management of peritoneal carcinomatosis in colorectal cancer
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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 - PowerPoint PPT PresentationTRANSCRIPT
Management of Peritoneal Carcinomatosis in Colorectal
CancerDr. 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;63:364–7Sadeghi 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
Sugarbaker et al. Cancer therapeutics 1998; 1: 213-325
0-39
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: 518-21Verwaal 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 2009 Feb;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?