Kaku Hokari

Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population.

Background Helicobacter pylori and non‐steroidal antiinflammatory drugs (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status of H. pylori infection in the background population may influence the incidence of H. pylori‐negative peptic ulcer disease. Objective To examine the incidence of H. pylori‐negative peptic ulcer disease without intake of NSAIDs in Japan. Patients A total of 398 patients who had no eradication therapy for H. pylori prior to this study, including 246 patients with gastric ulcer (GU) and 152 patients with duodenal ulcer (DU), were enrolled. Methods H. pylori status was assessed by rapid urease tests, histological examinations (haematoxylin & eosin stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy specimens were taken from the antrum within 3 cm of the pyloric and two from the middle corpus of the stomach, along the greater curvature. Patients were asked a series of questions regarding risk factors, including the use of NSAIDs. The presence of gastritis, gastric atrophy and intestinal metaplasia was examined according to the updated Sydney system. Results Of the 246 patients with GU, 12 patients (4.9%) were considered to be H. pylori‐negative. Of the 152 patients with DU, two patients (1.3%) were considered to be H. pylori‐negative. Hence, a total of 14 patients were found to be H. pylori‐negative. Nine of them were taking NSAIDs. Consequently, the frequency of H. pylori‐negative ulcer without intake of NSAIDs was 1.3%. There was no significant difference in the frequencies of H. pylori‐negative patients between the GU and DU groups. Conclusion The incidence of H. pylori‐negative peptic ulcer disease without intake of NSAIDs was very low in the Japanese population. Eur J Gastroenterol Hepatol 12:635‐640

Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection and CYP2C19 genetic polymorphism

Rabeprazole is a new, potent, proton pump inhibitor. The metabolism of rabeprazole is less dependent on CYP2C19 genetic polymorphism.

A prospective evaluation of new rapid urease tests before and after eradication treatment of Helicobacter pylori, in comparison with histology, culture and 13C-urea breath test.

BACKGROUND The rapid urease test is a simple and cost-effective method to detect Helicobacter pylori in biopsy specimens. The aim of this study was to evaluate the accuracy of two new rapid urease tests, Helicocheck and PyloriTek, before and after eradication. METHODS A total of 278 patients, including 115 patients who had not undergone eradication of H pylori and 163 patients after eradication treatment, were enrolled. Eight biopsy specimens were taken from both the antrum and the body of the stomach for histology, culture, and two rapid urease tests. Assessment of H pylori infection was determined by the combination of histology, culture, and (13)C-urea breath test. RESULTS Overall sensitivity, specificity, and positive and negative predictive values of the Helicocheck before eradication were 91.0%, 100%, 100%, and 62.5%; PyloriTek, 92.0%, 100%, 100%, and 65.2%. Those of Helicocheck after eradication were, respectively, 60. 5%, 99.2%, 95.8%, and 89.2%; PyloriTek, 60.5%, 99.2%, 95.8%, and 89. 2%. For the Helicocheck, determination of the infection status of H pylori by biopsies from the gastric body had a significantly higher sensitivity than antral biopsies. After eradication, the combination of 1 antral biopsy and 1 biopsy from the body was not effective enough to improve the overall sensitivity. CONCLUSIONS Helicocheck and PyloriTek have equally satisfactory overall sensitivity before eradication treatment. However, the sensitivity of these rapid urease tests was lower after eradication than before eradication.

Phase I/II study of docetaxel/cisplatin/fluorouracil combination chemotherapy against metastatic esophageal squamous cell carcinoma.

Introduction: More effective regimens are urgently needed for squamous cell carcinoma of esophagus (SCCE), therefore, we conducted a phase I/II trial of a combination of docetaxel, platinum, and fluorouracil (TPF) for treating metastatic SCCE. Methods: This phase I/II trial (n = 12/39) was conducted in our institute from April 2005 to June 2008. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method. Results: The recommended dose of docetaxel was determined to be 50 mg/m2 in phase I. In phase II with a mean follow-up period of 13.3 months, the objective response rate was 66.6%, a median survival period of 13 months and PFS of 7 months was achieved, and the 1-year survival and PFS rates were 52.9% and 19.6%, respectively. Grade 3/4 toxicities of leukopenia, neutropenia, and anorexia were observed in 53.8%, 43.6%, and 25.6%, respectively. Conclusions: A TPF regimen against metastatic SCCE was well tolerated and achieved a favorable objective response rate and survival benefit compared with other recently reported regimens. Randomized phase III trials of the TPF regimen are warranted and urgently required.

