Serge van Ruth

PURPOSE: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin. PATIENTS AND METHODS: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival. RESULTS: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001). CONCLUSION: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer, it is important to diagnose peritoneal carcinomatosis as well as to detect location and size of peritoneal tumor dissemination in view of treatment planning. The aim of this study was to investigate the detection accuracy of computed tomography (CT). METHODS: Preoperative CT-scans from 25 consecutive patients with peritoneal carcinomatosis from colorectal or appendiceal origin were independently blindly reviewed by 2 radiologists. The presence and diameter of tumor deposits were noted in seven abdominopelvic areas. Intraoperative findings were regarded as the gold standard. Agreement was assessed using the Kappa index and the chi-square test. RESULTS: The presence of peritoneal carcinomatosis was detected in 60 and 76% of those patients by each of the radiologist. Detection of individual peritoneal implants was poor (kappa = 0.11/0.23) and varied from 9.1%/24.3% for tumor size <1 cm to 59.3%/66.7% for tumor size >5 cm. Overall sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) for tumor involvement per area were 24.5%/37.3%, 94.5%/90.4%, 53.0%/60.0%, 86.2%/84.4%, and 47.3%/50.8%, respectively. Accuracy of tumor detection varied widely per anatomic site. Statistically significant interobserver differences were noted, specifically for tumor size of 1-5 cm (P = 0.007) and localization on mesentery and small bowel (kappa = 0.30, P = 0.04). CONCLUSIONS: In colorectal cancer, CT detection of peritoneal carcinomatosis is moderate and of individual peritoneal tumor deposits poor. Interobserver differences are statistically significant. Therefore, preoperative CT seems not to be a reliable tool for detection of presence, size, and location of peritoneal tumor implants in view of treatment planning in patients with colorectal cancer.

BACKGROUND: Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome. METHODS: Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The following factors were studied for association with survival: perforation and obstruction of the primary lesion, location of the primary lesion, obstruction associated with carcinomatosis, presentation, tumour differentiation and histological type. Extent of disease and completeness of cytoreduction were also studied. Hazard ratios (HRs) were used to study these factors. RESULTS: Location of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.) 1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04 to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i. 1.21 to 4.16); P = 0.008) were associated with shorter survival. Important factors predicting survival were the number of affected regions (HR 1.38 (95 per cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR 1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other factor correlated with survival. CONCLUSION: The survival of patients with peritoneal carcinomatosis of colorectal origin is dominated by the extent of disease and the amount of residual tumour after cytoreduction.

BACKGROUND AND OBJECTIVES: Cytoreduction with hyperthermic intra-peritoneal chemotherapy (HIPEC) is a treatment with a high morbidity. Optimal patients selection can possible reduce toxicity and complications. PATIENTS AND METHODS: Complications and toxicity of 102 patients were studied. Toxicity was graded according National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A complication was defined as any post-operative event that needed re-intervention. Potential patients, tumor, and treatment factors were studied on their relation to complications. RESULTS: Grade 3, 4, or 5 toxicity was observed in 66 patients (65%). Eight patients died of treatment-related causes. Surgical complications occurred in 36 patients (35%). Fistulae were frequently encountered (18 patients). The risk of a complicated recovery was higher in carcinomatosis with recurrent colorectal cancer (P = 0.009) and in the case of more than five regions affected (P = 0.044), who had a Simplified Peritoneal Cancer (SPC) score of 13 (P = 0.012) and with an incomplete initial cytoreduction (P = 0.035). Patients with blood loss exceeding 6 L (P = 0.028) and those with three or more anastomoses also had an increased post-operative complication rate (P = 0.018). CONCLUSIONS: Toxicity of cytoreduction followed by HIPEC was 65% (Grade 3-5 NCI CTC), with a surgical complication rate of 35%. Patients with six or seven regions involved and those in whom complete cytoreduction cannot be reached are probably better off without this treatment.