Immunohistochemical localization of glutathione S-transferase-pi in human colorectal polyps.

AIM: To investigate the distribution of the placental form of glutathione-S-transferase (GST) in colon polyps in order to evaluate the role of GST-pi in these tissues. METHODS: Sixteen polyp tissues removed at colonoscopy were examined. Tissues were investigated histologically and ultrastructurally. GST-pi expression was also analysed immunohistochemically, using peroxidase anti-peroxidase (PAP) method and immunogold labelling method, for light and electron microscope respectively. RESULTS: All polyp tissues examined were adenoma of low, mild and high- grade dysplasia as shown in the histopathological reports. Nevertheless, the examination of the above specimens with electron microscope revealed that 3 of 9 adenoma of mild dysplasia had ultrastuctural features similar to high-grade dysplasia adenoma. GST-pi was variably expressed in adenoma, with the lowest relative levels occurring in low-grade adenoma and the highest levels found in high-grade adenoma. GST-pi was located mainly in undifferentiated epithelial cells. GST-pi positive particles were found in the cytoplasm and especially in the nucleus adjacent to the nuclear membrane of these cells. CONCLUSION: The overexpression of GST-pi in mild-grade adenomas with significant subcellular changes and in the majority of high-grade dysplasia adenoma suggests that this might be related to the carcinogenetic proceeding. Immunohistochemical localization of GST-pi in combination with ultrastructural changes indicate that GST-pi might be a sensitive agent for the detection of preneoplastic transformations in adenoma.

Herpes simplex virus type 1 in peptic ulcer disease: an inverse association with Helicobacter pylori.

AIM: To assess the frequency of herpes simplex virus type I in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to Helicobacter pylori(H pylori). METHODS: Biopsy specimens from 90 patients (34 with gastric ulcer of the prepyloric area and 56 with duodenal ulcer) were evaluated. Biopsies from 50 patients with endoscopically healthy mucosa were considered as the control group. The method used to identify herpes simplex virus-1 (HSV-1) was polymerase chain reaction. H pylori was detected by the CLO-test and by histological method. RESULTS: Herpes simplex virus-1 was detected in 28 of 90 patients with peptic ulcer (31%) [11 of 34 patients with gastric ulcer (32.4%) and 17 of 56 with duodenal ulcer (30.4%)] exclusively close to the ulcerous lesion. All control group samples were negative for HSV-1. The likelihood of H pylori negativity among peptic ulcer patients was significantly higher in HSV-1 positive cases than in HSV-1 negative cases (P = 0.009). Gastric ulcer patients with HSV-1 positivity were strongly associated with an increased possibility of Helicobacter pylori negativity compared to duodenal ulcer patients (P = 0.010). CONCLUSION: HSV-1 is frequent in upper gastro-intestinal tract ulcers but not in normal gastric and duodenal mucosa. There is an inverse association between HSV-1 and H pylori infection.

The role of sandostatin LAR in treating patients with advanced hepatocellular cancer.

BACKGROUND/AIMS: The overexpression of somatostatin receptors in the liver of some patients with hepatocellular carcinoma is well documented. The daily administration of octreotide in patients with advanced hepatocellular carcinoma was shown to have a marginal clinical effectiveness. The aim of the study was to estimate if and to what extent the administration of octreotide long-acting formulation (Sandostatin LAR) improves survival and quality of life in patients with advanced unresectable hepatocellular carcinoma. METHODOLOGY: Twenty-eight cirrhotic patients (stages A-B) with advanced hepatocellular carcinoma were enrolled in the study. Octreoscan scintigraphy for detection of STTR was performed in all cases. If it showed intense uptake in the liver, octreotide was administered as follows: Sandostatin 0.5 mg subcutaneous every 8 hours for 6 weeks. At the end of weeks 4-8 Sandostatin LAR 20 mg and at the end of week 12 and every 4 weeks Sandostatin LAR 30 mg intramuscularly. Patients' follow-up was worked out monthly. Thirteen patients unable to receive treatment were used as control group. RESULTS: Comparison of results between the 2 groups showed a significant difference in the median survival time (31 vs. 16 weeks, p = 0.037) and an improvement of quality of life (60% vs. 23.07%). Also, treated group showed a 72% reduction in the risk of dying during the follow-up period (p = 0.002). No alpha-fetoprotein reduction and decrease of the tumor mass was observed. CONCLUSIONS: In conclusion, the administration of Sandostatin LAR it appears to improve the survival and the quality of life in patients with advanced hepatocellular carcinoma.

