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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 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 • Liver and peritoneal surface are the most frequent sites of metastasis • Treatment of colorectal liver metastases well established
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
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
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
Dr Paul H Sugarbaker • Washington Hospital Centre • Pioneer of the combined treatment • “Sugarbaker’s protocol” • Cytoreductive surgery • Perioperative intraperitoneal chemotherapy
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
Cytoreductive Surgery • Prognostic indicators: • Prior Surgical Score (PSS) • Peritoneal Cancer Index (PCI) • Completeness of cytoreduction score (CCS)
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
Peritoneal Cancer Index (PCI) • Summary of lesion size and distribution of lesions • Correlates with outcome for peritoneal metastases in CRC
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
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
Role of diagnostic laparoscopy • Allows more accurate “staging” with minimal surgical trauma • Reliable prediction of cytoreduction index
Perioperative Intraperitoneal Chemotherapy • Hyperthermic intraperitoneal chemotherapy (HIPEC) • Intraoperative/ early postoperative – no standard protocol as yet • Aim: eradication of microscopic residual disease for curative intent
HIPEC - advantages • Intraperitoneal • Increases exposure of tumour to pharmacologically active molecules • Hyperthermia • enhances cytotoxicity • improves drug penetration • heat has anti-tumour effect itself
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
Surgeon manipulates all viscera to minimize adherence of peritoneal surfaces and allow uniform distribution of drugs
Duration: 30-90 minutes • Continuous irrigation • Temperature monitoring at inflow catheters and within peritoneal cavity - maintained at 42.5ºC
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
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
Results – the risks • Common complication: • bowel perforation • anastomotic leakage • prolonged ileus/ bowel fistulation/ intraabdominal bleeding/ pancreatitis/ haematological toxicity
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
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
Gomez Patilla A. et al. Rev Esp Enferm Dig 2009Feb;101(2):97-102, 103-6
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
Prognostic factors • Peritoneal cancer index • Completeness of cytoreduction • Presence of lymph node involvement • Age and performance status
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
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
Conclusion • Significant procedural morbidity/ mortality mandates careful selection • Large scale, randomized, prospective studies needed for clarification of the role of this aggressive approach
HIPEC • Disadvantages • Removal of white cells due to chemotherapy and heat leaves the patient vulnerable to intra- abdominal infection • limited tissue penetration 3-5mm
Postoperative care • Expected prolonged bowel rest • prolonged ileus due to extensive surgery • allowing more time for healing • total parenteral nutrition
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
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℃
Intraoperative chemotherapy • Reconstructive part of surgery follows • No anastomosis is constructed until after the intraoperative chemotherapy perfusion is completed
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
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?