Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer.

BACKGROUND: Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. METHODS: A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods. RESULTS: Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections. CONCLUSION: Microsatellite instability status was not an independent prognostic variable in these patients.

Rectal mobilization: the place of Denonvilliers' fascia and inconsistencies in the literature.

Confusion remains as to what is meant by Denonvilliers' fascia. This review searched the literature on pelvic surgical anatomy to determine whether there is agreement with Denonvilliers' original description and its implication in defining the correct anterior plane of dissection when mobilizing the rectum. The original French description of the fascia was translated into English and then compared both with French and with English studies identified by searching PubMed, Medline and Scopus from 1836 to June 2015. Special emphasis was given to the years between 1980 and 2015 in order to capture the literature pertinent to, and following on from, the description of total mesorectal excision for rectal cancer. The final literature search revealed 16 studies from the original 2150 citations. Much of the debate was concerned with the origin and development of the fascia, arising from either the 'fusion' or the 'condensation' of local primitive tissue into a mature 'multilayered' structure. Controversy regarding the correct plane of rectal mobilization occurs as a result of different interpretations by surgeons, anatomists and radiologists and bears little resemblance to Denonvilliers' original description. This may reflect wide anatomical variability in the adult pelvis or a form of dissection artefact. Further study is required to investigate this. Logically, for both men and women, the plane of rectal mobilization should be behind Denonvilliers' fascia and between it and the fascia propria of the rectum.

Long-term results following an anatomically based surgical technique for resection of colon cancer: a comparison with results from complete mesocolic excision.

AIM: Complete mesocolic excision (CME) has been advocated as likely to improve the long-term oncological outcome of colon cancer resection, although there is a paucity of long-term results in the literature. The aim of this study was to supplement our previously published results on colon cancer resection based on a standardized technique of precise dissection along anatomical planes with high vascular ligation and to compare our long-term results with those of recent European studies of CME. METHOD: Data were drawn from a prospective hospital registry of consecutive resections for colon cancer between 1996 and 2007, including follow-up to the end of 2012. The principal outcomes from potentially curative resections were 5-year Kaplan-Meier rates of local recurrence, systemic recurrence, overall survival and cancer-specific survival. Secondary outcomes for all resections were postoperative complications, number of lymph nodes retrieved and R0 status. RESULTS: For 779 potentially curative resections the local recurrence rate was 2.1% (95% CI 1.3-3.4), the systemic recurrence rate was 10.2% (95% CI 8.1-12.7), the 5-year overall survival rate was 76.2% (95% CI 73.0-79.0) and the cancer-specific survival rate was 89.8% (95% CI 87.3-91.9). For all 905 resections, rates of 14 surgical complications were low and not dissimilar to those in a comparable study. The median lymph node count was 15 (range 0-113). R0 status was confirmed in 883/905 patients (97.6%; 95% CI 96.4-98.5). CONCLUSION: For colon cancer, meticulous dissection along anatomical planes together with high vascular ligation results in few complications, a high R0 rate, low recurrence and high survival.

Circulating tumour cells and circulating nucleic acids as a measure of tumour dissemination in non-metastatic colorectal cancer surgery.

There is accumulating evidence for circulating tumour cells (CTCs) and circulating tumour nucleic acids (ctNAs) as prognostic and predictive biomarkers in colorectal cancer. Their role in the perioperative setting is evolving. These blood-borne biomarkers can potentially demonstrate tumour dissemination at time of colorectal cancer surgery and estimate the completeness of a surgical resection. CTCs and circulating ctNA levels at time of surgery, and persistent levels post-surgery, may correlate with poorer patient outcomes. These biomarkers can be utilised to refine surgical techniques to minimise tumour dissemination and determine the need for adjuvant therapy.

Impact of obesity on complications after resection for rectal cancer.

