Management of Pseudomyxoma Peritonei (PMP) and Colon Cancer Carcinomatosis by Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

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1 Surgical Oncology Department Management of Pseudomyxoma Peritonei (PMP) and Colon Cancer Carcinomatosis by Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). 21/04/2010

2 THERMOMETRY ml/min HEAT EXCHANGER 43-44, H.I.PE.C. PUMP Ice-Helmet COOLING MATT

3 Rational of HIPEC Hyperthermia High Concentration Chemotherapy (Peritoneal Plasma Barrier) Mechanical Washing of the Peritoneal Cavity (Cellular Entrapment)

4 HIPEC at IRCC (MK1) Abdominal cavity is inflow partially points closed (only the skin) and suspended by Skin 3 holders Outflow secured Tubes to the retractor by self-blocking Probes strips. The hand of the surgeon shakes the perfusate in the Temperature abdomen Probes Advantages 43,7 Very low leak of heat Total contact between 42,1 perfusate and muscular fascia at the top of cavity. More difficult to leak perfusate in O.R. 2 Y Inflow Tubes (18F): 4 5 abdominal Temperature Esophageal and Vescical In-Flow Temperature: 43,3 - Out-Flow Temperature: 41,5 - Flow: ml/min Double Heads pump controlled by computer for perfusate level J Surg Oncol Feb;82(2):138-40

5 HIPEC at IRCC Semiclosed Perfusion Mk 2 Closed Perfusion with hand acess

6 What is PMP? Pseudomyxoma Peritonei is a rare myxoid tumor (50-70 new cases per year in Italy ) Main Feature: Low number of neoplastic cells in a great amount of abscites mucinous

7 Clinical Presentation

8 Clinical Presentation

9 Ethiology Ethiology has been discussed: Up-to-date definition focusses on primary tumor from appendiceal adenoma or adenocarcinoma Rarely, myxoid ovarian cancer (or other primary tumors) are included

10 HIPEC in PMP & CRC

11 Definition Different biological behavior and features brought some difficulties in merging in univocal definition tumors with so different outcome and prognosis

12 HIPEC in PMP & CRC

13 Sugarbaker s classification distinguishes: 1) Disseminated Peritoneal Mucinosis (DPMA): Properly defined Pseudomixoma from benign mucinous adenoma of the appendix 2a) Intermediate Peritoneal Mucinous Carcinomatosis (PMCA-I) (Am.J.Surg.Pathol.2006;30:551) 2) Peritoneal Mucinous Carcinomatosis (PMCA): from mucinous adenocarcinoma of appendix wich includes a variety of biological behavior of carcinomatosis

14 Peritoneal Carcinomatosis Peritoneal Mucinosis HIPEC in PMP & CRC (PMCA) (DPMA)

15 Failure Sugarbaker s Classification Sometimes MUC2 (Am.J.Pathol.2002;161:551) should be quite difficult for pathologists CDX2 CK20 a clear (Histopathology and univocal 2006;49:381) definition of CK7/CK20 biology of Immunoprofile primary tumor (Am.J.Surg.Pathol.2006;30:1130) COX-2 (Cancer Lett. 2006) - EGFR (22/22) Improvement of immunohystochemistry and immunogenetics tests should enlighten some new aspects of those neoplasms (e.g.:overexpression of Muc-2 gene)

16 HIPEC in PMP & CRC Surgery is indicated also in very advanced cases

17 PMP: surgical contraindications Massive ileum inflation and/or mesoileum retraction Previous non radical surgery often brings to deep neoplastic cellular entrapment in scar tissues

18 PMP Radical surgery from the first step is mandatory

19 Surgical Treatment Cytoreduction alone 10 years O.S.: 21% (Ann. Surg 2005) Cytoreduction plus H.I.P.E.C. 10 years O.S.: 65% (Br.J.Surg 2005)

20 Peritoneal Carcinomatosis CLINICAL EXPERIENCE (October August 2010) 507 Operation for Peritoneal Carcinomatosis 82 Explorative Laparotomy (5 for Gatric cancer) 119 Debulking (Peritonectomy) without HAPP. 33 Citoreduction with EPIC 273 HIPEC 273 HIPEC In 263 Patients 79 Ovarian Cancers 72 Pseudomyxomi 54 Colo-Rectal Cancers 37 Mesotheliomas 17 Sarcomas 01 Desmoplastic Tumor 06 Gastric Cancer 07 Other Neoplasm

21 Mortality & Morbidity 273 Cytoreduction & HIPEC: October 1995 August 2010 Major Morbidity 60 pts/273 (21,9%) (PMP 27 pts/71=38,02%) 31 (11,3%) Reoperations Overall Mortality 9/271 (3,3 %) (PMP=0%)

