Familial polyposis coli.
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Colonic Neoplasms↗
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[Polyposis of the colon].
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Colonic Neoplasms↗
[X-ray diagnosis of the colonic polyposis (author's transl)].
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Adult↗
[Capsule endoscopy].
Video capsule endoscopy provides a noninvasive diagnostic approach to the entire small intestine. The main indications are suspected chronic or recurrent obscure intestinal bleeding, which can-not be clarified by esophago-gastro-duodenoscopy and colonoscopy. Further indications are polyposis syndromes, suspected Crohn's disease and malignomas of the small bowels. Esophago-gastroduodenoscopy and colonoscopy are essential preceding diagnostic procedures before capsule endoscopy.
Diagnosis, Differential↗
Frequent somatic mutations of the beta-catenin gene in intestinal-type gastric cancer.
The increased level of cytoplasmic beta-catenin through the mutations to either beta-catenin or adenomatous polyposis coli (APC) has been proposed as an important oncogenic step in various tumors. Gastric cancer showed frequent genetic alterations of the APC gene, and the risk for gastric cancer in familial adenomatosus polyposis patients is 10 times higher than that in the general population. These findings raise the possibility that mutations of beta-catenin may also be associated with the development of gastric cancer. We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers. All of these mutations were missense mutations, of which five are in the highly conserved aspartic acid 32 and two are in serine 29; all of these seven mutations were detected exclusively in intestinal-type gastric cancers (7 of 26; 26.9%), but not in the diffuse-type (0 of 17). We concluded that disruption of the APC/beta-catenin/T cell factor-lymphoid enhancer binding factor pathway might play an important role especially in the development of intestinal-type gastric cancer.
Base Sequence↗
New pancreas-preserving total duodenectomy technique.
Pancreas-preserving total duodenectomy (PPTD) was first described by Chung et al. in 1994. Since then, several surgeons have used PPTD to treat diseases that involve the duodenum diffusely but not the head of the pancreas, mostly familial adenomatous polyposis (FAP). The PPTD method has been changed in each report and seems to have improved over time. We performed PPTD on three patients with different diseases--one with intestinal hemorrhage due to small intestinal amyloidosis; another with numerous duodenal gastrinomas in a patient with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome (ZES); and the third with numerous duodenal polyposis and FAP--using a new method that is simpler and safer than those previously reported. When resecting the whole duodenum, we performed mucosectomy of the major papillar portion and saved the structure of the major papilla. After an approximately 8 mm long sphincteropapillotomy, the opened major papilla was anastomosed to an incisional opening of the small intestine. The orifice of the main pancreatic duct (MPD) was stented by a catheter, and the MPD was kept intact under direct vision during the operative procedures. The head of the pancreas was fixed with the small intestine by interrupted 4-0 silk sutures. Reconstruction of the alimentary tract was performed after either the Billroth I or the Billroth II method. This is the first report of PPTD in which the entire MPD was preserved to simplify the biliopancreatic-ductal reconstruction.
Adenomatous Polyposis Coli↗
Premalignant conditions of the small intestine.
Cancer of the small intestine is rare compared with other sites in the gastrointestinal tract. Of the four major primary small-bowel tumors (adenocarcinomas, lymphomas, carcinoid, and leiomyosarcomas), adenocarcinomas and lymphomas are associated with diseases that seem to increase the risk of developing these malignancies. In the case of immunoproliferative small intestinal disease and celiac disease, both of which are thought to predispose patients to the development of primary lymphoma, treatment of the predisposing conditions seems to decrease the risk of developing subsequent malignancy. Recognition of the increased risk associated with other conditions, such as immunodeficiency syndromes, nodular lymphoid hyperplasia, Crohn's disease, the gastrointestinal polyposis syndromes, hereditary nonpolyposis colon cancer, neurofibromatosis, long-standing ileostomy, and urinary diversion procedures, may lead to early diagnosis and improved survival.
Acquired Immunodeficiency Syndrome↗
Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice.
Germ-line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice, heterozygous for the Apc gene mutation, progressively develop small intestinal tumours in a manner that is analogous to that observed in the colon of patients with FAP (Su et al. 1992; Fodde et al. 1994; Moser et al. 1995). We have studied the effects of Apc gene mutation on murine intestinal and extra-intestinal, proliferatively active tissues. We have contrasted the histology to that of the age- and sex-matched wild-type C57BL/6 mice. Histological assessment of the normal appearing intestinal mucosa demonstrates minimal change in size of crypts. In contrast, villi are longer in the ileum of Apc(Min/+) mice relative to C57BL/6 mice at 12 and 15 weeks of age. Vigorous splenic haematopoiesis in Apc(Min/+) mice was seen at 12 and 15 weeks of age, as reflected by marked splenomegaly, increased splenic haematopoietic cells and megakaryocytes. Peripheral blood counts, however, did not differ between C57BL/6 and Apc(Min/+) mice at 15 weeks of age. Lymphoid depletion in Apc(Min/+) mice was characterized by diminished numbers of splenic lymphoid follicles and small intestinal Peyer's patches. The ovaries of 12- and 15-week-old Apc(Min/+) mice exhibited increased numbers of atretic follicles, and estrous cycling by serial vaginal smears showed tendency of elongation in the mutant mice during these age ranges. The testicles of 10-week-old Apc(Min/+) mice showed increased numbers of underdeveloped seminiferous tubules. Collectively, these data suggest that, in addition to its obvious effects upon intestinal adenoma formation, Apc gene mutation causes impairment of developmental and apparent differentiation blockade in proliferative tissues, including those of the haematopoietic system, lymphoid and reproductive tract.
