Considerations for Personalized Surgery in Patients with Papillary Thyroid Cancer Ralph P. Tufano 1 and Emad Kandil 2 Background: Personalizing treatment for papillary thyroid cancer (PTC) requires a multidisciplinary approach. The surgical management of PTC has long been based on retrospective studies focusing on endpoints that are of debatable significance. There is considerable debate in the literature regarding the optimal initial treatment for PTC. Many of these issues are discussed in this review. These debates have hindered the development of a tailored treatment strategy. Summary: The ability to optimally personalize a surgical plan for the treatment of PTC is ultimately dependent on an understanding of the biological behavior of that individual patient’s tumor. We are at the genesis of an age where molecular biology advances endeavor to profile a patient’s tumor behavior. This review summarizes current strategies for managing PTC, where we are with personalizing surgery for these patients, and where we hope to go. Thyroid surgery is one of the newest fields for the application of minimally invasive techniques and can now be accomplished endoscopically or with robotic assistance in many patients who therefore may benefit from these alternative approaches. Conclusion: When treating a patient with PTC, it seems prudent to weigh the many factors discussed in this review to individualize the most optimal surgical plan. Introduction T here is considerable debate in the literature regarding the optimal initial treatment for papillary thyroid cancer (PTC). Some of the issues debated include (i) the extent of thyroidectomy, (ii) whether to perform an elective central neck dissection (CND) for the clinically node-negative central neck, (iii) extent of lateral neck dissection when macroscopic nodal metastases are present, and (iv) the role of nontradi- tional thyroidectomy approaches such as video-assisted and robotic techniques in treating PTC. Although survival rates are excellent, large registry efforts have demonstrated that stage I, II, and III tumors have a defined risk of recurrence of 10%, 20%, and 30%, respectively (1–3). The inability to accurately identify the subsets of patients who are at greater risk for recurrence of PTC before primary treatment has in part spawned these debates and has hin- dered the development of a tailored treatment strategy. Personalizing treatment for PTC requires a multidisciplinary approach. The available evidence-based data and lack thereof should be well understood by the practitioners car- ing for a patient with PTC so as to tailor treatment accord- ingly. The surgical management of PTC has long been based on retrospective studies focusing on endpoints that are of de- batable significance. The ability to optimally personalize a surgical plan for the treatment of PTC is ultimately dependent on an understanding of the biological behavior of that indi- vidual patient’s tumor. We are at the genesis of an age where molecular biology advances endeavor to profile a patient’s tumor behavior to allow for a tailored treatment strategy. This review summarizes where we are with personalizing surgery for PTC and where we hope to go. Individualizing the Surgical Plan for the Thyroid and Central Compartment in Patients Undergoing Initial Surgery for PTC The rationale for total thyroidectomy for PTC identified preoperatively includes the frequent multifocal nature of the disease, the ability to reduce the risk of recurrence and to fa- cilitate radioactive iodine treatment, and the use of serum thyroglobulin levels and whole-body radioiodine scans during follow-up. Two Mazzaferri et al. studies support that total thyroidectomy reduces the risk of recurrence for PTC and perhaps improves survival (4,5). Most surgeons agree now that Portions of this review were presented at the Spring 2010 Meeting of the American Thyroid Association, ‘‘Thyroid Disorders in the Era of Personalized Medicine,’’ Minneapolis, Minnesota, May 13–16, 2010. 1 Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland. 2 Department of Surgery, Tulane Medical School, New Orleans, Louisiana. THYROID Volume 20, Number 7, 2010 ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2010.1645 771
Transcript
Considerations for Personalized Surgeryin Patients with Papillary Thyroid Cancer
Ralph P. Tufano1 and Emad Kandil 2
Background: Personalizing treatment for papillary thyroid cancer (PTC) requires a multidisciplinary approach.The surgical management of PTC has long been based on retrospective studies focusing on endpoints that are ofdebatable significance. There is considerable debate in the literature regarding the optimal initial treatment forPTC. Many of these issues are discussed in this review. These debates have hindered the development of atailored treatment strategy.Summary: The ability to optimally personalize a surgical plan for the treatment of PTC is ultimately dependenton an understanding of the biological behavior of that individual patient’s tumor. We are at the genesis of an agewhere molecular biology advances endeavor to profile a patient’s tumor behavior. This review summarizescurrent strategies for managing PTC, where we are with personalizing surgery for these patients, and where wehope to go. Thyroid surgery is one of the newest fields for the application of minimally invasive techniques andcan now be accomplished endoscopically or with robotic assistance in many patients who therefore may benefitfrom these alternative approaches.Conclusion: When treating a patient with PTC, it seems prudent to weigh the many factors discussed in thisreview to individualize the most optimal surgical plan.
