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Anal endosonography is an imaging technique for the anal sphincter system and offers analysis of its muscular integrity. It is generally assumed that measurement of the thickness of muscle layers is provided by sonography; however, reproductivity of such measurements have not yet been investigated. Methods: Study I: In 10 healthy volunteers, endoanal ultrasound was performed independently by two experienced investigators with two different ultrasound machines, and thickness of the muscle layers of the internal and external anal sphincter was assessed in the position of the intermediate dorsal anal canal in a randomized cross-over fashion. Study 2: In a study of similar design, sonography was performed in nine healthy volunteers by two investigators independently using a single ultrasound machine in three standardized positions (proximal/intermediate/distal anal canal) and the sphincter layers assessed in the left, right, and dorsal segment. Results: Study 1: Both the same investigator with different ultrasound scanners and different investigators with the same machine failed to obtain reproducible results with respect to internal and external anal sphincter muscle layer diameter (four bivariate correlations, all with p > 0.05). Study 2: Standardization of the probe position did not improve the agreement (2 x 9 bivariate correlations, all but two p> 0.05). Conclusion: At present, therefore, endoanal ultrasound does not provide reliable morphometric data on anal sphincter muscle diameter. This could explain previously conflicting observations of associations between anal sphincter morphometry and function. [ABSTRACT FROM AUTHOR]

Objective: A comparison of anal sonography with conventional electromyographic mapping in the evaluation of anal sphincter defects was the aim of this study. Methods: In 23 patients with defecatory problems referred for conventional needle electromyography (EMG), anal endosonography, with a 7.5-MHz, 355° scanner, was performed before EMG to determine the structural integrity of the external anal sphincter. If lesions were found, they were described in terms of location and extent. Subsequently, concentric needle EMG of the external sphincter was performed circumferentially to locate muscle parts exhibiting normal and diminished or missing muscle activity. Lesions found by EMG were also described like those found by sonography. Results: Of 23 patients, eight exhibited no abnormalities on EMG, and no muscle defects were identified endosonographically in any of these patients. In the remaining 15 patients, EMG showed either an incomplete pattern of interference or a complete absence of voluntary activity; in all of these patients endosonography also identified structural deficit. In 14 of these 15 patients, abnormalities were found at the same location with both endosonography and EMG. In the remaining patient, the two techniques identified structural and functional abnormalities at different locations. Conclusion: Although EMG is the gold standard for assessment of the functional relevance of muscle defects, anal endosonography yields a sensitivity and specificity of almost 100%. [ABSTRACT FROM AUTHOR]

Objective: To investigate esophageal sensory function in normal volunteers. Methods: The method of evoking cerebral potentials (EPs) after electrical stimulation of the esophagus was applied in eight healthy male volunteers, 20-40 yr old. Electrical stimulation was obtained via bipolar Ag/AgCI electrodes attached to a latex balloon mounted on a catheter. The balloon was inflated stepwise to perception and pain thresholds. At the perception threshold for balloon distension, the intensity of electrical stimulation was increased stepwise to perception threshold for electrical stimulation, and subsequently to 2-fold, 4-fold, and 8-fold perception threshold. EPs were recorded from the vertex (Cz) and forehead (Fz, reference) and compared between the increasing electrical stimulation intensities and between perception and pain thresholds for mechanical stimulation. Results: The results show that amplitudes of EPs significantly increased with increasing electrical stimulation intensities, whereas latencies of EPs were not affected. Latencies and amplitudes of EPs were comparable at perception and pain thresholds for esophageal distension. Conclusions: The study suggests that repetitive electrical stimulation of the human esophagus is predominantly mediated via vagal A-delta fibers. The unaltered EPs at the perception and pain thresholds suggest that vagal A-delta fibers are not involved in mediation of pain. The findings support the view that painful and nonpainful stimuli are mediated via different visceral afferents between the esophagus and brain in humans. [ABSTRACT FROM AUTHOR]

