Ductuloinsular tumors of the pancreas: endocrine tumors with entrapped nonneoplastic ductules.

Rare pancreatic neoplasms have been reported that show both endocrine and exocrine differentiation in the neoplastic components. In addition, pancreatic endocrine tumors may contain small, cytologically bland ductules intimately admixed with the endocrine component. It was recently suggested that these ductules represent an intrinsic part of the tumor, ie, that the ductules are neoplastic, and the term "ductulo-insular tumors of the pancreas" was proposed.

Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis.

Background: To determine at what stage during gastric carcinogenesis Epstein-Barr virus (EBV) enters the gastric epithelial cells, the presence of EBV was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomach-gastric carcinoma of the intact stomach (GCIS) and gastric stump carcinoma (GSC)-and their presumed precursor lesions.

Patients And Methods: Eleven patients with EBV positive GCIS and eight patients with EBV positive GSC, demonstrated by the highly sensitive EBV encoded RNA 1/2 (EBER1/2) RNA in situ hybridisation (RISH) technique, were studied. Paraffin wax embedded tissue available from preoperative gastric biopsies and tumour adjacent tissue from the resection specimens containing normal gastric mucosa, inflamed gastric mucosa, and preneoplastic lesions (intestinal metaplasia and dysplasia) was investigated by EBER1/2 RISH, in addition to EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1 (LMP-1) immunohistochemistry (IHC).

Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds.

Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk of pancreatic cancer in individuals with a family history of pancreatic cancer.

Suppression of tumor growth, invasion and angiogenesis of human gastric cancer by adenovirus-mediated expression of NK4.

Background: To improve the prognosis of patients with gastric cancer it is important to develop novel treatment modalities targeting the malignant behavior of tumor cells. Concerning this, NK4, which acts as HGF-antagonist and angiogenesis inhibitor, might be a potential therapeutic agent for gastric cancer. The HGF-c-MET pathway plays a pivotal role in gastric tumor growth, invasion, metastasis and angiogenesis.

De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine.

Little is known about the signaling mechanisms that determine the highly regular patterning of the intestinal epithelium into crypts and villi. With the use of mouse models, we show that bone morphogenetic protein (BMP)-4 expression occurs exclusively in the intravillus mesenchyme. Villus epithelial cells respond to the BMP signal.

[Cystadenomas with ovarian stroma in liver and pancreas: indications of embryonic migration of the gonadal epithelium].

Objective: To provide an embryological explanation for the presence of ovarian stroma in cystadenomas of the liver and pancreas.

Design: Investigation of patients and embryos.

Method: From 1997 to 2001 in the Academic Medical Centre, Amsterdam, the Netherlands, nine women were treated for a cystadenoma with ovarian stroma, six of which were situated in the liver and three in the tail of pancreas.

Adenocarcinoma in the anal canal after ileal pouch-anal anastomosis for familial adenomatous polyposis using a double-stapled technique: report of two cases.

Restorative proctocolectomy with an ileal pouch-anal anastomosis is thought to abolish the risk of colorectal adenoma development in patients suffering from familial adenomatous polyposis. Both after mucosectomy with a handsewn anastomosis and after a double-stapled anastomosis, rectal mucosa is left behind at the anastomotic site. This carries the potential for the development of polyps and a subsequent malignancy.

Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients.

Survival data of patients with pancreatic carcinoma are often overestimated because of incomplete follow-up. Therefore, the aim of this study was to approach complete follow-up and to analyse survival and prognostic factors of patients who underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and 2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma.

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation.

Wnt signaling defines the colonic epithelial progenitor cell phenotype, and mutations in the gene adenomatous polyposis coli (APC) that activate the Wnt pathway cause the familial adenomatous polyposis coli (FAP) syndrome and most sporadic colon cancers. The mechanisms that regulate the transition of epithelial precursor cells into their differentiated derivatives are poorly characterized. We report that Indian hedgehog (Ihh) is expressed by mature colonocytes and regulates their differentiation in vitro and in vivo.

Gene therapy for esophageal carcinoma: the use of an explant model to test adenoviral vectors ex vivo.

Adenoviral gene therapy might be a promising therapeutic strategy for esophageal carcinoma. However, adenoviral transduction efficacy in vivo is still limited. This efficacy can be improved by the insertion of an Arg-Gly-Asp (RGD) peptide in the HI-loop of the viral fiber knob.

Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis.

Background & Aims: Familial adenomatous polyposis because of germline mutation of the adenomatous polyposis coli gene is characterized by development of colorectal adenomas and, ultimately, colorectal cancer. The usefulness of colorectal mucosal compounds to predict the effect on adenoma development of primary chemoprevention with the nonsteroidal anti-inflammatory drug sulindac was evaluated.

Methods: A randomized, double-blind, placebo-controlled study of 41 subjects genotypically affected with familial adenomatous polyposis but phenotypically unaffected was conducted.

Quantitative assessment of gastric antrum atrophy shows restitution to normal histology after Helicobacter pylori eradication.

