Stephan Miehlke

The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract

Aliment Pharmacol Ther 31, 548–552

Complete Remission of Primary High-Grade B-Cell Gastric Lymphoma After Cure of Helicobacter pylori Infection

PURPOSE Treatment of low-grade gastric mucosa-associated lymphoid tissue lymphoma by eradication of Helicobacter pylori is reported to result in complete lymphoma remission in approximately 75% of cases. The effect that cure of the infection has on the course of a primary high-grade gastric lymphoma is largely uncertain. The aim of this study was to report the effect of cure of H pylori infection exerted in patients with high-grade B-cell gastric lymphoma. PATIENTS AND METHODS Eight patients (4 males and 4 females; age range, 26 to 85 years) with H pylori infection and high-grade lymphoma received eradication therapy before planned treatment. The effect of H pylori eradication on the course of high-grade lymphoma was assessed by analysis of surgical specimens (n = 2) or endoscopic biopsies (n = 6). RESULTS H pylori eradication was successful in all patients and led to complete remission of the lymphoma in seven patients. One patient has experienced partial remission. Two patients were referred to surgery, one of whom (stage II(1E)) had lymph node involvement, and the histologic work-up of the resected stomach revealed residual infiltrates of a low-grade lymphoma, which prompted consolidation chemotherapy. In one patient (initially stage I(1E)), abdominal lymphoma developed 6 months after eradication therapy, which regressed completely after chemotherapy. In four patients, no further treatment was given. Six patients continue in complete remission (range, 6 to 66 months). CONCLUSION Primary high-grade B-cell gastric lymphoma in stages I(E) through II(E1) associated with H pylori may regress completely after successful cure of the infection. Prospective trials are needed to investigate this treatment in larger numbers of patients.

The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany

Background: The H. pylori vacuolating cytotoxin encoded by vacA and the cytotoxin‐associated protein encoded by cagA are considered to be important virulence determinants that have been implicated in the development of peptic ulcers and gastric carcinoma. However, conflicting results regarding the association between these virulence factors and clinical disease have been reported from different geographic regions. Aims: To determine the frequency of vacA genotypes, vacuolating cytotoxin activity, and cagA in H. pylori isolates obtained from patients with gastric cancer in Germany. Methods: H. pylori isolates were obtained from 34 patients with gastric cancer and from 35 subjects with asymptomatic H. pylori gastritis. vacA genotypes and cagA were identified by PCR. Cytotoxic activity was determined by HeLa cell assays. Gastritis was assessed according to the updated Sydney System. Results: The H. pylori vacA s1,m1 genotype was significantly more frequent in patients with gastric cancer (24/34, 70.6%) as compared with controls (12/35, 34.3%) (p = 0.005). Cytotoxic activity was detected in 24 (70.6%) and 15 (42.9%) H. pylori isolates from gastric cancer patients and controls, respectively (p = 0.03). The cagA gene was identified in 30 (88.2%) and 21 (60%) H. pylori isolates in the respective groups (p = 0.01). Conclusions: Our study suggests a significant association between the H. pylori vacA s1,m1 genotype, cytotoxic activity, cagA, and gastric cancer. Detection of H. pylori possessing these virulence determinants may help to identify patients being at an increased risk to develop gastric cancer in our population. Int. J. Cancer 87:322–327, 2000.

Grapefruit juice ingestion significantly reduces talinolol bioavailability

Our objectives were to evaluate the effect of single and repeated grapefruit juice ingestion relative to water on the oral pharmacokinetics of the nonmetabolized and P‐glycoprotein‐transported drug talinolol in humans and to assess the potential impact of grapefruit juice ingestion on P‐glycoprotein and intestinal uptake transporters.

Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

ABSTRACT Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults:

Introduction Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. Methods General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. Results The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Conclusion Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients’ follow up are proposed in the guideline.

Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol.

St Johns wort (SJW) is known to induce cytochrome P450 (CYP) 3A4 and P‐glycoprotein through pregnane X‐receptor activation. Our study evaluated the effects of long‐term SJW administration on oral and intravenous pharmacokinetics of the nonmetabolized in vivo probe of P‐glycoprotein, talinolol, in relation to intestinal P‐glycoprotein expression. In a controlled, randomized study (N=9), the pharmacokinetics of oral (50 mg) and intravenous talinolol (30 mg) was determined before and after 12 days SJW (900 mg daily, Jarsin 300®). Duodenal biopsies were taken and MDR1 genotypes assessed. SJW reduced the oral talinolol bioavailability by 25% (P=0.049) compared with water control. A 93% increase in oral clearance (P=0.177) and a 31% reduction in area under the serum concentration time curve (AUC; P=0.030) were observed. Renal and nonrenal clearance (CLNR), elimination half‐life, peak serum drug concentration (Cmax), and time to reach Cmax were not significantly altered. After intravenous talinolol, SJW affected only CLNR (35% increase compared with water, P=0.006). SJW increased MDR1 messenger ribonucleic acid (mRNA) as well as P‐glycoprotein levels in the duodenal mucosa. Subjects with the combined MDR1 genotype comprising 1236C>T, 2677G>T/A, and 3435C>T polymorphisms had lower intestinal MDR1 mRNA levels and displayed an attenuated inductive response to SJW as assessed by talinolol disposition. Long‐term SJW decreased talinolol AUC with a corresponding increase in intestinal MDR1 expression, suggesting that SJW has a major inductive effect on intestinal P‐glycoprotein. Interestingly, the magnitude of induction appeared to be affected by MDR1 genotype.

Oral Budesonide for Maintenance Treatment of Collagenous Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND & AIMS Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation. METHODS This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on >or=4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (<or=3 stools per day) at week 6 were subsequently randomized to double-blind oral treatment with budesonide 6 mg/d or matching placebo for 6 months. Relapse was defined as >3 stools per day on >or=4 consecutive days (and included patients withdrawn because of adverse events). RESULTS Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events. CONCLUSIONS Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

Budesonide Is Effective in Treating Lymphocytic Colitis: A Randomized Double-Blind Placebo-Controlled Study

BACKGROUND & AIMS Budesonide is effective in treating collagenous colitis, but no treatment is established for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS Forty-two patients (median age, 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/d) or placebo for 6 weeks. Nonresponders at week 6 were given open-label budesonide (9 mg/d) for 6 additional weeks. A complete colonoscopy and histologic and quality-of-life analyses were performed at baseline and at week 6. The primary end point was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients who left the study in clinical remission were followed for relapse. RESULTS At week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo (P = .010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histologic remission was observed in 73% of patients given budesonide compared with 31% given placebo (P = .030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were retreated with and responded again to budesonide. CONCLUSIONS Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.

A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin

Background and Aim. Failure of primary anti‐H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high‐dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin.