Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intestinal Polyposis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources

Suppression of intestinal neoplasia by DNA hypomethylation.

We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-aza-deoxycytidine, reduced the average number of intestinal adenomas from 113 in the control mice to only 2 polyps in the treated heterozygotes. Hence, DNA methyltransferase activity contributes substantially to tumor development in this mouse model of intestinal neoplasia. Our results argue against an oncogenic effect of DNA hypomethylation. Moreover, they are consistent with a role for DNA methyltransferase in the generation of the C to T transitions seen at high frequency in human colorectal tumors.

Adenomatous Polyposis Coli↗

The double-barreled wet ileostomy: an alternative method for simultaneous urinary and intestinal diversion without intestinal anastomosis after total colectomy and pelvic exenteration.

BACKGROUND: Although the number of cases of locally advanced colorectal cancer related to familial adenomatous polyposis (FAP) has decreased as a result of a better understanding of the disease, the condition still can offer therapeutic challenges. CASE PRESENTATION: We report a case of a rectal tumor with prostate invasion associated with FAP, treated with neoadjuvant radiotherapy and total extended proctocolectomy with cystoprostatectomy. The reconstruction was undertaken with a double-barreled ileostomy with ureteral reimplantation on the distal segment of the ileostomy. Data including surgical aspects, post-operative complications, and outcome were evaluated. CONCLUSION: The double-barreled wet ileostomy is a technically straightforward and safe procedure that is easily executed and may be an alternative to simultaneous diversion in extreme situations. To the best of our knowledge, this is the first description of this procedure in the literature.

Adenocarcinoma↗

PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine.

Based on recent reports that peroxisome proliferator-activated receptor delta (PPARdelta) activation promotes tumourigenesis, we have investigated the role of this protein in Apc-mediated intestinal tumourigenesis. We demonstrate that the inactivation of Apc in the adult small intestine, while causing the expected nuclear accumulation of beta-catenin, does not cause the expected increase in PPARdelta mRNA or protein but conversely, the levels of PPARdelta mRNA and protein are lowered. Furthermore, we find that ApcMinPPARdelta-null mice exhibit an increased predisposition to intestinal tumourigenesis. Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies.

Adenomatous Polyposis Coli Protein↗

[Colon carcinoma: molecular diagnosis and therapy].

Colorectal cancer (CRC) is one of the most frequent cancers in Western countries. The identification of individuals at risk and the early diagnosis of CRC are of critical importance since a large proportion can be prevented or cured by surgical removal before metastasis has occurred. With increasing understanding of the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes feasible to detect genetic alterations by molecular techniques. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) as well as early stages of spontaneous CRC can be diagnosed by molecular characterization of the adenomatous polyposis coli (APC) gene, the ras oncogene and other genes, respectively, in DNA from peripheral blood, stool or intestinal biopsies. At present, careful patient and family history, physical examination, testing for occult blood as well as colonoscopy are still the key elements, however, for clinical patient management. Molecular diagnosis will hopefully soon complement these analyses and should result in a reduction of morbidity and mortality from CRC. Further, gene therapy offers some potential to prevent or treat CRC.

Adenomatous Polyposis Coli↗

Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes.

The DPC4 (SMAD4) gene plays a key role in the TGFbeta signaling pathway. We inactivated its mouse homolog Dpc4 (Smad4). The homozygous mutants were embryonic lethal, whereas the heterozygotes showed no abnormality. We then introduced the Dpc4 mutation into the Apc(delta716) knockout mice, a model for human familial adenomatous polyposis. Because both Apc and Dpc4 are located on chromosome 18, we constructed compound heterozygotes carrying both mutations on the same chromosome by meiotic recombination. In such mice, intestinal polyps developed into more malignant tumors than those in the simple Apc(delta716) heterozygotes, showing an extensive stromal cell proliferation, submucosal invasion, cell type heterogeneity, and in vivo transplantability. These results indicate that mutations in DPC4 (SMAD4) play a significant role in the malignant progression of colorectal tumors.

Adenocarcinoma↗

Massive lower intestinal bleeding--a decade of experience.

BACKGROUND: Lower gastrointestinal bleeding is defined as hemorrhage orginating distal to the ligament of Treitz. Its diagnosis is difficult, often requiring endoscopy, angiography and isotope scans. METHODS: All patients with massive lower gastrointestinal bleeding seen in three gastroenterology centers of Armed Forces during an 11 year period between 1988 and 1999 were retrospectively analysed. RESULTS: A total of 91 patients with massive lower gastro intestinal bleeding were seen during 11 years. The mean age of the patients was 38.9 years and 64 were males. Aetiological diagnosis was: Non-specific ulcers--11, Ileal tuberculosis--8, NSAID enteropathy--8, Enteric fever--7, Meckel's diverticulum--7, Polyps--6, Ulcerative colitis--5, Carcinoma colon--5, Colonic diverticulosis--5, No cause found--5, Polyposis coli--5, Jejunal diverticulae--3, Angiodysplasia colon--3, Radiation colitis--3, Ischaemic colitis--3, Ileal tumor--2, Ileal angiodysplasia--2, Intestinal Lymphoma--2, Bechet's syndrome--1. Bleeding stopped on conservative therapy in 18 patients (including 5 where no diagnosis could be made). Diagnosis was made in 36 patients on fiber-optic colonoscopy done during active bleeding. Remaining patients were subjected to emergency laparotomy and diagnosis was obvious on inspection of abdominal contents in 25 cases. The diagnosis was finally made in remaining 12 cases by intraoperative endoscopic examination through an ileotomy. Four patients died, only one of them due to rebleed after surgery from an additional lesion. CONCLUSIONS: Compared with experience in Western countries, massive lower gastro-intestinal hemorrhage in India affects younger patients, has different causes and carries a lower mortality. Colonoscopy is useful in making diagnosis during active lower intestinal bleeding in about one-third cases. Exploratory laparotomy and Intra-operative endoscopy are complimentary to above examination and can make the diagnosis in most of the remaining cases.