Introduction
There is considerable debate in the literature regardingthe optimal initial treatment for papillary thyroid cancer
(PTC). Some of the issues debated include (i) the extent ofthyroidectomy, (ii) whether to perform an elective centralneck dissection (CND) for the clinically node-negative centralneck, (iii) extent of lateral neck dissection when macroscopicnodal metastases are present, and (iv) the role of nontradi-tional thyroidectomy approaches such as video-assisted androbotic techniques in treating PTC. Although survival ratesare excellent, large registry efforts have demonstrated thatstage I, II, and III tumors have a defined risk of recurrence of10%, 20%, and 30%, respectively (1–3).
The inability to accurately identify the subsets of patientswho are at greater risk for recurrence of PTC before primarytreatment has in part spawned these debates and has hin-dered the development of a tailored treatment strategy.Personalizing treatment for PTC requires a multidisciplinaryapproach. The available evidence-based data and lackthereof should be well understood by the practitioners car-ing for a patient with PTC so as to tailor treatment accord-ingly.
The surgical management of PTC has long been based onretrospective studies focusing on endpoints that are of de-batable significance. The ability to optimally personalize asurgical plan for the treatment of PTC is ultimately dependenton an understanding of the biological behavior of that indi-vidual patient’s tumor. We are at the genesis of an age wheremolecular biology advances endeavor to profile a patient’stumor behavior to allow for a tailored treatment strategy. Thisreview summarizes where we are with personalizing surgeryfor PTC and where we hope to go.
Individualizing the Surgical Plan for the Thyroidand Central Compartment in Patients UndergoingInitial Surgery for PTC
The rationale for total thyroidectomy for PTC identifiedpreoperatively includes the frequent multifocal nature of thedisease, the ability to reduce the risk of recurrence and to fa-cilitate radioactive iodine treatment, and the use of serumthyroglobulin levels and whole-body radioiodine scans duringfollow-up. Two Mazzaferri et al. studies support that totalthyroidectomy reduces the risk of recurrence for PTC andperhaps improves survival (4,5). Most surgeons agree now that
Portions of this review were presented at the Spring 2010 Meeting of the American Thyroid Association, ‘‘Thyroid Disorders in the Era ofPersonalized Medicine,’’ Minneapolis, Minnesota, May 13–16, 2010.
1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.2Department of Surgery, Tulane Medical School, New Orleans, Louisiana.
THYROIDVolume 20, Number 7, 2010ª Mary Ann Liebert, Inc.DOI: 10.1089/thy.2010.1645
771
a total thyroidectomy is preferred over a thyroid lobectomy forthe majority of patients with known PTC before surgery (6).
Today, the advent of high-resolution ultrasonography andhighly sensitive serum thyroglobulin assays as methods em-ployed for follow-up of PTC have helped to create the con-tention surrounding elective CND. Although most wouldagree that patients should undergo formal central lymph nodedissection as designated by the American Thyroid Association(ATA) consensus statement (7) on CND for clinically apparentlymph node metastases (macroscopic lymph nodes), there isongoing debate regarding prophylactic central lymph nodedissection in the clinically negative central N0 neck, especiallyfor those patients deemed low risk with early stage disease.
