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Hyperthermic intraperitoneal chemotherapy
- 1. DR. YAJNADATTA SARANGI GUIDEDBY-DR. SUNIL KUMAR ASST. PROFESSOR DEPT. OF GENERAL SURGERY HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY
- 2. BASICS Principle ofgiving intraperitoneal chemotherapy in presence of high temperature for peritoneal metastasis. Almost always given combined with Cyto reductive surgery
- 3. PERITONEAL CARCINOMATOSIS Shedding,implantation and dissemination of a tumor, either localized or widespread to peritoneum and serosal surface of intra peritoneal viscera as well as adjacent structure of abdominal cavity Traditionally considered as end stage disease With palliative chemo median survival was 6 month
- 4. DR. Paul Sugarbaker Pioneerin CRS AND HIPEC IN HIS EXTENSIVE STUDY IN PERITONEAL CARCINOMATOSIS HE SHOWED A ASTONISHING RESULT OF MEDIAN SURVIVAL OF 17 YR
- 7. 3 routeby which a malignancy spread 1.hematogenous 2.lymphatics 2.transcoelemic(peritoneal carcinomatosis) Transcoelemic route is responsible for peritoneal carcinomatosis Peritoneal carcinomatosis occurs due to exfoliation or breach of serosa Thus peritoneal carcinomatosis should not be equated with generalized disease instead local disease. PC respond poorly to systemic chemo due to PLASMA PEROTONEAL BARRIER So concept of HIPEC is to give intra peritoneal chemotherapy after clearing all macroscopic disease(CRS)
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- 9. Rationale Synergistic cytotoxiceffect of heat (42 to 43 degree) and chemotherapy Hyperthermia itself has anticancer activity This temperature causes protein denaturation, impairs DNA repair and inhibit oxidative metabolism Vasodilatation improving tumor oxygenation which improves effect of chemotherapeutic agent Heat increases optimal diffusion of chemotherapy Heat increases concentration of chemo drugs in peritoneum
- 10. HIPEC almostalways given in association with cyto reductive surgery CRS take care of macroscopic disease in peritoneal cavity HIPEC takes care of microscopic disease in peritoneal cavity Chemotherapeutic drugs like mitomycin C have a high intra peritoneal concentration than plasma concentration
- 11. CT drugshave limited penetration through nodule So for HIPEC to be effective only when residual tumor size after CRS not more than 2mm(2.5mm) Completeness of cytoreduction is one of the significant factor affecting survival after HIPEC Staging laparoscopy
- 12. CYTOREDUCTIVE SURGERY Removalof all visible peritoneal deposits, peritoneum,omentum and involved other organs.
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- 14. CRS Midline incision All 13 region evaluated Peritoneum from right and left hemidiphgram, right and left paracolic gutter and pelvic peritoneum excised(peritonectomy) Adjacent organ removed if necessary Greater omentum , lesser omentum removed Glissonian capsule if required
- 15. Target of CRSCC-0 OR CC-1
- 16. HIPEC TECHNIQUES 3 methodsto administer intraperitoneal chemotherapy OPEN(COLLOSIUM) CLOSED SEMICLOSED
- 17. Open Technique Hyperthermicsolution administered and manually stirred Uniformly distribute hyperthermia solution to all quadrant of abdomen ADVANTAGE-uniformly distributed in all quadrant DISADVANTGE-difficult to maintain temperature theoretical exposure to team
- 19. Semiclosed HIPEC Abdomencovered with plastic sheet and small opening given through which surgeon manipulates Disadv-Non uniform distribution Adv-temperature better controlled
- 21. Closed HIPEC Abdomen closedcompletely and through multiple catheter chemo administered. Advantages-earlier achievement of required temperature Safer for care givers Disadvantage- non uniform distribution
