contrast enhanced. Fat saturation on post contrast images helps identify the tumour10. A differential diagnosis for PNSTs is chronic hypertrophic ganglioneuritis12. This is a chronic inflammatory demyelinating neuropathy of unknown origin. MRI revealed enlargement of the nerve root extending into the vertebral foramen at C1-2 leading to spinal cord compression. The enlarged nerve root was isointense on T1W and hyperintense to paraspinal muscles on T2W images with marked homogeneous contrast enhancement. These imaging features are similar to PNSTs and thus hypertrophic neuritis is a differential diagnosis for PNSTs. Nephoblastoma is a rare tumour seen in young dogs, commonly German Shepherds. The tumour is intradural-extramedullary and located consistently between T10 and

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L2. It is thought that the tumour arises from ectopic embryonic remnants of renal tissue. The lesion is isoattenuating to spinal cord on non contrast CT, the mass lesion will lead to attenuation of epidural fat. CT myelography confirms the presence of a mass lesion although determination of intradural-extramedullary vs intramedullary origin can be difficult. On MR nephroblastoma is isointense to the spinal cord on T2W images, isointense on T1W images with moderate to strong contrast enhancement13 As with CT it can be difficult to determine intradural-extramedullary vs intramedullary origin2 Intramedullary neoplasms are rare in dogs and cats. Most are glial tumours- astrocytoma, oligodendroglioma and ependymomas. In a study of intramedullary neoplasms these accounted for 16% of all tumours of the spinal cord seen by the authors 14 and primary intramedullary tumours accounted for 66% of this 16%. Primary neoplasms were more likely to affect young dogs in the cervical region. Secondary tumours were more likely in the thoracolumbar spinal cord segments14. In the study by Pancotto et al 2013 astrocytomas and oligodendrogliomas were similar and characterised by ovoid to elliptical mass lesions that were well marginated, located eccentrically within the spinal cord. Astrocytomas and oligodendrogliomas were T1W iso-hypointense, T2 and STIR hyperintense and moderately contrast enhancing. Ependymomas appeared as focal to multisegmental fusiform centrally located lesions that were heterogeneously T1W isointense to hypointense, T2 hyperintense and markedly contrast enhancing. Of the secondary tumours two cases of transitional cell carcinoma were described. These were focal intramedullary masses that were T1W isointense and mildly but uniformly contrast enhancing. Metastatic haemangiosarcomas had a variable appearance on T1W images but were typically hyperintense on T2W images14. So to answer the question: What do we know and where can we go? We know that MRI plus IV contrast is the preferred method of imaging for spinal neoplasia but if this is not available then CT +/- myelography and IV contrast is where you can go. References 1. Bagley RS. Spinal neoplasms in small animals. The Veterinary Clinics Of North America Small Animal Practice. 2010;40: 915-‐927. 2. Thrall DE. Textbook of veterinary diagnostic radiology: St. Louis : Saunders Elsevier, c2013.

6th ed., 2013. 3. Dernell WS, Van Vechten BJ, Straw RC, LaRue SM, Powers BE, Withrow SJ. Outcome following treatment of vertebral tumors in 20 dogs (1986-‐1995). Journal Of The American Animal Hospital Association. 2000;36: 245-‐251. 4. Drost WT, Love NE, Berry CR. Comparison of radiography, myelography and computed tomography for the evalution of canine vertebral and spinal cord tumors in sixteen dogs. Veterinary radiology and ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association (USA). 1996.

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5. da Costa RC, Samii VF. Advanced imaging of the spine in small animals. The Veterinary Clinics Of North America Small Animal Practice. 2010;40: 765-‐790. 6. Kippenes H, Gavin PR, Bagley RS, Silver GM, Tucker RL, Sande RD. Magnetic resonance imaging features of tumors of the spine and spinal cord in dogs. Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association. 1999. 7. Petersen SA, Sturges BK, Dickinson PJ, Pollard RE, Kass PH, Kent M, et al. Canine Intraspinal Meningiomas: Imaging Features, Histopathologic Classification, and Long-‐Term Outcome in 34 Dogs. Journal of Veterinary Internal Medicine. 2008;22: 946-‐953. 8. McDonnell JJ, Tidwell AS, Faissler D, Keating J. Magnetic Resonance Imaging Features of Cervical Spinal Cord Meningiomas. Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound. 2005;46: 368-‐374. 9. Kawahara Y, Niiro M, Yokoyama S, Kuratsu J. Dural congestion accompanying meningioma invasion into vessels: the dural tail sign. Neuroradiology. 2001;43: 462-‐465. 10. Rudich SR, Feeney DA, Anderson KL, Walter PA. Computed tomography of masses of the brachial plexus and contributing nerve roots in dogs. Veterinary Radiology & Ultrasound: The Official Journal Of The American College Of Veterinary Radiology And The International Veterinary Radiology Association. 2004;45: 46-‐50. 11. Kraft S, Ehrhart EJ, Gall D, Klopp L, Gavin P, Tucker R, et al. MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF PERIPHERAL NERVE SHEATH TUMORS OF THE CANINE BRACHIAL PLEXUS IN 18 DOGS. Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association. 2007. 12. Rudenas S, Summers BA, Saveraid T, Denning A, Marioni-‐Henry K. Chronic Hypertrophic Ganglioneuritis Mimicking Spinal Nerve Neoplasia: Clinical, Imaging, Pathologic Findings, and Outcome after Surgical Treatment. VETERINARY SURGERY. 2013;42: 91-‐98. 13. McConnell JF, Garosi LS, Dennis R, Smith KC. Imaging of a spinal nephroblastoma in a dog. Veterinary Radiology & Ultrasound: The Official Journal Of The American College Of Veterinary Radiology And The International Veterinary Radiology Association. 2003;44: 537-‐541. 14. Pancotto TE, Rossmeisl JH, Zimmerman K, Robertson JL, Werre SR. Intramedullary Spinal Cord Neoplasia in 53 Dogs (1990-‐2010): Distribution, Clinicopathologic Characteristics, and Clinical Behavior. Journal of Veterinary Internal Medicine. 2013;27: 1500-‐1508.

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IS HYPERADRENOCORTICISM A SURGICAL DISEASE? AN INTERNIST’S PERSPECTIVE

David B Church

The Royal Veterinary College, University of London Hyperadrenocorticism (HAC) has been a well-recognised clinical problem in both dogs and cats for over a century, there continues to be debate regarding the best methods of diagnosing this condition and the optimum protocols for managing both pituitary dependent and adrenal dependent hyperadrenocorticism. These notes will concentrate on some of the more recent issues pertaining to its management.

Treatment of pituitary dependent hyperadrenocorticism There are effectively two broad choices for treating PDH, medical options or surgical options. The medical options involve the use of agents which either directly or indirectly result in varying degrees of adrenocorticolysis while the surgical options involve correcting the clinical problem by removing either the offending functional pituitary neoplasm or the principal target organs (both adrenal cortices) for the autonomously produced adrenocorticotrophic hormone. Medical treatment While numerous agents have been proposed as effective in managing PDH currently the only two consistent compounds remain trilostane and mitotane. Trilostane Trilostane is a synthetic, orally active steroid analogue that competitively inhibits 3β hydroxysteroid dehydrogenase and hence synthesis of several steroids, including cortisol and aldosterone. In dogs peak trilostane concentrations are seen within 1.5 hours of dosing and decrease to baseline values in about 18 hours. Trilostane is variably absorbed after oral administration, at least partly due to its poor water solubility. Absorption is enhanced by administering the drug with food and this practice should always be encouraged in the clinical setting. Trilostane’s safety as well as both short and long term efficacy in controlling hyperadrenalism in dogs has been documented in numerous publications over the last 15 years. In essence the drug seemed to be generally effective in approximately 75-80% of cases of PDH although differences in opinions regarding how to optimise efficiency and minimise adverse effects has resulted in a rather broad range of dosing recommendations – both in terms of the daily dose and the dosing frequency. Trilostane caused a significant reduction in both the mean basal and post-ACTH cortisol concentrations after 10 days of treatment in all four studies. In one study the

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post ACTH cortisol concentration decreased to less than 250 nmol/l within one month in 81% of dogs and in another 15% at some time whilst on treatment. These improvements were maintained in the study population for the duration of the trial. In the study targeting lower post ACTH cortisol values all dogs were well or acceptably controlled (post ACTH cortisol ≤ 75 nmol/l and ≤125 nmol/l respectively) although as mentioned previously, in some dogs these goals were only obtained by marked increases in the daily dose1. The current suggested starting dose rate for dogs with PDH is 2-4 mg/kg once daily given with food. As trilostane is supplied in 10, 30, 60 and 120 mg capsules some mg/kg variation can occur and it is generally recommended to start on the lower end of the dose range. In a proportion of dogs twice daily dosing has been explored in an attempt to achieve adequate adrenal suppression. Because of individual variation it is important each animal is re-evaluated regularly with both a clinical examination and ACTH stimulation test and the dose adjusted based on these findings. Generally control can be reliably achieved in 70 to 80% of cases if dogs are re-examined and an ACTH stimulation test performed approximately 10 to 14 days, 30 days and 90 days after starting therapy. It is important that all ACTH stimulation tests are performed 2-4 hours after trilostane administration and interpreted in conjunction with the clinical findings. If the post ACTH cortisol concentration is below the sensitivity of the assay (generally 30nmol/L) the trilostane dose may be reduced. If the post ACTH cortisol concentration is more than 1.5 times the upper limit of the laboratory’s normal range for basal cortisol then the dose of trilostane is increased. If the post ACTH cortisol concentration is between these two values and the patient appears to be clinically well controlled then the dose should remain unaltered. If the post-ACTH cortisol suggests adequate adrenocortical suppression but clinical signs are not well controlled sometimes improved control can be achieved by administering trilostane twice daily. Estimating urinary corticoid-creatinine ratio has proved a poor method of monitoring trilostane therapy at least partly because of increased urinary secretion of cross-reacting 17keto-steroid metabolites. Once the clinical condition of the animal and trilostane dose has been stabilized, dogs should be examined and an ACTH stimulation test performed every 3 to 6 months. Based on the results of these ACTH stimulation tests, regular dose adjustments can be made to achieve ongoing satisfactory adrenal suppression. In the author’s opinion, “satisfactory adrenal suppression” could be defined as basal and stimulated plasma cortisol levels within the relevant laboratory’s normal range for basal plasma cortisol concentration. In general trilostane is well tolerated. Upto 10% of dogs receiving trilostane may develop mild side-effects including lethargy, depression, inappetance, vomiting and diarrhoea which are usually self-limiting or corrected by adjusting the total dose or dose frequency. Clearly one of the difficulties is that these signs are relatively vague and while they may be attributable to a direct adverse drug reaction, they could also be caused by