An open-label, non-comparative, non-interventional, multi-center, post-authorization safety study on the administration of rabeprazole to adults with gastro-esophageal reflux disease.

BACKGROUND: Rabeprazole produces a profound and long-lasting inhibition of gastric acid secretion. The aim of the study was to monitor the safety and efficacy of rabeprazole administered to patients with erosive or symptomatic non-erosive reflux disease, in real-life healthcare settings. METHODS: Male and female patients, aged ≥18 years, with endoscopy diagnosed GERD were included; patients received at least 8 weeks treatment with rabeprazole. Changes in severity of symptoms recorded on the Likert scale were analysed using marginal homogeneity tests. RESULTS: 186 patients were enrolled across 17 study sites; 127 patients (68.3%) completed the study. Almost 75% of patients had an initial diagnosis of GERD with Grade A or B esophagitis. The most commonly reported adverse events (AEs) were diarrhea, flatulence, dizziness, cough, abdominal pain, upper abdominal pain and somnolence. Over half of AEs were unrelated to study drug; 1 severe AE of diarrhea was possibly related to study drug. No new AEs were reported not included in the current version of Summary of Product Characteristics. Rabeprazole was effective in reducing the symptoms of GERD; the Likert scale scores of symptoms decreased significantly for all patients from 0-4 weeks and 4-8 weeks. CONCLUSIONS: In our study, rabeprazole was safe and effective in reducing the symptoms of GERD.

Natural course of inoperable esophageal cancer treated with metallic expandable stents: quality of life and cost-effectiveness analysis.

BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy and safety of endoscopic therapy with self-expanding metallic endoprostheses in the management of malignant esophageal obstruction or stenosis and the cost-effectiveness of the method in patients suffering from primary esophageal carcinoma. All patients with inoperable esophageal cancers treated with either laser palliation or endoprosthesis insertion were studied retrospectively. METHOD: Between May 1997 and December 2002 obstruction of the esophagus was diagnosed in 78 patients (52 male, 26 female, age range 53-102 years, mean 72.3 years). The etiology of obstruction was squamous cell carcinoma (n = 42) and adenocarcinoma of the esophagus (n = 36). The site of obstruction was in the upper (n = 1), in the middle (n = 38) and in the lower esophagus (n = 39). In 16 cases the gastroesophageal junction was also involved. Four patients had broncho-esophageal fistulas. In all cases the tumor was considered non-resectable. A total of 89 Ultraflex metal stents were introduced endoscopically. In 46 patients dilation with Savary dilators prior to stent placement was required. RESULTS: Stents were placed successfully in all patients. After 48 h, all patients were able to tolerate solid or semisolid food. During the follow-up period eight patients developed dysphagia due to food impaction (treated successfully endoscopically). Eleven patients presented with recurrent dysphagia 4-16 weeks after stenting due to tumor overgrowth and were treated with placement of a second stent. The median survival time was 18 weeks. There was no survival difference between squamous cell and esophageal adenocarcinoma. A cost-effective analysis was performed, comparing esophageal stenting with laser therapy. The mean survival and the cost were similar. A small difference of 156 Euro was noted (3.103 Euro and 2.947 Euro for each group of patients, respectively). A significant improvement in quality of life was noted in patients that underwent stenting (96% and 75%vs 71% and 57% for the first 2 months). CONCLUSION: Placement of self-expanding metal stents is a safe and cost effective treatment modality that improve the quality of life, as compared with other palliative techniques, for patients with inoperable malignant esophageal obstructions. In cases of expansion of the mass a second stent can be used; however, the overall survival of these patients, is poor.