Differential diagnosis of chronic pancreatitis and pancreatic cancer in brush cytology specimens.

Discrimination between chronic pancreatitis and pancreatic carcinoma can be complicated, particularly in brush cytology specimens. Previous studies have shown that the oxygen insensitivity of the histochemical reaction to detect glucose-6-phosphate dehydrogenase activity based on neotetrazolium reduction can be used for discriminating malignant cells from nonmalignant cells. In the present study, we investigated the value of the assay for differential diagnosis between the two pancreatic diseases. Oxygen insensitivity in ductal epithelial cells in normal human pancreas, chronic pancreatitis, and pancreatic carcinoma was determined by quantitative image analysis in sections of biopsies and in brush cytology preparations. In sections, the reaction in the absence of oxygen was a proper reflection of glucose-6-phosphate dehydrogenase activity, whereas in the presence of oxygen only malignant cells showed a significant reaction. Of 39 brush cytology specimens, diagnosis of all 11 cases of pancreatitis and 28 cases of cancer with the oxygen insensitivity test were in agreement with independent measures of chronic pancreatitis and cancer. The oxygen insensitivity test is a simple and valuable tool in addition to conventional pathology for differential diagnosis between pancreatitis and pancreatic cancer, both in biopsies and in brush cytology specimens.

Loss of heterozygosity and immunohistochemistry of adenocarcinomas of the esophagus and gastric cardia.

PURPOSE: Adenocarcinomas of the distal esophagus and gastric cardia are two tumors that have many features in common. They have similar prognoses, treatment modalities, and patterns of dissemination. The etiology is different, with gastroesophageal reflux disease playing a major role for esophageal adenocarcinoma, in contrast to adenocarcinoma of the gastric cardia. In the present study, we investigated several genetic and immunohistochemical features of adenocarcinomas of the distal esophagus and gastric cardia. EXPERIMENTAL DESIGN: Sixty-two resection specimens of either adenocarcinoma of the esophagus or adenocarcinoma of the gastric cardia were carefully selected. The genetic analysis included loss of heterozygosity of several tumor suppressor genes known to be involved in esophagogastric carcinogenesis. Immunohistochemical studies included the analysis of p53, c-Met, c-erbB-2, beta-catenin, and cyclooxygenase-2. In addition, a mutation analysis of the Tcf1 gene was done by direct sequencing. RESULTS: Patients with cardiac carcinoma had a significantly worse tumor stage and poorer differentiation on histology. Loss of heterozygosity analysis did not reveal significant differences between esophageal adenocarcinoma and cardiac adenocarcinoma. Immunohistochemical analysis revealed significantly more nuclear accumulation of beta-catenin and overexpression of cyclooxygenase-2 in patients with esophageal adenocarcinoma, compared with patients with cardiac carcinoma. No mutation was found in the Tcf1 gene in either tumor type. CONCLUSIONS: Although adenocarcinomas of the distal esophagus and gastric cardia have many features in common, we have found some evidence that they might form two different entities.

Helicobacter pylori infection of gastric mucin cell metaplasia: the duodenum revisited.

The histological material of 158 Billroth II gastrectomy specimens, used for a former study that established a relationship between duodenal ulcers and the presence of gastric metaplastic epithelium in the duodenal bulb, was reinvestigated for the presence of Helicobacter pylori. The results show that in all duodenal ulcer patients with gastric mucin cell metaplasia H. pylori colonized the metaplastic epithelium accompanied by an inflammatory response. The intestinal mucosa was always negative for H. pylori. H. pylori-positive patients also had the micro-organism in their gastric antrum. The results further support the hypothesis that infection of gastric mucosa in the bulb by H. pylori underlies duodenal ulcer disease.

Alterations of the p53 tumor-suppressor gene and K-ras oncogene in perihilar cholangiocarcinomas from a high-incidence area.

We observed a clustering of cholangiocarcinoma in a part of West Virginia. We analyzed the frequency and type of alterations in the p53 tumor-suppressor gene and the K-ras oncogene to determine whether cholangiocarcinomas from this high-incidence area differ from other cholangiocarcinomas at the molecular level. We studied 12 carcinomas of patients from the high-incidence area (West Virginia group), and 15 carcinomas of patients from nearby states (non-West Virginia group). Over-expression of the p53 gene product, accompanying most mutations in the p53 gene, was determined by immunohistochemistry. p53 sequence analysis of exons 5, 6, 7, and 8 of the p53-immunohistochemical-positive carcinomas was also performed. K-ras codon 12 mutations were detected by the polymerase chain reaction and allele-specific oligonucleotide hybridization. Significantly more cholangiocarcinomas from the West Virginia group were p53-immunohistochemical-positive than from the non-West Virginia group (67% vs. 20%; p < 0.05). p53 mutations did not differ in the 2 groups in respect to site or specific type. No differences were found between the 2 groups regarding K-ras mutations (17% vs. 27%). Although the higher frequency of p53-immunohistochemical positivity in the West Virginia group may reflect a different etiology of these cholangiocarcinomas, explaining the high incidence in this area, results of p53 sequence analysis were not different in the West Virginia group. The high incidence may be explained by difference in carcinogenic dose or a different etiology not reflected in p53 or K-ras alterations.