Owen F. Dent

Clinicopathological staging for colorectal cancer: An International Documentation System (IDS) and an International Comprehensive Anatomical Terminology (ICAT)

The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread.

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.

Anastomotic leakage after curative anterior resection results in a higher prevalence of local recurrence

The aim of this study was to determine whether leakage from a colorectal anastomosis following potentially curative anterior resection for rectal cancer is an independent risk factor for local recurrence.

Pathologic Determinants of Survival Associated with Colorectal Cancer with Lymph Node Metastases A Multivariate Analysis of 579 Patients

Background. Patients with colorectal carcinoma found to have regional lymph node metastases after curative resection form a large and prognostically diverse group. This study aims to determine which pathology variables have independent prognostic effects.

Factors affecting survival after excision of the rectum for cancer: a multivariate analysis.

PURPOSE: The aim of this study was to identify and categorize the independent prognostic effects of patient, clinical, operative, and pathology variables on long-term survival after anterior resection or abdominoperineal excision of the rectum for cancer. METHODS: Proportional hazards regression analysis was used to analyze prospective data from 709 patients who underwent surgery at Concord Hospital during a 23-year period. No patient received adjuvant therapy. RESULTS AND CONCLUSIONS: After adjusting for age and clinicopathologic stage, significantly poorer survival was experienced by males, patients with extensive tumor adherent to other organ(s), those with a high-grade tumor or a tumor showing venous invasion, those who had a postoperative cardiovascular or respiratory complication, and those who did not undergo surgery by a colorectal surgeon specialist. The nature of the operation performed had no independent effect on survival.

Surgical Technique and Survival in Patients Having a Curative Resection for Colon Cancer

AbstractPURPOSE: This study was performed to determine whether the adoption of a standardized technique for resection of colon cancer, based on mobilization along anatomic planes, resulted in improved survival after adjustment for other known prognostic factors. METHODS: Patients undergoing a potentially curative, elective colonic resection at Concord Hospital from 1971 to 1995 were included. None received adjuvant therapy. Data were recorded prospectively. Overall survival and colon-cancer–specific survival were examined by the Kaplan-Meier method and proportional-hazards regression in relation to patient and tumor characteristics and the introduction of a standardized surgical technique in 1980. RESULTS: Overall five-year survival rose from 48.1 percent before 1980 to 63.7 percent after 1980 (P < 0.0001); cancer-specific survival rose from 66.4 percent to 76.6 percent (P = 0.002). Factors that did not change significantly before and after 1980 were patient age and gender, tumor site, stage, grade, serosal surface involvement, and apical node metastases. The proportion of tumors ≥5 cm in diameter decreased after 1980 (61.9 to 49.2 percent, P = 0.001) but survival was unrelated to size. Venous invasion rose after 1980 (9 to 15.8 percent, P = 0.014). Multiple regression with adjustment for age, stage, grade, venous invasion, serosal surface involvement, and apical node metastases showed significantly shorter overall survival before the introduction of the standardized technique (hazard ratio, 1.5; 95 percent confidence interval, 1.2–1.8) and significantly shorter colon-cancer–specific survival (hazard ratio, 1.7; 95 percent confidence interval, 1.3–2.2). The proportion of patients having a noncurative operation because of residual tumor in a line of resection (excluded from the survival analyses) fell from 10.6 percent (confidence interval, 7–15.3 percent) before 1980 to 3.2 percent (confidence interval, 2–4.9 percent) after 1980. CONCLUSION: As in rectal cancer surgery, mobilization of the colon along anatomic planes is an important principle that influences outcome and needs to be emphasized.

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.

Bowel symptoms in an apparently well population.

The aim of this study was to determine the prevalence of various kinds of bowel behavior and symptoms thought to be indicative of colorectal cancer in people randomly selected from the community. A probability sample of 330 dwellings in the inner western suburbs of Sydney yielded 202 completed interviews with occupants aged 30 years and older. Eight percent reported annoying abdominal pain that had lasted for two weeks or more in the preceding six months, while 19 percent reported a feeling of incomplete evacuation at least once every two weeks. Blood on the toilet paper was reported by 14 percent and blood in the toilet bowl by 2 percent. Twenty-one percent said they always looked at their stool in the toilet bowl and 34 percent always looked at the toilet paper after using it, but 43 percent seldom or never looked at either their stool or the paper. Of the 75 who said they looked at their stool about half the time or more, two (3.1 percent) reported seeing blood during the preceding six months. Symptoms that may be associated with colorectal cancer are common in apparently well adults. Whilst this includes bleeding from the rectumin toto, it may not be true for blood seen specifically in the toilet bowl. Because this latter symptom has potential discriminating value, it may be worthwhile to promote public education encouraging people to inspect their stools regularly, and to visit their doctor if blood is seen.

Further data on the validity of the informant questionnaire on cognitive decline in the elderly (IQCODE)

The validity of the long and short forms of the IQCODE was studied in a group of 144 elderly ex‐servicemen whose wives served as informants. The study examined the association of the IQCODE with clinical diagnosis of dementia, a battery of neuropsychological and psychological tests, CT scan findings and psychosocial characteristics of informants. For comparison, the validity of the Mini‐Mental State Examination was also examined using the same standards. The IQCODE was found to perform as well as the Mini‐Mental as a screening test for dementia. Unlike the Mini‐Mental, it was not influenced by premorbid intelligence or education. However, it was influenced by other non‐cognitive factors: the affective state and personality of the subject, the affective state of the informant and the quality of the relationship between the subject and the informant. The short and long forms of the IQCODE were highly correlated and had equal validity.

Risk factors for prolonged ileus after resection of colorectal cancer: an observational study of 2400 consecutive patients.

Objective:Prolonged ileus—the failure of postoperative ileus to resolve within a few days after major abdominal surgery—leads to significant medical consequences for the patient and costs to the hospital system. The aim of this retrospective analysis of prospectively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer. Methods:Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995–2009. Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression. Results:Prolonged ileus occurred in 14.0% of patients. Statistically significant independent predictors of prolonged ileus were male sex (OR: 1.7, P < 0.001), peripheral vascular disease (OR: 1.8, P < 0.001), respiratory comorbidity (OR: 1.6, P < 0.001), resection at urgent operation (OR: 2.2, P < 0.001), perioperative transfusion (OR: 1.6, P < 0.010), stoma constructed (OR: 1.4, P < 0.001), and operation lasting ≥3 hours (OR: 1.6, P < 0.001). Conclusions:These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them. These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment.