Diarrhea caused by proton pump inhibitor administration: comparisons among lansoprazole, rabeprazole, and omeprazole.

BACKGROUND: The number of patients who require treatment with proton pump inhibitors (PPIs) is increasing in Japan. One of their adverse effects is diarrhea. OBJECTIVES: We investigated the incidence of diarrhea caused by 3 different PPIs: lansoprazole, rabeprazole, and omeprazole. METHODS: Patients using PPIs for >1 month were enrolled. Enrolled patients recorded daily stool frequency, stool consistency using the Bristol Stool Scale Form, and impaired quality of life caused by diarrhea for 1 month. Their attending physicians described the types and dosages, and duration of PPI administration, as well as other necessary information. RESULTS: A total of 255 patients participated. Mean age of the patients was 70.7 years old. During the 1-month observation period, 3.5% of the patients complained of diarrhea. There was no significant difference for the incidence of diarrhea among the 3 types of PPIs. Furthermore, no correlations between diarrhea and length and dosage of PPI administration were found. CONCLUSIONS: The incidence of diarrhea in patients receiving long-term therapy did not differ among 3 different PPIs. ClinicalTrials.gov identifier: UMIN ID 000005300.

Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41-94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I-II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

Interleukin-8 regulates expression of Reg protein in Helicobacter pylori-infected gastric mucosa.

BACKGROUND & AIM: Chronic inflammation induced by Helicobacter pylori infection is closely associated with epithelial cell proliferation and apoptosis, which are related to cellular turnover in gastric mucosa. Reg protein is a regenerating gene product and a potent growth factor for gastric mucosal cells, however, little is known regarding its association with the pathogenesis of H. pylori infection. The aim of this study was to investigate Reg protein production and its regulation in H. pylori-associated gastritis. METHODS: Gastric fundic biopsy samples were taken from patients with and without H. pylori infection. In vivo expression of Reg protein was examined by Western blotting and immunohistochemistry methods. The effects of interleukin (IL)-8 on Reg protein expression and transcriptional activation of the Reg gene in ECC10 cells were investigated by Western blotting and luciferase assays, respectively. RESULTS: Reg expression was found localized in the deeper part of gastric fundic glands and clearly shown in chromogranin A-positive cells in the gastric corpus. Semiquantitative immunohistochemistry and Western blotting results for Reg expression were significantly associated with polymorphonuclear neutrophil activity and chronic inflammation of gastric mucosa. IL-8 production in the gastric mucosa was significantly augmented by H. pylori infection, while IL-8 dose-dependently stimulated Reg protein production and Reg promoter activity in vitro in cultured ECC10 cells. CONCLUSION: The present study showed for the first time that Reg protein may be a potent stimulator of gastric epithelial cells in H. pylori-infected human gastric mucosa stimulated by IL-8. Further, our findings provide evidence of a novel link between Reg protein and H. pylori infection, which may help explain the molecular mechanisms underlying H. pylori-associated diseases, including gastric cancer.

Crystal violet chromoendoscopy with mucosal pit pattern diagnosis is useful for surveillance of short-segment Barrett's esophagus.

