[Eosinophilic Esophagitis - Update - Pathogenesis, Diagnosis and Therapy]. / Eosinophile Ösophagitis ­ Neues zur Pathogenese, Diagnostik und Therapie.

Eosinophilic esophagitis (EoE) is a clinicopathological condition of the esophagus that has become increasingly recognised over the last decade. EoE represents a chronic immune-mediated inflammatory disease of the esophagus. In adults dysphagia is the predominant symptom. Upper gastrointestinal endoscopy is required in order to take biopsies from the esophagus. The diagnose is confirmed histologically by typical eosinophilic infiltration of the esophagus mucosa. Until now there is no approved therapy world-wide although we know that topic and systemic steroids are highly effective in EoE. Elimination diet is another option and in well selected patients endoscopic balloon dilation represents a therapeutic possibility.

[Diagnostic and therapeutic management of helicobacter pylori: a survey among German gastroenterologists in private practice]. / Diagnostisches und therapeutisches Management der Helicobacter-pylori-Infektion: eine Umfrage unter niedergelassener Gastroenterologen in Deutschland.

Purpose: The acceptance and realization of clinical guidelines in daily routine practice is unknown. The aim of this study was to evaluate the behaviour of private gastroenterologists in Germany with respect to the diagnostic and therapeutic management of H. pylori infection in times of increasing antibiotic resistance. Methods: Between 12/2014 and 02/2015 a standardized questionnaire with 19 multiple choice questions were sent to 1507 private gastroenterologists in Germany. The data were electronically captured and analyzed using SurveyMonkey. Results: The response rate was 36 % (540 questionnaires). 65 % of responders prescribe first line therapy by themselves and mainly use standard triple therapies. In patients with intolerance to penicillin, 81 % prescribe Italian triple therapy and 19 % prescribe bismuth quadruple therapy. Risk factors for primary clarithromycin resistance (migrational background, previous macrolide exposure) are routinely assessed by only a minority of responders (22 % and 17 %, respectively). Forty-one percent of responders perform eradication control by themselves mainly using a 13C urea breath test (54 %). In second line therapy, 42 % are prescribing bismuth quadruple therapy and 24 % fluoroquinolone triple therapy. After second line therapy, 58 % of responders are performing eradication control by themselves. Of those, 70 % always take biopsies for antibiotic susceptibility testing. Conclusions: The results of our survey suggest that most private gastroenterologists in Germany adhere to current guidelines for H. pylori management; however, some relevant deviations seem to exist. Our data might be useful for further developments of clinical guidelines and their communication among the medical community.

[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

[Microscopic colitis: clinical presentation, treatment and outcome of 494 patients]. / Mikroskopische Kolitis: klinische Manifestation, Therapie und Outcome in 494 Patienten.

BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic disorders characterized by watery diarrhea. AIM: To evaluate prospectively the clinical features, response to treatment and outcomes in a large group of patients with CC and LC. PATIENTS AND METHODS: Patients with histologically confirmed CC and LC were prospectively enrolled to complete a questionnaire on onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment success and concomitant diseases. RESULTS: A total of 494 patients (CC, n = 287, LC, n = 207) were available for analysis. The mean age at diagnosis was 65 in CC and 61 years in LC with a identically female predominance (76 % of patients) in both groups. Prior to diagnosis the mean duration of symptoms was 37 in CC and 23 months in LC. CC and LC patients share similar pattern of clinical symptoms. Concomitant autoimmune disorders were more common in CC patients (48.4 %) than in LC patients (29.6 %). Sustained clinical remission was reported by 35.5 % of CC and 38,6 % of LC, but more CC patients (47.7 %) received medication such as corticosteroids, antibiotics, bismuth or 5-aminosalicyclic than LC patients (16.9 %). 18.6 % of CC patients and 17.6 % of LC were regularly using NSAIDs. CONCLUSION: Collagenous and lymphocytic colitis are frequently diagnosed in elderly female patients. CC and LC share similar symptom pattern, but concomitant autoimmune disease were more common in CC than in LC patients.

[Eosinophilic esophagitis - update - pathogenesis, diagnosis and therapy]. / Eosinophile Ösophagitis - Neues zur Pathogenese, Diagnostik und Therapie.