Cervical lymph node metastasis occurs commonly inPTC. The prevalence ranges from 20% to 90%, with anaverage of 60% (7–10). Lymph node metastasis is thought tobe an independent risk factor for local recurrence (11,12).Recurrences rates are high in patients with macroscopic butnot with microscopic lymph node involvement. Bardet et al.reported a 10%–30% prevalence of recurrence associatedwith macroscopic lymph node involvement, whereas thosewithout had a much lower recurrence rate (13). This cer-tainly argues for compartment-oriented nodal dissectionwhen gross nodal disease is present to help reduce the riskof nodal recurrence in the neck. To further confound thesituation, despite earlier reports of no adverse effects onsurvival, emerging evidence from large population-basedstudies demonstrates an increase in mortality with regionallymph node metastases (14,15). A major limitation is that allof these studies suffer from many confounders that make itdifficult to interpret the significance of the findings for andagainst elective CND.
The ATA published guidelines for thyroid nodules andwell-differentiated thyroid cancer in 2006 and recommendedroutine CND for PTC, but failed to distinguish betweentherapeutic and elective indications (16). In these guidelines,they indicated that ‘‘routine CND should be considered forpatients with PTC.’’ They based this recommendation on thepossibility that this might improve survival, might reduce therisk for nodal recurrence, and could be achieved with lowmorbidity. This aspect of the initial guidelines led to consid-erable debate. The literature often cited in favor of CND isfrequently difficult to interpret due to the failure to distin-guish between therapeutic and elective/prophylactic indica-tions and extent of dissection. Due to these issues, the ATA’ssecond edition of these guidelines (6) took a softer stance onthe subject. The recommendation now states that therapeuticCND for patients with clinically involved central or lateralneck lymph nodes should accompany total thyroidectomy toprovide clearance of disease from the central neck. Prophy-lactic central-compartment neck dissection (ipsilateral orbilateral) may be performed in patients with PTC with clini-cally uninvolved central neck lymph nodes, especially foradvanced primary tumors (T3 or T4). Near-total or total thy-roidectomy without prophylactic CND may be appropriatefor small (T1 or T2), noninvasive, clinically node-negativePTCs and most follicular cancer. Further, these guidelines goon to state that these recommendations should be interpretedin light of available surgical expertise. For patients with small,noninvasive, apparently node-negative tumors, the balance ofrisk and benefit may favor simple near-total thyroidectomywith close intraoperative inspection of the central compart-
ment with compartmental dissection only in the presence ofobviously involved lymph nodes. This approach may increasethe chance of future locoregional recurrence, but overall thisapproach may be safer in less experienced surgical hands (6).
The ATA consensus statement on CND (7) emphasizes thatit is important to define the terminology used to classify theprocedure. An elective or prophylactic lymph node dissectioninvolves removing lymph nodes that are normal on preop-erative and or intraoperative assessment (7). A therapeuticlymph node dissection involves removing lymph nodes thatare clinically or pathologically abnormal based on examina-tion, imaging, or intraoperative assessment. The goal of de-fining the terminology and classification scheme for CND is toallow investigators to communicate without ambiguity andcompare the efficacy of these interventions. For the first time,this consensus statement defines the extent of CND as uni-lateral or bilateral. Bilateral CND is preferred as the initialmanagement of clinically involved central nodes with thera-peutic intention. However, there is controversy regardingwhether the extent of dissection needs to be ipsilateral to thethyroid tumor alone or bilateral (17,18). If any surgical treat-ment of central neck nodes is considered necessary or ap-propriate, unilateral CND may be a reasonable alternative tobilateral CND, especially as initial management of the clini-cally negative central N0 neck to minimize the risk of asso-ciated potential complications. The consensus statementoutlines and standardizes the boundaries for the CND. Inparticular, the CND should include levels VI and VII lymphnodes from the cricoid cartilage down to the innominate ar-tery (Figs. 1 and 2). Operative reports should clearly describethe extent (unilateral vs. bilateral) and the intent (elective vs.therapeutic) of CND. Lack of standardized reporting has beenpartially responsible for the debate regarding the role ofelective or prophylactic CND in PTC.