BACKGROUND: Because of a rapid increase in the incidence of Barrett's cancer, the appropriate surveillance method for Barrett's esophagus is of interest. Methylene blue chromoendoscopy has been reported to be an effective and inexpensive method to improve biopsy surveillance of Barrett's epithelium. However, the usefulness of this method in short-segment Barrett's esophagus cases is still controversial. AIMS: This study was undertaken to evaluate the abilities of crystal violet and methylene blue chromoendoscopy to detect potentially dysplastic Barrett's epithelium in cases with short-segment columnar-appearing epithelium of the esophago-gastric junction. PATIENTS AND METHODS: Four hundred patients with endoscopically suspected short-segment Barrett's esophagus were enrolled and randomly assigned to receive chromoendoscopy with 0.05% crystal violet, 0.1% crystal violet, 0.5% methylene blue, or 1.0% methylene blue. During crystal violet and methylene blue chromoendoscopy, biopsy specimens were obtained from stained and unstained columnar-appearing epithelium of the esophago-gastric junction, and the detection rates of Barrett's epithelium were evaluated. The value of pit pattern diagnosis was also evaluated as a possible way to detect dysplastic Barrett's epithelium. RESULTS: Chromoendoscopy with 0.05% crystal violet detected histologically confirmed Barrett's epithelium with the highest sensitivity (89.2%) and specificity (85.7%). Crystal violet clearly stained both dysplastic and nondysplastic Barrett's epithelia and made the surface pit pattern easy to observe without using magnifying endoscopy. CONCLUSIONS: The combination of crystal violet chromoendoscopy and pit pattern diagnosis is considered to be useful for the surveillance of short-segment Barrett's esophagus.

Peroxisome proliferator-activated receptor gamma-dependent and -independent growth inhibition of gastrointestinal tumour cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a ligand-activated transcription factor. Although ligand-induced cellular differentiation and growth inhibition have been mostly studied on human cancers expressing PPARgamma, it is unclear if the transcriptional activation of PPARgamma is the main mechanism of growth inhibition. In this study, we investigated whether there is a link between growth inhibitory effect and transcriptional activation of PPARgamma in several gastrointestinal tumour cell lines. The transcriptional activation potential of PPARgamma was assessed by reporter gene assay employing a PPRE-luciferase vector, and growth inhibitory effect of PPARgamma was investigated by (3)H-thymidine incorporation assay, in the presence or absence of thiazolidinedione ligands, rosiglitazone and troglitazone. As expected, in the case of cell lines positive for the transcriptional activation potential of PPARgamma (T.Tn, MKN-45 and LoVo), both the ligands induced growth inhibition. However, in case of some other cell lines negative for the transcriptional activation potential of PPARgamma (TT, AGS and HCT-15), troglitazone still showed a growth inhibitory effect. Administration of the PPARgamma antagonist GW9662 did not reverse this growth inhibitory activity of troglitazone. The introduction of dominant negative mutants of PPARgamma did not suppress the activity either. These observations suggest that while rosiglitazone inhibits cellular growth predominantly through transcriptional activation of PPARgamma, troglitazone can induce it both in PPARgamma-dependent and -independent pathways.

Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori-associated gastritis.

TLR4, a member of pattern recognition receptors, is the main receptor of LPS. MD-2 physically associates with TLR4 on the cell surface and confers LPS responsiveness. Helicobacter pylori LPS is one of the major virulence factors for induction of gastritis. We demonstrated in this study the role of MD-2 in TLR4-dependent signaling in H. pylori-associated gastritis. Gastric biopsy samples collected from patients with and without H. pylori infection and four gastric cancer cell lines were used for this study. TLR-4 and MD-2 expression in biopsy specimens and the cell lines was examined by using RT-PCR. Localization of TLR-4 in histological sections was evaluated by immunohistochemistry. For in vitro functional assays, we established stable transfectants of AGS cells expressing TLR4 and MD-2. Cellular distribution of TLR4 was examined by flow cytometry. NF-kappaB activation and activation of IL-8 and MD-2 promoters were assessed by reporter gene assay. H. pylori infection up-regulated the TLR4 and MD-2 expression in gastric mucosa. TLR4 staining was observed predominantly in epithelial cells, located in both the cytoplasm and at the apical surface. MD-2 transfection in AGS cells markedly increased cell surface expression of TLR4 and augmented the activation of NF-kappaB and IL-8 promoter upon stimulation with H. pylori LPS. Live H. pylori also stimulated transcriptional activation of MD-2. This study revealed that MD-2 expression is elevated in gastric epithelial cells during H. pylori infection, suggesting that the TLR4/MD-2 system is a potent receptor complex involved in the response to H. pylori LPS in the stomach.