Eosinophilic esophagitis (EoE) is a clinicopathological condition of the esophagus that has become increasingly recognised over the last decade. EoE represents a chronic immune-mediated inflammatory disease of the esophagus. In adults dysphagia is the predominant symptom. Upper gastrointestinal endoscopy is required in order to take biopsies from the esophagus. The diagnose is confirmed histologically by typical eosinophilic infiltration of the esophagus mucosa. Until now there is no approved therapy world-wide although we know that topic and systemic steroids are highly effective in EoE. Elimination diet is another option and in well selected patients endoscopic balloon dilation represents a therapeutic possibility.

[Microscopic colitis--new insights relevant to clinical practice]. / Mikroskopische Kolitis--neue praxisrelevante Erkenntnisse.

Microscopic colitis is an increasingly recognised chronic inflammatory bowel disease associated with watery, non-bloody diarrhoea. In addition, many patients suffer from abdominal pain, nocturnal diarrhoea, urgency and incontinence. The two traditional histological subtypes are collagenous colitis and lymphocytic colitis. A novel third subgroup is the so-called incomplete microscopic colitis which is clinically indistinguishable. At present, budesonide is the only evidenced-based effective therapy, however many problems in the long-term treatment strategy are still unsolved. The present paper reviews new developments in microscopic colitis which are relevant for clinical practice.

[Successful treatment of Lichen planus esophagitis with topical budesonide]. / Erfolgreiche Therapie einer Lichen-planus-Ösophagitis mit topischem Budesonid.

Here we describe the first case of symptomatic Lichen planus oesophagitis that was successfully treated with topical budesonide. Lichen planus is a chronic inflammatory disorder of the skin and mucous membranes which is in some cases associated with oesophageal involvement and dysphagia. So far, anecdotal treatment approaches consisted of systemic steroids, retinoids or immunosuppressives. Our patient received oral budesonide suspension 2×1 mg per day for 8 weeks, followed by 2 × 0.5  mg for 3 months. At the end of treatment we observed a complete symptomatic, endoscopic and histological remission, which lasted for at least further 6 months after termination of treatment.

[Current value of quinolones in Helicobacter pylori therapy]. / Aktueller Stellenwert von Fluorchinolonen in der Helicobacter-pylori-Therapie.

Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones.

Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Surveillance of Barrett's esophagus includes endoscopic inspection with biopsy of suspicious lesions followed by four-quadrant biopsy of the remaining mucosa. We assessed the ability of probe-based confocal laser endomicroscopy (pCLE) to replace biopsy in the endoscopic evaluation of patients with Barrett's esophagus in a prospective and controlled setting. PATIENTS AND METHODS: A total of 68 patients who were referred for endoscopic assessment of Barrett's esophagus were included across three centers. pCLE recordings were interpreted live during the examination as well as in a blinded manner at least 3 months after endoscopy. pCLE diagnosis of neoplasia based on pre-defined criteria was compared with histopathology from suspicious as well as four-quadrant biopsies. RESULTS: A total of 670 pairs of biopsies and pCLE video sequences were available for analysis, with neoplasia (high-grade dysplasia or cancer) being histologically diagnosed in 8.3 %. Specificity and negative predictive value of pCLE in excluding neoplasia was 0.97 (90 %CI 0.95 - 0.98) and 0.93 (0.91 - 0.95) for the blinded evaluation, and 0.95 (0.90 - 0.98) and 0.92 (0.90 - 0.94) for the on-site assessment. Positive predictive values (PPVs) and sensitivity were rather poor for both settings (46 %/28 % [blinded] and 18 %/12 % [on-site], respectively). CONCLUSIONS: pCLE can be regarded as non-inferior to endoscopic biopsy in excluding neoplasia of Barrett's esophagus mucosa. However, due to its low PPV and sensitivity, pCLE may currently not replace standard biopsy techniques for the diagnosis of Barrett's esophagus and associated neoplasia. Further technical development of pCLE and a better understanding of its role in relation to other imaging technologies are necessary.

Antimicrobial resistance of Helicobacter pylori in Germany, 2015 to 2018.