Background/aims: Grading gastric mucosal atrophy in antrum biopsy specimens remains a controversial subject because of limitations in interobserver agreement. We previously described a reliable, quantitative method for grading atrophy of the corpus mucosa with excellent reproducibility and good correlation with the Sydney scores. The aims of the present study were to evaluate the applicability of this method for the grading of antral atrophy and to study the effect of Helicobacter pylori eradication on the antral mucosa.

Role of cyclooxygenase-2 in the development and treatment of oesophageal adenocarcinoma.

Background: Various studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Epidemiological studies have found that long-term use of NSAIDs is associated with a reduced incidence of colorectal, gastric and oesophageal cancers, while experimental and clinical studies have demonstrated that treatment with NSAIDs causes a statistically significant reduction in both the number and the size of polyps in familial adenomatous polyposis (FAP) patients.

Methods: In this review, the mechanisms by which NSAIDs exert their chemopreventive and antineoplastic effects are described.

Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive potential against colorectal carcinomas (CRCs). Inhibition of cyclooxygenase (COX)-2 underlies part of this effect, although COX-2-independent mechanisms may also exist. Nonsteroidal anti-inflammatory drugs appear to inhibit the initial stages of the adenoma-carcinoma sequence, suggesting a link to the APC/beta-catenin/TCF pathway (Wnt-signalling pathway).

Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon.

Background And Aims: The recent findings of bone morphogenetic protein (BMP) receptor Ia mutations in juvenile polyposis and frequent Smad4 mutations in colon cancer suggest a role for BMPs in the colonic epithelium and colon cancer. We investigated the role of BMP2 in the colon.

Methods: We assessed BMP receptor expression in cell lines using the reverse-transcribed polymerase chain reaction and immunoblotting.

Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus.

Background: Adenocarcinomas of the gastric cardia and distal oesophagus are at present often considered as one clinical entity because of their comparable increasing incidence, prognosis, and optimal treatment options. However, it is still a matter of debate whether these malignancies have the same pathogenesis and genotype.

Aims: The aim of this study was to analyse expression of cyclooxygenase 2 (COX-2) in cardia carcinomas, and correlate this expression with clinicopathological parameters and survival.

A genetically retargeted adenoviral vector enhances viral transduction in esophageal carcinoma cell lines and primary cultured esophageal resection specimens.

Objective: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells.

Summary Background Data: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry.

Cyclooxygenase-2 and gastric carcinogenesis.

Epidemiological studies have shown that the use of nonsteroid anti-inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best-known target of NSAIDs is the cyclooxygenase (Cox) enzyme. Two Cox genes have been cloned, of which Cox-2 has been connected with gastric carcinogenesis.

Experimental model of obstructive, chronic pancreatitis in pigs.

Background: We aimed to develop a reproducible, experimental model of obstructive pancreatitis for future analysis of surgical interventions, and characterized this model using functional, histological and biochemical parameters.

Animals And Methods: In 10 female pigs the pancreatic duct (PD) was ligated. After 4, 6 or 8 weeks the animals were sacrificed.

Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines.

Gastrointestinal carcinomas synthesize elevated levels of prostaglandin E(2) (PGE(2)), which has been mechanistically linked to carcinogenesis. Recently, microsomal prostaglandin E synthase-1 (mPGES-1) was cloned, which seems to be inducible and linked to cyclooxygenase-2 (Cox-2) in the biosynthesis of PGE(2). We examined expression of mPGES-1 in intestinal type gastric adenocarcinomas and in gastric cancer cell lines.

Pancreatic carcinoma in carriers of a specific 19 base pair deletion of CDKN2A/p16 (p16-leiden).

Purpose: The purpose is to document the clinical, pathological, and genetic features of pancreatic carcinoma (PC) in carriers of a specific p16-Leiden mutation (a 19-bp deletion in exon 2 of the CDKN2A gene).

Experimental Design: Clinical data and paraffin embedded tissue were obtained from 12 patients of p16-Leiden-positive families with PC. Because of the known 19-bp germ-line deletion, we could specifically analyze the genotype of the wild-type allele for loss of heterozygosity.

Timing and sequence of differentiation of embryonic rat hepatocytes along the biliary epithelial lineage.

To study the differentiation of hepatocytes along the biliary epithelial lineage in vivo, embryonic day 14 (E14) rat hepatocytes were isolated by differential centrifugation and transplanted as single-cell suspensions into the spleen of adult syngeneic rats. Hepatocytes and cholangiocytes were identified and their maturation characterized by the level of expression of alpha-fetoprotein (AFP), glutamate dehydrogenase (GDH), and carbamoyl phosphate synthetase I (CPS); annexin IV, annexin V, cytokeratin 19 (CK-19), and cystic fibrosis transmembrane conductance regulator (CFTR); and electron microscopy. By correlating morphologic changes with the timing in the expression of these markers, we show that the organization of the transplanted E14 hepatocytes into lobular structures is accompanied by the formation and maturation of bile ducts around these developing lobules.

Cyclooxygenase 2 expression and molecular alterations in Peutz-Jeghers hamartomas and carcinomas.

Purpose: Peutz-Jeghers syndrome (PJS) is a hamartomatous polyposis disorder with a high cancer risk. Debate exists about the premalignant potential of hamartomas. Also, treatment options other than surveillance are not available.