OBJECTIVES:Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. METHODS:Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. RESULTS:80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p < 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine (> 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. CONCLUSIONS:The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding.

BACKGROUND: The role of sorbitol malabsorption in patients with functional abdominal discomfort has not been finally clarified yet. Therefore, aim of this study was to evaluate the clinical significance of sorbitol malabsorption, diagnosed by sorbitol hydrogen breath testing in these patients. METHODS: Data of all patients referred to our hospital for hydrogen breath testing between May 1st, 2013 and December 31st, 2014 were retrospectively collected and analyzed. Patients with confirmed sorbitol malabsorption completed a symptom-based questionnaire before and after nutritional counseling. RESULTS: Five hundred and ten patients with functional abdominal discomfort (65.5% female, 34.5% male; mean age 45 +/- 16.4 years) were referred to our hospital for hydrogen breath testing. H-2-sorbitol breath tests were performed in 252 of these patients. In 122 of them (48%), sorbitol-malabsorption was diagnosed. In 66 of these patients (54%), the results of the symptom-based questionnaire showed a significant improvement of the frequency of abdominal discomfort (P< 0.001) and of the influence of these symptoms on daily life (P< 0.001) after sorbitol testing/nutritional counseling. CONCLUSIONS: Sorbitol malabsorption is a common finding in patients with functional abdominal discomfort. Dietary intervention positively affects abdominal symptoms in these patients.

BACKGROUND:Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against.PATIENTS AND METHODS:A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting.RESULTS:With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model.DISCUSSION:The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.

BACKGROUND AND STUDY AIM:Optimal therapy concepts in patients with laryngo-pharyngeal reflux (LPR) are still under discussion. Aim of this study was to evaluate long term symptom relief according to results in combined pH/multichannel impedance (MII) monitoring to predict therapy response and symptom relief during long term follow-up. PATIENTS AND METHODS:In patients with predominant LPR symptoms, pH/MII monitoring and subsequent proton pump inhibitor (PPI) therapy were evaluated retrospectively after a minimum follow-up period of 36months. Patients were asked to complete symptom based questionnaires. RESULTS:45 patients were evaluated and classified according to results of pH/MII. Twenty one patients showed a pathological finding in pH/MII. These patients reported significantly higher LPR-symptom intensity scores and a significantly higher LPR symptom-induced impairment of everyday life scores compared to patients with normal pH/MII monitoring at baseline and at follow-up. PPI associated symptom relief was significantly higher in patients with pathologic pH/MII monitoring (p=0.003). CONCLUSION:In conclusion, combined pH/MII monitoring can reliably predict therapy response to PPIs in LPR patients. With negative results, PPI therapy should be avoided. This approach should be assessed in future prospective clinical trials.

Background In eosinophilic esophagitis (EoE), dysphagia, which might reflect esophageal dysmotility, is the most common symptom. High-resolution manometry (HRM) has become widely accepted for evaluating esophageal motility disorders, but to date has been sparsely examined in EoE patients, particularly under therapy. The aim of this study was to evaluate HRM in symptomatic EoE-patients under topical steroid treatment. Methods In this prospective observational study, symptomatic EoE patients received HRM-examinations before and after 8 weeks of topical steroid treatment with budesonide. All HRM-abnormalities were assessed and interpreted according to the Chicago classification. The primary endpoint was the influence of topical steroid treatment on the intrabolus pressure (IBP). Clinical symptoms, endoscopic findings and histological esophageal eosinophilic load were also reported. Key Results Twenty symptomatic EoE patients were included. Overall success of budesonide therapy was 85% regarding complete histologic remission and 80% regarding complete clinical remission. High-resolution manometry showed abnormal esophageal motility in 35% of patients at baseline, which was resolved after therapy in 86% of these patients. Most frequent HRM-findings were early panesophageal pressurizations and weak persitalsis. There was no significant reduction of the IBP under therapy (before: 12.5 +/- 4.9 mmHg, after: 10.9 +/- 2.9 mmHg; p = 0.119). Conclusions & Inferences Although dysphagia is the leading symptom of EoE, HRM is able to identify esophageal motility disorders in only some EoE patients. Observed motility disorders resolve after successful treatment in almost all of these patients. Intrabolus pressure does not seem an optimal parameter for the monitoring of successful treatment response in EoE patients.

