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"The evolution of the solitary ulcer of the rectum"--an endoscopic and histopathological study.

A follow-up study of fourteen out of twenty-seven cases of solitary ulcer syndrome of the rectum was performed at one year's interval from the previous endoscopic and histologic examination. Most of the lesions consistently changed their aspect, resulting in incomplete irregular narrowings, polypoid protrusions or linear ulcers. The symptoms remained unchanged or slightly diminished. A striking difference was found in the histological pattern of the "evolved" ulcer in comparison to the active one, the former showing features of hyperplastic (metaplastic) colonic polyps as well as of the so called "transitional mucosa". It is suggested that chronic ischemia occurring in solitary ulcer of the rectum leads to "transitional mucosa" as an exaggerated regenerative phenomenon, hyperplastic (metaplastic) mucosa representing a later maturative phase. Possibly "transitional" mucosa may undergo dysplastic changes under the influence of environmental factors.

Adolescent↗

GENES and polyps.

Explore the source record for details and available documents.

Colonic Neoplasms↗

A case of multiple keratoacanthoma centrifugum marginatum: response to oral etretinate.

The patient was a 48-year-old man who had a history of colonic polyps. About 18 months before, a dark reddish nodule had appeared on his right forearm. By peripheral growth, this lesion had formed a crateriform prominence with central healing. Similar symptoms multiplied and expanded, the largest being about the size of a child's head. Given both the clinical and histologic evidence, a diagnosis of keratoacanthoma centrifugum marginatum (KCM) was made. Oral etretinate was administered, and an involution of verrucous plaque began after 4 weeks. After 8 weeks, the lesions faded, leaving pigmentation in some areas. This is a rare disorder, only 30 such cases having been reported worldwide, and the present case was the third in which oral etretinate was found to be effective.

Administration, Oral↗

Skin fibroblasts from individuals hemizygous for the familial adenopolyposis susceptibility gene show delayed crisis in vitro.

Normal human fibroblast cells have not been reported to escape crisis--that is, they die after about 24 doublings in culture. We have been studying the growth properties of skin fibroblast cells from persons in families with familial adenopolyposis of the colon (FAP). An individual hemizygous at the FAP locus will develop hyperplasia of the colonic epithelium followed by colonic polyps, both at an early age. Polyps themselves still retain a single functional FAP allele. A mutation or deletion in this allele in a polyp is hypothesized to lead to further loss of growth control; thus, a tumor is formed. We found that the in vitro life-span of skin fibroblast cells from FAP individuals and from some asymptomatic children were markedly extended when compared with normal individuals.

Adenomatous Polyposis Coli↗

The pathology of naturally-occurring bovine schistosomiasis in the Sudan.

The gross and histopathological lesions of naturally-occurring bovine schistosomiasis in the Sudan are detailed. Out of 61 animals examined, 53 were found infected with Schistosoma bovis, showing lesions in their livers, intestinal tracts and other organs. Apart from granulomas, periportal inflammatory infiltration, fibrosis and pigmentation of Kupffer cells, livers of infected cattle revealed peculiar lesions in the form of "nodular sclerosis", medial hypertrophy of portal veins and lymphoid nodule and follicle formation around parasites. In the intestines, variable manifestations of catarrh, with eosinophilic infiltration, granulomatous reaction and vascular changes, were observed. Pancreatic schistosomiasis was common and some animals had lesions in their lungs and lymph nodes. Urogenital lesions, rectal and colonic polyps, congestive splenomegaly, gastro-oesophageal variaces and Symmer's clay-pipe stem fibrosis of the liver were not seen in cattle. The haematological and serum protein findings in infected animals were included. The findings were related to the lesions observed and the need for detailed study of functional disturbances in bovine schistosomiasis is indicated.

Animals↗

Fecal ammonia in patients with adenomatous polyps and cancer of the colon.