Adenomatous Polyposis Coli↗
Juvenile polyposis and gastrointestinal carcinoma. A study of a kindred.
A kindred contained at least 10 members with single or multiple juvenile polyps of the stomach and large intestine. Several additional polyps had both adenomatous and juvenile features. Eleven members of the kindred have had gastrointestinal carcinoma of the stomach, duodenum, pancreas, or proximal colon. The pattern of inheritance in this kindred suggests either a single or two closely linked autosomal dominant determinants for gastrointestinal carcinoma and polyposis. Management of this kindred is complicated due to the occurrence of gastrointestinal carcinoma without polyposis.
Adenocarcinoma↗
Truncated mouse adenomatous polyposis coli reduces connexin32 content and increases matrilysin secretion from Paneth cells.
Heterozygous mutations in adenomatous polyposis coli (APC) is an early event in inheritable and sporadic colon cancer development. We recently found reduced connexin (Cx43) expression in intestinal cell lines with heterozygous Apc mutation. In this study we investigated Cx expression and the role of one mutated Apc allele in epithelia of multiple intestinal neoplasia (Min) mouse intestines by immunohistochemistry. Cx43 was not expressed in intestinal epithelia of Min and wild-type mice. Cx32 was specifically expressed in enterochromaffin cells in both mice types, and in Paneth cells of wild-type mice. In contrast, Min mice had nearly undetectable level of Cx32 in Paneth cells. Isolated small intestinal crypts from Min mice had markedly increased secretion of both lysozyme and matrilysin compared with wild-type mice. Absence of matrilysin in Min mice reduces adenoma development. Reduced Cx32 and increased matrilysin secretion from Paneth cells could be important to neoplastic development in the intestine.
Adenomatous Polyposis Coli↗
Intestinal and extra-intestinal tumor multiplicities in the Apc1638N mouse model after exposure to X-rays.
Seven-week-old Apc1638N mice were exposed to a single dose of 5 Gy total-body X-irradiation resulting in a 8-fold increase in the number of intestinal tumors and a reduction of the lifespan to an average of 6 months. The distribution of tumors along the intestinal tract as well as the adenoma/carcinoma ratio, were similar between non-irradiated and irradiated animals. Semi-quantitative PCR analysis of intestinal-tumor DNA revealed that 10 out of 14 tumors had lost the wild-type Apc allele. However, in contrast to spontaneous Apc1638N intestinal tumors in which the LOH event at the Apc locus involves the entire chromosome 18 (1), in 6 out of 10 tumors derived from X-irradiated animals the Apc loss is associated with only a partial intrachromosomal deletion. The remaining tumors have lost all chromosome 18 markers tested. In addition to the intestinal tumors, female Apc1638N mice are susceptible to the development of mammary tumors. Upon X-irradiation, Apc1638N mice show a striking 15-fold increase in mammary tumors. Moreover, Apc1638N mice spontaneously develop other extra-intestinal neoplasia, such as desmoid-like lesions similar to those associated with familial adenomatous polyposis (FAP), the human syndrome caused by germline mutations in the APC gene. Spontaneous desmoid growth is sex-dependent, as male Apc1638N mice develop 3-fold more desmoids than female mice. Interestingly, X-irradiation seemed to increase the number of desmoids per animal nearly twofold only in female Apc1638N mice. Five out of 9 desmoids found in Apc1638N mice exposed to X-ray displayed loss of the wild-type Apc allele.
Alleles↗
[Obstructive uropathy in Gardner's syndrome. Intra-abdominal desmoid tumor].
Desmoid tumours are benign neoplasias manifesting themselves clinically as aggressive fibromatoses. They may be sited both in mesenteric and retroperitoneal fat. Owing to the great size they reach and to their local infiltrative character they occasionally lead to the development of intestinal occlusive syndromes and, in exceptional cases, to obstructive uropathy of the upper urinary tract. Their incidence of presentation in the general population is low, however they develop more frequently in patients suffering from colonic polyposis in the family and they form part of the extracolonic manifestations of Gardner's syndrome. In 1987 we treated a young patient, a genetic carrier of familiar colonic polyposis who had presented relapse of a previous desmoid. The location of the tumour in narrow pelvis made its clinical debut as a intestinal pseudo-occlusion and determined a bilateral ureteral obstruction and the formation of a major urinoma. The joint utilization of instrumental maneuvers and surgical approaches enabled us to solve the intestinal and urological commitment satisfactorily. We carry out an overall review and analyse the data published on the incidence, prognosis and treatment of obstructive uropathy in Gardner's syndrome. We also carry out an updating on the biology of the desmoid tumour.