High-dose ecabet sodium improves the eradication rate of Helicobacter pylori in dual therapy with lansoprazole and amoxicillin

The additive effect of ecabet sodium in combination with dual therapy on Helicobacter pylori eradication was evaluated.

Evaluation of the effect of lansoprazole in suppressing acid secretion using 24-hour intragastric pH monitoring.

The acid-inhibitory effect of lansoprazole was evaluated in comparison with that of famotidine and omeprazole by using 24-h intragastric pH monitoring in 10 young, healthy Japanese volunteers. Lansoprazole 20 mg once daily in the morning was superior to famotidine 20 mg twice daily, omeprazole 20 mg once daily in the morning in reducing 24-h intragastric acidity. Unlike famotidine, whose acidinhibitory effect was observed mainly at night, both lansoprazole and omeprazole inhibited both daytime and nocturnal acid secretion, with the maximal effect occurring in the afternoon. Although the daily profile of acid-inhibitory action of lansoprazole was similar to that of omeprazole, the acid-inhibitory effect of lansoprazole was more potent than that of omeprazole at any time of the day. These results indicate that lansoprazole at a dosage of 30 mg once daily in the morning produced the most potent inhibition of acid secretion in young Japanese volunteers, compared with famotidine 20 mg twice daily and omeprazole 20 mg once in the morning

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients

Aim: The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated.

Immunological Helicobacter pylori urease analyzer based on ion-sensitive field effect transistor

Abstract Immunological Helicobacter pylori ( H. pylori ) urease analyzer (HPUA), based on a solid-phase tip coated with a monoclonal antibody toward H. pyloris urease and ion-sensitive field effect transistor (ISFET), was developed. In this system, H. pylori urease adsorbed on the solid-phase tip, after a 15-min immunological reaction with gastric mucus sample solution, was measured with a urease analyzer composed of a flow-through cell for urea solution equipped with the measuring and reference ISFETs. The pH change (ΔpH) of urea solution after 55 s of the enzymatic reaction inside the tip was measured by withdrawing about 1 μl of the urea solution toward the upstream of the tip, where the measuring ISFET is installed. It was confirmed that the present system could detect 0.2 mIU/ml of H. pylori urease. Clinical evaluations of the system were performed for 119 patients using urea breath test (UBT) as a gold standard, resulting in the sensitivity=33/36=92% and specificity=81/83=98%, respectively.

Detection of cerebroside sulfotransferase mRNA in human gastric mucosa and adenocarcinoma

Sulfatide is a major acidic glycolipid in human gastric mucosa, and its sulfation is catalyzed by cerebroside sulfotransferase (CST). To investigate the expression of the CST gene in human gastric cancer, a reverse transcription PCR method was developed with the use of endoscopic bioptic specimens. By this method, we examined the CST mRNA expression in 11 cases of gastric cancer, and in all the cases we detected various levels of the expression both in cancer tissues and in uninvolved adjacent tissues. The present assay method was suggested to be useful in the detection of CST mRNA from a limited amount of bioptic samples.

Traditional and non-traditional antimicrobial agents for H. pylori infection.

Triple therapy with a proton pump inhibitor plus two antibiotics is recently standard regimen for treatment of H. pylori infection. However, the agents that are used for H. pylori eradication are not always limited to drugs whose primary use is as an antimicrobial agent. Anti-H. pylori activity has been reported for nontraditional antimicrobials such as proton pump inhibitors, bismuth compounds, mucosal defensive agents, and some other agents. Proton pump inhibitors and their acid-activated derivatives have significant activities against H. pylori, potent inhibitors of urease, proton motive force, and ATPase of H. pylori. Some bismuth compounds and compound of a mixture of ranitidine hydrochloride and bismuth citrate were shown to inhibit the growth of H. pylori in vitro, to eradicate H. pylori in vivo, and to decrease the development of H. pylori secondary resistance to antibiotics. The mechanism of bactericidal action of bismuth compounds has not been clear. Mucosal defensive agents that enhance defense factors of gastro-duodenal mucosa are locally acting anti-ulcer drugs. Each mucosal defensive agent was found to have direct or indirect different activities against H. pylori in vitro. Though studies attempting to improve the eradication rate by the addition of mucosal defensive agents to conventional therapy have been tried, additive effects of these agents were equivocal. Therapeutic approaches with other agents such as Lactobacillus, lactoferrin, and dietary constituents to cure H. pylori infection are under investigation. Non-traditional antimicrobials by them selves are unable to cure H. pylori infection in spite of anti-H. pylori activities. Studies are needed to establish the clinical utility of non-traditional antimicrobial agents in prevention and eradication of H. pylori infection since eradication of antibiotic resistance H. pylori would become a difficult problem.