Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

结肠非低张双重造影的应用

本文应用结肠非低张双重对比灌肠造影诊断结肠病变,这是一种简单的方法。本文根据150例的实践径验介绍了技术、病人的准备、有关造影剂的问题和正常所见,并通过具体的病例阐述了结肠非低张双重对比检查的临床应用价值,并指出了本法的不足之处。     

SUCCESSFUL ENDOSCOPIC CLOSURES OF COLONIC PERFORATIONS REQUIRING ABDOMINAL DECOMPRESSION AFTER ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY COLON CANCER

Endoscopic submucosal dissection (ESD) for colorectal cancer is not widely accepted because of its technical difficulty and the risk of perforation. In addition, the risk of peritonitis cannot be completely eliminated even if a perforation is closed successfully. Reported here are two cases of early colon cancer in which the patients sustained iatrogenic perforations of the ascending colon during conventional endoscopic mucosal resection and of the sigmoid colon during ESD, respectively, requiring abdominal decompression with an 18 G Medicut needle. Both of these perforations were successfully treated by endoscopic clipping. In conclusion, conservative medical management may be possible in patients who have undergone successful closure of colonic perforations using endoscopic clipping. In order to perform immediate endoscopic closure, abdominal decompression has been useful to decrease patient discomfort and colonic lumen collapse. Now, CO₂ insufflation is being used effectively for the prevention of pneumoperitoneum.     

The pros and cons of fecal occult blood testing for colorectal neoplasms

Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult^® are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant^® and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended.Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%–98%, yet the predictive value of a positive test for cancer is only about 10%: hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading.On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.     

结直肠癌中雄激素受体及其与临床病理学特征关系的研究

应用放射性配基结合分析法，检测了４０例结直肠癌及部分癌旁正常粘膜组织中的雄激素受体（ＡｎｄｒｏｇｅｎＲｅｃｅｐｔｏｒ，ＡＲ），同时分析了ＡＲ水平与临床病理学变化的关系。证实结直肠癌ＡＲ数目（３３．７±２３．３ｆｍｏｌ／ｍｇ蛋白）明显低于癌旁５ｃｍ以外粘膜（５３．９±３２．４ｆｍｏｌ／ｍｇ蛋白），Ｐ＜０．０１，而其亲和力则无变化；结直肠癌时ＡＲ数目变化与女性、直肠癌、高分化癌及早期癌关系密切。提示ＡＲ与结直肠癌关系密切，本实验为临床上结直肠癌的诊断及内分泌治疗提供了初步资料。     

Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content

Pharmaceutical Research -     

A nonspecific colonic ulcer occurring after hepatectomy: Report of a Case

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.     

Colonic Motility in Profoundly Disabled People: A comparison of massage and laxative therapy in the management of constipation

This pilot study compared abdominal massage with laxative treatment in the management of constipation in 32 profoundly disabled, institutionalised adults. A randomised cross-over design was used. After an initial 16-day baseline measurement phase without any treatment, there followed two seven-week treatment phases separated by a one-week washout period. Each subject received seven weeks of massage and seven weeks on his or her previous laxative regimen. Primary outcome measures were gastro-intestinal and segmental transit times, measured at the end of the baseline phase and of each treatment phase. Secondary measures included stool frequency, size and consistency, the requirement for enemas and an assessment of patient well-being.The median value of total colonic transit time was 183 hours for the baseline phase and 159 hours for all treatment phases. There was no evidence of any statistically significant treatment differences between laxative and massage therapy for right, left or rectosigmoid segments either separately or in total. Analysis of secondary outcome measures also failed to find any treatment preferences.These results reveal the grossly abnormal colonic transit times of the study population at all times. The effects of laxative and massage therapy within this environment were not demonstrably different.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Characterization of acetate uptake by the colonic epithelial cells of the rat

The characteristics of acetate uptake by colonic epithelial cells of the rat were studied. Clear saturation kinetics of acetate uptake were not observed in these experiments at either 0° C or 30° C. A decrease in the pH of the medium markedly increased the acetate uptake. The activation energy for acetete uptake derived from an Arrhenius plot was about 6.1 kcal/mole. Among the inhibitors tested, no effective inhibition of acetate uptake at 0° C was observer. Metabolic inhibitors severely inhibited transport at 30° C. Inhibition of acetate uptake by other short chain fatty acids, which was non-competitive, was observed. The finding that efflux from the cells was stimulated in the presence of compounds such as pyruvate and bicarbonate supported the notion of a close interrelationship between weak electrolyte transports in vivo. Although the H⁺ gradient across the cell membrane is suggested to be one of the factors determining the uptake rate, it seems difficult to explain all the results in this way.