Joint Hospital Surgical Grand Round 2/2/2013Princess Margaret Hospital

HM Li

Pseudomyxoma peritonei Low grade malignant disease within the

peritoneal cavity, with characteristic mucus production and accumulation

Wide spectrum of diseases of intraperitoneal extravasations of mucus secretion of various causesDisseminated peritoneal adenomucinosis (DPAM)Peritoneal mucinous carcinomatosis (PMCA)

Peak incidence: 5th decade, female > maleIncidence: 1-2 per million per year

Appendiceal neoplasms and Psuedomyxoma peritonei: a population based studySmeenk et.alEur J Surg Oncol 2008; 34:196-201

Presenting symptomsIncrease intra-abdominal

pressure: bloating, reflux, hernia (new-onset), uterovaginal prolapse

Mimicking acute appendicitis – at laparotomy / laparoscopy

Palpable abdominal lump: ovarian mass, omental cake

Non-specific abdominal painConstitutional symptoms:

anorexia, weight loss, ascites

Disease progressionPeritoneal seedingAdhesionIntestinal compression obstructionDeathFeatures of aggressive diseases

Short time interval from first to subsequent presentations

Poor general condition (cachexia, muscle wasting)

P/E: multiple solid lumps

InvestigationBlood: ↓Hb, ↑CRP, ↑ESR,

↑CEA/CA125/CA19.9Imaging:

Xray: usually not helpful in diagnosis; except when complications arise (e.g. IO)

USG: Non-mobile echogenic ascites Homogenous tumour deposits Scalloping of liver and spleen Small mucinous vesicles Guidance for less viscous areas for diagnostic

paracentesis

Contrast CT:

Ebrahim et.alSA Journal of radiology Sep2011: 79-81

MRI: Similar morpholocial features shown by CTT2 weighted images enable differentiation

between mucinous and fluid ascites

ManagementSurgery

Complete cytoreductionDebulking

ChemotherapyIntraperitoneal chemotherapySystemic chemotherapy

Debulking + ChemotherapyTraditional approachRemoval of mucin and tumour bulk +/- limited resectional procedures

Right hemicolectomyPartial omentectomy Hysterectomy and bilateral oophorectomy’

Repeated laparotomies for symptomatic recurrences Ineffective and dangerous for risk of bowel

injury, fistula formation, or death

Combined treatment ApproachComplete cytoreductive surgery (CRS)Intra-operative hyperthermic intraperitoneal

chemotherapy (HIPEC)Early post-operative intraperitoneal

chemotherapy (EPIC)

New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndromeSugarbakerLancet Oncol 2006; 7:69-76

Complete cytoreductive surgery (CRS)Aim: remove macroscopic tumour (no residual

tumour deposit >2.5mm in diameter)Peritonectomy

Right and left parietal peritonectomyBilateral subdiaphragmatic peritonectomyPelvic peritonectomyGreater and lesser omentectomy

Visceral resection of involved organsRight hemicolectomy, AR, HBSO, splenectomy,

cholecystectomy, liver capsulectomy, gastrectomy, distal pancreatectomy, small bowel resection

Intraperitoneal chemotherapyAim: microscopic clearance after effective

surgical cytoreductionEradicates cells and small-volume peritoneal

disease by a local effect Chemotherapeutic agents enter tumour cells by

diffusion and penetrate tumour nodules up to 2-3mm

Mitomycin C – intraoperative IPC 5-Fluorouracil for 4-5 days postoperative IPCCisplatin, paclitaxel – under evaluation

Hyperthermic intraperitoneal chemotherapy (HIPEC)Coliseum techniqueChemotherapeutic agents (Mitomycin) are

heated to 42C within the abdomen perfusion of intra-peritoneal organs

HeatAnti-neoplastic effectsSynergize cytotoxicity of the chemotherapeutic

agentsAugment the penetration of drug into tissues

PeritonectomySugarbaker Surg Oncol Clin N Am 2003; 12: 703-727

Value of laparoscopy before CRS and HIPEC for Peritoneal carcinomatosisIversen et.al; British Journal of Surgery 2013; 100: 285–292

Coliseum techniqueChemotherapeutic agents (Mitomycin) are

heated to 42C within the abdomen perfusion of intra-peritoneal organs

HeatAnti-neoplastic effectsSynergize cytotoxicity of the chemotherapeutic

agentsAugment the penetration of drug into tissues

Hyperthermic intraperitoneal chemotherapy (HIPEC)

Early postoperative intraperitoneal chemotherapy (EPIC)5-Florouracil for 5 days, on POD0Infusion via the tenchkoff catheterChemotherapeutic agent stay within the

peritoneum for 23 hours than drain for an hour for 5 times

Complications of combined approachDeath rate 1-2%

Sepsis (associated with intestinal fistulae)Cardiovascular and respiratory complications

