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The value of a barium enema in the investigation of patients with rectal carcinoma.

A review of 545 patients with clinically diagnosed rectal carcinoma was conducted to determine the diagnostic usefulness of pre-operative barium enema and the frequency with which it was employed. Only 118 patients underwent pre-operative barium enema (21.7%). This successfully outlined the whole colon in 107 (90%). Synchronous carcinomas were detected in 9.3% of patients who underwent complete barium enema, compared to 4.3% of those who underwent laparotomy alone (P less than 0.05). Polyps were found in 23.4% of patients who had a barium enema but in only 14.7% of those who did not (P less than 0.05). Twenty-nine per cent of synchronous carcinomas and 11% of polyps were proximal to the descending colon and would have been beyond the reach of a flexible sigmoidoscope. Barium enema remains a useful investigation in patients with rectal carcinoma. It will outline the whole colon in most cases and will result in the detection of more synchronous carcinomas and polyps than if the surgeon relies on operative palpation alone.

Barium Sulfate↗

ASGE guideline: the role of endoscopy in the diagnosis, staging, and management of colorectal cancer.

This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of experts. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement and revision needed to clarify aspects of this statement and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to the recommendations.

Biopsy, Needle↗

[Results of coloscopy screening in 2005--an Internet-based documentation].

BACKGROUND AND OBJECTIVE: In October 2002 screening coloscopy was introduced into the National Cancer Prevention Programme in Germany. The results of an online registry are presented here. METHODS: Data from consecutive screening colonoscopies in the practices of the 280 participating gastroenterologists, performed in asymptomatic subjects, were collected in an online registry. Number and histology of colorectal polyps and carcinomas, complication rates of colonoscopy and polypectomy were registered. Advanced adenoma was defined as an adenoma >10 mm in diameter, with villous or tubulovillous histology, or presence of high-grade dysplasia. RESULTS: A total of 109989 colonoscopies (43% in males) were evaluated from October 2003 to July 2005. Tubular and villous adenomas were found in 16.2% and 3.8%, respectively, whereas invasive cancers were diagnosed in 0.7%. Advanced adenomas amounted to 6.1%.The majority of carcinomas were detected in early stages (UICC stages I and II in 48 and 22 %, respectively). -In most of the polyps immediate polypectomy was carried out. The complication rate was low and no deaths were observed: cardiopulmonary complications occurred in 0.10% of the colonoscopies, bleeding in 0.79% of polypectomies most of which were managed endoscopically (surgery in 0.04% of polypectomies). Perforation occurred in 0.02% of the colonoscopies and 0.10% of polypectomies. CONCLUSIONS: Neoplasias of the colon were detected in about 20% of persons who had taken part in a colonoscopy screening programme: most of the lesions were immediately removed by polypectomy. The high rate of early stages of colorectal cancers detected by screening colonoscopy is an indirect indicator of mortality reduction. In Germany screening colonoscopy has a low risk.

Adenoma↗

Colonic tumors.

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Biopsy↗

One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon.

BACKGROUND: Fecal occult-blood testing and sigmoidoscopy have been recommended for screening for colorectal cancer, but the sensitivity of such combined testing for detecting neoplasia is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence of neoplasia and the sensitivity of one-time screening with a fecal occult-blood test plus sigmoidoscopy. METHODS: Asymptomatic subjects (age range, 50 to 75 years) provided stool specimens on cards from three consecutive days for fecal occult-blood testing, which were rehydrated for interpretation. They then underwent colonoscopy. Sigmoidoscopy was defined in this study as examination of the rectum and sigmoid colon during colonoscopy, and sensitivity was estimated by determining how many patients with advanced neoplasia had an adenoma in the rectum or sigmoid colon. Advanced colonic neoplasia was defined as an adenoma 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Classification of subjects according to the findings was based on the most advanced lesion. RESULTS: A total of 2885 subjects returned the three specimen cards for fecal occult-blood testing and underwent a complete colonoscopic examination. A total of 23.9 percent of subjects with advanced neoplasia had a positive test for fecal occult blood. As compared with subjects who had a negative test for fecal occult blood, the relative risk of advanced neoplasia in subjects who had a positive test was 3.47 (95 percent confidence interval, 2.76 to 4.35). Sigmoidoscopy identified 70.3 percent of all subjects with advanced neoplasia. Combined one-time screening with a fecal occult-blood test and sigmoidoscopy identified 75.8 percent of subjects with advanced neoplasia. CONCLUSIONS: One-time screening with both a fecal occult-blood test with rehydration and sigmoidoscopy fails to detect advanced colonic neoplasia in 24 percent of subjects with the condition.