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relative hypoadrenocorticism through either a direct effect of over-dosage or possible adrenal necrosis. Given trilostane’s relatively short duration of action, hypoadrenocorticism might not be considered an expected consequence. However while clinically significant hypoadrenocorticism is a relatively uncommon event in hyperadrenocorticoid dogs receiving trilostane, it is particularly important for clinicians using trilostane to be aware of the potential for an animal receiving the drug to develop fulminant hypoadrenocorticism. It is because of this potential, that patients should be monitored regularly to insure there is adequate adrenal reserve. Although trilostane seems to be well tolerated by most dogs, in one study acute death was described in two dogs two and four days after starting therapy and another two developed signs and biochemical evidence of hypoadrenocorticism. One of these dogs recovered with appropriate therapy. The other died despite withdrawal of trilostane and administration of appropriate therapy. The question of how a drug with the capacity to suppress cortisol levels for no more than 20 hours could create clinically significant hypoadrenocorticism remains unanswered. Interestingly, trilostane’s mechanism of action in controlling canine hyperadrenocorticism may be more complex than originally proposed. Increasing evidence suggests its effects maybe at least partly-mediated through its capacity to modify other enzymes in the steroid synthetic pathway (including possible inhibition of 21-hydroxylase or 11α-hydroxylase) and/or up-regulation of one of the isoforms of 11-βhydroxysteroid-dehydrogenase resulting in enhanced conversion of cortisol to its inactive metabolite cortisone. Effectively this means trilostane may also reduce the clinical signs of hyperadrenocorticism by activating cortisol-deactivating enzymes in peripheral tissues thereby uncoupling to a variable extent the link between plasma cortisol concentrations and the biological effects of cortisol. As a result some animals can seem to have greater clinical improvement than would be expected on the basis of their ACTH stimulation test results and also vice versa – ie some animals don’t seem to be as well controlled clinically as would be predicted by their ACTH simulation test results, suggesting this “peripheral cortisol inactivating activity” may not always be equally expressed between individuals. Additionally, there is mounting evidence to suggest the initial increased ACTH levels likely to be seen in a PDH patient receiving trilostane (due to the reduced cortisol levels) may result in adrenocortical damage through enhanced ACTH-stimulated adrenal blood flow with consequent haemorrhage and adrenocortical necrosis. This hypothesis is supported by robust experimental evidence demonstrating increased adrenocortical blood flow and adrenal haemorrhage in response to increased plasma ACTH concentrations in a number of different species2. It is further supported by the enhanced bilateral adrenomegaly and accompanying characteristic hypoechogenic adrenocortical margins that not infrequently accompanies sub-acute trilostane treatment. Finally further support is provided by the sporadic reports of adrenal haemorrhage and necrosis seen in the small proportion of dogs with adrenal histopathology in which trilostane has created acute but long-term hypoadrenocorticism.

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Mitotane The traditional and in many parts of the world still the most common method for managing PDH has been long term mitotane administration. The essence of this regime is to destroy most of the hyperplastic adrenal cortex. The remaining tissue provides normal plasma cortisol concentrations despite being subjected to almost supraphysiological levels of ACTH. In other words the animal no longer has the capacity to raise its plasma cortisol level above 20-50 nmol/l. This magnitude of adrenal destruction is essential to achieve significant clinical improvement. This "chemical adrenalectomy" can be achieved using two different protocols, one aimed at achieving complete and permanent adrenocorticolysis and the other at reducing adrenocortical activity to normal levels through partial adrenocorticolysis. The second protocol has been generally accepted as the favoured method and involves administration of mitotane (25 mg/kg/12hr with food) for five to seven days. During this period water consumption, appetite and general demeanour are CLOSELY monitored. If any of these parameters change for more than 12 hours the mitotane therapy is stopped. Animals are evaluated with an ACTH response test 48 hours after the last dose of mitotane. Adrenal destruction is deemed satisfactory when both pre and post ACTH cortisols are similar and below the MID-RANGE for the laboratory's normal basal cortisol concentration. In approximately 15% of cases this may require a second or more courses of daily mitotane. Once satisfactory adrenal destruction has been achieved it can be maintained by once or twice weekly mitotane administration (25 mg/kg/12hr with food on one or two days per week). Patients can be rechecked with an ACTH response test once every 8-12 weeks to ensure adequate control is being maintained. Animals treated in this way cannot mount an appropriate stress response to trauma or illness. Consequently, from the start of mitotane therapy prednisolone should always be available and the owners instructed to administer 1-2 mg/kg orally in an emergency while awaiting veterinary attention. The alternative protocol involves using mitotane on a daily basis for a longer period and attempting to bring about irreversible adrenocorticolysis and subsequently managing patients with glucocorticoid supplementation. Both protocols have disadvantages. With complete chemical adrenalectomy approximately 30% of patients have sufficiently severe side-effects to justify suspending treatment and the reported relapse rate can be as high as 39%. With the more widely used method of creating and maintaining induction and remission by inducing a selective degree of adrenocorticolysis, the continuous requirement for ACTH stimulation tests along with similar relapse rates makes this regime complicated, involved and often expensive.

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Surgical correction of PDH As can be seen from the above, both trilostane and mitotane can be considered effective in correcting clinical signs and hormonal abnormalities in approximately 80 - 85% of cases with pituitary dependent hyperadrenocorticism. Unfortunately this means a substantial number of affected dogs will not respond to standard medical therapy and in these cases a practical alternative needs to be considered sooner rather than later. The potential frustrations of managing PDH medically are further exacerbated as the response of individual patients to both drugs is variable and as a result, a great deal of time, effort and expense in modifying dosing regimes and testing adrenal function can be required to achieve a satisfactory outcome. Hypophysectomy Investigators at the University of Utrecht have reported considerable success using hypophysectomy, however, this is a specialised surgical procedure with currently a high level of peri-operative complications and, despite apparently complete removal of the adenohyphysis, common relapses such that over 30% of patients which survive need some form of additional management within 12 months of surgery. Another therapeutic alternative is bilateral adrenalectomy.

Bilateral adrenalectomy Although this procedure has been proposed as a possible treatment for some time, reported difficulties in the post-operative management of the adrenalectomised patient possibly has resulted in the technique not achieving widespread acceptance as a feasible alternative to chemical adrenalectomy. However the surgery itself is relatively simple and management of the surgically-induced “panhypoadrenocorticism” is relatively inexpensive and uncomplicated by potential hyperadrenocorticoid relapses. In the author’s opinion the reported difficulties with this procedure can be largely overcome by reducing the potential for perioperative glucocorticoid and mineralocorticoid deficiencies with a continuous hydrocortisone infusion at an initial rate of 0.5mg/kg/hr until the animal is taking food and water orally and then changing to a combination of cortisone acetate (0.5mg/kg/24h) with or without fludrocortisone for long term replacement therapy3. In the author’s experience this procedure has proved a practical alternative for the treatment of PDH in the dog. Because of a general reluctance to try surgical correction when a medical alternative is available, until recently bilateral adrenalectomy has usually only been attempted in PDH patients in which trilostane or mitotane, or both, have not been effective. However more recently the frustrations of managing PDH patients with trilostane and/or mitotane and, at least in the UK, the expense of these treatment regimes has meant in terms of efficacy, consistency and price, surgical correction is becoming increasingly attractive. ADRENAL TUMORS

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Generally a functional adrenocortical tumour (ADH) is most effectively treated via surgical removal. This results in the removal of the animal's principle source of cortisol, as the glucocorticoid (GC) secreting sections of the contralateral adrenal gland are invariably atrophic and at least temporarily non-functional. Consequently, GC replacement intra- and post-operatively is essential for a successful recovery. Use of hydrocortisone sodium succinate as a continuous infusion (0.5 mg/kg/hr for 12-24 hours then 0.2 mg/kg/hr for 24 hours) provides adequate GC replacement in the short term post-operative period. Once the animal is eating, oral replacement therapy using cortisone acetate (1mg/kg/12hr, decreasing over two weeks) is usually satisfactory. Cortisone is preferable in this situation as its shorter half-life should reduce the time for the contralateral gland to regain GC secreting capacity. Obviously not all cases of adrenal neoplasia will be appropriate surgical candidates. In those patients were surgery is not an option it may be worth considering palliative therapy with trilostane. 1 Braddock J et al Aust Vet J 2003, 81:600-72; 2 Burkhardt WA et al Domest Anim Endocrinol 2011, 40:155-64; 3 Church D In: Small Animal Clinical Pharmacology 2nd edtn 2008, 517-527.

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THYROID CARCINOMA: SURGERY VS RADIOACTIVE IODINE

Lauren Lacorcia BVSc(Hons) MVSc MANZCVS DipACVIM The University of Melbourne FVAS U-Vet Werribee Animal Hospital, Werribee,

Victoria.

Feline thyroid carcinoma. Hyperthyroidism is the most common endocrinopathy in cats and a condition that small animal clinicians are generally quite comfortable in diagnosing. It is due to malignant thyroid carcinoma in 1-3% of cats and as the disease is usually functional1, cats tend to present with signs of thyrotoxicosis rather than for signs related to a cervical mass. The challenge becomes identifying the subset of hyperthryoid cats with malignant disease, important as therapeutic recommendations differ from those for benign disease. Medical and dietary options do not destroy malignant tissue, leaving the potentially curative options of surgery and/or radioiodine therapy preferred for malignant disease. Medical management can resolve signs of thyrotoxicosis, and methimazole or carbimazole are commonly used to stabilise patients prior to definitive therapy. Longer term, the trophic effects of increased TSH, elevated in some cats managed with these drugs, may exacerbate tumour growth1.

Most feline thyroid carcinomas are well differentiated adenocarcinomas. They may be well encapsulated and freely mobile, imitating benign adenoma or adenomatous hyperplasia or may be large, locally invasive, and form multiple local masses through the cervical region, thoracic inlet and mediastinum2. As benign disease is bilateral in 70% of cats3 and/or ectopic thyroid tissue may be present, the presence of multiple masses is not definitive for carcinoma. Local vascular and capsular invasion and cellular pleomorphism or mitoses may be seen histopathologically but cellular morphology of adenomas and carcinomas is usually similar, making differentiation of benign and malignant disease on the basis of cytology, small biopsies and occasionally even whole tumours challenging2, 4. Metastasis is reported in up to 71% of cases, predominantly to regional lymph nodes and lungs2.

The median age of cats diagnosed with thryoid carcinoma was 12-13 years in two series, similar to those with benign disease, and there were no distinguishing examination or clinicopathologic findings (though 2/21 cats were hypercalcaemic and two had non-functional masses)2, 4.We tend to be clinically concerned about malignancy in cats with large, irregular, multiple or fixed cervical masses on palpation, total T4 levels > 200 nmol/L at initial diagnosis or those initially refractory to medical therapy or standard radioiodine doses. We know that the thyroid glands of cats managed with methimazole or carbimazole undergo hyperplasia and will continue to enlarge over time. The prevalence of marked serum T4 elevations, large thyroid masses, intrathoracic or multifocal tumours and refractoriness to anti-thyroid medications increases significantly over time in cats managed with medical therapy for several years, making these factors harder to interpret in chronic cases5. The suspicion of thyroid carcinoma may accordingly increase over time, but biopsies were not performed in the large cross-sectional study performed by Petersen et.al. and overt metastasis was seen in only 2/35 suspected cases. However, carcinoma is a slowly progressive disease and the argument that cats with more than three nodules or large masses off the midline (away from the embryological migration tract of the thyroid gland) are more likely to have carcinoma than simple ectopic disease may be a reasonable one.

