Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis.
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Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation. (+info)
Elevated reticulocyte count--a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report.
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In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-platinum, and with bleomycin carries a significant, albeit extremely small, risk for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine is a novel cytotoxic drug with promising activity against pancreatic adenocarcinoma. We are reporting on one patient with metastatic duodenal papillary carcinoma developing HUS while on weekly gemcitabine therapy. The presenting features in this patient were non-cardiac pulmonary oedema, renal failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made on the day of admission of the patient to this institution. Upon aggressive therapy, including one single haemodialysis and five plasmaphereses, the patient recovered uneventfully, with modestly elevated creatinine-values as a remnant of the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS instituted for progressive carcinoma, thus far has not caused another episode of HUS. (+info)
Descriptive epidemiology of small intestinal malignancies: the German Cancer Registry experience.
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In the first population-based analysis of certain epidemiologic features of primary malignancies of the small intestine in Germany, we used data from the Saarland Cancer Registry (1982-1993) and from the former National Cancer Registry of the German Democratic Republic (1976-1989). The age-standardized incidence rates for ages 0-74 years is 3.3-6.2 per million per year. The average incidence rates of the federal state Saarland are for men about 1.3 times and for women about 1.4 times the rate of the former German Democratic Republic. After the age of 30 years, the incidence rates increased with increasing age. Incidence rates for carcinoids levelled off after the age of 54 years. Rates for men were 35-40% higher than for women after adjusting for age. The risk for carcinomas, malignant carcinoids and malignant lymphoma were higher for men than for women. (+info)
Surgery to cure the Zollinger-Ellison syndrome.
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BACKGROUND AND METHODS: The role of surgery in patients with the Zollinger-Ellison syndrome is controversial. To determine the efficacy of surgery in patients with this syndrome, we followed 151 consecutive patients who underwent laparotomy between 1981 and 1998. Of these patients, 123 had sporadic gastrinomas and 28 had multiple endocrine neoplasia type 1 with an imaged tumor of at least 3 cm in diameter. Tumor-localization studies and functional localization studies were performed routinely. All patients underwent surgery according to a similar operative protocol, and all patients who had surgery after 1986 underwent duodenotomy. RESULTS: The 151 patients underwent 180 exploratory operations. The mean (+/-SD) follow-up after the first operation was 8+/-4 years. Gastrinomas were found in 141 of the patients (93 percent), including all of the last 81 patients to undergo surgery. The tumors were located in the duodenum in 74 patients (49 percent) and in the pancreas in 36 patients (24 percent); however, primary tumors were found in lymph nodes in 17 patients (11 percent) and in another location in 13 patients (9 percent). The primary location was unknown in 24 patients (16 percent). Among the patients with sporadic gastrinomas, 34 percent were free of disease at 10 years, as compared with none of the patients with multiple endocrine neoplasia type 1. The overall 10-year survival rate was 94 percent. CONCLUSIONS: All patients with the Zollinger-Ellison syndrome who do not have multiple endocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure. (+info)
Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial.
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OBJECTIVE: This prospective, randomized, single-institution trial was designed to evaluate the role of prophylactic gastrojejunostomy in patients found at exploratory laparotomy to have unresectable periampullary carcinoma. SUMMARY BACKGROUND DATA: Between 25% and 75% of patients with periampullary cancer who undergo exploratory surgery with intent to perform a pancreaticoduodenectomy are found to have unresectable disease. Most will undergo a biliary-enteric bypass. Whether or not to perform a prophylactic gastrojejunostomy remains unresolved. Retrospective reviews of surgical series and prospective randomized trials of endoscopic palliation have demonstrated that late gastric outlet obstruction, requiring a gastrojejunostomy, develops in 10% to 20% of patients with unresectable periampullary cancer. METHODS: Between May 1994 and October 1998, 194 patients with a periampullary malignancy underwent exploratory surgery with the purpose of performing a pancreaticoduodenectomy and were found to have unresectable disease. On the basis of preoperative symptoms, radiologic studies, or surgical findings, the surgeon determined that gastric outlet obstruction was a significant risk in 107 and performed a gastrojejunostomy. The