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The nonspecificity of histological findings reported for flat adenomas.

Flat adenomas have been reported to be associated with an increased risk of high grade dysplasia and with a genetic predisposition to numerous colonic polyps. Histological findings reported for flat adenomas are dysplastic glands superficial to nondysplastic glands and a thickness of dysplastic mucosa that does not exceed twice that of nondysplastic mucosa. We assessed the specificity of these histological findings with regard to a colonoscopically flat appearance in a series of 127 sequentially accessioned adenomas from 52 patients without adenomatous polyposis coli or inflammatory bowel disease. Thirty-two of the 127 adenomas (25%) from 20 of 52 patients (36%) showed the histological findings outlined above; none of these polyps was grossly flat and none had high grade dysplasia. The predictive values of these histological features for patients younger than 50 years old and for the presence of five or more polyps in a patient were 15% and 25%, respectively. We conclude that the histological findings previously reported for flat adenomas are not specific for that entity and are not uncommonly seen in grossly typical appearing adenomatous polyps. These histological findings also are not associated with high grade dysplasia. They can be seen in polyps from individuals without clinically recognized polyposis, and are relatively poor indicators of young age or increased polyp number, features that could potentially indicate a clinically unrecognized polyposis syndrome. The histological findings in and of themselves thus appear to confer no additional cancer risk to the individual or to the individual's family members over and above that associated with an adenoma.

Adenoma↗

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation.

Colorectal cancer risk is associated with biochemical markers for B-vitamin deficiency, insulin resistance and colonic inflammation, suggesting that these three conditions are each involved in colon carcinogenesis. We expected that dietary supplements of folic acid, n-3 fatty acids and calcium would reduce the markers and thus possibly cancer risk. We therefore randomised 98 participants, with previous colonic polyps or intramucosal carcinomas, to a combined treatment of supplementary folic acid, fish oil and calcium carbonate, or placebos for 28 days. Blood and faecal samples were obtained prior to and at the conclusion of the intervention and analysed for plasma folate, homocysteine, insulin, free fatty acids, triglycerides and faecal calprotectin. In addition, plasma vitamin B12, thiamin, glucose and C-reactive protein were assessed. Our supplemental strategy modestly affected some of the biomarkers associated with folate metabolism and insulin resistance, but had no effect on those associated with colonic inflammation. This pilot study demonstrates the feasibility and practicality of clinical trials aimed at reducing diet-related biochemical risk markers for colon cancer. We suggest that long-term intervention studies with tumour-related end points should be undertaken when the intervention agents used are found effective in short-term biochemical risk marker trials.

Adenoma↗

Unusual features in a patient with neurofibromatosis type 1: multiple subcutaneous lipomas, a juvenile polyp in ascending colon, congenital intrahepatic portosystemic venous shunt, and horseshoe kidney.

We report a case that draws attention to a hitherto undescribed association of neurofibromatosis type 1 (NF1) with juvenile polyp, congenital intrahepatic portosystemic venous shunt, multiple subcutaneous lipomas, and horseshoe kidney. Our patient has fulfilled the National Institutes of Health consensus conference criteria for NF1 by having neurofibromas, axillary freckling, Lisch nodules, and café-au-lait spots. There is no family history of NF1 and his 7-year-old son has no stigmata of NF1. On the other hand, the patient's family had a presumably dominant inheritance of horseshoe kidney: the father, proband, sister, and son of the other sister had a horseshoe kidney. The patient was investigated for mutations in the NF1 gene and PTEN, but no germline mutations were detected. The differential diagnosis for such a collection of hamartomatous, cutaneous, and vascular disorders includes the Proteus, Bannayan-Riley-Ruvalcaba, and Cowden syndromes. None of these diagnoses was convincingly confirmed in this patient.

Abnormalities, Multiple↗

Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer.

The clinical course of familial adenomatous polyposis (FAP) varies considerably between patients. Prediction of the severity of the disease is important in the interest of effective cancer prevention. We examined whether age at diagnosis of FAP due to gastrointestinal symptoms and age at death due to colorectal cancer are related to the site of mutation in the responsible gene. 225 families with FAP were screened for mutations. The deletion of 5 base pairs at codon 1309 within exon 15 (known to be the most common mutation) was identified in 20 families; other mutations within exons 7-15 were found in 49 families. In patients with the 5 base-pair deletion at codon 1309, gastrointestinal symptoms and death from colorectal cancer occurred about 10 years earlier than in patients with other mutations. The 1309 mutation leads to development of colonic polyps at a younger age, thus giving rise to an earlier malignant transformation. This relationship should be taken into account in strategies for preventing cancer in patients with FAP.

Adenomatous Polyposis Coli↗

Colonic fermentation of complex carbohydrates in patients with familial adenomatous polyposis.

Decreased production of butyric acid by colonic carbohydrate fermentation may predispose to colonic carcinogenesis, with the implicit assumption that the decrease in faecal butyrate found predates the development of the tumour. The influence of the genetic predisposition to colonic tumours and the presence of colonic polyps on in vitro fermentation of carbohydrates was examined. Stool samples from 11 normal controls and 20 patients with familial adenomatous polyposis (FAP) were incubated anaerobically with a range of carbohydrates. Fermentation patterns were similar for glucose and raffinose. These sugars produced different short chain fatty acid (SCFA) patterns from the two polysaccharides, starch and arabinogalactan, which differed one from the other. The FAP gene carriers with polyps produced less butyrate than normal controls (p < 0.005) and gene carriers without polyps (p < 0.05). There were corresponding decreases in the molar ratios of butyrate. Gene carriers without polyps produced less absolute amounts of acetate than normal controls (p < 0.05) and slightly less total SCFAs (p < 0.05) but were otherwise not significantly different. The decreased production of butyrate noted by other workers may be secondary to the tumours rather than a contributory cause.

Adenomatous Polyposis Coli↗

Measurement of mucosal capillary hemoglobin oxygen saturation in the colon by reflectance spectrophotometry.

BACKGROUND: Advances in optical and computer technology have enabled the development of a device that uses white-light reflectance spectrophotometry to measure capillary hemoglobin saturation in intestinal mucosa during colonoscopy. METHODS: Studies were performed with the colon oximeter in anesthetized animals and patients undergoing colonoscopy. RESULTS: Mean (SD) mucosal hemoglobin saturation in the normal colon was 72% (3.5%). In an animal model, ischemia induced by arterial ligation and hypoxemia via hypoxic ventilation each resulted in a decrease of over 40% in the mucosal saturation. In patients with colon polyps, ischemia induced by epinephrine injection, stalk ligation with a loop, or clipping of the polyp stalk each resulted in a decrease of over 40% in the mucosal saturation (p < 0.02). In contrast, saline solution injection did not decrease the mucosal saturation. CONCLUSIONS: A novel device for measuring capillary hemoglobin saturation in intestinal mucosa during colonoscopy is capable of providing reproducible measurements in normal patients and clearly detects dramatic decreases in saturation with ischemic and hypoxic insults.

Aged↗

Early experiences with computed axial tomography colonography.

BACKGROUND: Computed axial tomography (CT) colonography is the latest radiologic technique to be used to image the large bowel. We studied its role as a diagnostic tool in colorectal practice. METHODS: One hundred and three patients suspected of having colorectal pathology underwent CT colonography. RESULTS: CT colonography suggested a diagnosis of colonic carcinoma in 18 patients, and 17 of these underwent surgery. A colorectal neoplasm was not found in only 1 patient who had extrinsic colonic compression by an ovarian cyst. Twenty-one patients had suspected colonic polyps on scanning. Subsequent endoscopy in 19 of these patients confirmed the presence of polyps in only 10. CT colonography also revealed valuable extracolonic pathology: 8 occult noncolonic neoplasms and 163 other incidental findings. CONCLUSIONS: CT colonography has good patient compliance and is a useful diagnostic modality in detecting colorectal neoplasms. Its main advantage over other such investigative tools is its ability to detect extracolonic pathology.

Adult↗

Safety and efficacy of argon plasma coagulator ablation therapy for flat colorectal adenomas.