OBJECTIVES: National and international guidelines recommend empiric first-line treatments of individuals infected with Helicobacter pylori without prior antimicrobial susceptibility testing. For this reason, knowledge of primary resistance to first-line antibiotics such as clarithromycin is essential. We assessed the primary resistance of H. pylori in Germany to key antibiotics by molecular genetic methods and evaluated risk factors for the development of resistance. METHODS: Gastric tissue samples of 1851 yet treatment-naïve H. pylori-positive patients were examined with real-time PCR or PCR and Sanger sequencing for mutations conferring resistance to clarithromycin, levofloxacin and tetracycline. Clinical and epidemiological data were documented and univariable and multivariable logistic regression analyses were conducted. RESULTS: Overall primary resistances were 11.3% (210/1851) to clarithromycin, and 13.4% (201/1497) to levofloxacin; resistance to tetracycline (2.5%, 38/1497) was as low as combined resistance to clarithromycin/levofloxacin (2.6%, 39/1497). Female sex and prior antimicrobial therapies owing to unrelated bacterial infections were risk factors for clarithromycin resistance (adjusted OR (aOR) 2.3, 95% CI 1.6-3.4; and 2.6, 95% CI 1.5-4.5, respectively); older age was associated with levofloxacin resistance (aOR for those ≥65 years compared with those 18-35 years: 6.6, 95% CI 3.1-14.2). CONCLUSIONS: Clarithromycin might still be recommended in first-line eradication therapies in yet untreated patients, but as nearly every tenth patient may carry clarithromycin-resistant H. pylori it may be advisable to rule out resistance ahead of treatment by carrying out susceptibility testing or prescribing an alternative therapy.

Less favorable clinical outcome after diagnostic and interventional double balloon enteroscopy in patients with suspected small-bowel bleeding?

BACKGROUND AND STUDY AIMS: Double balloon enteroscopy (DBE) is a new endoscopic technique that allows diagnosis and therapeutic interventions of small-bowel lesions. One of the main indications for DBE is suspected small-bowel bleeding (SSBB). Data about clinical outcome after DBE are limited. The aim of the present study was to prospectively assess the short-term clinical outcome of this procedure. PATIENTS AND METHODS: Of all consecutive patients undergoing DBE for various indications, follow-up results in patients with SSBB were analyzed. Standardized questionnaires were used, including assessment of gastrointestinal symptoms, especially signs of gastrointestinal bleeding, blood transfusions, demand for re-intervention, and hospitalization. RESULTS: Of a total of 180 DBEs performed in 124 patients during a 2-year period, SSBB was the indication in 84 patients (M/F = 46/38; mean age 63 years) who underwent a total of 111 DBEs. Of these patients 52 could be followed (mean follow-up 2 months, range 1-5 months). In this subgroup, positive findings were obtained in 30 (mostly angiodysplasia), with therapeutic interventions being performed in 18 of these patients. At follow-up, the rate of re-bleeding in patients who had undergone interventions (20%) was similar to that in patients who had not (18%). CONCLUSION: In this pilot study, DBE did not seem to have a major effect on re-bleeding. Better patient selection or modification of therapeutic regimens appears to be necessary to better utilize DBE in SSBB.

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

St John's 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.

Clinical symptom tool that raises the index of suspicion for eosinophilic oesophagitis in adults and drives earlier biopsy for definitive diagnosis.

BACKGROUND: Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GERD) present with overlapping symptomatology and it is challenging to distinguish EoE from GERD clinically before endoscopy. AIM: To investigate the prognostic value of a set of clinical symptoms and laboratory values in patients with EoE and GERD. METHODS: In this prospective, single-centre, observational study, we compared clinical and laboratory data from 202 patients with EoE or GERD (10 relevant characteristics). Those characteristics showing potential significance in a univariate analysis were then included in a multivariate analysis. RESULTS: The set of 10 characteristics (10-marker set) was able to distinguish between EoE and GERD with good reliability (correct assignment, i.e. agreement with subsequent EGD, of 94.4%). Reduction of the set to the six statistically and clinically most relevant markers continued to give good reliability (88.9%), and further stepwise reduction led to four-marker sets comprising history of atopy, history of food impaction, proton pump inhibitor refractory symptoms and either immunoglobulin E or peripheral eosinophilia, with correct assignment rates of 91.3% and 85.1% respectively. CONCLUSIONS: We have developed a simple and easily applicable clinical/laboratory marker set that helps to distinguish EoE from GERD earlier in the treatment course, thus guiding the endoscopist to perform biopsies from the oesophagus to ensure the diagnosis. The application of the scoring system is expected to diagnose EoE earlier and avoiding delay of adequate treatment.

Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.

BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.

Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a randomized, double-blind, placebo-controlled multicentre trial.

BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.