Dysphagie ist ein weit gefasster Sammelbegriff für Schluckstörungen. Die differenzialdiagnostische Eingrenzung kann im klinischen Alltag bereits durch eine ausgiebige Anamnese und fachspezifische Untersuchung gelingen. Dennoch bedarf es zur diagnostischen Sicherung und Ausschluss von Differenzialdiagnosen weiterer apparativer Diagnostik. Mittlerweile steht uns eine Vielzahl von diagnostischen Möglichkeiten zur Verfügung. In dieser Übersicht soll die endoskopische Diagnostik detailliert dargestellt werden. Trotz moderner Bildgebung ist jedoch eine ausreichende klinische Expertise und möglichst ein interdisziplinäres Gremium zur gemeinsamen Diskussion und Therapiefestlegung im täglichen Alltag entscheidend.

Aim Diagnosis of laryngopharyngeal reflux (LPR) has dramatically increased over the last years. For diagnosis of gastroesophageal reflux, a newly designed pharyngeal probe (Dx-pH) was recently introduced. It is also recommended to guide therapy decision in antireflux surgery. However, diagnostic results are questionable. Therefore, we establish a reliable reference group with asymptomatic patients after total gastrectomy and, thus, complete extinction of gastric acid production. Methods Pharyngeal pH monitoring was performed in 10 consecutive patients with history of total gastrectomy. All patients were off proton pump inhibitor (PPI) therapy and followed a non-acid diet during the complete measurement period. Results All procedures were performed without any complication. Six of the 10 asymptomatic gastrectomy patients (60%) had pathological results derived from the validated reference values (Ryan score) in pharyngeal pH monitoring. Conclusion Pathological pH values assessed by the Dx-pH device, usually interpreted as pathological aerosolized acidic gastroesophageal and/or laryngopharyngeal reflux, are obviously dissociated from gastric acid production. Further studies are required to determine diagnostic value of the new system. Therefore, the pharyngeal pH monitoring system seems currently not to be useful to guide any diagnostic or therapeutic decisions, in particular if surgical therapy is considered.

Hintergrund: Patienten mit eosinophiler Ösophagitis (EoE) leiden typischerweise an Dysphagie oder Bolusimpaktationen. Überwiegend retrospektiv erhobene Daten suggerieren, dass sich bei einigen EoE-Patienten auch mittels High-Resolution Manometrie (HRM) eine gestörte Speiseröhrenmotilität nachweisen lässt. In der vorliegenden prospektiven Studie wurden EoE-Patienten mittels HRM auf ösophageale Motilitätsstörungen untersucht. Zudem wurde evaluiert, inwieweit eine Therapie mit topischen Steroiden HRM-Befunde bei EoE-Patienten beeinflusst.

AIM: To determine the laryngeal H+ K+-ATPase and pharyngeal pH in patients with laryngopharyngeal reflux (LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS: Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area (immunohistochemistry and PCR analysis). Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+ K+-ATPase. Quantitative real-time RT-PCR for each of the H+ K+-ATPase subunits was performed. The pH values were assessed in the aerosolized environment of the oropharynx (DxpH Catheter) and compared to a subsequently applied combined pH/MII measurement.RESULTS: Twenty patients with LPR symptoms were included. In only one patient, the laryngeal H+ K+-ATPase was verified by immunohistochemical staining. In another patient, real-time RT-PCR for each H+ K+-ATPase subunit was positive. Fourteen out of twenty patients had pathological results in DxpH, and 6/20 patients had pathological results in pH/MII. Four patients had pathological results in both functional tests. Nine out of twenty patients responded to PPIs.CONCLUSION: The laryngeal H+ K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms. Alternative hypotheses for the pathomechanism are needed. The role of pharyngeal pH-metry remains unclear