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A combination of thoracic radiography and nuclear scintigraphy is commonly used in an attempt to differentiate benign from malignant disease. Patchy or irregular isotope uptake, extention down the neck and into the mediastinum or presece of metastasis may be features of carcinoma but scintigraphy alone cannot distinguish benign from malignant disease1. Cats with three or more abnormal thyroid nodules or extension into the thoracic inlet and cranial mediastinum on scintigraphy (factors considered more consistent with malignancy) frequently had benign ectopic tissue on histopathology in one study2. Conversely, 4/14 cats with thyroid carcinoma in the same report had scintigraphic findings consistent with benign disease. Five of these cats had had prior bilateral (3) or unilateral (2) thyroidectomy, in some cases multiple times, with disease recurrence, and this may be more suggestive of malignant behaviour. In a large series of cats undergoing scintigraphy, most within a year of diagnosis of hyperthyroidism, only 3.9% had multifocal disease6. In a referral population of 120 cases where more cats were referred for refractory disease or recurrence after thyroidectomy, 20-25% had multiple areas of hyperfunctioning thyroid tissue or the presence of ectopic thyroid tissue7. Not all of these were biopsied, but 6/8 cats with intrathoracic thyroid tissue had benign disease on histopathology. Even with an abnormal thyroid and apparent metastasis on imaging, scintigraphic findings and lung cytology in hyperthyroid cats with primary pulmonary neoplasia can also appear similar to those with metastatic thyroid carcinoma8. These results make confident prediction of carcinoma without biopsy almost impossible.

If the overall clinical picture is suggestive of thyroid carcinoma, how do we treat? In people, thyroidectomy followed by radiactiove iodine therapy to treat any residual disease or micrometastases is the standard therapy for functional differentiated carcinoma. In the series of 14 cats discussed above, 5 cats had already failed thryoidectomy. 8/14 were treated with thyroidectomy and without adjunctive therapy local recurrence occurred in 7/8 cats2. Thyroid scintigraphy is recommended even for benign disease prior to surgery to localise hyperfunctioning tissue due to the frequency of bilateral (which may palpate as unilateral) or ectopic disease that may result in surgical failure. Histopathology should be routinely performed as carcinoma may appear benign. Radioiodine (131I) can be considered as adjunctive therapy but doses 3-10x above those used for benign disease are needed to achieve ablation of malignant tissue due to less efficient iodine concentration by the cells and sheer tissue volume1, 2. In another series, seven cats with confirmed carcinoma managed with surgery (modified extracapsular technique) followed by high-dose (1110 MBq IV) radioiodine 1-10 months later (due to treatment failure) had complete resolution of disease within 6 weeks of radioiodine therapy4. Median survival of these cats was 20.5 months (range 10-41), with all dying of non-thyroidal illness. Radioiodine therapy is generally well tolerated, though deaths have been reported in debilitated cats following standard or high-dose radioiodine when cats were not medically stabilised prior to therapy2. In the seven cats managed with combination therapy, it was proposed that the surgery stabilised the patients better for the isolation period following radioiodine therapy and in people it is also known to limit local radiation side effects4. Anaesthetic and surgical risks were not discussed. High dose therapy is expected to make cats hypothyroid. This can reduce glomerular filtration rate and lead to azotaemia and reduced survival9, so routine supplementation with thyroxine is sensible for all cats receiving ablative therapy and is essential if azotaemia develops, regardless of whether other clinical signs of hypothyroidism are present or not.

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Ablative radioiodine therapy (1100 MBq SQ) without prior debulking therapy has also been reported to achieve good outcomes (median survival 814 days, range 181-2381 days) but 1/8 cats failed to respond to therapy and another relapsed within 6 months of therapy after initial clinical and scintigraphic disease resolution10. Combination therapy seems more successful based on low case numbers, but half of the cases in Hibbert et.al.’s report above had intrathoracic (3) or metastic (1) disease and the two populations are not directly comparable. The cat that did not seem respond to 131I did become responsive again to antithyroid drugs and the cat which relapsed had pulmonary metastases at presentation. Concerns with 131I as a sole therapy include variable radioiodine uptake by tumour cells, the consequences of necrosis of large tissue volumes and potentially longer hospitalisation times1. One case of persistent pancytopenia within six months of therapy was reported but the cat was also FIV positive10. Surgery requires anaesthesia, adds cost, can still cause hypothyroidism if bilateral thyroidectomy is performed and carries additional risks (hypoparathyroidism- usually transient, laryngeal paralysis and Horner’s syndrome). These risks may be higher with invasive masses. The decision to perform debulking surgery prior to radioiodine therapy may be influenced by these factors and also on the location of the neoplastic tissue. Cervical surgery is much less invasive than thoracotomy, which would not be recommended for ectopic carcinoma. Incisional biopsy rather than attempted resection may also be more appropriate in cats with locally infiltrative cervical masses. Radioiodine therapy alone is indicated for unresectable or metastatic disease, provided the abnormal tissue concentrates iodine or technetium on scintigraphy1.

Canine thyroid carcinoma Thyroid neoplasia accounts for between 1.1 and 3.8% of all canine tumours, with incidental adenomas common findings at necropsy but < 10% of clinical premortem diagnoses due to benign adenoma11. Most are due to carcinoma, with median age at diagnosis 9-11 years, and golden retievers, beagles, boxers and Siberian huskies being overrepresented11. Familial medullary thyroid carcinoma is reported in Alaskan malamutes12. Histologic subtype has not been shown to have prognostic significance though anaplastic tumours have a worse prognosis. 40-60% of dogs have bilateral thyroid involvement, but the metastatic rate is higher than for feline thyroid carcinoma: 35-40% at presentation and up to 80% by the time of death, with higher rates reported for higher tumour volumes or bilateral disease11, 13. Metastasis occurs most commonly to the regional lymph nodes and lungs. Ectopic thyroid carcinoma may also be found midline anywhere from the tongue base to the heart.

60% of dogs with thyroid carcinoma are euthyroid, 30% hypothyroid and only 10% hyperthyroid with attendant clinical signs, most dogs presenting instead for a ventral cervical mass11. Masses are typically locally invasive and usually well differentiated, with features of capular or vascular invasion on histopathology that confirm the diagnosis. Histologic subtype is not predictive of outcome in dogs when tumours are well differentiated11. Invasion of local cervical structures may cause cough, dyspnoea, stridor, dysphonia, dyphagia, anorexia, Horner’s syndrome or facial oedema11. Paraneoplastic hypercalcaemia is occasionally present. Haemodilution results in cytology confirming thyroid origin in only half the cases, and as with cats criteria of malignancy are uncommon. Ultrasound can confirm thyroid origin and assess vascularity, invasiveness and the cervical and retropharyngeal nodes. It can guide fine needle aspirate sampling; needle aspirates are considered unsafe due to tumour vascularity. CT or MRI scans can be used to assess the mass and draining lymph

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nodes and are more accurate for determining tumour extent, metastasis and invasiveness14, 15. Use of iodinated contrast will delay effective radioiodine therapy by 4-6 weeks. Scintigraphy demonstrates normal thyroid tissue and often shows abnormal uptake by the primary mass and can assess for scintigraphically functional metastases, ectopic tissue or residual local disease after thyroidectomy. Metastasis detection is more sensitive after surgery when the primary mass is no longer uptaking the bulk of the isotope11. Thoracic radiographs are still required for screening as metastases may not be functional or visible on scintigraphy; occasionally the converse is true16.

Imaging and palpation under anaesthesia are relevant to determine if the tumour is freely movable (1cm) in all directions. If this is the case and and no is seen metastasis (25-50% of cases), surgical excision alone achieves the best overall survival (median 3 years) even if disease is bilateral17, 18. This applies to marginal resections and even when capular invasion and tumour thrombi are present on histopathology. At present there is no proven benefit to adjunctive therapy in dogs with mobile resectable masses, even if there is histologic residual disease. Approximately half of bilateral resection cases will require chronic therapy for hypothyroidism +/- hypoparathyroidism17.

Median survival is 6-12 months for more invasive tumours and there is greater risk of surgical complications11. Surgical debulking can be considered if the tumour is compressing the trachea or oedophagus for immediate relief, otherwise non-surgical therapy is preferred.

For large, non-resectable tumours without overt metastasis, definitive external-beam radiation therapy has been used, with stabilisation or reduction in tumour size reported in one series of 25 dogs but maximal reduction taking 8-22 months, making it less ideal if local compression is occurring13. Progession free survival was 80% at 1 year and 72% at 3 years, with a mean of 45 months. Similar to surgical resection, the metastatic rate was lower for non-progressive tumours.Toxicity to the larynx, trachea and oesophagus and delayed hypothyroidism may be seen, though adverse effects are usually well tolerated and this modality is also effective for local disease control for incompletely resected masses (MST > 2 years)11. Concerns with using radioiodine in dogs are uneven isotope uptake within the tumour, that technetium does not predict

131I uptake and activity within the tumour and that efficacy is poor in large tumours19, but unlike standard radiation therapy it may also be effective against (scintigraphically) functional metastases. Radioiodine is becoming a common modality for unresectable, residual or metastatic thyroid carcinoma, with median survival times of 27-30 months for non-resectable masses and 1 year for dogs withmetastatic disease19, 20. It is still uncertain whether 131I is beneficial if used as adjunctive therapy following apparently complete excision, whether debulking a tumour prior to therapy is useful or whether surgery if 131I has reduced tumour size to an operable level prolongs survival. Ideal case selection, scintigraphic isotope and treatment dose are also uncertain. Currently dosage is empiric, with a maximal dose of 148 MBq/kg recommended to avoid fatal pancytopenia, and routine haematologic monitoring recommended for 3 months post-therapy20. Hypothyroidism is also expected and supplementation required after treatment. Survival may be more prolonged in supplemented cases and in humans suppression of TSH is utilised routinely to prevent trophic effects on the neoplasm17.

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Chemotherapy can achieve partial responses in 30-50% of cases and may be a useful adjunct in non-resectable or gross metastatic disease but alone does not achieve ecomparable survival times to other modalities11.

