1. Management of pseudomyxoma peritonei Rockson Wei Queen Mary Hospital Joint Hospital Surgical Grand Round 25 th July, 2009

2. Pseudomyxoma Peritonei  Definition  Low grade malignant disease within the peritoneal cavity  Characterized by 1. Production and accumulation of mucous 2. Mucinous implants

3. Epidemiology  Incidence ~ 1 per million a year  Over 80% from appendix or ovary  Other sites: pancreas, bile duct, colon, gall bladder and urachus R.M. Smeenket al Appendiceal neoplasms and pseudomyxoma peritonei: A population based study Euro J Surg Oncol 2008; 34, 196-201

4. Clinical presentation  Abdominal pain and distension  Symptoms from the primary tumor  mimicking appendicitis  inguinal hernia  ovarian mass  “Jelly belly”  Abundant intraperitoneal mucous Qu Z, Liu L Management of pseudomyxoma peritonei World J Gastroenterology 12 (38): 6124–7

7. Natural history  Peritoneal seedlings lead to fistula and adhesion  Excessive mucous accumulation compresses intestine  Compromise gastrointestinal function  Intestinal obstruction  Ends in mortality unless radically treated

8. Histopathology  Low grade malignancy  Originate from tumours of appendix / ovary  Mucinous (cyst)adenoma  Mucoceles  Mucinous (cyst)adenocarcinoma

9. Management  Traditional strategy  Repeated surgical debulking procedures  Intraperitoneal or systemic chemotherapy  Leucovorin  Floxuridine  10 year survival only 20% Culliford AT, Paty PB Surgical debulking and intrapertioneal chemotherapy for established peritoneal metastases from colon and appendix cancer Ann Surg Oncol 8 (10): 787

10. Management  Combined treatment strategy 1. Peritonectomy with electrosurgery  Maximum radical oncological cytoreductive surgery 2. Intra-operative hyperthermic intraperitoneal chemotherapy  Eliminates microscopic or minimal residual disease  Hyperthermia increases drug effectiveness 3. Early post-operative intraperitoneal chemotherapy Sugarbaker New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome Lancet Oncol 7 (1): 69–76

11. Indications for combined treatment 1. Large volume of noninvasive peritoneal carcinomatosis 2. Low volume peritoneal seeding of invasive cancer 3. Perforated gastrointestinal cancers 4. Gastrointestinal cancer with ovarian involvement Sugarbaker Management of peritoneal surface malignancy using intraperitoneal chemotherapy and cytoreductive surgery Manual for physicians and nurses 1998

12. Peritonectomy  Removal of all tumour tissues from the parietal and visceral peritoneum  Large tumour nodules must be resected and all visible tumors removed  Small cancer deposits on the visceral peritoneum are also individually electroevaporated

13. Hyperthermic intraperitoneal chemotherapy (HIPEC)  Aim: to eradicate microscopic residual disease for curative intent  Performed after completion of peritonectomy  Catheters are inserted to dependant positions  Thermocouples continuously monitor the inflow, outflow, and intraperitoneal cavity temperatures  Temporary abdominal skin closure  Intraperitoneal temperature maintained 42.5 ℃

14. HIPEC setup diagram

15. HIPEC agents  Depends on the tumor histological characteristics.  Pseudomyxoma peritonei - Appendix, colon and stomach  Cisplatin (CDDP; 25 mg/m2 per liter)  Mitomycin C (MMC; 3.3 mg/m2 per liter)  Ovary, mesothelioma and others  Cisplatin (CDDP 43 mg/m2 per liter)  Doxorubicin (15.25 mg/m2 per liter)

16. HIPEC  Advantages:  Hyperthermic conditions increase cytotoxicity  Heat has anti-tumour effects  Prolonged retention improve drug penetration  Manual intra-op chemotherapy allows uniform distribution of drug  Eliminates platelets, neutrophils & monocytes  Diminishes promotion of tumour growth associated with wound healing process

17. HIPEC  Disadvantages  Removal of white cells due to chemotherapy and heat leaves the patient vulnerable to intra- abdominal infection  Strict aseptic technique is required during administration of chemotherapy

18. Early postoperative intraperitoneal chemotherapy  5-Florouracil is utilized  Commenced immediately after operation  Infusion via Tenckhoff catheter  Chemotherapy agent dwell in the abdomen for 23 hours and drain for 1 hour  Repeat 5 times

19. Effectiveness of combined treatment SeriesPatient Number 5 year survival 10 year survival Follow up (months) 3 year disease free survival (%) Traditional treatment Miner et al9780215712 Gough et al5653321443 Combined treatment Sugarbaker et al38586803862 Smeenk et al10360505156 Moran et al100723070 Elias et al3666604855 Deraco et al33972974 Guner et al288051 Loungnarath et al275223

20. Extrapolation of combined treatment Disease stateNumber of patients 3 year survival Primary and recurrent carcinoma of colon / rectum with carcinomatosis 4541 Stage IV gastric cancer1331 Recurrent abdominopelvic sarcoma5043 Peritoneal surface malignancy4827  Multiple peritoneal metastases  Not readily reproducible  Controversial Sugarbaker 1990, 1998a, 1998b, 2003

21. Summary  Combined treatment (Sugerbaker)  Peritonectomy  Intra-operative hyperthermic intraperitoneal chemotherapy  Early post-operative chemotherapy  Effective for pseudomyxoma peritonei