Dysphagia is a broad collective term for swallowing disorders. In daily clinical practice further differential diagnostic determination is possible by means of a comprehensive anamnesis and specialist examination. Nevertheless further apparatus-based diagnosis is required for confirmation as well as to exclude differential diagnoses. In the meantime a multitude of diagnostic possibilities are available. This overview is intended to provide a detailed description of endoscopic diagnostics. However despite modern imaging the decisive factors in everyday practice are sufficient clinical expertise and wherever possible interdisciplinary case conferences to discuss and decide on treatment.

In this case report we present a 60-year-old male patient with overt midgastrointestinal bleeding of a primary ileal pleomorphic liposarcoma diagnosed by video capsule endoscopy (VCE). Clinical work-up for final diagnosis and the pathological background of this uncommon tumorous entity of the small bowel will be discussed in this paper.

AIM:To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease (GERD) and the response to proton pump inhibitor (PPI) therapy.METHODS:Retrospectively, 683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement (pH/MII) were analyzed. All patients had previously undergone standard PPI treatment (e.g., pantoprazole 40 mg/d or comparable). Four hundred sixty patients were at least 10 d off PPIs (group A), whereas 223 patients were analyzed during their ongoing PPI therapy (group B). In addition, all patients completed a standardized symptom- and lifestyle-based questionnaire, including the therapeutic response to previous PPI trials on a 10-point scale. Uni- and multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs.RESULTS:In group A, positive predictors (PPs) for response in empirical PPI trials were typical GERD symptoms (heartburn and regurgitation), a positive symptom index (SI) and pathological results in pH/MII, along with atypical symptoms, including hoarseness and fullness. In group B, regular alcohol consumption was associated with the therapeutic response. The PPs for pathological results in pH/MII in group A included positive SI, male gender, obesity, heartburn and regurgitation. In group B, the PPs were positive SI and vomiting. Analyzing for positive SI, the PPs were pathological pH and/or MII, heartburn regurgitation, fullness, nausea and vomiting in group A and pathological pH and/or MII in group B.CONCLUSION:Anamnestic parameters (gender, obesity, alcohol) can predict PPI responses. In non-obese, female patients with non-typical reflux symptoms, pH/MII should be considered instead of empirical PPIs.

Flexible endoscopy is increasingly developing into a therapeutic instead of a purely diagnostic discipline. Improved visualization makes early lesions easily detectable and allows us to decide ad hoc on the required treatment. Deep enteroscopy allows the exploration of even the small bowel - for long a "white spot" for gastrointestinal endoscopy - and to perform direct treatment. Endoscopic submucosal dissection is a considerable step forward in oncologically correct endoscopic treatment of (early) malignant lesions. Though still technically challenging, it is increasingly facilitated by new manipulation techniques and tools that are being steadily optimized. Closure of wall defects and hemostasis could be improved significantly. Even the anatomy beyond the gastrointestinal wall is being explored by the therapeutic use of endoluminal ultrasound. Endosonographic-guided surgery is not only a suitable fallback solution if conventional endoscopic retrograde cholangiopancreatography fails, but even makes necrosectomy procedures, abscess drainage, and neurolysis feasible for the endoscopist. Newly developed endoscopic approaches aim at formerly distinctive surgical domains like gastroesophageal reflux disease, appendicitis, and cholecystitis. Combined endoscopic/laparoscopic interventional techniques could become the harbingers of natural orifice transluminal endoscopic surgery, whereas pure natural orifice transluminal endoscopic surgery is currently still in its beginnings.