remaining 87 patients were thought by the surgeon not to be at significant risk for duodenal obstruction and were randomized to receive either a prophylactic retrocolic gastrojejunostomy or no gastrojejunostomy. Short- and long-term outcomes were determined in all patients. RESULTS: Of the 87 patients randomized, 44 patients underwent a retrocolic gastrojejunostomy and 43 did not undergo a gastric bypass. The two groups were similar with respect to age, gender, procedure performed (excluding gastrojejunostomy), and surgical findings. There were no postoperative deaths in either group, and the postoperative morbidity rates were comparable (gastrojejunostomy 32%, no gastrojejunostomy 33%). The postoperative length of stay was 8.5+/-0.5 days for the gastrojejunostomy group and 8.0+/-0.5 days for the no gastrojejunostomy group. Mean survival among those who received a prophylactic gastrojejunostomy was 8.3 months, and during that interval gastric outlet obstruction developed in none of the 44 patients. Mean survival among those who did not have a prophylactic gastrojejunostomy was 8.3 months. In 8 of those 43 patients (19%), late gastric outlet obstruction developed, requiring therapeutic intervention (gastrojejunostomy 7 patients, endoscopic duodenal stent 1 patient; p < 0.01). The median time between initial exploration and therapeutic intervention was 2 months. CONCLUSION: The results from this prospective, randomized trial demonstrate that prophylactic gastrojejunostomy significantly decreases the incidence of late gastric outlet obstruction. The performance of a prophylactic retrocolic gastrojejunostomy at the initial surgical procedure does not increase the incidence of postoperative complications or extend the length of stay. A retrocolic gastrojejunostomy should be performed routinely when a patient is undergoing surgical palliation for unresectable periampullary carcinoma. (+info)
Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice.
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The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines. It encodes a common cytoplasmic signaling molecule shared by the transforming growth factor-beta, activin, and bone morphogenic pathways. We recently inactivated its mouse homologue Smad4 and demonstrated its role in the malignant progression of benign adenomas to invasive adenocarcinomas by analyzing mice with Apc and Smad4 compound mutations. Although simple Smad4 homozygotes were embryonically lethal, the heterozygotes were fertile and appeared normal up to the age of 1 year. Upon further investigation, however, they have developed inflammatory polyps in the glandular stomach and duodenum. By PCR genotyping and immunohistochemical staining, the wild-type Smad4 allele has been lost in the polyp epithelial cells, ie., loss of heterozygosity. On the other hand, we have not found any mutations in such genes as K-Ras, H-Ras, N-Ras, p53, or PTEN. Histologically, the polyps are similar to human juvenile polyps showing moderate stromal cell proliferation and infiltrations by eosinophils and plasma cells. In addition, foci of adenocarcinoma with signet ring cells are also found. These results are consistent with a recent report that germ-line SMAD4 mutations are found in a subset of familial juvenile polyposis. (+info)
Primary duodenal MALT lymphoma.
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Primary duodenal MALT lymphoma (MALToma) is a very rare neoplasm arising from the mucosa-associated lymphoid tissue of the duodenum. We report a 55-year-old woman with MALToma located in the descending duodenum and accompanying Helicobacter pylori infection of the stomach. We performed operative resection due to involvement of the papilla of Vater and submucosal tumor infiltration. Despite wide mucosal spreading, postoperative examination revealed only a small amount of MALToma cells infiltrating into the submucosa. No invasion into the adjacent structure or metastasis to regional lymph nodes was confirmed, suggesting the disease could have been controlled by eradication of Helicobacter pylori. (+info)
Establishment and analysis of biological characteristics of a human duodenal carcinoma cell line, WDC-1.
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BACKGROUND: Duodenal carcinoma is very rare and its culture cell lines have rarely been established. METHODS: Tumor cells separated from a surgically resected primary tumor of duodenal carcinoma were put into culture. The patient was an 81-year-old female and had metastatic lymph nodes. We investigated the biological characteristics of the culture cells including in vitro cell kinetics, karyotype, expression of tumor markers and integrins and tumorigenicity and histology in nude mice. RESULTS: A new cell line, designated WDC-1, was established. This duodenal carcinoma cell line proliferated in a monolayered sheet with a doubling time of 50 h. The histological findings of the xenograft in nude mice were similar to those of the primary tumor. WDC-1 cells produced carcinoembryonic antigen and expressed 1 integrin and very late antigen (VLA)-4d in vitro. CONCLUSIONS: A duodenal carcinoma cell line was established, which is rare and may contribute to progress in understanding the biological features of duodenal cancer. (+info)