AIM: The prevalence of obesity in Australia is high and increasing, with associated serious negative effects on health. The technical complexity of rectal cancer surgery is exacerbated in obese patients, which may compromise outcomes. The aim of this study was to examine the association between obesity and complications after resection of rectal cancer. METHOD: Data were drawn from a comprehensive prospective registry of rectal cancer resections performed from 2007 to 2011 by members of the colorectal surgical unit in a tertiary referral hospital and in a single private hospital with which they were affiliated. RESULTS: Of 255 patients who had a resection for rectal cancer during the study period, 95 (37%) were classified as obese on the basis of a body mass index (BMI) ≥ 30 kg/m(2) . Among 24 postoperative complications the only significant differences for obese patients were higher rates of wound complications (16% vs 8%, P = 0.038), small bowel obstruction (4% vs 0%, P = 0.019) and prolonged ileus (18% vs 8%, P = 0.011). The total number of complications did not differ significantly between obese and nonobese patients, and there was no difference between obese and nonobese patients in the rates of reoperation and postoperative death. CONCLUSION: This study did not support an association between obesity and early postoperative complications after resection of rectal cancer.

Magnetic resonance imaging cannot predict histological tumour involvement of a circumferential surgical margin in rectal cancer.

AIM: Several recent studies have attempted to evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting the likelihood of tumour involvement of the postoperative circumferential resection margin (CRM) in rectal cancer with the intention of selecting patients who might benefit from neoadjuvant therapy and as a guide to surgery. The aim of this study was to assess whether such studies can provide a valid answer as to whether preoperative MRI can accurately predict CRM involvement by tumour. METHOD: The study design and methodology of studies on this topic were critically examined. RESULTS: Features identified as affecting the efficacy of these studies were: representativeness of patients, definition of the margin assessed by MRI and by histology, lack of blinding of surgeons and pathologists to MRI results, effect of neoadjuvant treatment, and number of patients studied. CONCLUSION: Because of methodological inadequacies in studies completed to date, there is insufficient evidence of the ability of a positive MRI result to predict an involved CRM. Although MRI may be able to identify a tumour that has extended to the mesorectal fascia and/or intersphincteric plane, logically, it cannot indicate where the surgical boundary of the resection will ultimately lie, and therefore cannot validly predict an involved CRM and should not be relied upon for this purpose.

Clinician opinion on the management of patients with hepatic colorectal metastases.

BACKGROUND AND AIMS: Clinical practice is determined by many different factors, but with the advent of evidence-based medicine, there may be a tendency to concentrate upon the scientific facts when decision-making rather than focusing on the patient. Furthermore, individual clinician opinion or bias may potentially influence patient management. This study outlines clinician opinion with regard to management of patients with hepatic colorectal metastases, and compares it to present practice in the Sydney metropolitan area. METHODS: Clinician opinion was assessed by using a questionnaire and compared to results from a prospective multicenter study looking at patterns of care of patients with hepatic colorectal metastases. RESULTS: Clinicians participating in the present study had a good knowledge of the current evidence concerning hepatic colorectal metastases and its treatment. However, there was a discrepancy between clinician knowledge that matched scientific evidence and actual clinical practice. CONCLUSIONS: This study suggests that clinician bias/opinion does influence patterns of care for patients with hepatic colorectal metastases.

K-ras mutation and loss of heterozygosity of chromosome 17p and survival in colorectal cancer.

BACKGROUND: The development of colorectal cancer (CRC) is thought to be a multistage process involving alterations to several types of genes, including oncogenes and tumour suppressor genes. This study examined the associations between allelic deletions of chromosome 17p in the region of the p53 gene and K-ras gene mutation and survival among CRC patients. METHODS: Resected specimens from 233 patients were examined. Point mutation of codon 12 of K-ras was assessed using a modified polymerase chain reaction method. Allelic deletion of 17p was demonstrated by loss of heterozygosity (LOH) with the marker Mfd144. RESULTS: Fifty-seven tumours (24%) showed somatic point mutation of codon 12 of K-ras and 86 tumours (37%) showed LOH of Mfd144. There were 107 tumours (46%) with either K-ras mutation or LOH and 18 tumours (8%) with both. Compared with patients with neither alteration, significantly poorer survival was experienced only by those with both alterations (P = 0.015). However, when this variable was introduced into a multivariate analysis controlling for the patient's age and tumour stage, it failed to show a statistically significant independent effect on survival. CONCLUSIONS: Point mutation of K-ras and LOH of Mfd144 in CRC does not add to the prognostic information already available from clinicopathological staging.