References

1. Scott-Moncrieff C. Feline Hyperthyroidism. In: Feldman EC, Nelson RW, Reusch CE, Scott-Moncrieff C, Behrend EN, editors. Canine and feline endocrinology. 4th edn. Elsevier Saunders, Missouri, 2015:136-195. 2. Turrel JM, Feldman EC, Nelson RW, Cain GR. Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986). Journal of the American Veterinary Medical Association 1988;193:359-364. 3. Naan EC, Kirpensteijn J, Kooistra HS, Peeters ME. Results of thyroidectomy in 101 cats with hyperthyroidism. Veterinary surgery : VS 2006;35:287-293. 4. Guptill L, Scott-Moncrieff CR, Janovitz EB et al. Response to high-dose radioactive iodine administration in cats with thyroid carcinoma that had previously undergone surgery. Journal of the American Veterinary Medical Association 1995;207:1055-1058. 5. Peterson ME, Broome MR, Rishniw M. Prevalence and degree of thyroid pathology in hyperthyroid cats increases with disease duration: a cross-sectional analysis of 2096 cats referred for radioiodine therapy. Journal of feline medicine and surgery 2015. 6. Peterson ME, Broome MR. Thyroid scintigraphy findings in 2096 cats with hyperthyroidism. Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association 2015;56:84-95. 7. Harvey AM, Hibbert A, Barrett EL et al. Scintigraphic findings in 120 hyperthyroid cats. Journal of feline medicine and surgery 2009;11:96-106. 8. Cook SM, Daniel GB, Walker MA et al. Radiographic and scintigraphic evidence of focal pulmonary neoplasia in three cats with hyperthyroidism: diagnostic and therapeutic considerations. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 1993;7:303-308. 9. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 2010;24:1086-1092. 10. Hibbert A, Gruffydd-Jones T, Barrett EL, Day MJ, Harvey AM. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of feline medicine and surgery 2009;11:116-124. 11. Scott-Moncrieff C. Canine thyroid tumours and hyperthyroidism. In: Feldman EC, Nelson RW, Reusch CE, Scott-Moncrieff C, Behrend EN, editors. Canine and feline endocrinology. 4th edn. Elsevier Saunders, Missouri, 2015:196-211. 12. Lee JJ, Larsson C, Lui WO, Hoog A, Von Euler H. A dog pedigree with familial medullary thyroid cancer. International journal of oncology 2006;29:1173-1182. 13. Theon AP, Marks SL, Feldman ES, Griffey S. Prognostic factors and patterns of treatment failure in dogs with unresectable differentiated thyroid carcinomas treated with megavoltage irradiation. Journal of the American Veterinary Medical Association 2000;216:1775-1779. 14. Taeymans O, Dennis R, Saunders JH. Magnetic resonance imaging of the normal canine thyroid gland. Veterinary radiology & ultrasound : the official journal

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of the American College of Veterinary Radiology and the International Veterinary Radiology Association 2008;49:238-242. 15. Deitz K, Gilmour L, Wilke V, Riedesel E. Computed tomographic appearance of canine thyroid tumours. The Journal of small animal practice 2014;55:323-329. 16. Daniel GB, Neelis DA. Thyroid scintigraphy in veterinary medicine. Seminars in nuclear medicine 2014;44:24-34. 17. Tuohy JL, Worley DR, Withrow SJ. Outcome following simultaneous bilateral thyroid lobectomy for treatment of thyroid gland carcinoma in dogs: 15 cases (1994-2010). Journal of the American Veterinary Medical Association 2012;241:95-103. 18. Klein MK, Powers BE, Withrow SJ et al. Treatment of thyroid carcinoma in dogs by surgical resection alone: 20 cases (1981-1989). Journal of the American Veterinary Medical Association 1995;206:1007-1009. 19. Worth AJ, Zuber RM, Hocking M. Radioiodide (131I) therapy for the treatment of canine thyroid carcinoma. Australian veterinary journal 2005;83:208-214. 20. Turrel JM, McEntee MC, Burke BP, Page RL. Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990-2003). Journal of the American Veterinary Medical Association 2006;229:542-548.

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ENDOSCOPIC DIAGNOSIS OF GASTRIC AND DUODENAL NEOPLASIA: HOW TO MAXIMISE RETURNS.

Julien Dandrieux Dr med vet BSc DipAVIM

Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Werribee, Victoria

Conflicts of interest: The author does not have any conflicts of interest. Gastric and intestinal neoplasia are relatively rare. Gastric cancer represents less than 1% of all malignancies in dogs. The most common gastric tumour in dogs is adenocarcinoma (70 to 80% of gastric tumors), whereas it is rare in cats. In this species lymphoma is most common. Other aggressive neoplasia include leiomyosarcoma, mast cell tumour, extra-medullary plasmacytoma, gastro-intestinal stromal tumours and fibrosarcoma.1 Benign neoplasia includes leiomyomas, hypertrophic gastropathy, and adenomas. Intestinal cancer has also been reported to be rare. Intestinal lymphoma is more frequent in cats (30% of all tumours) than dogs (6%).2 The second most frequent neoplasia is adenocarcinoma for both species, which is mostly found in the small intestine in cats and in the colon or rectum in dogs. Mast cell tumours in cats and leiomyosarcomas in dogs come in third place in the small intestine. Polyps are seen more commonly in the duodenum in cats and in the rectum in dogs.

The remainder of these notes is about the use of endoscopy for diagnosis purposes. Pre-endoscopy work up (e.g. imaging) or treatment will not be discussed. Flexible endoscopy enables the clinician to perform gastro-intestinal (GI) endoscopy to assess the oesophagus, stomach, and proximal part of the duodenum and colonoscopy to assess the colon and the distal part of the ileum. This modality is ideal to assess the mucosa, but deeper lesions might not be recognized. However, multiple biopsies under visual guidance can be taken, whereas typically one full-thickness biopsy per small intestine segment is taken at surgery.

Nothing on ultrasound, worth having a look? Abdominal ultrasound is often performed prior sampling to assess extra-intestinal and intestinal organs. The gastro-intestinal tract can be hard to image because of the presence of fluid and gas, which prevents thorough assessment. A study compared findings from abdominal ultrasound and endoscopy in 22 cases (dogs and cats) with confirmed gastric neoplasia.3 Gastric neoplasia was missed in 10 cases with ultrasound and in one case with endoscopy (which was also not identified on ultrasound). Definitive diagnosis was achieved in 59% of cases with endoscopy and in 27% with surgery. In half of the cases diagnosed with surgery, endoscopy was converted to surgery without attempting endoscopic biopsies. A total of 14% were diagnosed at necropsy. This study outlines the limitations of ultrasound to assess the stomach.

Which biopsy forceps to use? A recent publication compared different types of biopsy forceps to obtain duodenal biopsies.4 Comparison was made between 6

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different forceps in healthy dogs. Biopsies obtained with the larger capacity forceps were heavier than the other four. The presence of a spike had no bearing on crush artefacts in same size forceps or adequacy for histologic assessment. Interestingly, there was no significant difference in the depth reached with different forceps. This supports the use of the largest forceps to obtain larger biopsies.

How to take biopsies? Biopsies should be taken as perpendicular as possible to the mucosa to increase the likelihood of obtaining deep biopsies. This is easier to achieve in the stomach than in the small intestine. Ideally, intestinal biopsies should contain at least three villi with underlying lamina propria and extend up to the muscularis mucosa. To increase the yield in small intestine, the forceps cup is open and then retracted to be close to the endoscope tip. The tip is deflected toward the mucosa and air can be suctioned to bring the mucosa in close contact with the forceps cup (typically a “red out” appears on the screen at that stage). The forceps should be advanced a few millimetres (a blurry image becomes apparent) before closing the cup and retracting. This is the so-called “turn-and-suction” technique. 5

If a lesion is found such as a mass or an abnormal mucosa, samples should be taken from the lesion itself and from the adjacent tissue. This is especially important for large masses, which can have foci of necrosis or ulceration, which will be non-diagnostic on histology. On the other hand, nearby tissue can be infiltrated and a good source for diagnostic biopsies. Another strategy to increase diagnostic yield when sampling a mass is to take successive biopsies at the same location to reach deeper tissue.

It is crucial, even in the absence of any gross pathology, to take multiple biopsies along the entire length of the examined GI segments for histologic evaluation as some lesions will only be detected on histology.

How to orient biopsies? The biopsy is retrieved from the forceps with a 25G needle and unfolded. The tissue can then be placed directly into formalin or oriented on a piece of filter or other support. A description of this process is available in an ACVIM consensus statement.6 This last step is best discussed with the pathology laboratory you work with to determine which protocols work best to ensure proper orientation. Ideally, the pathology report should include the total number and quality of samples submitted to help the clinician to assess her/his technique. This feedback is invaluable to improve endoscopy skills.

How many biopsies to take? The number of biopsies that needs to be taken to diagnose a tumour has not been studied. In inflammatory disorders, the number depends on the quality of the samples.7 An extreme example is the need of 13 adequate biopsies to reach a diagnostic of crypt lesions with 99% confidence, compare to 28 marginal biopsies. The same is likely true with tumours. For this reason, I tend to routinely take 12 to 15 biopsies in the duodenum and in the stomach

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in the absence of overt lesions. If a lesion is identified, additional biopsies on and around the lesions are taken.

How to improve diagnosis of feline small cell lymphosarcoma? Intestinal small cell lymphosarcoma in cats can be challenging to diagnose as an overlap between inflammatory infiltrate and neoplastic infiltrate is seen in some cases and the disease is often multi-focal rather than generalised.8 A study nicely outlined the importance of obtaining ileal biopsies in this species.9 Eighteen cats diagnosed with small cell lymphosarcoma via endoscopy were retrospectively reviewed. Lymphoma was identified only in the duodenum in 7 cats, only in the ileum in 8, and in both locations in 3. In other words, eight cats would have been misdiagnosed with “inflammatory” disease without ileal biopsies. For this reason, ileal biopsies should ideally be routinely taken when scoping cats for chronic enteropathies.

Endoscopic mass removal? Snare electrocautery and laser ablation are not yet widely used in companion animals, but their use has been reported in the oesophagus,10 the stomach,11,12 and the colon.12,13 These techniques are likely to become routine and have the potential to be diagnostic and therapeutic.

Several recent developments in endoscopy are likely to become relevant for companion animals such as double balloon endoscopy, narrow-band imaging (NBI), capsule endoscopy, confocal microscopy, and endosonography. NBI in particular is now commonly found on newer endoscope and its use becomes widespread. More experience need to be gained, especially in clinical cases to really determine how useful these different modalities will be.