Adenoma↗

Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma.

The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.

Adenocarcinoma↗

Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas.

A cDNA, which we call DRA (for down-regulated in adenoma) has been isolated. Its mRNA is expressed exclusively in normal colon tissue, probably only in the mucosal epithelia. Expression of the DRA gene is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon. The DRA gene appears to be a single-copy gene present on chromosome 7, a chromosome associated with colorectal tumorigenesis. The predicted DRA polypeptide is an 84,500-Da protein that contains charged clusters of amino acids, primarily at the NH2 and COOH termini. Together with potential nuclear targeting motifs, an acidic transcriptional activation domain, and a homeobox domain, these elements suggest a transcription factor or a protein that may interact with transcription factors. Such a function may be consistent with a role in tissue-specific gene expression and/or as a candidate tumor-suppressor gene.

Adenocarcinoma↗

Exercise and tumor development in a mouse predisposed to multiple intestinal adenomas.

UNLABELLED: Epidemiological evidence suggests that physical activity may be protective against the development of colon cancer. Potential mechanisms remain largely unexplored due to the paucity of appropriate experimental models. PURPOSE: The purpose of this study was to examine the effect of exercise training on polyp development in an induced mutant mouse strain predisposed to multiple intestinal neoplasia (Min mouse). METHODS: Three-week-old male and female heterozygotes were randomly assigned to control (CON; 10 males, 6 females) or exercise (EX; 11 males, 11 females) groups. In the first week, EX mice were acclimated to treadmill running at 10-18 m x min(-1) for 15-60 min x d(-1). From 4-10 wk of age, mice ran at 18-21 m x min(-1) for 60 min. CON mice sat in Plexiglas lanes suspended above the treadmill for the same time periods. At 10 wk of age, the mice were sacrificed and the intestines removed, opened, and counted for polyps. RESULTS: Skeletal muscle oxidative capacity increased with training as shown by a 64% increase in citrate synthase activity in the gastrocnemius/soleus muscle of EX compared with CON (P = 0.009). There were no significant effects of exercise in the males and females combined on small intestine, colon, or total intestinal polyps (P > 0.05). When analyzed separately, however, there were fewer colon and total polyps in the EX than in the CON males, although the difference was not statistically significant (P = 0.06). CONCLUSIONS: These results suggest that seven weeks of exercise training do not affect the development of intestinal polyps in the Min mouse. Further studies are required to determine if a true sex difference exists or if variations on the current training protocol may affect tumor outcomes.

Adenoma↗

Signet ring cell carcinoma in a polyp of the colon. A case report of a six-year-old boy.

Undifferentiated adenocarcinoma of the colon occurring in a 6-year-old boy was presented. The tumor characterized by the signet ring cell appearance developed in a polyp of the descending colon. The signet ring cell carcinoma is in general a rare morphologic form of colonic carcinoma. According to our review of the literature there have been described 16 patients under 10 years of age with colonic or rectal carcinoma, disclosing 2 cases of undifferentiated or signet ring cell carcinoma including the present case. In children, mucin producing adenocarcinoma is the most predominant type of colonic carcinoma, and 48% of the colonic carcinomas are of signet ring cell carcinoma in children under 17 years of age.

Adenocarcinoma, Mucinous↗

Colonoscopy: how far is enough?