The proponents of elective/prophylactic central lymphnode dissection rationalize that the procedure removes po-tential sources of recurrence, increases the accuracy of stagingfor radioactive iodine ablation, permits accurate long-termsurveillance, and avoids the potential morbidity of a re-operation. Those who oppose elective/prophylactic centrallymph node dissection believe that the logic for routine re-moval of nodes that may harbor subclinical metastases isflawed. If removal of subclinical metastases alone were anindication for surgery without an appreciation for the clinicalsignificance of this disease, which certainly is debatable, thenthe same should theoretically apply to the lateral neck.Careful review of the literature finds no clear evidence ofbenefit in terms of lower recurrence or mortality rates for totalthyroidectomy with prophylactic/elective CND. The onlyconsistent finding is a higher rate of hypoparathyroidism forthis group. Opponents also fear that if prophylactic/electiveCND were universally adopted by all surgeons performingthyroidectomy, the risk of hypoparathyroidism and recurrentlaryngeal nerve injury may increase in the absence of signif-icant oncologic benefit to the patient (19–21). Although manyvery experienced surgeons have published very low compli-cation rates after total thyroidectomy, those results should notbe extrapolated to the majority of surgeons doing thyroidsurgery who are not routinely performing CND (22). Sosaet al. found that high-volume surgeons (defined as doing>100cases¼ 5 years) had 75% fewer complications than low-volume surgeons (4.3% vs. 16.1%) (23). There are no similar
772 TUFANO AND KANDIL
comparative studies done for outcomes related to centrallymph node dissection.
Lateral Neck Dissection for PTC
In contrast to the controversy over indications for electiveCND in PTC, the indications for lateral neck dissection areclearer. Lateral neck dissection for PTC should be performed ina compartment-oriented manner when there is clinical or cy-topathologic evidence of PTC in a lateral neck lymph node.Lymph nodes in the lateral neck (levels II–V), level VII (anteriormediastinum), and rarely in level I may be involved by thyroidcancer. For those patients in whom nodal disease is evidentclinically on preoperative ultrasound and nodal fine-needleaspiration or thyroglobulin measurement, or at the time ofsurgery, surgical resection may reduce the risk of recurrenceand possibly mortality. Functional compartmental en-bloc neckdissection is favored over isolated lymphadenectomy (‘‘berrypicking’’) with limited data suggesting improved mortality (6).
What may be less clear is which levels of the neck should beincluded in the lateral neck dissection. Recent literature hasadvocated for the routine removal of levels II, III, IV, and VBwhen there is evidence of nodal disease in the lateral neck. Aschematic right anterior oblique view indicating levels ofthe neck and upper mediastinum relevant to neck dissectionare summarized in Table 1 (Fig. 2). Lateral neck dissectioncan be safely accomplished through a low collar extension ofthe thyroidectomy incision that is cosmetically more accept-able than perpendicular incisions extending upward to themastoid tip (24,25).
Regardless of the initial treatment paradigm utilized forPTC, some patients will manifest persistent or recurrentdisease. Considerations for management of this diseasemust come from an understanding of its biological be-havior. Much of the persistent/recurrent disease today isdetected subclinically via surveillance strategies advocatedby the ATA guidelines (6,17). Ironically, despite theseimprovements in surveillance, NCI (SEER database) data
FIG. 1. Schematic anterior view of the neck indicatingboundaries of the central neck compartment (level VI): levelVI is bounded superiorly by the hyoid bone, inferiorly by thesternal notch, laterally by the carotid arteries, anteriorly bythe superficial layer of the deep cervical fascia, and poster-iorly by the deep layer of the deep cervical fascia. The centralcompartment dissection as defined by the American ThyroidAssociation consensus statement uses these boundaries fordissection except that the superior border is defined by thecricoid cartilage and the inferior border the innominate ar-tery to include level VII. Reprinted from ATA SurgeryWorking Group et al. (7) with permission.
FIG. 2. Schematic right anterior oblique view indicatinglevels of the neck and upper mediastinum (level VII) relevantto neck dissection. Reprinted from ATA Surgery WorkingGroup et al. (7) with permission.