Double balloon endoscopy consists of an endoscope and an overtube. Both have a latex balloon fitted at the tip, which can be inflated and deflated. The pushing phase consists in advancing the endoscope as for conventional endoscopy. The endoscope tip is maintained in place by inflating its balloon and the overtube is advanced up to the endoscope tip. The overtube balloon is inflated, and both the endoscope and overtube are pulled back (pulling phase). Thereafter, the endoscope balloon is deflated and the endoscope is advanced deeper in the small intestine. This technique has been used in human medicine to explore deeper parts of the small intestine for diagnostic and therapeutic purposes including location sources of GI bleeding, tumours, and polyps. This technique is deemed relatively safe with low complication rates (such as perforation, post-procedure pancreatitis, and bleeding). Oral and anal double balloon endoscopy has been described in healthy dogs.14,15 The endoscope could be advanced about 3m from the oral route in 90 minutes and about 2 meters from the ileo-caecal junction via the anal route in 60minutes. No complications were observed during and after the procedure including no obvious signs of pancreatitis (clinically and with measure of amylase and lipase). In one case report, a dog was diagnosed with lymphocytic-plasmacytic jejunitis by double balloon endoscopy.16 This technique is promising to detect focal inflammation or sources of bleeding, which cannot be reached with traditional endoscopy. However, there is only very

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limited report of its use currently. Narrow-band imaging is becoming increasingly available on newer endoscopes and is used to assess surface patterns and microvascular architecture.17 Only blue and green wavelengths are selected, which penetrate deeper and are better absorbed by haemoglobin. This enables improved assessment of blood vessels such as deeper mucosal and submucosal vessels and enhanced mucosal features. It has been shown to be helpful to differentiate pre- from malignant lesions and to detect early neoplasia, especially in Barrett’s oesophagus. It is used now also for gastric and colonic neoplasia. There are no current reports of its use in dogs and cats.

Capsule endoscopy is a non-invasive technique to evaluate the GI tract. A capsule containing a camera is ingested and will then transit through the intestines while capturing images. This potentially enables examination of the complete GI without requiring anaesthesia or sedation. Indications include locating a source of bleeding or detecting tumours. This method has been used to evaluate anthelmintic efficacy in conscious dogs.18 Capsule endoscopy has also been shown to be a valuable tool in dogs to detect small intestine lesions (iatrogenic placement of intestinal bead).19

Confocal endoscopy combines a conventional endoscope with a confocal microscope. This enables real-time in vivo assessment of the microstructure of the mucosa. This method has been described in the stomach and the duodenum of healthy dogs.20,21 There are no reports of using this method in unhealthy dogs yet, but potential applications include assessment of neoplastic and inflammatory diseases.

Endosonography combines a traditional endoscope with an ultrasound transducer.22 Not only does this enables assessment of the mucosal surface with endoscopy, but also the GI wall and organs in close contact (pancreas, liver, spleen, and kidneys) with ultrasonography. In comparison with standard ultrasound, endosonography is not affected by loss of signal due to interference from gas in the GI tract and enables assessment of deeply positioned organs. Endosonography in healthy dogs has been proven to be a very good tool to assess the stomach wall and pancreas as described in man.23 Endosonography has also been evaluated in dogs (n=25) with rectal polyploid lesions.24 Polyp extension was staged with endosonography prior to surgical excision. Agreement about polyp extension between endosonography and pathology was very good (23 cases out of 25). The two cases with involvement of the muscularis proria had a survival time of less than 1.5 months. Further work is needed to assess the true potential of endosonography in companion animals.

In conclusion, new exciting techniques are becoming available in veterinary medicine, but biopsies will most likely remain essential to reach a diagnosis. For this reason, we need to thrive to perfect our technique to obtain diagnostic biopsies. This requires close communication between the clinician and the pathology laboratory.

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1. Withrow SJ. Gastric cancer. In: Withrow SJ, Vail DM, Page RL, ediotrs. Small animal clinical oncology. 5th edn. Elsevier Saunders, St. Louis, 2007:402-404. 2. Selting KA. Intestinal tumors. In: Withrow SJ, Vail DM, Page RL, ediotrs. Small animal clinical oncology. 5th edn. Elsevier Saunders, St. Louis, 2007:412-423. 3. Marolf AJ, Bachand AM, Sharber J, Twedt DC. Comparison of endoscopy and sonography findings in dogs and cats with histologically confirmed gastric neoplasia. J Small Anim Pract 2015;56:339-344. 4. Goutal-Landry CM, Mansell J, Ryan KA, Gaschen FP. Effect of endoscopic forceps on quality of duodenal mucosal biopsy in healthy dogs. J Vet Intern Med 2013;27:456-461. 5. Mansell J, Willard MD. Biopsy of the gastrointestinal tract. Vet Clin North Am Small Anim Pract 2003;33:1099-1116. 6. Washabau RJ, Day MJ, Willard MD, et al. Endoscopic, biopsy, and histopathologic guidelines for the evaluation of gastrointestinal inflammation in companion animals. J Vet Intern Med 2010;24:10-26. 7. Willard MD, Mansell J, Fosgate GT, et al. Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. J Vet Intern Med 2008;22:1084-1089. 8. Al-Ghazlat S, de Rezende CE, Ferreri J. Feline small cell lymphosarcoma versus inflammatory bowel disease: diagnostic challenges. Compend Contin Educ Vet 2013;35:E1-5; quiz E6. 9. Scott KD, Zoran DL, Mansell J, Norby B, Willard MD. Utility of endoscopic biopsies of the duodenum and ileum for diagnosis of inflammatory bowel disease and small cell lymphoma in cats. J Vet Intern Med 2011;25:1253-1257. 10. Yas E, Kelmer G, Shipov A, Ben-Oz J, Segev G. Successful transendoscopic oesophageal mass ablation in two dogs with Spirocerca lupi associated oesophageal sarcoma. J Small Anim Pract 2013;54:495-498. 11. Teshima T, Matsumoto H, Michishita M, Takahashi K, KoyamaHl. Multiple inflammatory gastric polyps treated by endoscopic polypectomy with argon plasma coagulation in a dog. J Small Anim Pract 2013;54:265-268. 12. Foy DS, Bach JF. Endoscopic polypectomy using endocautery in three dogs and one cat. J Am Anim Hosp Assoc 2010;46:168-173. 13. Tsukamoto A, Ohno K, Irie M, et al. A case of canine multiple inflammatory colorectal polyps treated by endoscopic polypectomy and argon plasma coagulation. J Vet Med Sci 2012;74:503-506. 14. Sarria R, Lopez Albors O, Soria F, et al. Characterization of anal double balloon endoscopy in the dog. Vet J 2013;197:886-888. 15. Sarria R, Lopez Albors O, Soria F, et al. Characterization of oral double balloon endoscopy in the dog. Vet J 2013;195:331-336. 16. Ayala I, Latorre R, Soria F, et al. A case of lymphocytic-plasmacytic jejunitis diagnosed by double-balloon enteroscopy in a dog. J Am Anim Hosp Assoc 2011;47:262-267. 17. Boeriu A, Boeriu C, Drasovean S, et al. Narrow-band imaging with magnifying endoscopy for the evaluation of gastrointestinal lesions. World J Gastrointest Endosc 2015;7:110-120. 18. Lee AC, Epe C, Simpson KW, Bowman DD. Utility of capsule endoscopy for evaluating anthelmintic efficacy in fully conscious dogs. Int J Parasitol 2011;41:1377-1383.

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19. Appleyard M, Fireman Z, Glukhovsky A, et al. A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small-bowel lesions. Gastroenterology 2000;119:1431-1438. 20. Sharman MJ, Bacci B, Whittem T, Mansfield CS. In vivo histologically equivalent evaluation of gastric mucosal topologic morphology in dogs by using confocal endomicroscopy. J Vet Intern Med 2014;28:799-808. 21. Sharman MJ, Bacci B, Whittem T, Mansfield CS. In vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs. J Vet Intern Med 2013;27:1372-1378. 22. Gaschen L, Kircher P, Lang J. Endoscopic ultrasound instrumentation, applications in humans, and potential veterinary applications. Vet Radiol Ultrasound 2003;44:665-680. 23. Gaschen L, Kircher P, Wolfram K. Endoscopic ultrasound of the canine abdomen. Vet Radiol Ultrasound 2007;48:338-349. 24. Hayashi K, Okanishi H, Kagawa Y, Asano K, Watari T. The role of endoscopic ultrasound in the evaluation of rectal polypoid lesions in 25 dogs. Jpn J Vet Res 2012;60:185-189.

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PRE & POST-OPERATIVE RADIATION THERAPY: WHICH PATIENTS BENEFIT?

Elias Gumpel, DVM, Diplomate ACVR (RO)

Brisbane Veterinary Specialist Centre Albany Creek, QLD, Australia

External beam radiation therapy is often a vital component in the cure and/or control of a large number of tumours in veterinary patients. It is well-known that surgery alone cannot always achieve local tumour control, and radiation therapy (most commonly used in the post-operative setting) can often effectively eradicate the remaining subclinical or microscopic residual disease. However, there remain instances where pre-operative radiation therapy can be utilised effectively either in an attempt to make surgery less radical, or to downstage tumours prior to surgical resection. Both pre- and post-operative radiation therapy have specific advantages and disadvantages which must be carefully considered in order to determine the proper approach for each particular case. Why combine surgery and radiation therapy? In order to obtain a “cure”, all of the neoplastic cells must be eradicated in some form or another. Surgery has the superior advantage of being able to remove vast numbers of tumour cells in a single procedure, but surgery itself is not always capable of successfully removing every last tumour cell, which would likely result in local recurrence. A more radical surgery could be considered with a greater likelihood of obtaining a cure, but this carries increased risk of wound breakdown, potential loss of function, and may not always result in an aesthetically satisfactory outcome (McLeod & Thrall, 1989). In those instances where surgery may leave behind subclinical or microscopic disease, radiation therapy can often have high success rates in sterilisation of the remaining neoplastic cells, so the combination of these 2 modalities can provide high cure rates, and thus makes sound medical sense. Radiation therapy alone is highly unlikely to obtain local tumour control against most forms of cancer (with a few exceptions), so it is obvious that combination with another complementary modality is required in order to succeed where radiation cannot. Cell kill as a result of radiation therapy is a random process, whereby a given dose of radiation kills the same proportion of cells, not the same number of cells (McLeod & Thrall, 1989). This logically implies that, as the number of cells comprising a tumour increases, the dose of radiation required to eradicate all tumour cells also increases. Once normal tissue tolerance levels are factored into the equation, it becomes clear that the odds of local tumour control with radiation alone decrease as the tumour volume increases. A prior study found that the complete response rate to radiation therapy for canine tumours was 60% when the tumour volume was less than 8.3ml, but it dramatically decreased to only 15% if the tumour volume was greater than 8.3ml (McLeod & Thrall, 1989).

