Adjuvant chemotherapy for stage C colonic cancer in a multidisciplinary setting.

BACKGROUND: In this study of patients undergoing adjuvant chemotherapy for clinicopathological stage C colonic cancer after optimal surgery, the aims were: to describe their immediate experience of chemotherapy, to assess disease-free survival, to compare overall survival with that of a matched untreated historical control group, and to evaluate the associations between previously identified adverse risk factors and survival. METHODS: Data were drawn from a comprehensive, prospective hospital registry of resections for colorectal cancer between 1971 and 2004, with retrospective data on adjuvant chemotherapy. The main end point was overall survival. Statistical analysis employed the chi-squared test, Kaplan-Meier estimation and proportional hazards regression. RESULTS: From May 1992 to December 2004, there were 104 patients who received adjuvant chemotherapy. Duration of treatment, withdrawal from treatment, toxicity and other immediate treatment outcomes were similar to those in other equivalent studies. There were no toxicity-associated deaths. Overall survival was significantly longer in the treated patients than in the control group (3-year rates 81% and 66%, respectively, P = 0.009). A significant protective effect of adjuvant therapy was found (hazard ratio 0.5, 95% confidence interval 0.3-0.8, P = 0.001) after adjustment for histopathology features previously shown to be negatively associated with survival (high grade, venous invasion, apical node metastasis, free serosal surface involvement). CONCLUSIONS: For patients who have had a curative resection for lymph node positive colonic cancer in a specialist colorectal surgical unit and been managed by a multidisciplinary team, post-operative adjuvant chemotherapy is safe and provides the same survival advantage as seen in randomized trials.

Outcomes after admission on the day of elective resection for colorectal cancer.

BACKGROUND: When a policy encouraging day of surgery admission (DOSA) was introduced in public hospitals in New South Wales, Australia, there were concerns that patient outcomes would be compromised. The aim of the present study was to compare patients having an elective resection for colorectal cancer (CRC) on a DOSA and a non-DOSA basis in respect of postoperative complications, operative mortality and 2-year survival. METHODS: A comprehensive prospective computerized database is maintained for all patients undergoing a resection for CRC at Concord Hospital, Sydney, Australia. The present study is based on patients who had an elective resection during the transition to DOSA between January 2000 and December 2003. Background characteristics, comorbidity, perioperative factors, tumour pathology, postoperative morbidity and mortality, and overall survival were compared between 274 DOSA and 103 non-DOSA patients. RESULTS: Of the 24 postoperative complications considered there was a significant difference in only four: DOSA patients were less likely than non-DOSA patients to have a respiratory complication (16.1% vs 29.1%, P = 0.004), a prolonged organic confusional state (5.5% vs 23.3%, P < 0.001), acute drug withdrawal (0.4% vs 3.9%, P = 0.021) or multisystem failure (0.4% vs 3.9%, P = 0.021). There was no difference in operative mortality or 2-year survival. CONCLUSION: The present study shows that DOSA did not adversely affect a wide range of outcomes for patients having a resection for CRC. In fact the results suggest that DOSA may protect against respiratory complications and prolonged postoperative confusion.

Low microsatellite instability is associated with poor prognosis in stage C colon cancer.

PURPOSE: The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O(6)-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. PATIENTS AND METHODS: The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation. RESULTS: We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. CONCLUSION: MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.

What pathologic features influence survival in patients with local residual tumor after resection of colorectal cancer?

BACKGROUND: Local residual tumor predicts poor patient survival after resection for colorectal cancer. The aim of this study was to determine the prevalence of residual tumor in a line of resection in a large prospective series and to identify other pathology variables that may influence survival in the absence of distant metastases in such patients. STUDY DESIGN: This study was based on all patients who had a resection for colorectal cancer at Concord Hospital between 1971 and 2001. Patients were followed up annually until death or December 2002. Survival analysis used the Kaplan-Meier method and log rank test. Proportional hazards regression was used in multivariate modeling. RESULTS: The overall prevalence of residual tumor in a line of resection was 5.9%. Of 12 pathology variables examined, only high grade and apical node metastasis were independently associated with survival in the subset of 120 patients with residual tumor in a line of resection but without distant metastases. The 2-year survival rate for patients with neither of these adverse features was 46.4% (95% CI, 31.7% to 59.9%) as compared with only 7.7% (CI, 0.5% to 29.2%) in those who had both. CONCLUSIONS: These results show that presence of local residual tumor after colorectal cancer resection does not carry a universally poor prognosis. Two specific histopathologic features independently associated with diminished survival were identified.

Anastomotic leakage is predictive of diminished survival after potentially curative resection for colorectal cancer.

OBJECTIVE: The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival. SUMMARY BACKGROUND DATA: There are many known prognostic indicators following surgery for colorectal cancer (CRC). However, the impact of anastomotic leakage has not been adequately assessed. METHODS: Consecutive patients undergoing resection between 1971 and 1999 were recorded prospectively in the Concord Hospital CRC database. Total anastomotic leakage was defined as any leak, whether local, general, or radiologically diagnosed. Patients were followed until death or to December 31, 2002. The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival. Confidence intervals (CI) were set at the 95% level. RESULTS: From an initial 2980 patients, 1722 remained after exclusions. The total leak rate was 5.1% (CI 4.1-6.2%). In patients with a leak, the 5-year overall survival rate was 44.3% (CI 33.5-54.6%) compared to 64.0% (CI 61.5-66.3%) in those without leak. In proportional hazards regression-after adjustment for age, gender, urgent resection, site, size, stage, grade, venous invasion, apical node metastasis and serosal surface involvement-anastomotic leakage had an independent negative association with overall survival (hazard ratio [HR] 1.6, CI 1.2-2.0) and cancer-specific survival (HR 1.8, CI 1.2-2.6). CONCLUSION: Apart from its immediate clinical consequences, anastomotic leakage also has an independent negative association with survival.

Background and perioperative risk factors for prolonged hospital stay after resection of colorectal cancer.

BACKGROUND: The aim of this study was to identify independent background and perioperative risk factors for prolonged postoperative hospital stay among patients having a resection for colorectal cancer. METHODS: Data from 1095 consecutive resections performed by specialist colorectal surgeons between 1995 and 2001 were examined by multiple least squares regression. Each putative risk factor was coded 0 if absent and 1 if present and postoperative stay was measured in days, so that the unstandardized partial regression coefficients (B) represent days of additional stay if the factor was present. Confidence intervals are at the 95% level. RESULTS: Of 35 factors examined, the following 11 had a significant independent association with postoperative stay: urgent operation (B = 4.2, CI 2.2-6.2); preoperative stay>5 days (B = 4.2, CI 2.7-5.7); perioperative transfusion (B = 3.1, CI 2.2-4.2); adjacent organ or structure involved (B = 3.0, CI 1.2-4.9); stoma constructed (B = 2.6, CI 1.8-3.5); peripheral vascular disease (B = 2.3, CI 0.4-4.1); age > or =75 years (B = 2.2, CI 1.2-3.1); respiratory disease (B = 1.7, CI 0.5-2.8); American Society of Anesthetists' (ASA) classification>Class 2 (B = 1.5, CI 0.4-2.5); splenic flexure mobilized (B = 1.4, CI 0.5-2.3); private hospital (B = 1.4, CI 0.3-2.5). CONCLUSIONS: Together these factors accounted for only a fifth of the variability in length of stay and few, except possibly ASA, were susceptible of interventions that might reduce stay. Postoperative morbidity, which is largely unpredictable, remains the major cause of prolonged hospital stay.