PERSONALIZED SURGERY IN PATIENTS WITH PTC 773
demonstrate that in the last 30 years or more, the survival ratefor PTC has remained relatively the same. High-resolutionultrasonography and serum thyroglobulin assays with orwithout thyrotropin stimulation have led to a new category ofpatients with persistent/recurrent small volume disease ofuncertain clinical significance. Many authors have demon-strated that reoperative surgery for this disease, especially inthe central compartment, is safe. Efficacy of this surgery de-pends on what end point is being evaluated (26–28).
Guidelines for the management of the patient withrecurrent/persistent nodal disease are in order. Definitions ofmicroscopic and macroscopic nodal recurrences should helpto define which groups of patients could be observed versusthose that should be offered surgery. Reasonable and realisticexpectations should be set for the practitioners and patientsinvolved. When possible, compartmental dissection of theneck nodal region involved should be performed to reducethe risk of loco-regional recurrence and the morbidity of fur-ther reoperation. Many of these patients with persistent dis-ease have undergone multiple surgeries in the central orlateral compartments. Further attempts at formal compart-mental dissection must be met with a careful weighing of therisks and benefits to the patient. Perhaps the realistic goal ofall reoperative surgery should not be to render the serumthyroglobulin level undetectable but rather to prevent localdisease progression in critical areas of the neck. Long-termfollow-up of these patients is warranted to determine theoptimal surveillance and treatment paradigm.
The preceding controversies could all be rendered moot ifwe had a way to predict the biological behavior of PTC. Theability to test a fine-needle aspiration biopsy specimen dem-onstrating PTC for a molecular marker profile that could ac-curately stratify risk and prognosis would be ideal. Thismodel is becoming more realistic each passing day. Pioneersin this area like Nikiforov et al. and Xing et al. have demon-strated that the BRAF mutation in PTC predicts a poorerprognosis and that a test for the BRAF mutation can be donebefore any treatment intervention to optimize surgical treat-ment. This critical data could potentially help to determinewhich patients with PTC should have elective CND. It alsomay help to select patients with small PTCs who are able tosafely undergo minimally invasive surgery as well. Thesehypotheses must now be studied prospectively (29,30).
Minimally Invasive Thyroid Surgery, TransaxillaryRobotic Surgery, and PTC: Is There a Role?
After nearly a century of performing thyroid surgery es-sentially the way it was described by Dr. Theodor Kocher, thetechnique has rapidly evolved in the last few years. Thyroidsurgery is one of the newest fields for the application ofminimally invasive techniques. It can now be accomplishedendoscopically or with robotic assistance in many patientswho therefore may benefit from these alternative approaches.The development of thyroid surgery through smaller cervicalscars and the axilla may be a step toward better cosmeticoutcomes. Minimally invasive approaches were developed toimprove cosmetic results, minimize postoperative pain, andpotentially reduce the length of the hospital stay. These ap-proaches are a safe and feasible alternative to open thyroidsurgery while avoiding the need for a standard cervical collarincision. An improved understanding of the procedures andthe appropriate indications for their application will continueto evolve as new technologies emerge.
The most commonly used approach today is the transcer-vical minimally invasive video-assisted thyroidectomy(MIVAT) technique developed by Miccoli et al. in 2001 (31).
This approach is currently used for both partial and totalthyroidectomy. MIVAT is most commonly used for small thy-roid nodules. MIVAT is a safe and feasible alternative to openthyroid surgery in appropriately selected cases. A nodule mea-
Table 1. Levels of the Neck and Upper Mediastinum Relevant to Neck Dissection
Level Anatomical boundaries
I IA: anterior belly of digastric, hyoid bone, and midlineIB: (contains submandibular gland) anterior and posterior bellies of digastric and inferior border of mandible
II Skull base, stylohyoid muscle, horizontal line extending from hyoid bone to the posterior border of SCMIIA: anterior to spinal accessory nerveIIB: posterior to spinal accessory nerve
III Inferior edge of level II, strap muscles anteriorly, posterior edge of SCM posteriorly, and horizontal plane extendingfrom cricoid cartilage
IV Inferior edge of level III, strap muscles anteriorly, posterior edge of SCM posteriorly, and clavicle inferiorlyV Posterior to posterior edge of SCM, anterior to trapezius muscle, superior to clavicle, and inferior to skull base
Level V is divided into regions A and B by the horizontal plane extending from cricoid cartilageVI See Figure 1VII (Superior mediastinum): lies between the common carotid arteries and is superior to the aortic arch and inferior to the
upper border of the sternum
SCM, sternocleidomastoid.