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Radiation therapy in the post-operative setting This is likely the most common use for radiation therapy, although we still do not have a solid grasp on the optimal timing for starting radiation therapy following surgery (McLeod & Thrall, 1989). Post-operative irradiation is utilised when surgical resection has been deemed to be either narrow or incomplete through histologic evaluation, or when it is known (or at least highly suspected) that tumour cells were disseminated in the surgical field during the surgical procedure. Research has shown that radiation therapy can theoretically be started within 24 hours of the surgery, but the most common practice is to wait 10-14 days after surgery to allow for complete healing of the manipulated tissues prior to exposing them to radiation in order to minimise the potential for wound healing complications (McLeod & Thrall, 1989). The known advantages for using post-operative irradiation include: no delay in the timing of surgery as a consequence of acute radiation side effects, the full extent of the tumour is usually better understood following surgical resection when the tissues can be grossly evaluated, and there is no increased risk for wound healing complications since the manipulated tissues have not been previously exposed to radiation (McLeod & Thrall, 1989). While these advantages certainly make post-operative radiation therapy seem like a favourable approach, certain disadvantages do arise. Any tissue that is handled during surgery to remove a tumour must be included within the radiation field, since the potential for “seeding” of tumour cells intra-operatively must be respected (McLeod & Thrall, 1989). This can mean having to use much larger radiation treatment field than the radiation oncologist would prefer, since exposing more normal tissues to radiation increases the risk of side effects. Studies have also shown that the number of circulating neoplastic cells appears to increase after surgical manipulation of tumours, and this can potentially lead to higher metastatic rates (McLeod & Thrall, 1989). Even though removal of the gross tumour makes radiation therapy more likely to be effective by cytoreduction, surgical manipulation could disrupt the normal tissue blood supply to the surrounding tissues and lead to hypoxic regions within subclinical or microscopic residual tumour. These now-hypoxic tumour cells are 3 times more radioresistant due to the lack of sufficient oxygen as a radiation sensitising agent. Finally, the 10-14 day wait before starting radiation therapy allows for remaining tumour cells to repopulate, which could potentially impact the efficacy of radiation therapy (McLeod & Thrall, 1989). Radiation therapy in the pre-operative setting In veterinary medicine, pre-operative irradiation is used much less commonly than in the post-operative setting. This is likely due to, at least in part, the surgeon’s understandable desire to not want to handle or manipulate tissues that have been previously exposed to large, therapeutic doses of radiation. In this setting, radiation therapy is performed 1 – 3 months prior to the planned surgical procedure (McLeod & Thrall, 1989). By performing radiation therapy prior to surgery, there is no alteration of blood supply in the regions of subclinical or microscopic disease, so these neoplastic cells

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remain well-oxygenated and thus more radiosensitive. There is also no expected delay in starting the radiation protocol since the risk of post-operative wound healing complications is extremely low. The anticipated radiation field size is usually smaller when radiation therapy is performed prior to surgery, which means less risk of harmful radiation side effects. Studies have demonstrated that pre-operative irradiation can decrease the growth of disseminated neoplastic cells by > 90%. Following radiation therapy, the surgical approach can be more conservative as a result of macroscopic tumour shrinkage and sterilisation of the subclinical or microscopic disease, but it should always be remembered that the primary goal of pre-operative irradiation is to achieve control of the subclinical disease and allow the subsequent surgery to control the macroscopic disease (McLeod & Thrall, 1989). As with post-operative irradiation, the utilisation of pre-operative radiation therapy does come with some inherent disadvantages. If surgery is performed too soon following the radiation exposure, there is greater risk of wound healing complications, which could be highly problematic for the patient. The optimal timing for when surgery can be attempted following irradiation with minimal risk of complications is unknown, and the risk is likely to increase proportionally with the total dose of radiation prescribed in the protocol. Without the benefit of knowing the full extent of the tumour as with post-operative irradiation, the treatment field used with pre-operative irradiation is likely to be larger, thus increasing the risk of potentially harmful side effects (McLeod & Thrall, 1989). Specific Tumours Treated With Pre- and Post-Operative Irradiation It is widely established that surgery followed by definitive radiation therapy for cutaneous/subcutaneous mast cell tumours and soft tissue sarcomas is the treatment of choice for tumours that have been narrowly or incompletely excised, with local control rates as high as 80-90% reported. There are very rare instances where pre-operative radiation therapy will be performed on a surgically non-resectable mast cell tumour or soft tissue sarcoma in an attempt to downstage the mass and possibly be able to remove it surgically after irradiation. The following is not meant to be an all-inclusive list of tumours, but rather an overview of some common, and not-so-common tumours for which pre- and post-operative irradiation have been evaluated in published studies throughout the years.

1) Ceruminous gland carcinoma - Relatively rare tumour arising from the ear canal epithelial tissues in both dogs and cats. A 1994 paper evaluated 9 dogs and 9 cats that underwent treatment with either surgery alone, or surgery followed by post-operative radiation therapy. Five dogs and 6 cats were in the surgery + radiation therapy group. A lower recurrence rate was identified in the dogs and cats that underwent total ear canal resection/bulla osteotomy followed by radiation therapy as compared to those that only had a lateral ear canal resection performed (Theon, 1994).

2) Meningioma – The most commonly identified primary brain tumour in dogs. Various papers have been published on outcomes in patients undergoing surgery alone, radiation therapy alone, or combination surgery followed by

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radiation therapy. A 2002 paper evaluated 31 dogs with meningiomas. The MST was 7 months for dogs treated with surgery alone compared to 16.5 months in those dogs treated with surgery followed by radiation therapy (Axlund et al, 2002). Another paper published in 2011 specifically evaluated 7 dogs with frontal lobe meningiomas who began radiation therapy 3 weeks after cytoreductive surgery with a MST of 18 months (Uriarte et al, 2011). In 2008, a paper was published looking at 17 dogs with spinal cord meningiomas. Of these 17 dogs, 10 underwent surgery alone and 7 had surgery followed by post-operative irradiation. In the surgery alone group, 2 of the 10 dogs had confirmed tumour recurrence at 12 and 25 months post-op, and the remaining 8 dogs were eventually euthanised due to tumour recurrence with a mean survival time of 19 months. In the 7 dogs treated with surgery and radiation therapy, 3 were ultimately euthanised due to tumour recurrence at 18, 27, and 36 months post-op, 1 dog was still alive at the time of publication (41 months post-op), 2 died of unrelated causes at 72 and 78 months post-op, and 1 was lost to follow-up at 4 months post-op (Petersen et al, 2008).

3) Canine digit tumours – The role of adjuvant radiation therapy for these tumours has not yet been clearly defined. Surgical intervention alone for these tumours has been shown to have a statistically significant association with improved outcome, even if metastatic disease is present at the time of surgery. Further studies need to be undertaken to evaluate if radiation therapy (in those cases where surgical resection was deemed to be incomplete or narrow), can further improve survival times (Henry et al, 2005).

4) Canine oral malignant melanoma – This is the most commonly identified neoplasm of the oral cavity in dogs, and is generally reported to exhibit an aggressive biologic behaviour. Complete surgical resection is often very difficult due to the size, invasiveness, and location of this tumour within the oral cavity, but tumour size has been identified as a highly prognostic factor. Using the World Health Organisation (WHO) staging system for this tumour, where stage I = < 2cm diameter, stage II = diameter between 2 – 4cm, stage III = ≥ 4cm diameter and/or lymph node metastasis, and stage IV = distant metastasis. When treated with surgery alone, a 2007 publication reported the MST based on stage was 17 to 18 months, 5 to 6 months, and 3 months respectively for stage I, stage II, and stage III tumours, with death most commonly being attributed to the progression of metastatic disease as opposed to failure of local tumour control (Bergman, 2007). A separate study in 2005 evaluated the use of coarse fractionated radiation therapy (larger dose per fraction, once weekly radiation treatments, lower overall total dose) with or without carboplatin chemotherapy. Of the 13 dogs in this study treated with radiation alone, the MST was 305 days with a range of 108 – 585 days (Murphy, 2005). When dogs with macroscopic vs microscopic (post-op RT) oral melanoma were treated with radiation therapy in a 2003 publication, the recurrence rate was 26% for dogs treated with post-op irradiation but the recurrence rate jumped up to 45% in dogs who were irradiated without prior surgery (Proulx et al, 2003). This would seem to indicate that surgical resection prior to irradiation is preferable, but this particular paper was unable to establish a statistical significance for this with the data set they obtained, whereas the presence of bone lysis was found to be significantly associated

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with a greater risk for recurrence.

5) Canine nasal tumours – the role of surgery when combined with both orthovoltage and megavoltage irradiation for canine nasal tumours has been evaluated in a limited number of studies. A 1994 publication evaluated 42 dogs with various types of primary nasal tumours – of these 42 dogs, 12 were treated with only coarse fractionated irradiation using mostly megavoltage (high energy) radiation therapy, although 1 dog received orthovoltage (low energy) radiation therapy, 14 dogs were treated with a dorsal rhinotomy prior to coarse fractionated irradiation, and most were treated with orthovoltage, the remaining 16 dogs underwent no treatment. There was no statistically significant difference in median survival times noted for dogs treated with radiation therapy alone and those treated with surgery and radiation. However, the disease-free interval was found to be statistically significant, with dogs undergoing dorsal rhinotomy followed by orthovoltage radiation therapy having a 36% recurrence rate at 52 weeks compared to 67% of those dogs treated with radiation alone (Morris et al, 1994). It is worth noting that the dose delivered through low energy, orthovoltage radiation is preferentially absorbed by bone as opposed to soft tissue, whereas there is virtually no difference in radiation dose absorption in bone and soft tissue when using high energy, megavoltage radiation therapy. Thus, treating gross nasal tumour with orthovoltage is highly unlikely to be able to deposit enough therapeutic dose into the soft tissues of the tumour, since a greater amount of dose will be absorbed by the bone surrounding the tumour than the tumour itself. It would appear then, that dogs with nasal tumours could therefore benefit from surgical debulking followed by orthovoltage irradiation, but this treatment protocol has not yet been found to have a statistically significant improved survival over treatment with megavoltage radiation therapy alone. A more recent 2005 publication evaluated 53 dogs with nasal tumours that underwent megavoltage irradiation, and 11 of the 53 dogs subsequently underwent surgical removal of residual tumour following irradiation. The median survival time for dogs in the radiation + surgery group was 47.7 months, which was significantly longer than the 19.7 month MST for dogs in the radiation-only group (Adams et al, 2005).

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A DENTAL PERSPECTIVE ON ORAL TUMOUR MANAGEMENT

Dr. Anthony Caiafa BVSc BDSc MANZCVS North Coast Veterinary Specialists, Tanawha, Sunshine Coast

Lecturer in Veterinary Dentistry James Cook University, Townsville Queensland Australia

Intraoral radiography

Clinicians are aware that no imaging modality is accurate enough to diagnose the extent of oral tumour invasion. In human oral oncology, a combination of imaging modalities is used to assist in formulating a more accurate determination of tumour spread. A combination of intraoral and/or extraoral plain imaging (panoramic or OPG) combined with CT scans improved determination of tumour spread.

In veterinary oral oncology, extraoral plain imaging with or without CT/MRI scans has been the mainstay for diagnosis and management of oral tumours. The use of intraoral imaging has been limited in veterinary oral oncological management mainly due to poor accessibility.