The correlation between high intakes of protein and high incidence of human colonic cancer is unexplained. Appreciable amounts of ammonia are generated in the large bowel through bacterial degradation of proteins and peptides, and experimental studies indicate that ammonia may select for neoplastic growth. Fecal concentrations of ammonia did not differ among 17 patients with former colonic adenomas [40.6 +/- 4.5 (SE) mM], 17 patients with former colonic cancer (51.4 +/- 3.9 mM), and 16 healthy controls (46.4 +/- 6.1 mM). By use of an in vitro fecal incubation system, possible alterations in bacterial fermentation and formation of ammonia were investigated. Fecal suspensions were incubated for 6 and 24 hours with and without addition of fermentable substrates (ispaghula husk, wheat bran, albumin, and glucose; 10 mg/ml). The in vitro production of ammonia in unsupplemented fecal homogenates from both groups of patients was comparable with the production found in homogenates from healthy controls, and the response to fermentable substrates was similar in all three groups. Addition of albumin caused a marked increase in the production of ammonia, and addition of glucose increased bacterial assimilation of ammonia considerably. These well-known characteristics of bacterial metabolism of ammonia apparently did not differ between healthy individuals and patients investigated more than three months after colonoscopic polypectomy or colonic cancer resection.

Adenoma↗

Whole-grain intake and cancer: an expanded review and meta-analysis.

Whole grains are nutrient rich and may protect against chronic disease. To study this, we previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found consistently lower risk in those with high than in those with low whole-grain intake. Questions remained concerning other cancers, dietary assessment, quantity consumed, confounding, and differential study quality. Here we expand the review to 40 case-control studies of 20 cancers and colon polyps. Odds ratios are < 1 for 46 of 51 mentions of whole-grain intake and for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low intake. The pooled odds ratio for high vs. low whole-grain intake among the 45 mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to 0.78 across four types of dietary questionnaires. Odds ratios were < 1 in 9 of 10 mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone-related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8 other cancers. Most pooled odds ratios for specific cancers were in the range of 0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled odds ratio was similar in studies that adjusted for few and many covariates. Dose-response associations were stronger in studies using food-frequency questionnaires than in more quantitative questionnaires. The case-control evidence is supportive of the hypothesis that whole-grain intake protects against various cancers.

Adult↗

Bilateral testicular enlargement and seminoma in a patient with acromegaly.

Growth hormone (GH) excess has been associated with soft tissue changes and an increase in the incidence of colonic polyps and gastrointestinal cancer. We describe a patient with endogenous GH excess caused by a pituitary tumour, resulting in acromegaly. The patient had bilateral testicular enlargement, with tumour of the right testicle. Pituitary MRI revealed a macroadenoma. After resection of the pituitary tumour, GH levels fell below 0.5 ng/ml, with acromegaly resolution. Testicular resection revealed seminoma. Following acromegaly resolution, the enlarged remaining testicle decreased in size. The implications of the testicular enlargement and seminoma in the presence of a GH-secreting tumour are discussed.

Acromegaly↗

Non steroidal anti-inflammatory drugs and COX-2 inhibitors as anti-cancer therapeutics: hypes, hopes and reality.

Non-steroidal anti-inflammatory drugs (NSAIDs) and specific inhibitors of cyclooxygenase (COX)-2, are therapeutic groups widely used for the treatment of pain, inflammation and fever. There is growing experimental and clinical evidence indicating NSAIDs and COX-2 inhibitors also have anti-cancer activity. Epidemiological studies have shown that regular use of Aspirin and other NSAIDs reduces the risk of developing cancer, in particular of the colon. Molecular pathology studies have revealed that COX-2 is expressed by cancer cells and cells of the tumor stroma during tumor progression and in response to chemotherapy or radiotherapy. Experimental studies have demonstrated that COX-2 over expression promotes tumorigenesis, and that NSAIDs and COX-2 inhibitors suppress tumorigenesis and tumor progression. Clinical trials have shown that NSAIDs and COX-2 inhibitors suppress colon polyp formation and malignant progression in patients with familial adenomatous polyposis (FAP) syndrome. Recent advances in the understanding of the cellular and molecular mechanisms of the anti-cancer effects of NSAIDs and COX-2 inhibitors have demonstrated that these drugs target both tumor cells and the tumor vasculature. The therapeutic benefits of COX-2 inhibitors in the treatment of human cancer in combination with chemotherapy or radiotherapy are currently being tested in clinical trials. In this article we will review recent advances in the understanding of the anti-tumor mechanisms of these drugs and discuss their potential application in clinical oncology.

Angiogenesis Inhibitors↗

Micronutrients and cancer risk.