Table 2. Indications and Relative Contraindications
for Minimally Invasive Video-assisted Thyroid Surgery
IndicationsA thyroid nodule <3 cm in diameterT1 papillary thyroid cancerTotal thyroid volume <30 mL
Relative contraindicationsHistory of thyroiditisHistory of neck radiationGraves diseaseHistory of MIVATTotal thyroid volume >30 mL
suring 3.0 cm or less is ideal for this approach. As MIVAT con-tinues to evolve, the indications for the procedure also evolve.
Nodule diameter above 3 cm, malignant nodules, history ofthyroiditis, and Graves disease are currently relative contra-indications. Some groups have reported that MIVAT canbe safely used in patients with the above-mentioned criteria(32–34).
The indications for this procedure have also expanded toinclude low- and intermediate-risk PTC (35). Indicationsand relative contraindications to MIVAT are summarized inTable 2. Long-term follow-up is warranted to assess oncologicefficacy.
The use of wristed instruments and the elimination of op-erator tremor have significantly expanded the applications ofthe robotic approach to head and neck surgery. Robot-assisted transaxillary thyroidectomy is feasible with properinstrumentation and an experience with robotic surgery.This approach was originally developed in South Korea byDr. Woong Chung at Yonsei University College of Medicinein Seoul. He reported his experience with 338 patients whounderwent robot-assisted endoscopic thyroid operations us-ing a gasless, transaxillary approach (36).
When compared to MIVAT, utilizing the robot in an indi-rect endoscopic approach provides a significantly broaderview of the thyroid bed. The wrist movements of the robotinstrumentation provide a greater degree of movement thanthe use of straight endoscopic instruments, while eliminatingoperator tremor.
Contraindications to this new approach include enlargedthyroids with Graves disease and advanced thyroid cancer.
Until there is longer-term follow-up for these patients, theremust be cautious enthusiasm for the universal adoption andacceptance of these techniques in PTC. We bear an obligationto our patients and society to cautiously and ethically studythe implementation of this new technology, especially for thetreatment of PTC.
When treating a patient with PTC, it seems prudent toweigh all of these factors discussed in this review to indi-vidualize the most optimal surgical plan.
Disclosure Statement
The authors declare that no competing financial interestsexist.
References
1. Hundahl SA, Cady B, Cunningham MP, Mazzaferri E,McKee RF, Rosal J, Shah JP, Fremgen AM, Stewart AK,Holzer S 2000 Initial results from a prospective cohort studyof 5583 cases of thyroid carcinoma treated in the UnitedStates during 1996. U.S. and German Thyroid Cancer StudyGroup. An American College of Surgeons Commission onCancer Patient Care Evaluation study. Cancer 89:202–217.
3. Samaan NA, Schultz PN, Hickey RC, Goepfert H, HaynieTP, Johnston DA, Ordonez NG 1992 The results of variousmodalities of treatment of well differentiated thyroid carci-nomas: a retrospective review of 1599 patients. J Clin En-docrinol Metab 75:714–720.
4. Mazzaferri EL, Young RL, Oertel JE, Kemmerer WT, PageCP 1977 Papillary thyroid carcinoma: the impact of therapyin 576 patients. Medicine (Baltimore) 56:171–196.
5. Mazzaferri EL, Young RL 1981 Papillary thyroid carcinoma:a 10 year follow-up report of the impact of therapy in 576patients. Am J Med 70:511–518.
6. American Thyroid Association (ATA) Guidelines Taskforceon Thyroid Nodules and Differentiated Thyroid Cancer,Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL,Mandel SJ, Mazzaferri EL, McIver B, Pacini F, SchlumbergerM, Sherman SI, Steward DL, Tuttle RM 2009 RevisedAmerican Thyroid Association management guidelines forpatients with thyroid nodules and differentiated thyroidcancer. Thyroid 19:1167–1214.