It must be said that all imaging modalities can under or overestimate the extent of oral tumour invasion

Benefits of intraoral radiographs for oral pathology and tumour management

• Easy to perform. Size 4 (57mm X 76 mm) or 5 film ideal. • May be the only imaging necessary when dealing with benign

lesions/cysts/tumours especially in the rostral maxilla/rostral mandible/body of mandible. There may be no need for more expensive imaging such as CT scan or MRI

• Can be combined with plain extraoral imaging to assist in tumour management • Assists in diagnosing/ managing nasal pathology (and jaw fractures) • Aid in the detection of post-surgical complications such as fractured roots,

pulp necrosis and bony sequestrae Drawbacks of intraoral radiographs for tumour management

• Only 2 dimensional image • Soft tissue imaging is relatively poor • May not be diagnostic for more caudal tumours, CT is better • Requires about 40% mineral loss in bone/tooth to see radiolucency • Tumours of soft tissues/tongue better imaged by MRI • As with other radiographic imaging modalities- may be difficult to determine

spread of tumour within the mandibular canal Some dental/oral complications seen following oral tumour resection

• Retained tooth roots, damage to teeth and possible pulp necrosis and infection

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• Malocclusions including mandibular drift following surgery: Rostral/body mandibulectomy caudal to the symphysis, caudal mandibulectomy including ramus and condylar head and total mandibulectomy

• TMJ dysfunction • Dry mouth and oral disease following irradiation of the head

Prevention/Correction of mandibular drift and hard palate trauma from mandibular canine tooth

• Rim excision for benign/early detected malignant tumours** • Tooth extraction of maloccluded tooth (teeth) • Crown reduction and pulpotomy therapy (requires extra/ intraoral

radiography) • Odontoplasty (requires extra/ intraoral radiography) • Rigid internal fixation preferably with small locking plates to stabilise

mandible in case of rostral/body mandibulectomy +/- use of bone replacement materials

• Orthodontic brackets/elastic chain^ ** Murray R., Aitken M. and Gottfried S. The Use of Rim Excision as a Treatment for Canine Acanthomatous Ameloblastoma. JAAHA, March/April 2010, 46. 91-96

^ Bar-Am Y and Verstraete F. Elastic training for the prevention of mandibular drift following mandibulectomy in dogs; 18 cases (2005-2008) Vet Surg. 2010 Jul; 39(5): 574-580

Reconstructive techniques in human and veterinary oral oncology

• Radial/fibula vascular flaps. First performed in 1989. • Ability to place implants and crowns to alleviate poor mastication and

aesthetics • Use of compressive matrix infused with human BMP and locking plates*^^

* Boaz A., Verstraete F., Huey D. Cissell D. and Kyriacos A. Regenerating Mandibular Bone Using rhBMP-‐2: Part 1— Immediate Reconstruction of Segmental Mandibulectomies. Vet Surg., Jan., 2014 1-7.

^^ Boudrieau R. Initial Experience With rhBMP-‐2 Delivered in a Compressive Resistant Matrix for Mandibular Reconstruction in 5 Dogs Vet Surg., 44, 2015 443-458

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FEMORAL NERVE ENTRAPMENT IN A DOG WITH DIFFUSE

IDIOPATHIC SKELETAL HYPEROSTOSIS

A Lai1, J Culvenor1, C Bailey1, S Davies2

1North Shore Veterinary Specialist Centre, Sydney, Australia

2Veterinary Imaging Associates, Sydney, Australia

Objective: To report femoral neuropathy caused by nerve entrapment associated with diffuse idiopathic skeletal hyperostosis (DISH). Study design: Case report. Study population: Seven-year-old female spayed Boxer dog. Results: Entrapment of the right femoral nerve due to DISH caused a femoral nerve deficit and atrophy of muscle groups associated with the affected nerve. A combination of computed tomography and magnetic resonance imaging was performed to provide a diagnosis. Amputation of the right transverse process of the sixth lumbar vertebra at the level of nerve entrapment relieved the neurological abnormality. Conclusions: Nerve entrapment leading to neuropraxia may occur concurrently with DISH and surgery in this case was successful in restoring function. Clinical relevance: Peripheral neuropathy from nerve entrapment should be considered in patients with DISH. Surgical amputation of impinging osseous structures may be indicated for relief of femoral neuropathy.

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THE EFFECT OF INTRAMEDULLARY PIN SIZE AND PLATE WORKING LENGTH ON PLATE STRAIN IN LOCKING COMPRESSION PLATE-ROD

CONSTRUCTS

TJ Pearson1, MR Glyde1, GL Hosgood1, R Day2

1College of Veterinary Medicine, Murdoch University, Perth, Australia 2Department of Medical Engineering & Physics, Royal Perth Hospital, Perth,

Australia Objective: To investigate the effect of intramedullary (IM) pin size and plate working length on plate strain in locking compression plate-rod (LCPR) constructs. Study design: In vitro study. Sample population: Synthetic fracture gap model. Methods: LCPs with monocortical locking screws were tested with no pin (LCPMono) and IM pins of 20% (LCPR20), 30% (LCPR30) and 40% (LCPR40) of IM diameter. Two screws per fragment modelled a long (8 hole) and short (4 hole) plate working length. Strain responses to axial compression were recorded at 6 regions of the plate via 3D digital image correlation. Results: The addition of an IM pin of any size provided a significant decrease in plate strain. For the long working length, LCPR30 and LCPR40 had significantly lower strain than the LCPR20 and plate strain was significantly higher adjacent to the screw closest to the fracture site. For the short working length, there was no significant difference in strain across any LCPR constructs or at any region of the plate. Plate strain was significantly lower for the short working length compared to the long working length for LCPMono and LCPR20 but not LCPR30 and LCPR40.

Conclusions: The increase in plate strain encountered with a long working length can be overcome by the use of a pin of 30-40% IM diameter. Where placement of a large diameter IM pin is not possible, screws should be placed as close to the fracture gap as possible to minimize plate strain and distribute it more evenly over the plate.

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NEGATIVE PRESSURE WOUND THERAPY USING A PORTABLE, SINGLE-USE DEVICE FOR FREE SKIN GRAFTS ON THE DISTAL

EXTREMITY IN 7 DOGS

AJ Miller, RG Cashmore, AM Marchevsky, MH Havlicek, PM Brown, SM Fearnside

Small Animal Specialist Hospital, North Ryde, NSW, Australia

Objective: To describe clinical experience with a portable, single-use negative pressure wound therapy device after application of full-thickness meshed skin grafts to wounds on the distal extremity of dogs. Study design: Retrospective case series. Study population: Seven dogs were treated with portable NPWT after receiving skin grafts; six as the result of tumour resection and one due to trauma. Methods: Medical records were reviewed and data recorded on patient signalment, cause and location of wound, surgical technique, application and maintenance of portable NPWT, graft survival and outcome, and complications encountered with the system. Results: Negative pressure wound therapy was provided for between 4 and 7 days. Five patients were discharged from hospital during the treatment period. Application and maintenance of the portable device was technically easy. No major complications were encountered. Minor complications consisted of fluid accumulation in the evacuation tubing. All dogs had successful outcomes with each achieving 100% graft survival. Conclusions: Application and maintenance of the portable device was technically straightforward. All dogs receiving portable NPWT after transfer of a free skin graft to the distal extremity had a successful outcome.

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OZONATED WATER IS INFERIOR TO ALCOHOL FOR DISINFECTING HANDS

C. Appelgrein1, G.Hosgood1, A.L. Dunn2, O. Schaaf3

1 Murdoch University, Murdoch, Western Australia, Australia 2 Adelaide Veterinary Specialists and Referral Centre, Adelaide, South Australia,

Australia 3University of Adelaide, Roseworthy, South Australia, Australia Objective: To compare the efficacy of ozone to an alcohol-based hand rub for hand disinfection. Study design: In vivo crossover trial (prEN 12791). Study population: Twenty veterinary students. Methods: Subjects treated their hands with the reference procedure (propan-1-ol 60%) for 3 min or with ozone (4ppm) for 3 min. For each trial, the pre-wash bacterial counts were determined for the fingertips of both hands. Post-wash bacterial counts were determined from one hand (immediate effect), and from the other hand that had been gloved for 3 h (delayed effect). A non-inferiority analysis was performed. Results: The investigation indicated that ozone is inferior to propan-1-ol 60% hand rub for hand asepsis. Ozone left higher residual bacterial counts on the fingertips than propan-1-ol 60% immediately after hand washing, and although it showed a mild sustained effect, it resulted in delayed counts higher than that obtained after disinfection with propan-1-ol 60%. Conclusion: Ozone cannot be recommended as a substitute for propan-1-ol 60% as a hand disinfectant.

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LOCKING PLATES VERSUS COMPRESSION PLATES FOR ILIAL WING FRACTURES IN DOGS

G Dodds

Veterinary Specialist Services, Underwood, Queensland, Australia

Objective: Locking plates are gaining popularity in the veterinary industry as an alternative to compression plates due to their described theoretical benefits. These benefits include reduced periosteal devascularisation and reduced implant failure in thin or osteopaenic bone due to the altered biomechanics of the locking versus the compression plate. No studies have demonstrated these benefits in a clinical setting. This case series describes the use of locking plates compared with compression plates for the management of ilial wing fractures in dogs at a referral centre in Brisbane. Study design: Retrospective case series. Study population: 13 Dogs (n = 6 locking plates, n = 7 compression plates) Methods: Medical records (January 2010 - January 2015) and radiographs were reviewed. Inclusion criteria included dogs that had a lateral plate applied to the ilial wing following fracture where follow-up radiographs were available. Signalment, age, body weight and complications including screw backing out and infection rates were evaluated. Results: Complications developed in two of seven dogs with compression plates (29%). These included one refracture and one surgical site infection with delayed union. There were no reported complications in the locking plate group. Incidence of screw back out was similar for both groups. Mean weight was higher for the locking plate group (21.6kg) than the compression plate group (8.8kg). Mean age, follow up time and length of stay were similar for both groups. Conclusions: This case series demonstrated that locking plates are a suitable alternative to traditional compression plating techniques for stabilization of ilial shaft fractures in dogs.

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A RETROSPECTIVE REVIEW OF PERIOPERATIVE ANTIMICROBIAL CYCLING IN VETERINARY ORTHOPAEDIC SURGERY

EM Hoffman

Veterinary Specialist Services, Queensland, Australia.

Background: Rotating antimicrobial protocols for perioperative surgical and ICU use in human hospitals has documented an improvement in the antibiotic sensitivity profiles of bacteria cultured from surgical and ICU infections. An equivalent assessment of rotating antimicrobials for perioperative surgical use has not been reported in the veterinary literature. Objective: to evaluate the effect of a strict rotational perioperative antimicrobial protocol on surgical site infection rate, pathogens cultured and susceptibility profiles in a veterinary orthopaedic hospital. Study design: Retrospective case study. Methods: Monthly cycling of two different antibiotic classes for perioperative surgery use was instituted into the hospital in 2012. Prior to this change, a first generation cephalosporin only was used. All orthopaedic cases in the hospital were reviewed three years before and three years after the change and all surgical infections were evaluated. Results: A total of 78 infections from 1200 surgical patients were documented. Fifty one infections (rate = 8.5%) occurred prior to the rotating antimicrobial protocol and 28 infections (rate = 4.65%) occurred following the change in antimicrobial protocol. The number of multi-resistant infections decreased from 18 (3%) to 3 (0.5%). The bacterial resistance profiles did not change. Conclusions: Three years after implementing a rotational antimicrobial protocol to the hospital the surgical infection rate decreased. In addition the number of multi-resistant infections reduced, however the sensitivity profiles of the multi-resistant bacteria remained similar.