Serious morbidity 30-40%Sepsis (chest, intra-abdominal, wound, urinary)Anastomotic leakageFistula formationReoperation for bleedingThromboembolism

Survival benefit noted with complete CRS

Complete CRS had a survival of 70% at 20 yearsNew standard of care for appendiceal epithelial

neoplasms and pseudomyxoma peritonei syndromeSugarbaker; Lancet Oncol 2006; 7:69-76

Debulking procedures5YSR ~40%~90%: disease recurrence within 2 year and

require multiple debulking proceduresCombined cytoreductive surgery and IPEC

5YSR ~75%5YDFS: 38-74%Mortality 1-2%Significant morbidity ~40%

Improved survival of patients with PMP receiving intraperitoneal chemotherapy with cytoreductive surgery - a systemic review and meta-analysis; McBride et.al; Journal of surgical research 2013: 1-7

ConclusionPMP is a rare disease, yet it can cause

significant morbidity and mortality if left untreated

Combined approach of complete cytoreductive surgery and IPC had been replacing the use of debulking surgeryImproved survivalSignificant morbidity

References Peritoneal pseudomyxoma: results of a systematic policy of complete cytoreductive surgery

and hyperthermic intraperitoneal chemotherapy; Elias et.al; British Journal of Surgery 2008; 95: 1164-1171

Pseudomyxoma peritonei: a French multicenter study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy; Elias et.al: EJSO 2010; 36:456-462

Tumour Review: Pseudomyxoma peritonei; Smeenk et.al; Cancer Treatment Reviews 2007; 33: 138-145

Appendiceal neoplasms and pseudomyxoma peritonei: a population based study; Smeenk et.al; EJSO 2008; 34: 196-201

Pseudomyxoma peritonei: review of the controversy; Bradley et.al; Current Diagnostic Pathology 2007;13: 410-416

Operative findings, early complications, and long-term survival in 456 patients with pseudomyxoma peritonei syndrome of appendiceal origin; Youssef et.al; Diseases of the colon and rectum 2011;54(3): 293-299

Overview of pseudomyxoma peritonei; Harshen et.al; Clinical Oncology 2003; 15: 73-77 Critical Analysis of Treatment failure after complete cytoreductive surgery and

perioperative intraperitoneal chemotherapy for peritoneal dissemination from appendiceal mucinous neoplasms; Yan et.al; Annals of surgical oncology 2007; 14(8): 2289-2299

Evaluation of complete cytoreductive surgery and two intraperitoneal chemotherapy techniques in pseudomyxoma peritonei; Sorensen et.al; EJSO 2012; 38: 969-976

The importance of the learning curve and surveillance of surgical performance in peritoneal surface malignancy programs; Kusamura et.al; Surg Oncol Clin N Am 2012; 21: 559-576

Management of peritoneal surface malignancy; Sugarbaker et.al; Surg Oncol Clin N Am 2003: 12: xxi-xxiv

References New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei

syndrome; Sugarbaker; Lancet Oncol 2006; 7: 69-76 Peritonectomy procedures; Sugarbaker et.al; Surg Oncol Clin N Am 2003; 12: 703-727 NICE guideline 2004 Outcome differences between debulking surgery and cytoreductive surgery in patients

with pseudomyxoma peritonei; Andreasson et.al; ESJO 2012; 38: 962-968 Pseudomyxoma peritonei; Mukherjee et.al; Surgery (Oxford) 2004; 22: 238-241 Pseudomyxoma peritonei; Curr Probl Surg 2008; 45: 527-575 Pseudomyxoma peritonei – a rare entity (CT); Ebrahim et.al; SA Journal of Radiology

2011: 79-81 Secondary cytoreduction and perioperative intraperitoneal chemotherapy after initial

debulking of pseudomyxoma peritonei: a study of timing and the impact of malignant dedifferentiation; Chua et.al; J Am Coll Surg 2010; 211: 526-535

The etiology, clinical presentation, and management of pseudomyxoma peritonei; Moran et.al; Surg Oncol Clin N Am 2003; 12: 585-603

Improved survival of patients with PMP receiving intraperitoneal chemotherapy with cytoreductive surgery - a systemic review and meta-analysis; McBride et.al; Journal of surgical research 2013: 1-7

Value of laparoscopy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis; Iversen et.al; British Journal of Surgery 2013; 100: 285-292

Disseminated Peritoneal Adenomucinosis and peritoneal mucinous carcinomatosis - A clinicopathologic Analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to pseudomyxoma peritonei; Ronnett et.al; The American Journal of Surgical Pathology 1995; 19(12): 1390-1408

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