[Show abstract][Hide abstract] ABSTRACT: Locally advanced rectal cancer is commonly treated by neoadjuvant therapy and the resultant tumour response can be quantified histologically. This therapy may also induce radiation colitis, which also can be graded. The aim of this study was to assess the grading of tumour regression and of radiation colitis and their relationship to other prognostic parameters.
Between 2000 and 2006, 75 patients (23 women; median duration of follow up, 58 months) with rectal cancer were evaluated. Sixty-three had short-course radiotherapy and 12 had long-course radiotherapy. Tumour regression was graded histologically using the three-point Ryan system: patients with grades 1 and 2 were considered as responders and patients with grade 3 were considered as nonresponders. Radiation colitis was graded histologically as mild, moderate or severe, as described previously (J Pathol 2006; 210: P25).
Twenty-nine patients were classified as responders and 46 as nonresponders. The former were less likely to be lymph node positive compared with the latter (P=0.001). Tumour response did not correlate with local recurrence. Responders showed a disease-free survival (not overall survival) advantage at 2 and 5 years over nonresponders. Responders showed a higher rate of postoperative abdominal complications. Histological evidence of regression was demonstrated in patients treated with short-course radiotherapy. There was no relationship between radiation colitis grade and abdominal complications.
Radiation colitis grade does not correlate with postoperative complications. More abdominal complications occurred in patients receiving long-course radiotherapy.
[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who have been treated with broad-spectrum antibiotics, patients with serious underlying co-morbidities and the elderly are at greatest risk. Over 80% of CDIs reported are in people aged over 65. Due to the alarming increase in its frequency, appearance of more virulent strains and occasional need for life-saving surgical intervention, a more coherent multidisciplinary approach is needed. Combination of rapid turn round time and accurate diagnosis will result in a better management of CDI and a timely implementation of infection control measure. Discontinuation of causative agents such as antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of CDI have been reported in about 20-25% of cases, this may increase to 45-60% after the first recurrence. Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis is made to avoid sepsis or bowel perforation. Colectomy may improve the outcome of the patient with systemic or complicated Clostridium difficile colitis. This article reviews the changing epidemiological picture, microbiology, histopathology and both medical and surgical managements.
Techniques in Coloproctology 06/2010; 14(2):97-105. DOI:10.1007/s10151-010-0574-3 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Physical inactivity is responsible for 13–14% of colon cancer, an attributable risk greater than family history. Epidemiological
evidence shows that PA is protective against colon cancer but is inconclusive as to whether it is protective of rectal cancer
or has equal effects on male and female risk of colorectal cancer. The effect of exercise interventions on the risk of colorectal
cancer is currently not known; however, the results of a recently published 12-month training programme are encouraging. Although
inferences can be made from epidemiological studies, no optimal exercise regimen can be confidently prescribed for protection
against colorectal cancer. The limited available evidence demonstrates potential benefits of being physically active before
diagnosis of colorectal cancer for disease-specific survival and prognosis. Studies undertaken on survivors of colorectal
cancer provide the basis for future research which should be designed to more directly investigate the effect of exercise
interventions on clinical outcome measures. Markers/mechanisms by which the impact of PA may be measured include GTT, chronic
inflammation, immune function, insulin levels, IGF, genetics and obesity. Research studies have been proposed to help assess
whether these markers are beneficially affected by PA, either before or after diagnosis of colorectal cancer. This chapter
reviews our current understanding of the significant impact of PA on the risk of, and survival from, colorectal cancer and
provides directions for future research which will underpin future health care policies and practices.
Exercise and Cancer Survivorship, 01/2010: pages 153-172;
[Show abstract][Hide abstract] ABSTRACT: Pre-operative radiotherapy may induce radiation colitis and tumour regression. Histological evaluation of radiation colitis needs to be reproducible to assess disease progression. The severity of radiation colitis can be assessed and graded according to its histological features. Increased severity of disease appears to be associated with a higher degree of cellular atypia and a lesser eosinophilic infiltrate. The severity of histological changes does not appear to be associated with post-operative complications. Tumour regression is an interesting phenomenon, the histological grading of which is of prognostic importance. Patients treated with long course radiotherapoy appear to have more incidences of postoperative complications. However, these are though to be related to the degree of tumour regression rather than to the type of radiotherapy.