156

QUANTITATIVE HISTOLOGICAL EVALUATION OF THE SOFT PALATE IN DOGS AFFECTED BY BRACHYCEPHALIC OBSTRUCTIVE AIRWAY

SYNDROME

KR Crosse1, JP Bray1, GMB Orbell2, CA Preston3

1Massey University, Palmerston North, NZ 2NZVP, Palmerston North, NZ

3 Pet Emergency and Specialist Centre, Malvern East, VIC, Australia Objective: To histologically examine tissue obtained from the thick rostral portion of the soft palate in severely affected brachycephalic dogs via folded flap palatoplasty, and to quantitatively compare the histological findings with a similar region in control dogs. Study design: Prospective study. Methods: Nine dogs examined for treatment of brachycephalic obstructive airway syndrome were prospectively recruited into the study. Following palatoplasty, the resected portion of soft palate was fixed in formalin and prepared for histological evaluation under H&E staining. The soft palate were also resected post mortem from four mesaticephalic control dogs and prepared in the same manner. Tissues of the soft palate were examined in transverse section by one pathologist. Assessments of the palatinus muscles, interstitium, lamina propria and salivary tissue were recorded and collated. Quantitate analysis was performed with ImageJ software. Results: When compared to the control dogs, the histological findings of the clinically affected dogs showed a marked increase in acute and chronic muscle degeneration and necrosis. This was typified by swollen, hypereosinophilic fibres with centralized nuclei, myofibre atrophy, loss of cross striations and fragmented sarcoplasm. There was significantly less muscle tissue, more stroma and more salivary tissue in affected dogs compared to control dogs. Conclusions: Increased thickness of the palate is not due to muscle hypertrophy or fat deposition but is instead due to increased collagenous stroma in the lamina propria, generalised oedema and increased volumes of salivary tissue. There is also reduction of muscle mass, especially within the paired palatinus muscles which may have consequences for palate function.

157

THE USE OF COMBINATION VINBLASTINE AND TOCERANIB PHOSPHATE (PALLADIA®) FOR TREATMENT OF GRADE II AND III

MAST CELL TUMOURS IN DOGS

J Olsen, M Thomson

Veterinary Specialist Services, Underwood, Queensland, Australia Background and Objectives: Mast cell tumours are the most common cutaneous neoplasm of the dog. This study aims to determine outcomes for canine patients with mast cell tumours treated with combination agent chemotherapy using Vinblastine and Toceranib phosphate (Palladia®). Study design: A retrospective case series of 34 canine patients with Patnaik grade II and III or Kiupel low and high-grade mast cell tumours treated at Veterinary Specialist Services with combination Vinblastine and Palladia® from 2011-2015. These were subdivided into 3 groups; patients who received neo-adjuvant therapy, patients who received adjuvant therapy following resection and patients being managed for gross metastatic disease. Results: This study demonstrated a 100% biological response rate in dogs with measurable disease. A complete response was seen in 37% and a partial response in 63%. The overall median survival time was 411 days. The median survival time for the neo-adjuvant group was not reached. The median survival times for the adjuvant and metastatic disease groups were 546 days and 148 days, respectively. The only statistically significant prognostic indicators identified were the Kiupel histological grade of the tumour, if the disease was metastatic and whether there was disease progression following initiation of therapy. Toxicity was noted in 62% of patients, the majority of these affecting the gastrointestinal system. However, most were considered mild and were self-limiting or only required temporary chemotherapy discontinuation. Conclusions: Combination Vinblastine and Palladia® chemotherapy is effective, with a high biological response rate, for treatment of mast cell tumours in dogs.

158

OUTCOMES OF CELLOPHANE BANDING WITH NO ATTENUATION

FOR TREATMENT OF EXTRAHEPATIC PORTOSYSTEMIC SHUNTS IN DOGS

K Leidreiter, D Cook, P Moses

Veterinary Specialist Services, Underwood, Queensland, Australia.

Objectives: To report outcomes in dogs treated for single congenital extrahepatic portosystemic shunt (CEHPSS) by cellophane banding with no attenuation. To identify pre-operative prognostic factors for these dogs. Study design: Retrospective study. Study population: Dogs (n=25) with CEHPSS that were cellophane banded without attenuation. Methods: Medical records of dogs with CEHPSS treated by cellophane banding without attenuation were reviewed. Long-term follow up information was obtained by telephone interview with referring veterinarians and/or owners. Factors associated with outcome were examined. Results: No major immediate post-operative complications occurred in this study. Long term follow up data was obtained for 22 of 25 dogs; median follow up was 37 months (range 4 – 126 months). Zero dogs died in the first month post-operatively following surgery. Thirteen dogs (59.1%) were not receiving medical therapy and had no clinical signs. Five dogs (22.7%) had not been offered a diet with standard protein by the owner and had no clinical signs. Three dogs (13.6%) showed improvement with occasional clinical signs and required ongoing therapy. Eighteen (81.8%) dogs had no clinical signs at final contact. One dog (4.5%) was euthanased eight months after surgery following the development of multiple acquired shunts. Conclusions: In this study, dogs with CEHPSS treated with cellophane banding with no attenuation have a good prognosis. The comparative low complication rate seen in this study may indicate that attenuation of CEHPSS is not required. A larger study may be required to acquire statistical significance.

159

COMPARISON OF PERI-OPERATIVE WOUND PARAMETERS IN CATS UNDERGOING FLANK VERSUS MIDLINE OVARIECTOMY

MJ Swaffield1, S Molloy2, VJ Lipscomb2

1Fitzpatrick Referrals, Surrey, UK

2Royal Veterinary College, Hertfordshire, UK Objectives: To compare perioperative wound parameters and pain score between flank and midline ovariectomy (OVE) in cats. Study design: Prospective, randomised cohort study. Study population: Thirty-eight client owned entire female cats of any age and breed admitted for routine OVE at a first opinion university teaching hospital. Methods: Cats were assigned randomly to the midline or flank group. Perioperative management protocols were standardised for both groups. Wound parameter data (licking, redness, swelling, discharge, breakdown), modified Glasgow pain score (MGPS), and reaction to wound palpation was recorded prior to surgery, at 1 hour postoperatively, at discharge the same day, and at 3 days and 10 days post-operatively. Length of surgery and anaesthesia, and any intraoperative complications or additional postoperative interventions or therapy required was also recorded. Results: Incidence of wound swelling was significantly higher in cats that had a midline OVE at the time of discharge on the day of surgery (P=0.029), and at 3 days (P=0.027) and 10 days (P=0.01) postoperatively. Reaction to wound palpation was significantly higher in cats that had a flank OVE at 1 hour after surgery (P=0.0009) and at discharge on the same day (P=0.019). There were no statistically significant differences between anaesthetic or surgery times, intraoperative complications, incidence of wound breakdown or MGPS between groups. Conclusions: Cats undergoing midline OVE have an increased risk of swelling at the surgical site. Despite this, cats in this group were more comfortable on wound palpation in the immediate postoperative period. This is a novel study comparing wound complications between midline and flank feline OVE and greater numbers are required to draw definitive conclusions.

160

COMPUTED TOMOGRAPHY FINDINGS AND OUTCOMES AFTER SURGERY FOR DERMOID SINUSES: A CASE SERIES

C Appelgrein, G Hosgood, SL Rees, J Richardson

College of Veterinary Medicine, Murdoch University, Perth, Australia Objective: To describe the computed tomography (CT) findings and outcomes after surgery for eight dogs with dermoid sinuses. Study design: Case series. Study population: 8 dogs Methods: Medical records reviewed and summarised. Results: Six Rhodesian ridgebacks and a Labrador each with a dorsal cervical sinus (4 type IIa, 2 type IIIa, 1 type Va), and a Labrador X poodle with an occipital dermoid sinus (type Ib) were included. Computed tomography with contrast showed a superficial, ring-enhancing, fluid-filled cyst with a contrast-enhancing, soft tissue-attenuating tract extending from the skin to the cyst, and then deeper to the cyst to the level of the nuchal ligament. The tract often extended in a tangential direction below the cyst but the final termination of the tract below the nuchal ligament was not always clearly discernible on the CT. The dermoid sinuses were excised in 7/8 dogs. At surgery, the tract often extended further ventrally, below the nuchal ligament, terminating on the vertebrae (spinous process or lamina). Most distal attachments involved a thread-like extension of the sinus, usually deeper than could be discerned from the CT. Closed suction drainage was placed in 6/7 dogs. Seroma formation was a complication after drain removal in 5/6 dog, requiring re-drainage in 1 dog. Conclusion: Pre-operative CT facilitates the diagnosis of a dermoid sinus and directs surgical planning but careful dissection beyond the dilated end of the sinus is important for complete excision.

161

EFFECT OF CASSETTE OPEN TIME ON STRENGTH OF MULTI-USE POLYDIOXANONE AND COMPARISON TO SINGLE-USE

POLYDIOXANONE

Olaf Schaaf1, Mark Glyde2, Robert E Day3, Giselle Hosgood2

1University of Adelaide, Adelaide, South Australia 2Murdoch University, Murdoch, Western Australia

3Royal Perth Hospital, Department of Medical Engineering and Physics, Perth, Western Australia.

Objectives: Determine and compare the tensile strength (TS), diameter, and tensile stress of 2-0 USP (3 Metric) polydioxanone for three brands of multi-use cassette suture, over a six months storage period (Day 0,31,62,90,121,149,180) and three brands of single-use foil packeted suture (Day 0). Study design: In-vitro study. Methods: Cassette sutures tested: PDX (PDX-C), Surgicryl (PDO-C), MonoDox (MDO-C). Foil sutures tested: MonoPlus® (PDX-F), Surgicryl (PDO-F), PDS II (PDS-F). All sutures were kept in an identical temperature, light and humidity controlled environment. Cassette sutures had aerobic bacterial cultures taken on Day180. Results: PDO-F and PDX-F were the strongest foil sutures. PDX-C was the strongest and slowest degrading cassette suture and was the only cassette suture not to lose significant TS before its recommended four month use by date. However all cassettes lost significant TS by five months at significantly different rates. All microbial cultures were negative. Clinical significance: Cassette polydioxanone had comparable initial TS to foil sutures, but two of the three cassette sutures lost significant TS before their use by dates when stored in ideal conditions. Surgeons should consider the effect of time and storage conditions on cassette polydioxanone when choosing suture material and may wish to consider using foil suture when cassettes approach their use by dates and reliably high TS is required.

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