Survival after curative resection of lymph node negative colorectal carcinoma. A prospective study of 910 patients.

BACKGROUND: Approximately half of all patients treated for colorectal carcinoma by bowel resection have neither lymph node metastases nor known residual tumor (clinicopathologic Stages A and B). The aim of this study was to compare the survival of these patients with that of the general population and to explain any significant difference. METHODS: Prospectively collected data recorded for 910 patients from one institution during a period of 21.5 years were used in the analysis. Patient follow-up ranged from 6 months to 21.5 years. The "Survival" procedure, developed by the Finnish Cancer Registry, was used to compare the observed survival of patients with their expected survival, based on age- and sex-matched data from the population of New South Wales. Survival analysis was performed by the Kaplan-Meier method. Multivariate models were examined using Cox proportional hazards regression. RESULTS: Males with tumor spread beyond the muscularis propria (Stage B) was the only group with significantly poorer survival than expected. The reduced survival in this group was due to the effects of four clinical variables (cardiovascular complication, permanent stoma, urgent operation, respiratory complication) and one pathologic variable (direct spread involving a free serosal surface) acting independently. CONCLUSION: The survival of patients with clinicopathologic Stages A or B tumors closely matched their expected survival as predicted from the general population. Males with Stage B tumors were the only exception and their significantly reduced survival was largely due to clinical, as distinct from pathologic factors. These findings suggest that the risk of occult metastases is low for patients with Stages A and B tumors using this classification.

Frequency of intermediate admissions and place of death of patients with advanced colorectal cancer.

An analysis was made of the place of death and the degree of institutional support required following surgery in patients with colorectal cancer (CRC) who had distant metastases. There was a high incidence of intermediate admissions to an acute hospital, and most patients died in an acute hospital bed. The number of readmissions and the place of death were not influenced by the patients' age, sex, site of tumour or their home situation at the time of diagnosis. In view of the high demand for acute surgical beds, there is a need to develop more appropriate facilities to care for patients in the terminal phase of this disease.

How useful is pre-operative computerized tomography scanning in staging rectal cancer?

This study evaluates prospectively the reliability of computerized tomography (CT) in the pre-operative staging of 80 patients with rectal cancer. The scans were performed and reviewed by one radiologist without knowledge of either the operative findings or the final clinicopathological stage of the tumours. Fourteen of 60 patients (23%) who had a potentially curative resection were correctly staged by CT. The tumour was understaged in 28 patients (47%) and was overstaged in 18 patients (30%). CT did not identify the one patient with histological demonstration of invasion of an adjacent organ was equivocal or incorrect in 10 others on the question of adjacent organ invasion. CT failed to define accurately local tumour spread confined to the rectal was (positive predictive value (PPV) 23%), identify venous invasion (PPV 35%) or involved regional lymph nodes (PPV 42%). However, the negative predictive value for excluding synchronous liver metastases was 90%, and 11 patients who subsequently developed histologically confirmed local recurrence were all correctly diagnosed on CT. These findings suggest that pre-operative examination of patients with rectal cancer by CT is not routinely justified specifically for purposes of staging the disease.

Pre-operative isotope liver scanning in clinicopathological staging of patients with large bowel cancer.

Isotope liver scanning is an accurate technique for detecting liver metastases from large bowel cancer. In this retrospective study of patients who had a resection for bowel cancer, the accuracy of liver scanning was 95%. However, the scan accuracy as defined by median survival time was insufficient to detect liver metastases missed by the surgeon at operation and did not alter the clinicopathological stage of the patient's disease.