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Management of Peritoneal Carcinomatosis in Colorectal Cancer

Management of Peritoneal Carcinomatosis in Colorectal Cancer. Dr. Chan Kwan Kit Queen Mary Hospital. Colorectal Cancer (CRC). High incidence with significant morbidity and mortality Metastasis on presentation or as recurrent disease commonly encountered

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Management of Peritoneal Carcinomatosis in Colorectal Cancer

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  1. Management of Peritoneal Carcinomatosis in Colorectal Cancer Dr. Chan Kwan Kit Queen Mary Hospital

  2. Colorectal Cancer (CRC) • High incidence with significant morbidity and mortality • Metastasis on presentation or as recurrent disease commonly encountered • Liver and peritoneal surface are the most frequent sites of metastasis • Treatment of colorectal liver metastases well established

  3. Peritoneal Carcinomatosis (PC) • “Death sentence” • Median survival: 6 – 9 months • Treatment of palliative intent • systemic chemotherapy • symptomatic relief • emergency operation for complications e.g. intestinal obstruction/ perforation Chu DZ et al. Cancer 1989;63:364–7 Sadeghi B et al. Cancer 2000; 88: 358-63 Jayne DG et al.British Journal of Surgery 2002;89:1545–50

  4. Pathophysiology of PC • Consequence of full thickness invasion of bowel wall by invasive carcinoma • “Iatrogenic” during primary surgery • dissected lymphatics/ bowel lumen • blood spillage from the surgical field

  5. Breakthrough? • Jayne et al.: 58% of all patients with synchronous PC had no other systemic metastasis • Sugarbaker et al.: peritoneal cavity is the only metastatic site in 25% of patients with recurrent CRC Hypothesis: PC as a locoregional disease still susceptible to treatment of curative intent

  6. Dr Paul H Sugarbaker • Washington Hospital Centre • Pioneer of the combined treatment • “Sugarbaker’s protocol” • Cytoreductive surgery • Perioperative intraperitoneal chemotherapy

  7. Cytoreductive Surgery • Removal of macroscopic tumour on visceral and parietal peritoneum • Significant involvement of visceral peritoneum may necessitate organ resections • Significant involvement of parietal peritoneum may necessitate formal peritonectomy procedures

  8. Cytoreductive Surgery • Prognostic indicators: • Prior Surgical Score (PSS) • Peritoneal Cancer Index (PCI) • Completeness of cytoreduction score (CCS)

  9. Prior Surgical Score • PSS-0: biopsy only • PSS-1: 1 region • PSS-2: 2-5 regions • PSS-3: >5 regions Higher PSS associated with reduced survival

  10. Peritoneal Cancer Index (PCI) • Summary of lesion size and distribution of lesions • Correlates with outcome for peritoneal metastases in CRC

  11. Sugarbaker et al. Cancer therapeutics 1998; 1: 213-325 0-39

  12. Peritoneal Cancer Index • Sugarbaker in 1999: • PCI < 10: 50% five-year survival • PCI 11-20: 20% five-year survival • PCI > 20: 0% five-year survival Pestieau SR, Sugerbaker PH. Dis Colon Rectum 2000; 43:1341–1348 • Not applicable when tumour deposit at crucial anatomical site not amenable for resection

  13. Completeness of Cytoreduction Score • Size of persisting tumour after cytoreduction • CCS-0: no visible tumour • CCS-1: tumours <2.5mm • CCS-2: tumours 2.5mm - 2.5cm • CCS-3: tumours >2.5cm Principle prognostic indicator – helps intraoperative decision making

  14. Role of diagnostic laparoscopy • Allows more accurate “staging” with minimal surgical trauma • Reliable prediction of cytoreduction index

  15. Perioperative Intraperitoneal Chemotherapy • Hyperthermic intraperitoneal chemotherapy (HIPEC) • Intraoperative/ early postoperative – no standard protocol as yet • Aim: eradication of microscopic residual disease for curative intent

  16. HIPEC - advantages • Intraperitoneal • Increases exposure of tumour to pharmacologically active molecules • Hyperthermia • enhances cytotoxicity • improves drug penetration • heat has anti-tumour effect itself

  17. HIPEC - advantages • Large volume removes tissue debris and blood products • Diminishes the promotion of tumour growth associated with wound healing process through elimination of platelets/ neutrophils/ monocytes