Adult↗
Tumor-associated Apc mutations in Mlh1-/- Apc1638N mice reveal a mutational signature of Mlh1 deficiency.
Apc1638N mice, which are heterozygous for a germline mutation in Apc, typically develop three to five spontaneous intestinal tumors per animal. In most cases this is associated with allelic loss of wildtype Apc. We have previously reported that the multiplicity of intestinal tumors is increased dramatically by crossing Apc1638N with an Mlh1-deficient mouse strain that represents an animal model of hereditary non-polyposis colorectal cancer (HNPCC). The increased tumor multiplicity in these mice was associated with somatic mutations in the Apc tumor suppressor gene. Here, we have examined the nature and distribution of 91 Apc mutations implicated in the development of intestinal tumors in Mlh1-/- Apc1638N animals. Protein truncation mutations were detected in a majority of tumor samples, indicating that the prevailing mechanism of Apc mutation in tumors is altered from allelic loss to intragenic mutation as a result of Mlh1 deficiency. The observed mutations were a mixture of base substitutions (27%) and frameshifts (73%). Most frameshifts were detected within dinucleotide repeats and there were prominent mutational hotspots within sequences of this sort at codons 927-929, 1209-1211 and 1461-1464. The observed Apc mutations caused protein truncation upstream of the third 20 amino acid beta-catenin binding domain and the first Axin-binding SAMP repeat, yielding Apc proteins that are predicted to be deficient in destabilizing beta-catenin. Our results reveal a characteristic mutational signature in Apc that is attributable to Mlh1 deficiency. This demonstrates a direct effect of Mlh1 deficiency in the mutation of Apc in these tumors, and provides data that clarify the role of Mlh1 in mammalian DNA mismatch repair.
Adaptor Proteins, Signal Transducing↗
Pathogenesis of carcinoma of the papilla of Vater.
Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.
Adenocarcinoma↗
Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue.
The gastrointestinal glutathione peroxidase (GI-GPx) is believed to prevent absorption of hydroperoxides. GI-GPx is expressed in the intestine together with the other three glutathione peroxidase isoenzymes, raising the question of the physiological role of the different GPx types. We therefore studied the cellular and subcellular distribution of GI-GPx in normal and malignant tissue obtained from patients with colorectal cancer or familial polyposis by immunohistochemistry. In healthy ileum epithelium GI-GPx was preferentially enriched in Paneth cells. In unaffected crypts of colon and rectum, it decreased gradually from the ground to the luminal surface. In crypt ground, GI-GPx was uniformly distributed, whereas in cells at the luminal surface it was concentrated in structures capping the nuclei at the apical pole. In colorectal cancer, GI-GPx expression depended on the stage of malignant transformation. In early stages, GI-GPx was increased and pronouncedly associated with the vesicular structures. In progressed stages of malignancy, structures disintegrated and GI-GPx distribution became more diffuse. These observations support the hypothesis that GI-GPx, apart from being a barrier against hydroperoxide absorption, might be involved in cell growth and differentiation.
Adenomatous Polyposis Coli↗
Regulation of caspase expression and apoptosis by adenomatous polyposis coli.
The adenomatous polyposis coli (APC) gene, a member of the WNT pathway, has been shown to assign intestinal epithelial cells to a program of proliferation or differentiation through regulation of the beta-catenin/TCF-4 complex. Wild-type APC, in certain cellular contexts, appears to induce differentiation and apoptosis, although mutant forms of APC, known to produce polyps and ultimately cancers, may suppress these events. Here, we show that mutant forms of APC can induce repression of select terminal caspases as a potential means of attenuating responses to apoptotic stimuli. Using gene expression profiling to interrogate the intact intestines of Apc(+/min) mice harboring numerous polyps, we identified a reduction in the mRNA expression of both caspases 3 and 7. We additionally identified a reduction in protein levels of caspase-3, caspase-7, and caspase-9 in human colon cancer specimens known to harbor APC mutations. A reduction in caspase protein levels resulted in resistance to apoptotic-inducing agents and restoration of caspase levels reinstated apoptotic capacities. Consistent with Wnt pathway involvement, dominant negative TCF/LEF induced caspase protein expression. These data provide support for the hypothesis that one of the functions of APC is the regulation of caspase activity and other apoptotic proteins by controlling their expression levels in the cell.
Adenomatous Polyposis Coli Protein↗
Histological detection of microadenomas in the diagnosis of familial adenomatous polyposis.
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Adenoma↗
Adenomatous polyps in the anal transitional zone after ileal pouch-anal anastomosis for familial adenomatous polyposis: treatment by transanal mucosectomy and ileal pouch advancement.
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Adenomatous Polyposis Coli↗