1. Joint Hospital Surgical Grand Round 2/2/2013 Princess Margaret Hospital HM Li

2. 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 causes Disseminated peritoneal adenomucinosis (DPAM) Peritoneal mucinous carcinomatosis (PMCA) Peak incidence: 5 th decade, female > male Incidence: 1-2 per million per year Appendiceal neoplasms and Psuedomyxoma peritonei: a population based study Smeenk et.al Eur J Surg Oncol 2008; 34:196-201

3. Presenting symptoms Increase 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 pain Constitutional symptoms: anorexia, weight loss, ascites

4. Disease progression Peritoneal seeding Adhesion Intestinal compression  obstruction Death Features of aggressive diseases Short time interval from first to subsequent presentations Poor general condition (cachexia, muscle wasting) P/E: multiple solid lumps

5. Investigation Blood: ↓ Hb, ↑ CRP, ↑ ESR, ↑ CEA/CA125/CA19.9 Imaging: 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

6. Contrast CT: Ebrahim et.al SA Journal of radiology Sep2011: 79-81

7. MRI: Similar morpholocial features shown by CT T2 weighted images enable differentiation between mucinous and fluid ascites

8. Management Surgery Complete cytoreduction Debulking Chemotherapy Intraperitoneal chemotherapy Systemic chemotherapy

9. Debulking + Chemotherapy Traditional approach Removal of mucin and tumour bulk +/- limited resectional procedures Right hemicolectomy Partial omentectomy Hysterectomy and bilateral oophorectomy’ Repeated laparotomies for symptomatic recurrences Ineffective and dangerous for risk of bowel injury, fistula formation, or death

10. Combined treatment Approach Complete 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 syndrome Sugarbaker Lancet Oncol 2006; 7:69-76

11. Complete cytoreductive surgery (CRS) Aim: remove macroscopic tumour (no residual tumour deposit >2.5mm in diameter) Peritonectomy Right and left parietal peritonectomy Bilateral subdiaphragmatic peritonectomy Pelvic peritonectomy Greater and lesser omentectomy Visceral resection of involved organs Right hemicolectomy, AR, HBSO, splenectomy, cholecystectomy, liver capsulectomy, gastrectomy, distal pancreatectomy, small bowel resection

12. Intraperitoneal chemotherapy Aim: microscopic clearance after effective surgical cytoreduction Eradicates 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 IPC Cisplatin, paclitaxel – under evaluation

13. Hyperthermic intraperitoneal chemotherapy (HIPEC) Coliseum technique Chemotherapeutic agents (Mitomycin) are heated to 42C within the abdomen  perfusion of intra- peritoneal organs Heat Anti-neoplastic effects Synergize cytotoxicity of the chemotherapeutic agents Augment the penetration of drug into tissues

14. Peritonectomy Sugarbaker Surg Oncol Clin N Am 2003; 12: 703-727 Value of laparoscopy before CRS and HIPEC for Peritoneal carcinomatosis Iversen et.al; British Journal of Surgery 2013; 100: 285– 292

15. Coliseum technique Chemotherapeutic agents (Mitomycin) are heated to 42C within the abdomen  perfusion of intra- peritoneal organs Heat Anti-neoplastic effects Synergize cytotoxicity of the chemotherapeutic agents Augment the penetration of drug into tissues Hyperthermic intraperitoneal chemotherapy (HIPEC)

16. Early postoperative intraperitoneal chemotherapy (EPIC) 5-Florouracil for 5 days, on POD0 Infusion via the tenchkoff catheter Chemotherapeutic agent stay within the peritoneum for 23 hours than drain for an hour for 5 times

17. Complications of combined approach Death rate 1-2% Sepsis (associated with intestinal fistulae) Cardiovascular and respiratory complications Serious morbidity 30-40% Sepsis (chest, intra-abdominal, wound, urinary) Anastomotic leakage Fistula formation Reoperation for bleeding Thromboembolism

18. Survival benefit noted with complete CRS Complete CRS had a survival of 70% at 20 years New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome Sugarbaker; Lancet Oncol 2006; 7:69-76

19. Debulking procedures 5YSR ~40% ~90%: disease recurrence within 2 year and require multiple debulking procedures Combined 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

20. Conclusion PMP 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 surgery Improved survival Significant morbidity

21. 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

22. 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

23. Thank You