Total colonoscopy is arguably the best method available for examination of the colon and rectum. Colonoscopy costs are high and rising and it may be that in the future practitioners will be unable to afford to colonoscope all of the patients presently being examined. This retrospective study was undertaken in an attempt to examine the cost, in terms of lesions missed, of a limited endoscopy programme. During a 15 year period, 1426 colonoscopies were performed at Wellington Hospital, New Zealand. Total colonoscopy was possible in 79% of all patients. Three perforations occurred. Nine patients bled and two required blood transfusion after biopsy or 'snaring' of polyps. After exclusion of patients with continuous inflammatory bowel disease (IBD) 75% of all lesions were found in or distal to the descending colon. More cancers were found in patients colonoscoped because of bleeding. Thirty-two of 93 cancers diagnosed were proximal to the descending colon but 18 presented with bleeding. A further seven had a radiological abnormality. Only 7.5% of colorectal cancers would be missed by flexible sigmoidoscopy (65 cm) and 75% of the costs of total colonoscopy would be avoided if only patients presenting with bleeding and IBD were offered total colonoscopy and patients with radiological abnormalities were treated according to the abnormality. This compromise, based on the data presented, may represent a rational way to reduce colonoscopy costs.

Colonic Neoplasms↗

Low rate of microsatellite instability in young patients with adenomas: reassessing the Bethesda guidelines.

BACKGROUND AND AIM: Screening adenomas for microsatellite instability (MSI) in patients younger than 40 yr of age has been recommended by the Bethesda Guidelines as a means of identifying patients at risk for hereditary nonpolyposis colorectal cancer (HNPCC). We sought to determine the rate of MSI in adenomas removed from individuals under 40 yr of age over a 5-yr period in a university general gastroenterology practice. METHODS: We identified patients between 18 and 39 yr of age with endoscopically removed adenomatous colorectal polyps. Patients with polyposis syndromes, inflammatory bowel disease, or colorectal carcinoma were excluded. A three-generation family history was obtained via telephone interview. Endoscopic and histology reports were reviewed. Adenomas were tested for MSI using the BAT26 and BAT40 microsatellite markers, and expression of the MSH2 and MLH1 proteins was assessed by immunostaining. RESULTS: A total of 34 patients had 46 adenomas removed endoscopically. Out of 34 patients, 14 (41%) had a family history of colorectal cancer and 3 were from Amsterdam criteria positive families. A total of 28 of 46 adenomas (61%) were distal to the splenic flexure. Polyps ranged in size from 2 to 20 mm and averaged 6.6 mm. Five polyps (11%) were tubulovillous adenomas, and the remainder were tubular adenomas. None of the polyps were serrated adenomas and none demonstrated high-grade dysplasia. Among the 40 adenomas available for testing, none demonstrated MSI using either BAT26 (0/40) or BAT40 (0/21), nor did any of the polyps tested demonstrate loss of either MSH2 or MLH1 expression (0/16). CONCLUSION: Screening adenomas from patients younger than 40 yr of age for MSI was ineffective in identifying potentially new cases of HNPCC. New strategies that improve on the current clinical and molecular screening methods should be developed so that at-risk individuals can be identified and referred for germline testing before developing their first cancer.

Adaptor Proteins, Signal Transducing↗

DNA content in carcinoma of the rectum and rectosigmoid.

Using single cell cytometry the pattern of DNA content in preoperative samples from 131 carcinomas of the rectum and rectosigmoid has been studied. For comparison, 21 carcinomas of the colon, 44 colorectal polyps and mucosa adjacent to the tumours were also included. The biopsies were classified into near diploid (ND), near diploid with aneuploid cells (ND-anc) and aneuploid (AN). A more specific subclassification of aneuploid samples was not consistent because of a commonly occurring multiclonality, where different clones dominated different parts of the tumours. Fifteen of all 130 representatively sampled rectal carcinomas were ND; however, all the ND scores were based on a single sample. Among 31 multiply-sampled carcinomas none registered as ND in all samples. There were no principal differences in patterns of DNA profiles between rectal and colon carcinomas. Five samples from the pericancerous mucosa and samples from 4 adenomas showed non-ND patterns, which may be a premalignant sign. The main conclusions of these results are that rectal carcinomas, even if they contain a substantial ND cell population, to a very great extent contains cells with an abnormal DNA content. The carcinomas can be classified according to their pre-operatively estimated DNA content. The clinical relevance of this will be judged when the patients have been followed for longer time periods.

Adenocarcinoma↗