- 22. BELMONT Technique(closed) First2 L of isotonic fluid administered at 43 to 44 degree At 40 degree CT agent added Also given IV chemo simultaneously(BIDIRECTIONAL CHEMOTHERAPY) Drain inserted in all five peritonectomy region
- 23. Duration ofHIPEC depends on drugs MITOMYCIN C-90MINS OXALIPLATIN -30MINS
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- 25. Types of intraperitonealchemotherapy regimen 1.Neoadjuvant intraperitoneal plus intravenous chemotherapy Pt in whom PC diagnose at staging laparoscopy both IV and IP chemotherapy given to downgrade PC prevent dissemination Definitive surgery done after 3-4 cycles Disadvantage-extensive adhesion occurs
- 26. 2.Intraoperative HIPEC plusintravenous chemotherapy Most widely used IP chemo at time of CRS and IV Chemo after CRS 2.EPIC(Early postoperative intraperitoneal chemotherapy) IP chemo given through drains on POD 1 to 5 Drugs given over 1 hour and drains are clamped for next 23 hour
- 27. 4.Adjuvant intraperitoneal andsystemic chemotherapy through drain place through index CRS adjuvant chemo given
- 28. Indications of CRSand HIPEC Psedomyxoma peritoni Peritoneal mesothelioma Primary colon and rectal cancer with peritoneal seeding(M1C) Colorectal carcinoma with peritoneal cytology positive Ovarian carcinoma with PC Primary gastric cancer
- 29. Contraindications to CRs+HIPEC Poor performance status(ECOG <2) Presence of extrabdominal metastasis Diffuse widespread PC Presence of unresectable liver metastasis Presence of more than 3 or more resectable metastasis in liver Evidence of ureteric or billiary obstruction More than one site of small bowel involvement or gross involvement of small bowel Even small volume disease in hepatodudenal ligament PCI MORE THAN 17 (20)
- 30. complication Morbidity(22-34%) Mortality(.8-1.4%) Hematological toxicity Entero cutaneous fistula Sepsis Intrabodminal sepsis Wound morbidity
- 31. Higher thePCI higher the morbidity Hematological toxicity more after mitomycin C Pulmonary complications due to subdiphgramtic peritoneal stripping Oxaliplatin associated with higher intraabdominal bleeding
- 32. M1C STAGE4 DISEASE Previously palliation preferred
- 33. Verwal etal- Palliation and chemo vs CRS and HIPEC Better survival with hipec PRODIGE 7TRIAL Oxaliplatin HIPEC and CRS better survival NCCN-good PS, limited PC(PCI LESSTHAN 17),R0 OR CC-0/1 Consider neoadjuvant FOLFIRIWith Bevacizumab before CRS and HIPEC Mitomycin C vs oxaliplatin in HIPEC
- 35. Prophylactic HIPEC incolorectal carcinoma T4a N2 Mucinous histology Incomplete resection in emergency setting
- 36. Psedomyxoma peritonei Gelatinousascitis and multifocal peritoneal epithelial implants secreting copious globules of extra cellular mucin Most commonly associated with appendicular adenocarcinoma 3 types Disseminated peritoneal carcinomatosis(DPAM) Peritoneal mucinous carcinomatosis(PMCA) PMCA with intermediate prognosis Excellent survival after CRS and HIPEC Sugarbaker et al- median survival of 17 year
- 37. GASTRIC CANCER 3 scenario Prophylactic HIPEC in advanced gastric cancer to prevent PC In established case of PC Palliative for intractable ascitis Mitomycin c and cisplatin used
- 38. Ovarian cancer Majorityare stage 3(spread through PT cavity) at diagnosis CRS+HIPEC preferred for patient with stage 3 and 4 Epithelial ovarian carcinoma with no residual disease more than 1cm Paclitaxel and cisplatin are standard NCCN – CISPLATIN
- 39. PERITONEAL MESOTHELIOMA Patientwith PCI score less than 20 ideal candidate Epitheloid variant showed better response than sarcomatoid and biphasic variant IP cisplatin standard
- 40. Conclusion Patients ofCRS, PMP,Ovarian carcinoma with peritoneal carcinomatosis should offered HIPEC and CRS HIPEC preferred if only CC0 OR CC1 achieved by CRS i.e less than 2.5mm Best results are with appendicular adenocarcinoma with PC(PMP)
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