An abundance of epidemiologic evidence, based on numerous and remarkably consistent observations that persons who consume high intakes of fruits and vegetables have reduced risks of most human cancers, supports the concept that micronutrients may play important roles in the prevention of human cancers. Many studies suggest that carotenoid compounds in fruits and vegetables may be important in reducing risk of lung cancer. At least some forms of fiber may contribute to reduced risk of colon cancer, but recent analyses of colonic polyps suggest that folic acid may also play a protective role. Evidence for breast cancer is more limited but protective associations with vitamin A from both carotenoid and preformed sources have been seen in several studies. Although we cannot be certain which compounds are responsible, the evidence is overwhelming that an abundant intake of fruits and vegetables can play an important role in reducing cancer incidence.

Diet↗

Genotoxic activity in human faecal water and the role of bile acids: a study using the alkaline comet assay.

Human faecal waters from 35 healthy non-smoking volunteers (23 from England and 12 from Sweden) consuming their habitual diet were screened for genotoxicity by the single-cell gel electrophoresis (comet) assay using a human colon adenocarcinoma cell line (CACO-2) as the target. Hydrogen peroxide induced DNA damage was categorized as low, intermediate or high for tail moments greater than 5, 17 and 32, respectively: 11 samples were highly genotoxic, four were intermediate, one was low and 19 showed no activity. Endonuclease III treatment significantly increased DNA damage for all except the non-genotoxic faecal waters, suggesting that faecal water genotoxicity may be due, at least in part, to oxidative damage. Faecal water cytotoxicity has previously been attributed to the bile and fatty acid content. In the comet assay no DNA damage was induced by deoxycholate or lithocholate at normal physiological concentrations, suggesting that the genotoxicity of faecal water was due to other substances. Both bile acids induced DNA damage above 300 microM, levels often found in patients with colonic polyps and there was a significant increase in genotoxicity after endonuclease III treatment indicative of oxidative DNA damage.

Adult↗

APC mutations in FAP-associated desmoid tumours are non-random but not 'just right'.

Analysis of APC mutations in colonic and duodenal tumours from familial adenomatous polyposis (FAP) patients has shown that the site of the first hit, the germline mutation, can predict the type and position of the somatic mutation or 'second hit'. The two APC mutations are selected on the basis of a 'just right' level of beta-catenin signalling in intestinal tumours achieved through retention of some of the seven 20-amino-acid beta-catenin degradation repeats. Desmoids are a life threatening extra-colonic manifestation in FAP patients. These aggressive tumours of mesenchymal origin are, at present, poorly characterized in terms of mutational APC spectra. We have investigated somatic mutations in the largest cohort of FAP-associated desmoids to date, and combined our results with previously published data. Somatic mutations were found to occur non-randomly and the position of the germline mutation shown to be a major determinant of the somatic mutation, a characteristic shared with intestinal tumours from FAP patients. In contrast to colonic polyps, loss of heterozygosity in desmoids involved deletion rather than mitotic recombination. While tumours from the colorectum and upper gastrointestinal tract usually retain one to two and three to four beta-catenin degradation repeats, respectively, most desmoids preferentially retain two repeats (P < 0.001, chi2 test). In addition, most desmoids with two APC hits (87%, 26/30) had one mutated allele with no 20-amino acid repeats (P < 0.001). This feature, unique among FAP tumours, indicates that a mutation deleting all repeats from one allele may be an important component in maintaining appropriate levels of beta-catenin signalling levels in desmoid tumour cells.

Adenomatous Polyposis Coli↗

The role of the plastic surgeon in the treatment of Gardner's syndrome: a report of two cases.

Gardner's syndrome is a hereditary disease manifested by multiple colonic polyps that progress to malignancy at an early patient age and also manifested by multiple lesions of the different germ layers including sebaceous cysts, lipomas, fibromas, and osteomas of the facial bones. The plastic surgeon often is asked to treat these patients for the more mundane manifestations of the disease such as inclusion cysts or lipomas. At times, however, the plastic surgeon may be faced with an unusual presentation. Two such unusual cases are presented here, the first being a hemangioma of the hand, which has never been described in a patient with Gardner's syndrome, and the second being a fibroma of the left cheek requiring excision by an intraoral approach.

Adult↗