7. American Thyroid Association Surgery Working Group;American Association of Endocrine Surgeons; AmericanAcademy of Otolaryngology-Head and Neck Surgery;American Head and Neck Society; Carty SE, Cooper DS,Doherty GM, Duh QY, Kloos RT, Mandel SJ, Randolph GW,Stack BC Jr., Steward DL, Terris DJ, Thompson GB, TufanoRP, Tuttle RM, Udelsman R 2009 Consensus statement onthe terminology and classification of central neck dissectionfor thyroid cancer. Thyroid 19:1153–1158.
8. Qubain SW, Nakano S, Baba M, Takao S, Aikou T 2002Distribution of lymph node micrometastasis in pN0 well-differentiated thyroid carcinoma. Surgery 131:249–256.
9. Noguchi S, Noguchi A, Murakami N 1970 Papillary carci-noma of the thyroid. I. Developing pattern of metastasis.Cancer 26:1053–1060.
10. Rotstein L 2009 The role of lymphadenectomy in the man-agement of papillary carcinoma of the thyroid. J Surg Oncol99:186–188.
11. Mazzaferri EL, Jhiang SM 1994 Long-term impact of initialsurgical and medical therapy on papillary and follicularthyroid cancer. Am J Med 97:418–428.
12. Shah JP, Loree TR, Dharker D, Strong EW, Begg C, Vlamis V1992 Prognostic factors in differentiated carcinoma of thethyroid gland. Am J Surg 164:658–661.
13. Bardet S, Malville E, Rame JP, Babin E, Samama G, DeRaucourt D, Michels JJ, Reznik Y, Henry-Amar M 2008Macroscopic lymph-node involvement and neck dissectionpredict lymph-node recurrence in papillary thyroid carci-noma. Eur J Endocrinol 158:551–560.
14. Lundgren CI, Hall P, Dickman PW, Zedenius J 2006 Clini-cally significant prognostic factors for differentiated thyroidcarcinoma: a population-based, nested case-control study.Cancer 106:524–531.
15. Tisell LE, Nilsson B, Molne J, Hansson G, Fjalling M, JanssonS, Wingren U 1996 Improved survival of patients withpapillary thyroid cancer after surgical microdissection.World J Surg 20:854–859.
16. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL,Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, TuttleRM; American Thyroid Association Guidelines Taskforce2006 Management guidelines for patients with thyroidnodules and differentiated thyroid cancer. Thyroid 16:109–142.
17. Son YI, Jeong HS, Baek CH, Chung MK, Ryu J, Chung JH, SoYK, Jang JY, Choi J 2008 Extent of prophylactic lymph node
PERSONALIZED SURGERY IN PATIENTS WITH PTC 775
dissection in the central neck area of the patients with pap-illary thyroid carcinoma: comparison of limited versuscomprehensive lymph node dissection in a 2-year safetystudy. Ann Surg Oncol 15:2020–2026.
18. Koo BS, Choi EC, Yoon YH, Kim DH, Kim EH, Lim YC 2009Predictive factors for ipsilateral or contralateral centrallymph node metastasis in unilateral papillary thyroid car-cinoma. Ann Surg 249:840–844.
19. Scheumann GF, Gimm O, Wegener G, Hundeshagen H,Dralle H 1994 Prognostic significance and surgical man-agement of locoregional lymph node metastases in papil-lary thyroid cancer. World J Surg 18:559–567; discussion567–568.
20. Sawka AM, Brierley JD, Tsang RW, Thabane L, Rotstein L,Gafni A, Straus S, Goldstein DP 2008 An updated systematicreview and commentary examining the effectiveness of ra-dioactive iodine remnant ablation in well-differentiated thy-roid cancer. Endocrinol Metab Clin North Am 37:457–480.
21. Mazzaferri EL, Doherty GM, Steward DL 2009 The pros andcons of prophylactic central compartment lymph node dis-section for papillary thyroid carcinoma. Thyroid 19:683–689.
22. Stavrakis AI, Ituarte PH, Ko CY, Yeh MW 2007 Surgeonvolume as a predictor of outcomes in inpatient and outpatientendocrine surgery. Surgery 142:887–899; discussion 887–899.
23. Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA,Udelsman R 1998 The importance of surgeon experience forclinical and economic outcomes from thyroidectomy. AnnSurg 228:320–330.
24. Farrag T, Lin F, Brownlee N, Kim M, Sheth S, Tufano RP2009 Is routine dissection of level II-B and V-A necessary inpatients with papillary thyroid cancer undergoing lateralneck dissection for FNA-confirmed metastases in other lev-els. World J Surg 33:1680–1683.
25. Lee BJ, Wang SG, Lee JC, Son SM, Kim IJ, Kim YK 2007Level IIb lymph node metastasis in neck dissection forpapillary thyroid carcinoma. Arch Otolaryngol Head NeckSurg 133:1028–1030.
26. Clayman GL, Shellenberger TD, Ginsberg LE, Edeiken BS,El-Naggar AK, Sellin RV, Waguespack SG, Roberts DB,Mishra A, Sherman SL 2009 Approach and safety of com-prehensive central compartment dissection in patients withrecurrent papillary thyroid carcinoma. Head Neck 31:1152–1163.
27. Schuff KG, Weber SM, Givi B, Samuels MH, Andersen PE,Cohen JI 2008 Efficacy of nodal dissection for treatment ofpersistent/recurrent papillary thyroid cancer. Laryngoscope118:768–775.
28. Farrag TY, Agrawal N, Sheth S, Bettegowda C, Ewertz M,Kim M, Tufano RP 2007 Algorithm for safe and effectivereoperative thyroid bed surgery for recurrent/persistentpapillary thyroid carcinoma. Head Neck 29:1069–1074.
29. Xing M, Clark D, Guan H, Ji M, Dackiw A, Carlson KA, KimM, Tufaro A, Ladenson P, Zeiger M, Tufano R 2009 BRAFmutation testing of thyroid fine-needle aspiration biopsyspecimens for preoperative risk stratification in papillarythyroid cancer. J Clin Oncol 27:2977–2982.
30. Yip L, Nikiforova MN, Carty SE, Yim JH, Stang MT, TublinMJ, Lebeau SO, Hodak SP, Ogilvie JB, Nikiforov YE 2009Optimizing surgical treatment of papillary thyroid carci-noma associated with BRAF mutation. Surgery 146:1215–1223.
31. Miccoli P, Berti P, Raffaelli M, Conte M, Materazzi G, GalleriD 2001 Minimally invasive video-assisted thyroidectomy.Am J Surg 181:567–570.
32. Lombardi CP, Raffaelli M, Princi P, Lulli P, Rossi ED, FaddaG, Bellantone R 2005 Safety of video-assisted thyroidectomyversus conventional surgery. Head Neck 27:58–64.
33. Lombardi CP, Raffaelli M, Princi P, De Crea C, Bellantone R2006 Video-assisted thyroidectomy: report on the experienceof a single center in more than four hundred cases. World JSurg 30:794–800; discussion 801.
34. Ruggieri M, Straniero A, Genderini M, D’Armiento M, Fu-marola A, Trimboli P, Gargiulo P 2007 The size criteria inminimally invasive video-assisted thyroidectomy. BMCSurg 7:2.
35. Miccoli P, Pinchera A, Materazzi G, Biagini A, Berti P,Faviana P, Molinaro E, Viola D, Elisei R 2009 Surgicaltreatment of low- and intermediate-risk papillary thyroidcancer with minimally invasive video-assisted thyroidec-tomy. J Clin Endocrinol Metab 94:1618–1622.
36. Kang SW, Lee SC, Lee SH, Lee KY, Jeong JJ, Lee YS, NamKH, Chang HS, Shung WY, Park CS 2009 Robotic thyroidsurgery using a gasless, transaxillary approach and the daVinci S system: the operative outcomes of 338 consecutivepatients. Surgery 146:1048–1055.
Address correspondence to:Ralph P. Tufano, M.D., FACS
Department of Otolaryngology-Head and Neck SurgeryJohns Hopkins School of Medicine
