Shuji Maekawa

Levofloxacin based triple therapy as a second-line treatment after failure of helicobacter pylori eradication with standard triple therapy.

BACKGROUND Successful eradication of Helicobacter pylori infection after failure of standard triple therapy is difficult. The efficacy and safety of levofloxacin based triple therapy as a first-line therapy has-been studied. AIMS The aim was to evaluate the efficacy and tolerability of levofloxacin based therapy after a failed standard triple therapy. PATIENTS We conducted a prospective, uncontrolled study of a consecutive series of 33 patients who failed eradication with 1 week of lansoprazole-amoxicillin-clarithromycin triple therapy. METHODS The subjects were retreated with 1 week of LA-LVFX triple therapy (lansoprazole, 30 mg twice daily; amoxicillin, 1000 mg twice daily: levofloxacin, 200 mg twice daily). Cure of infection was defined as negative results from culture, histology and a urea breath test 4 to 8 weeks after the second-line therapy. RESULTS The eradication rate was 69.7% (23/33) by both intention-to-treat and per-protocol analyses (95% confidence interval=61-79%). Seven (21.2%) patients experienced mild side-effects, such as soft stools and taste disturbance. No patient stopped the medication on account of adverse effects. CONCLUSIONS Levofloxacin based triple therapy is an effective second-line treatment after a failed standard triple therapy.

Glut1 expression in T1 and T2 stage colorectal carcinomas: its relationship to clinicopathological features.

Glucose uptake is mediated by glucose transporter (Glut) proteins, which exhibit altered expression in a variety of malignant neoplasms. Glut1 expression is thought to be a potential marker for malignant transformation. The aim of the present study was to investigate the expression of Glut1 protein in colorectal adenomas, T1 and T2 stage carcinomas. Immunohistochemical detection of Glut1 protein was examined in 141 formalin-fixed and paraffin-embedded colorectal tumour specimens (57 adenomas, 84 carcinomas). The degree of Glut1 immunostaining of a specimen was graded according to the proportion of Glut1-positive cells in it; absent (positive cells are 0%), weakly positive (less than 10%), moderately positive (10-50%), and strongly positive (more than 50%). Glut1 expression was present in 18% of the adenomas with low-grade dysplasia, and in 63% of the adenomas with high-grade dysplasia. The positivity in such lesions was usually weak, but was moderate in 8% of the adenomas with high grade dysplasia. For the carcinomas, there were significant correlations between Glut1-positivity and depth of invasion (T1 45% versus T2 74%, P<0.01), histological differentiation (well 49% versus moderately to poorly 74%, P< 0.05) and morphological type (polypoid 42% versus depressed 73%, P< 0.05), if the cut-off value was set at 10% of cells. In conclusion, we clarified the relationship between Glut1 expression and clinicopathological features in T1 and T2 stage colorectal carcinomas, and our results suggested a high malignant potential of the depressed-type carcinoma.

Impact of clarithromycin resistance and CYP2C19 genetic polymorphism on treatment efficacy of Helicobacter pylori infection with lansoprazole- or rabeprazole-based triple therapy in Japan.

Objective Helicobacter pylori treatment failure is thought to be due mainly to polymorphic cytochrome P450 2C19 (CYP2C19) genetic polymorphism, associated with proton pump inhibitor metabolism, and antimicrobial susceptibility. This report has ascertained which was more important, CYP2C19 polymorphism or antimicrobial susceptibility, when using 1-week lansoprazole-based or rabeprazole-based triple therapy in Japan. Design An open, randomized, parallel group study. Setting One hundred and forty-five subjects with H. pylori-positive gastritis or peptic ulcers were randomly assigned to receive 30 mg lansoprazole twice daily (LAC group), 10 mg rabeprazole twice daily (RAC20 group), or 20 mg rabeprazole twice daily (RAC40 group), with 1000 mg amoxicillin twice daily and 400 mg clarithromycin twice daily for 1 week. Antimicrobial resistance testing was performed by E-test. More than 4 weeks after completion of treatment, H. pylori status was assessed by 13C-urea breath test, histology, and culture. Results Cure rates expressed as intention-to-treat and per-protocol analyses, respectively, were 79.6 and 83.0% with LAC, 85.4 and 89.1% with RAC20, and 83.3 and 88.9% with RAC40. In the case of clarithromycin-sensitive strains, the cure rates were more than 97%, regardless of CYP2C19 polymorphism. However, treatment succeeded in only one out of 16 clarithromycin-resistant strains. Conclusions The key to successful eradication of H. pylori, using lansoprazole or rabeprazole with clarithromycin and amoxicillin, is clarithromycin susceptibility, not CYP2C19 polymorphism.