  18. Surgeon manipulates all viscera to minimize adherence of peritoneal surfaces and allow uniform distribution of drugs

  19. Duration: 30-90 minutes • Continuous irrigation • Temperature monitoring at inflow catheters and within peritoneal cavity - maintained at 42.5ºC

  20. Chemotherapeutic agent Varies with centres e.g. mitomycin C, oxaliplatin Mitomycin C being the commonest choice – large molecular weight substance confining to peritoneal cavity for long time periods

  21. Results – the risks • Mortality 2-10% and morbidity 25-45%, predominantly determined by surgery-related factors • extent of surgery • number of anastomoses • volume of blood loss

  22. Results – the risks • Common complication: • bowel perforation • anastomotic leakage • prolonged ileus/ bowel fistulation/ intraabdominal bleeding/ pancreatitis/ haematological toxicity

  23. Results - survival benefit? • Glehen et al.: • multi-institutional retrospective study • median survival 19.2 months, irrespective of cytoreduction extent • 19% 5-year survival Glehen et al. J Clin Oncol 2004; 22: 3284-92 • Elias et al. & Verwaal VJ et al.: • the only two randomized, prospective studies • Elias: 60% survival at two years • Verwaal: median survival 22.2 months Elias et al. Ann Surg Oncol 2004; 11: 518-21 Verwaal VJ et al. Ann Surg Oncol 2005; 12: 65-71

  24. Results - survival benefit? • With complete macroscopic cytoreduction (CCS-0) • average survival from 32.4 – 60 months Glehen et al. J Clin Oncol 2004; 22: 3284-92 Elias et al. Ann Surg Oncol 2004; 11: 518-21 Verwaal VJ et al. Ann Surg Oncol 2005; 12: 65-71 Sugarbaker PH. Tech Coloproctol 2005; 9: 95-103

  25. Gomez Patilla A. et al. Rev Esp Enferm Dig 2009Feb;101(2):97-102, 103-6

  26. Patient selection • No survival benefit for patients with synchronous metastases to other organs • Aggressive treatment of large volume, high grade cancer is unlikely to translate into long-term benefit

  27. Prognostic factors • Peritoneal cancer index • Completeness of cytoreduction • Presence of lymph node involvement • Age and performance status

  28. Validation? • Reported trials are of significant heterogeneity • No standard protocol e.g. timing of chemotherapy/ use of hyperthermia • Only two randomized trials published – relatively small scale

  29. Conclusion • Peritoneal carcinomatosis from colorectal origin carries dismal prognosis with conventional treatment • “Combined treatment” - cytoreductive surgery with intraperitoneal chemotherapy may represent a new option of care in peritoneal-only metastatic disease

  30. Conclusion • Significant procedural morbidity/ mortality mandates careful selection • Large scale, randomized, prospective studies needed for clarification of the role of this aggressive approach

  31. HIPEC • Disadvantages • Removal of white cells due to chemotherapy and heat leaves the patient vulnerable to intra- abdominal infection • limited tissue penetration 3-5mm

  32. Postoperative care • Expected prolonged bowel rest • prolonged ileus due to extensive surgery • allowing more time for healing • total parenteral nutrition

  33. Peritonectomy • Peritoneum divided into 6 parts • greater omentectomy and splenectomy • left upper quadrant peritonectomy • right upper quadrant peritonectomy • lesser omentectomy and cholecystectomy • pelvic peritonectomy and resection of rectosigmoid colon • antrectomy/ gastrectomy

  34. Hyperthermic intraperitoneal chemotherapy (HIPEC) • Setting up: • After completion of cytoreductive surgery • Catheters are inserted to dependent positions • Temperatures at the inflow/ outflow/ intraperitoneal cavity continuously monitored • Temporary abdominal skin closure • Intraperitoneal temperature maintained 42.5℃

  35. Intraoperative chemotherapy • Reconstructive part of surgery follows • No anastomosis is constructed until after the intraoperative chemotherapy perfusion is completed

  36. Early postoperative intraperitoneal chemotherapy • 5-fluorouracil is utilized usually • Commenced on day 1 after operation • Infusion via Tenckhoff catheter • Chemotherapy agent dwells in the abdomen for 23 hours and drain for 1 hour • Duration: 4-5 days

  37. Counter-argument • Peritoneal carcinomatosis with low PCI and CCS may represent more favourable tumour biology • Opinions vary widely and no consensus could be reached • Genetics study? Molecular features of tumour?

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