Peritoneal Surface Malignancies. Ira Allen Jacobs, MD, FACS Surgical Oncology San Diego, CA

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1 Peritoneal Surface Malignancies Ira Allen Jacobs, MD, FACS Surgical Oncology San Diego, CA

2 Cancer dissemination routes Hematogenous metastases Lymphatic metastases Implants on peritoneal surfaces

3 Surgically Directed Chemotherapy Route Timing

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5 Tumor cell entrapment hypothesis Rapid progression of PSM Treatment is surgery alone Causes high incidence of surgical treatment failure

6 Prior limited benefits with intraperitoneal chemotherapy Limited penetration of drug Non-uniform drug distribution Long-term access

7 Cytoreductive Surgery and Hyperthemic Intraperitoneal Chemotherapy 1. Complete surgical removal 2. Hyperthermic Intraperitoneal Chemotherapy 3. Bowel reconnection or ileostomy/colostomy.

8 Cytoreduction 1. Greater omentectomy and splenectomy 2. Left subdiaphragmatic peritonectomy 3. Right subdiaphragmatic peritonectomy 4. Lesser omentectomy and cholecystectomy with stripping of the omental bursa 5. Complete pelvic peritonectomy 6. Partial or complete gastrectomy

9 Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy for Peritoneal Surface Malignancy: Experience with 501 Procedures. Journal of the American College of Surgeons - Volume 204, Issue 5 (May 2007 )

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12 Hyperthermia-Intrapertioneal Chemotherapy Alone cytotoxic Synergistic with chemotherapy ( C) Intraperitoneal chemotherapy is given just after cytoreduction but before any anastomosis

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15 Patient Selection for Treatment

16 Histopathology

17 Preoperative CT Scan

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19 Peritoneal Cancer Index

20 Peritoneal Cancer Index 0-39

21 PCI Survival PCI Survival Pestieau and Sugarbaker <10 50% 5ys Elias <16 60% 3ys Elias % 5ys >16 33% 3ys >20 0% 5ys

22 Completeness of Cytoreduction Score

23 Completeness of Resection CC Scoring RR Scoring CC0- No disease CC1-<.25cm CC cm2.5cm CC3->2.5cm R0-Complete Removal R1-Microscopic Margins R2a-<0.5cm R2b cm R2c- >2.0cm

24 Complete Cytoreduction

25 Incomplete Cytoreduction

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28 Current Indications for CS/IPC

29 Pseudomyxoma Peritonei False mucinous tumor of the peritoneum Extensive mucous accumulation Mucinous adenomas of appendix Mucus producing GI adenocarcinomas

30 HIPC Appendiceal Tumors Author Year Institution No. Pts Method 3 yr survival 5 yr survival Morbidity Morality Sugarbaker 1999 D.C. 385 MMC Witkamp 2001 Amsterdam 46 MMC 81 NA 39 8 PISO 2001 Regensburg 17 CIS 75 NA Shen 2003 Salem 23 MMC 61 NA NA NA Deraco 2004 Milan 33 Cis/MMC NA Guner 2004 Hanover 28 CIS/MMC/FU NA Loungnarath 2005 Lyon 27 CIS/MMC

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32 Peritoneal Mesothelioma cases per year in US Rule out spread from primary pleural malignancy Wide spectrum of biological aggressiveness

33 Median survival of diffuse malignant peritoneal mesothelioma using traditional treatment modalities Authors Year No. of patients Median Survival (months) Chailleux et al /167 10* Antman et al /180 15* Sridhar et al /50 9.5* Markman et al Yates et al /272 14* Neumann et al Eltabbakh et al

34 Results of treatment of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma Chief Investigator n - Median survival (months) Survival rates (%) 1-year 2-year 3-year 5-year 7-year Sugarbaker Alexander Deraco 49 NA Glehen Loggie Morris 15 NA

35 Morbidity and mortality of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal mesothelioma. Chief Investigator n - Morbidi ty (%) Hematologi cal toxicity (%) Blood loss (cc) Op duration (hours) Reoperati on (%) Mortality (%) Hospital stay (days) Sugarbaker * * Alexander * Deraco Glehen Loggie Morris * *

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37 Peritoneal Carcinomatosis occurs in 4-12% Synchronous-7% Metachronous - 4.5% 146 patients a year in Northern California

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39 Verwall VJ, Ruth SV, debree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. JCO 2003:

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42 Results of treatment of peritoneal surface malignancy with cytoreductive surgery and perioperative intraperitoneal chemotherapy Disease State No. of Patients 10-Year Survival Appendix cancer with carcinomatosis and pseudomyxoma peritonei syndrome after complete cytoreduction Primary and recurrent colon or rectal cancer with carcinomatosis and complete cytoreduction % 70 25% Recurrent abdominopelvic sarcoma with sarcomatosis following complete cytoreduction 50 43% Peritoneal surface malignancy a.peritoneal mesothelioma b.papillary serous cancer c.primary peritoneal adenocarcinoma % Symptomatic malignant ascites 16 0%

43 Morbidity and Mortality Morbidity % (23%) Most common anastomotic leaks/fistula Mortality % (4%)

44 Outside Referrals for Northern California Total of 19 patients referred with 11 pts undergo peritoneal perfusion. Total paid was $ 1,035,224 with only $71,462 paid to physicians $ 94,111 per patient Currently Baltimore is only referral center.

45 Cytoreduction with HIPEC Experimental In the highly selective patient with excellent prognostic indicators HIPEC is clinically effective.