INTRODUCTION: argon-plasma coagulation (APC) has been used safely and efficaciously in multiple settings including colon polyp treatment. The aim of this study was to evaluate APC efficacy and safety in the treatment of flat colorectal adenomas. MATERIALS AND METHODS: APC ablation was prospectively performed and evaluated in 22 consecutive patients with colorectal adenomas, 11 of which had large sessile adenomas that were treated with piecemeal polypectomy and APC ablation of residual adenomatous tissue, whereas the remaining eleven patients with flat or carpet-like adenomas were only treated with APC. The mean initial longitudinal extension of adenomas to be treated with APC was 22 mm (range, 20 to 40 mm). RESULTS: the mean age of patients was 70 years. Adenomas were found most frequently in the rectum (50%) and cecum (23%). Complete ablation was achieved in 90.9% of adenomas. Recurrence was observed in 20% of patients, all of them in the rectum, after a mean follow-up period of 16.3 months (range, 8 to 35). All recurrences were managed satisfactorily. No major complications were seen. CONCLUSIONS: argon plasma coagulator ablation of flat colorectal adenomas is an efficacious and safe technique, specially in the right colon, but results must be confirmed in controlled trials with a higher number of patients.

Adenoma↗

The potential benefits of dietary and/or supplemental calcium and vitamin D.

Osteoporosis is a significant problem in women and men. In addition, as osteoporosis has garnered more attention there should be more attention than ever placed on the potential benefits of calcium and vitamin D. Clinicians need to inform patients that there are numerous healthy dietary sources of calcium and vitamin D. Calcium and vitamin D supplements seem to act synergistically to reduce fracture risk in men and women; therefore, they need to be taken together to impact fracture risk. In addition, almost every randomized trial of an effective osteoporosis drug therapy has utilized calcium and vitamin D to enhance the efficacy of the drug itself. Several forms of calcium supplements are commercially available today and clinicians need to understand the similarities and differences between them. Calcium and vitamin D in moderation also have a good safety profile and may actually have benefits far beyond osteoporosis therapy. For example, calcium may increase high-density lipoprotein (HDL), prevent colon polyps, reduce blood pressure, reduce kidney stone recurrence, and may promote weight loss. Vitamin D may reduce the risk of some cancers, provide an enhanced response to some chemotherapeutic agents, prevent type I diabetes, and may reduce tooth loss along with calcium. Clinicians need to encourage individuals to receive the recommended daily allowance of these two agents because they seem to have an impact on numerous health conditions besides osteoporosis.

Adult↗

Paraneoplastic cerebellar degeneration and limbic encephalitis in a patient with adenocarcinoma of the colon.

The rare association of two neurological paraneoplastic syndromes, paraneoplastic cerebellar degeneration and limbic encephalitis occurred in a 55 year old woman with a microscopic adenocarcinoma in a colonic polyp. Complete removal of the tumour by polypectomy brought about a favourable recovery from limbic encephalitis but the cerebellar ataxia remained. High titres of antineuronal nuclear antibody resembling anti-Hu were demonstrated in serum by immunohistochemistry using rat brain as a substrate. The antibody identified a protein band of 41 kDa on a Western immunoblot.

Adenocarcinoma↗

Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis.

BACKGROUND AND AIM: The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. METHODS: Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. RESULTS: In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. CONCLUSION: There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC.

Adolescent↗

Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Hereditary Colorectal Tumors Registry.

OBJECTIVE: To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). SUMMARY BACKGROUND DATA: The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern. METHODS: Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation. RESULTS: Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times. CONCLUSIONS: The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP.

Adenomatous Polyposis Coli↗

Fecal bile acids in patients with adenomatous polyps of the colon. Case-control study.