22 Personal Casuistry (P.M.P.): 109 Patients submitted to surgery (118 observed) 30 Palliative operations 12 Exploratory laparotomies 18 Debulking without P.C.H (ileum inflation) 2 debulking in 2 steps 3 Cytoreduction + EPIC In 10 cases of palliative operation: previous non radical operations 71 PMP ( in 76 operations) cytoreducted and submitted to HIPEC ( three in 2 steps, 1 in 3 steps) 19 Adenomas 50 Adenocarcinomas of Appendix 1 ovarian 38 submitted to previous non radical operations (range 1-4) 3 reoperations+hipec for recurrence: 1 after 4 years, 1 after 3 years and 1 at 18 m. 8 single bulky disease radical excision after HIPEC

23 Extension of cytoreductiom before HIPEC (71 Operations) 65 Great omentum resection 64 Right diaphr. peritonectomies 59 Pelvic peritonectomies 50 Resection of rectum 20 Hysterectomies / 18 oophorectomies 51 Spleenectomies 32 Left diaphr. peritonectomies 52 Colonic resections 45 right / 7 trasverse-left colon 50 Glisson s capsule removal 45 Cholecistectomies 45 Lesser omentum resections Epiploic peritonectomies 33 tripus/liver ligament 32 jejunal or ileum resections 5 Total Gastrectomies 7 Partial Gastric resect. 6 Pancreatic resections 8 Appendectomies ********************* 91 Bowel anastomosis 59 Jejunostomies 51 Ileum diversions

24 PMP : Overall Survival PMP Survival 1.0 Cumulati ve Survival Months from surgery

25 PMP : Disease Free Survival PMP: Disease Free Survival 1.0 Survival probabilit y (%) Months from Surgery

26 N.S. O.S. and PCI N.S. 1,0 PCI>16 PCI<16 0,8 0,6 Survival probability (%) 0,4 0,2 0, Months from Surgery

27 P<0,014 O.S. and Histology P<0, DPAM PMCA Survival probability (%) Months from Surgery

28 O.S. and Preop. Chemotherapy P<0, CT not done CT done Months from Surgery

29 HIPEC in PMP: HIPEC in PMP & CRC Conclusions Acceptable but high Morbidity rate Acceptable perioperative mortality Cytoreduction plus HIPEC in management of PMP allows 10 years O.S. in more than 80% of patients

30 Peritoneal Carcinomatosis by Colon Cancer

31 (sv a 2 anni 43% versus 16%) (Verwaal,J.Clin.Oncol 2003,21:3737) Verwaal et al. - J. Clin. Oncol

32 S. CTH HIPEC R0 5y Sv.=45% Progression Free Surv 7,7 months 12,6 months P=0,02 Median Disease Surv 12,6 months 22,2 months P=0,028

33 HIPEC in PMP & CRC

34 HIPEC in PMP & CRC

35 HIPEC in PMP & CRC

36 Prognostic Factors (Glehen) Completness of Cytoreduction Median sv. 32m -> 8,4m Extension of the disease PCI < 13 = median Sv34m PCI >13 = median Sv.14,4m Histologic Differentiation Median sv. 30m -> 14,4m Linf Mts Median sv. 31,2m -> 18m

37 Exclusion Criteria (from 2004) >=G3) => N2 More than three Liver Mts PCI>16

38 Sv (23 Pts) versus (25 Pts) 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 1995/2003 Median SV 16, ,4 P<0,0001 P<0,004 P<0, /2009 Median SV 25, ,1 mesi mesi mesi mesi

39 HIPEC in PMP & CRC

40 Complicanze :22/48 (45,8%) % Complications P M 39% P<0,28 F 55% P<0,48 P<0,5 Before % Very Important: Patient Selection P<0,01 After % P<0,1 N Periton. N.S. N.S. N Anastom. N.S. N.S PCI <16 CC0 T<10h 42% 43% 37,9% PCI >16 CC1-2 T>10h 53% 55% 57,8%

41 Scond Look after CTH (after 6 Months) I Group 16 pt : minimal PC (10p) 62% PC -> 16 HIPEC II Group 4 pz: Ovarian Metastasis (3)75% PC -> 3 HIPEC III Group 9 pz Cancer perforated 33% PC -> 3HIPEC PCI = 10,4 Complication 14%

42 Second Look 3 months after CTH 5 Pts con minimal PC e/o Krukenberg 4/5 PC 5 HIPEC PCI = 5 No Complications F.U. max 28 months 3 NED 2 AWD

43 HIPEC in PMP & CRC

44 HIPEC in PMP & CRC

45 Exlusion Criteria HIPEC in PMP & CRC Patients Selection Second >=G3) => N2 More than three Liver Mts PCI>16 Look?

46 The End Thank for Attention

47