Adolescent↗

Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions.

Adenomatous polyposis coli (APC) promoter hypermethylation has been reported frequently in normal gastric mucosa, but it remained to be clarified whether this occurs in every individual. In this study, methylation of the APC promoter was analyzed in histologically normal-appearing gastric mucosa samples by methylation-sensitive single-strand conformation analysis and by a methylation-sensitive dot blot assay. Epithelial cell samples were collected by microdissection from tissue sections. Equal amounts of methylated and unmethylated APC alleles were found in all gastric mucosa samples from patients without any gastric lesions (20 samples). Allele-specific methylation analysis showed that the methylation of the APC promoter was monoallelic; however, which allele was methylated depended on the cell type. Increased or decreased methylation was found in 10 of 36 (28%) normal gastric mucosa samples adjacent to a gastric or esophageal adenocarcinoma. No allelic loss was found at the APC locus. Modification of the methylation status was also found in 3 of 21 (14%) normal-appearing gastric mucosa samples adjacent to intestinal metaplasia. In contrast, all normal mucosa samples in cases with chronic gastritis but without metaplasia or dysplasia showed a monoallelic methylation pattern. Our results indicate the following: (a) In normal gastric mucosa, the APC promoter shows monoallelic methylation, which is not due to imprinting but most likely due to allelic exclusion; (b) the excluded allele differs between foveolar and glandular epithelial cells; (c) the APC methylation pattern is frequently altered in normal-appearing gastric mucosa of gastric or esophageal adenocarcinoma patients; and (d) such alterations also occur in normal gastric mucosa adjacent to intestinal metaplasia.

Adenocarcinoma↗

The adenoma-carcinoma sequence in the colorectum--early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential.

The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis.

Adenoma↗

Proctocolectomy and pelvic pouch--is a diverting stoma dangerous for the patient?

OBJECTIVE: A diverting loop ileostomy was previously considered mandatory for minimizing the effects of septic complications in pelvic pouch surgery. During the past decade there has been a trend towards omission of the loop ileostomy without obvious signs of increased numbers of pouch complications or impaired long-term function. The aim of the present study was to evaluate the risk of complications associated with the construction and closure of the loop ileostomy itself. PATIENTS AND METHODS: Complications following diverting loop ileostomies in 143 patients subjected to restorative pelvic pouch surgery during the period 1983-97 were studied retrospectively by evaluation of case records. RESULTS: In the period between discharge after pelvic pouch surgery and closure of the loop ileostomy, 20 (14%) patients were hospitalized because of excessive stoma flow and 19 (13%) patients were treated for other surgical complications, of whom 10 (7%) required surgical intervention. In the early postoperative period (within 30 days) after closure of the loop ileostomy, 18 (13%) patients suffered complications necessitating surgery. Another 12 (8%) patients were hospitalized because of intestinal obstruction that could be treated conservatively. CONCLUSION: The proportion of complications associated with diverting loop ileostomies in pelvic pouch surgery was considerable. A randomised controlled multicentre study is ethically defensible and is recommended.

Adenomatous Polyposis Coli↗

[Molecular etiology of colorectal carcinogenesis, clinical manifestations and therapy].

Mutations of tumor suppressor genes, of the mismatch DNA repair system, and of the TGF-beta-II-receptor are the main causes for a higher risk of colorectal cancer. Among mutations of the Ape gene, which characterize the clinical manifestation of the familial polyposis (FAP), point mutations are dominating which create new stop codons or arise from deletions or insertions of nucleotides causing frame shifts. Because the binding site of beta-catenin is localized in the C-terminus of the Ape protein, disturbances result in the cellular signal transfer from its loss. Consequently, the interactions of the usually formed Ape-beta-catenin complex with the cytoskeleton and the cadherin system in the plasma membrane as well as the translocation of beta-catenin into the nucleus cannot be realized. Mutations in the genes of the mismatch DNA repair system and of the TGF-beta-II-receptor, the main defects of the HNPCC (hereditary nonpolyposis colorectal cancer), are exclusively identified in sequences of microsatellites. Because the majority of Apc gene mutations is also localized in repetitive motifs even in CpG islands primary disturbances are to postulate in the methylation pattern of the genes producing germline and somatic mutations. Generally, complexly connected reactions are involved in this cascade of colorectal cancer genesis. This fact explains the relatively late clinical manifestation of the disease and offers the possibility to identify carriers with an increased risk of colorectal cancer development in order to integrate them into a programme of control and preventive medicine. Beside the known treatment by surgery and cytostatics, inhibitors of prostaglandin synthesis gain therapeutic significance. Cancerogenesis can be efficiently suppressed by inhibition of the COX-2-induction (cyclo-oxygenase-2). There is a lack of clinical experience for a decision whether a high intraluminal level of butyrate in the large intestine can delay colorectal carcinogenesis.

Adenomatous Polyposis Coli↗