Populations with a high colonic cancer incidence excrete larger amounts of bile acids in their feces. Patients with adenomatous polyps of the colon are at a greater risk of developing colonic cancer. Therefore, we studied the fecal bile acid excretion pattern in 12 patients with adenomatous polyps in comparison to 12 control subjects matched for age and sex. Analysis of bile acids was performed using liquid-gel chromatography for the separation of free, conjugated and sulfated bile acids and gas liquid chromatography for quantitation. This case-control study did not confirm the previous finding of an increased fecal bile acid excretion in patients with adenomatous polyps. Total bile acid excretion, the pattern of the primary and major secondary bile acids and their mode of conjugation were essentially the same for both groups. This negative result may be explained by similar dietary habits of both groups.

Adenoma↗

Computer-aided detection for virtual colonoscopy.

Colon cancer is one of the leading causes of cancer deaths in the developed countries. Most colon cancers can be prevented if precursor colon polyps are detected and removed. Virtual colonoscopy, or CT colonography, has shown promise to be the future screening tool for polyp detection, with a number of studies performed at academic institutions showing high sensitivity and specificity. Two main factors limiting CT colonography in general use are its excessive interpretation time and the variable sensitivity among readers. This article discusses the potential of computer-aided detection to address these problems. We also review the current state of research in this field and the future roles and challenges of CAD for CT colonography.

Algorithms↗

Virtual colonoscopy for colorectal cancer screening: current status.

Computed tomography colonography (CTC) (also known as 'virtual colonoscopy') is a noninvasive method of imaging the colon using helical CT. Although CTC has been shown to be useful for certain clinical indications, it has not yet been endorsed as a colorectal cancer screening test. The purpose of this article is to review the current status of CTC for colorectal cancer screening. CTC is an accurate method to detect colonic polyps and to select patients who would benefit from colonoscopy. The major advantages of CTC over conventional colonography include its relatively low risk and greater tolerance by patients. In this article, the CTC procedure and results of clinical trials are reviewed, as well as potential pitfalls related to CTC performance and interpretation. Finally, radiation dose, the discovery of incidental extracolonic findings with CTC, bowel preparation methods, and computer-aided diagnosis are addressed.

Colonic Neoplasms↗

Breast cancer and polyps of the colon. A case-control study.

A case-control study was conducted involving 145 patients with breast cancer and 144 controls. A pansigmoidoscopy was performed in each case and control. There was no statistically significant difference in the length of the colon explored (cases, 50.3 cm; controls, 48.9). The odds ratio for adenomatous polyps was 2.65 (confidence limits, 1.56 and 3.74). As adenomas of the colon can be considered as precursors of colon cancer, this study demonstrates new evidence of the close relationship between breast and colon cancer. These results show the usefulness of performing a pansigmoidoscopy in all breast cancer patients and, if positive, the removal of all of the polyps through the colonoscope.

Adenoma↗

Failure of colonoscopy to detect colorectal cancer: evaluation of 47 cases in 20 hospitals.

BACKGROUND: Colonoscopy is the gold standard for the detection of colon polyps and cancers, but failed detections can occur and the reasons are incompletely understood. METHODS: During a retrospective evaluation of the sensitivity of barium enema and colonoscopy in 20 Indiana Hospitals, we encountered 47 cases of colorectal cancer in which a colonoscopy performed within 3 years of the diagnosis had not detected the cancer. Cases were reviewed for location of tumor, extenuating factors, pathologic features, delay in diagnosis from failed detection, and who performed the examination. RESULTS: Failed detection was more likely when colonoscopy was performed by a nongastroenterologist than a gastroenterologist (odds ratio 5:36, 95% CI [2.94,9.77]). Twenty-seven cancers were "missed," and 20 were estimated to be not reached. However, the location of missed tumors and a general absence of adequate documentation of cecal intubation suggested that some cecal and ascending colon cancers recorded as missed may actually have been not reached. Variation in sensitivity among gastroenterologists suggested that meticulous examination is also important in maximizing sensitivity. CONCLUSIONS: These cases suggest several factors that might improve the quality and sensitivity of colonoscopy: (1) examiners should receive adequate training, (2) cecal intubation rates should be high, (3) cecal intubation should be verified by specific landmarks in all cases, (4) failure to reach the cecum should be followed by prompt barium enema, and (5) meticulous examination would appear to improve sensitivity for cancer detection.

Aged↗