ABSTRACT
BACKGROUND: In a previous study we identified 206 patients with colorectal adenocarcinoma in the Northern Cape province of South Africa, diagnosed between January 2002 and February 2009. The age-standardised incidence was 4.2/100 000 per year world standard population. This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. OBJECTIVES: The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the Northern Cape. METHODS: Formalin-fixed paraffin wax-embedded tissue blocks from 87 colorectal adenocarcinomas identified in the previous study were retrieved. Standard immunohistochemical staining methods were used to detect the expression of hMLH1 and hMSH2 (i.e. products of the hMLH1 and hMSH2 genes) in the tumours using heat-induced antigen retrieval and diaminobenzidene as a chromogen. Results. In 8 blocks there was insufficient tumour tissue and in 1 case the immunohistochemical staining failed, probably owing to poor fixation, leaving 78 cases for analysis. In 11 cases hMLH1 was deficient and in 6 cases hMSH2 was deficient. Overall, 21.8% of cancers were deficient for hMLH1 or hMSH2. CONCLUSION: Presuming that 80% of all hMLH1 deficiencies are due to hypermethylation of the gene, we found 10.5% of colorectal cancers in an area with a low incidence of colorectal cancer to be deficient in the product of the mismatch repair gene/s. This is approximately three times the reported rate in high-incidence areas.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Repair Enzymes/genetics , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Adenocarcinoma/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Female , Gene Expression , Humans , Incidence , Male , Middle Aged , MutL Protein Homolog 1 , MutL Proteins , South Africa/epidemiologyABSTRACT
BACKGROUND AND STUDY AIM: Colonic perforation is a serious complication of colonoscopy, with surgical repair usually indicated. The aim was to compare acute strength of various endoscopic colonic closure techniques by assessing air leak pressures in a previously described ex vivo experimental apparatus. METHODS: Standardized colonic perforations were created using fresh porcine colon and subsequently closed on a bench. Six techniques included surgical suture (gold standard), QuickClips, T-tags, over-the-scope-clip (OTSC) system, and two types of flexible stapler (Covidien). After closure, each specimen was fixed in the apparatus and pressure was gradually increased until air bubbles were seen. Leak pressure was the primary outcome parameter. Closure using the gold standard (first 15 experiments) resulted in a mean leak pressure of 86.9 mmHg (SD 7). Using a noninferiority design a sample size of 12 specimens for each closure technique was determined. RESULTS: Mean colotomy leak pressures in millimeters of mercury (mmHg) and difference (with 95% confidence intervals [CI]) between each technique and the gold standard were: QuickClips 85.1 (difference -1.8; 95% CI -7.0 to 3.9); T-tags 53.9 (difference -33.0; -39.0 to -27.0); OTSC 90.3 mmHg (difference 3.4; -6.1 to 12.9); 15-mm shaft stapler 98.5 mmHg (difference 9.7; 0.8 to 18.5) and 8-mm shaft stapler 96.6 mmHg (difference 11.6; 1.5 to 21.7). CONCLUSIONS: OTSCs, QuickClips, and both flexible staplers produced results comparable to hand-sewn colotomy closure in this ex vivo porcine colonic model. These devices seem to be prime candidates for further evaluation in survival animal studies.