Die Bougierungstherapie stellt eine etablierte Therapieform benigner und maligner Stenosen der Speiseröhre dar. Die schwerwiegendste Komplikation stellt die Perforation des Ösophagus dar. Sie wird mit 0,5 – 1,0% der Fälle angegeben. Zur Vermeidung dieser ist nach Angabe der DGVS die Einschätzung des Vorschubwiderstands durch den Endoskopiker entscheidend. Dies erfolgt bisher ausschließlich subjektiv. Objektive Kriterien existieren nicht; für Ausbildung und Lehre gibt es keine geeigneten Modelle.

Introduction Treatment of persistence to proton pump inhibitors or non-acid reflux episodes in patients with gastroesophageal reflux disease is challenging. Prucalopride, a selective high affinity serotonin (5-HT 4 ) receptor agonist, might offer a possible new therapeutic alterative. Case presentations We report four chronically constipated female gastroesophageal reflux disease-patients with reflux symptoms and an increased number of reflux episodes in combined esophageal pH and multichannel impedance monitoring treated with prucalopride (2mg per day). Symptoms were persistent to proton pump inhibitors and ranitidine. Gastroesophageal reflux was detected by pH or multichannel impedance (MII) monitoring. Numbers of all reflux episodes as well as non-acid reflux episodes were reduced in all of our patients. The objective findings were concordant with subjective reports of symptom relief. There were no major adverse events in any patient during therapy with prucalopride. Conclusion Administration of prucalopride showed promising results in the treatment of persisting or weakly and/or non-acid reflux episodes in our case series in four constipated patients. Therefore, prucalopride can be regarded as a possible therapeutic option in the treatment of standard proton pump inhibitor-persistent reflux in the chronically constipated patient. However, further prospective trials are needed to prove our findings.

Hintergrund: Die Pathopyhsiologie des laryngopharyngealen Reflux (LPR) ist unklar. Eine Korrelation zwischen dem LPR und der Gastroösophagealen Refluxkrankheit (GOR) wird angezweifelt. Im Larynx ansässige Protonenpumpen (H+K+-ATPase) wurden im Tiermodell bereits identifiziert und könnten für den LPR verantwortlich sein. Ziel der Studie ist die Korrelation von laryngealer H+K+-ATPase Expression im Larynxepithel mit pharyngealem pH Monitoring bei Patienten mit suspiziertem LPR.

Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. Whereas p53 controls DNA damage and IEC survival during the initiation stage, loss of p53 during tumor progression is associated with increased intestinal permeability, causing formation of an NF-kappa B-dependent inflammatory microenvironment and the induction of epithelial-rnesenchymal transition. Thus, we propose a p53-controlled tumor-suppressive function that is independent of its well-established role in cell-cycle regulation, apoptosis, and senescence.

BACKGROUND:Barrett esophagus (BE) is a major risk factor for adenocarcinoma of the distal esophagus. Reliable detection of BE during upper endoscopy is therefore mandatory. According to most guidelines, diagnosis of BE requires both endoscopy and histology for confirmation. However, since adenocarcinomas were also described in patients with indeterminate BE, i.e. endoscopic visible columnar metaplasia but no histological confirmation of goblet cells or vice versa, debate has risen on the risk of malignancy and the need for endoscopic surveillance in such patients.PATIENTS AND METHODS:The study was aimed to assess long-term follow-up data on 209 patients with indeterminate BE (on histopathology or endoscopy) initially examined between 1999 and 2000. Patients or referring physicians were contacted concerning the most recent endoscopic and histopathological results.RESULTS:Follow-up data could be assessed in 149/209 patients (65.1%) after a mean follow-up period of 9.4 years (SD ±2.4 years). Neoplasia was not reported for any patient. The previous endoscopic-histopathological diagnoses could be confirmed in 3 patients only. In the group with endoscopic diagnosis of BE but no histopathological confirmation, BE was described histopathologically in 1 patient during follow-up.CONCLUSION:Persistence of indeterminate BE is poor during long-term follow up. The risk of cancer appears to be negligible. Hence, surveillance of these patients appears equivocal.