[Show abstract][Hide abstract] ABSTRACT: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics.
We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI.
We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations.
Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.
[Show abstract][Hide abstract] ABSTRACT: Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta-analysis of prospective observational studies to quantify gender-specific risk associated with increased leisure-time physical activity (LT-PA).
We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. We used random-effects meta-analyses to estimate summary risk ratios (RR) and 95% confidence intervals (95% CI) for uppermost vs lowermost categories of physical activity. To investigate dose-response, we explored risks ratios as a function of cumulative percentiles of physical activity distribution.
Fifteen datasets from 14 articles, including 7873 incident cases, were identified. For colon cancer, there were inverse associations with LT-PA for men (RR: 0.80; 95% CI: 0.67-0.96) and women (0.86; 0.76-0.98). LT-PA did not influence risk of rectal cancer. The dose-response analysis was consistent with linear pattern reductions in risk of colon cancer in both genders. There was evidence of moderate between-study heterogeneity but summary estimates were broadly consistent across potential confounding factors.
Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.
[Show abstract][Hide abstract] ABSTRACT: Adenomas are the precursors to colorectal cancer. Malignant adenomas represent an early form of colorectal cancer, in which cancer has invaded by direct continuity through the muscularis mucosa into the submucosa. The management of these malignant adenomas depends upon their histological risk factors and the patient's general condition.
A literature review of publications regarding the malignant adenoma/polyp using Medline was performed.
The three main histological characteristics associated with an increased risk of residual disease and the potential for metastases are completeness and margin of excision, degree of differentiation and Haggitt level of invasion.
The dilemma as to which course of action is in the best interest of the patient with high-risk adenoma, be it either therapeutic polypectomy alone or surgical resection, is best resolved by a multidisciplinary team involving the surgeon, pathologist and endoscopist, taking the patient's condition and wishes into account.
[Show abstract][Hide abstract] ABSTRACT: The early molecular changes preceding the onset of mucosal inflammation in colitis and their temporal relationship with gut permeability remain poorly defined. This study investigated functional and transcriptomic changes in mdr1a(-/-) mice lacking the intestinal transporter P-glycoprotein, which develop colitis spontaneously when exposed to normal enteric flora.
Mdr1a(-/-) mice were housed in specific pathogen-free conditions to slow colitis development and compared to congenic controls. Mucosal permeability and cytokine secretion were analyzed in ex vivo colon. Gene expression in colonic mucosal and epithelial preparations was analyzed by microarray and qPCR. Colonocyte responsiveness to bacterial antigens was measured in short-term culture.
Colon from 4-5-week-old, disease-free mdr1a(-/-) mice was histologically normal with no evidence of increased permeability compared to controls. However, these tissues display a distinctive pattern of gene expression involving significant changes in a small number of genes. The majority of upregulated genes were associated with bacterial recognition and the ubiquitin-proteasome system and were gamma-interferon (IFN-gamma) responsive. Expression of the antiinflammatory factor pancreatitis-associated protein (PAP) and the related gene RegIIIgamma were markedly reduced. Colonocytes from 4-5-week mdr1a(-/-) exhibit similar transcriptomic changes, accompanied by higher basal chemokine secretion and increased responsiveness to LPS. Significant increases in colonic permeability were associated with older (12-16-week) mdr1a(-/-) mice displaying molecular and functional evidence of active inflammation.
These studies show that early epithelial changes associated with altered responsiveness to bacteria precede increased permeability and mucosal inflammation in this model of colitis, highlighting the importance of P-glycoprotein in regulating interactions with the commensal microflora.