Effect of Helicobacter pylori-Induced Cyclooxygenase-2 on Gastric Epithelial Cell Kinetics: Implication for Gastric Carcinogenesis

Background. Cyclooxygenase (COX)‐2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis.

Leukocytapheresis therapy for steroid-naïve patients with active ulcerative colitis: its clinical efficacy and adverse effects compared with those of conventional steroid therapy.

Background: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long‐term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid‐sparing, well‐tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid‐naïve patients with active UC for comparison with those of conventional steroid therapy.

HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection.

Background and Aims:  It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)‐DQB1*0401 plays an important role in the development of atrophic gastritis in H. pylori infected patients. The aim of the present study was to investigate the relationship between HLA‐DQB1 genotype and cancer development.

Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection.

Objectives Helicobacter pylori infection causes chronic gastritis and induces cyclooxygenase (COX)-2 expression. The relationship between gastritis and COX-2 expression is not well understood, especially long after the organism has been eradicated. We designed a study to elucidate this relationship. Methods Four endoscopic gastric biopsies from each of 118 H. pylori-infected subjects were assessed for COX-2 expression immunohistochemically, gastritis, by an updated Sydney System. In the 107 successfully eradicated subjects, the assessment was repeated once yearly, for 3 years. Results After successful eradication, COX-2 expression was reduced significantly regardless of site. Atrophy improved significantly and intestinal metaplasia improved but not in the antrum greater curvature. After 1 year COX-2 expression was not significantly different in the epithelia with and without intestinal metaplasia. Correlation between COX-2 expression and neutrophil score in the antrum (r = 0.214, P = 0.042) and inflammation in the corpus (r = 0.234, P = 0.025) disappeared after eradication. COX-2 expression correlated well with atrophy and metaplasia before and after eradication. No significant reduction in COX-2 or improvement in gastritis was found in subjects with eradication failure. Conclusion H. pylori infection is associated with the enhancement of COX-2 expression in the gastric mucosa. Eradication therapy reduces COX-2 expression and hence may reduce the risk of cancer development.

High-grade neuroendocrine carcinoma of the lung presenting an unusual spread mimicking pleural mesothelioma associated with dermatomyositis.

Neuroendocrine tumors of the lung comprise a heterogeneous group of tumors that represents a spectrum of disease from typical carcinoid tumors to the high-grade neuroendocrine carcinomas (large-cell neuroendocrine carcinomas and small-cell carcinomas). The high-grade neuroendocrine carcinomas are characterized by early metastasis and poor prognosis. The peripheral location and especially the massive pleural spread are rare for a high-grade neuroendocrine carcinoma. We report a case in which a high-grade neuroendocrine carcinoma, associated with dermatomyositis, presented an unusual pattern of progression, mimicking malignant pleural mesothelioma on diagnostic imaging.

Excessive alcohol intake enhances the development of synchronous cancerous lesion in colorectal cancer patients

Background and aimsWe examined the potential impact of alcohol drinking on the incidence of synchronous colorectal cancer.Patients and methodsThis study comprised 191 men with colorectal cancer who had undergone surgical resection. Synchronous colorectal cancer was found in 16 patients (8.4%). The relationship between synchronous colorectal cancer and alcohol intake was analyzed by multivariate methods. Cumulative alcohol intake was assessed by the drinking index (weekly average multiplied by years of drinking).ResultsThere was higher incidence of associated adenoma in the synchronous cancer group. Heavy cumulative intake (drinking index 9800 or higher) was associated with significantly higher risk synchronous colorectal cancer than in nondrinkers (odds ratio 6.8). The association of alcohol intake with the risk of synchronous colorectal cancer was not affected by the type of alcohol beverages.ConclusionThis study demonstrated that excessive alcohol intake might be an independent risk factor for synchronous colorectal cancer. The screening program based on this information may prevent the synchronous lesions being missed.

Relationship Between Gastric Ulcer and Helicobacter pylori VacA Detected in Gastric Juice Using Bead-ELISA Method

Background. VacA is an important pathogenetic factor produced by Helicobacter pylori. VacA has often been detected in supernatants of liquid cultures or lysates of whole bacterial cells. However, no studies have ever tried to assay VacA produced in the human stomach. We applied a very sensitive and simple method, bead‐ELISA, to detect VacA in gastric juice.