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Background: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates.Methods: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival.Results: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 +/- 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834.Conclusions: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival. [ABSTRACT FROM AUTHOR]

Background As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. Aim To establish the definition of failure of a treatment to provide adequate relief (F- PAR) to support this management and referral process in patients with chronic constipation. Methods We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. Results The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). Conclusions We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief. [ABSTRACT FROM AUTHOR]

Objective: Colonoscopy is the accepted gold standard for screening of neoplastic colorectal lesions, but the substantial miss rate remains a challenge. Computed virtual chromoendoscopy with the Fujinon intelligent colour enhancement (FICE) system is a new dyeless imaging technique that might allow higher rates of adenoma detection. Methods: This is a prospective randomised five tertiary care centre trial of colonoscopy in the FICE mode versus standard colonoscopy with targeted indigocarmine chromoscopy (control group) in consecutive patients attending for routine colonoscopy. Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens. Results: 871 patients were enrolled, and 764 patients (344 female, mean age 64 years) were subjected to final analysis 1368 in the FICE group, 396 in the control group). In total, 236 adenomas (mean of 0.64 per case) were detected in the FICE group and 271 adenomas )mean of 0.68 per case) in the control group )p = 0.92). There was no statistically significant difference in the percentage of patients with ⩾1 adenoma between the control group (35.4%) and the FICE group 135.6%) )p = 1.0). For the differential diagnosis of adenomas and non-neoplastic polyps, the sensitivity of FICE (92.7%) was comparable with that of indigocarmine (90.4%) (p = 0.44). Conclusions: At colonoscopy, adenoma detection rates are not improved by virtual chromoendoscopy with the FICE system compared with white light endoscopy with targeted indigocarmine spraying. However, FICE can effectively substitute for chromoscopy concerning the differentiation of neoplastic and non-neoplastic lesions. [ABSTRACT FROM AUTHOR]

Background and aims: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear. Methods: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining. Results: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls. Conclusions: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of gastroparesis can be difficult in everyday clinical practice. The aim of this anonymous survey of members of the Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte e.V. (ALGK) was to investigate the management of gastroparesis care in Germany., Material and Methods: The ALGK conducted a member survey using a standardized anonymous questionnaire including 11 questions from 14.04.2023 to 29.04.2023. The questions covered diagnostic and therapeutic procedures as well as various aspects of the management of gastroparesis., Results: The response rate was 21.4% (62 members). Only 6.56% of all respondents assessed the prevalence of gastroparesis correctly as estimated by current epidemiological publications. 68.85 % of all respondents used gastric emptying scintigraphy for diagnosis. 51.61% regarded an individualized therapy as the most important treatment goal, taking into account etiology and impact of symptoms, compared to symptomatic treatment of leading clinical symptom in 43,55 %. First choice treatment was medical treatment in 41.94%, dietary recommendations in 27.42% and endoscopic interventions in 24.2%. 100% of respondents used prokinetics, 40.32% used antiemetics while only 4.84% used analgesics. Insufficient availability of medical treatment options represents a need of action for 85.48%, compared to lacking official approval of available drugs for this indication for 48,39% of all respondents. Treatment options with little evidence were used quite frequently (e.g. use of herbal therapies in 43.55%)., Discussion: Overall, the frequency of gastroparesis was underestimated in the current survey. Endoscopic options are quite often used as first-line treatment. Although symptom-guided treatment is important for the majority of respondents, prokinetics are predominantly used., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Endoscopic retrograde cholangiopancreatography [ERCP] is a complex procedure with a flat learning curve. It is associated with the risk of serious complications such as pancreatitis, bleeding, cholangitis and perforation. Endosonography should therefore also be offered for the precise indication of the higher-risk ERCP. Numerous factors influence the success of ERCP. In addition to structured training for the initial acquisition of skills and a minimum number of ERCPs of varying degrees of difficulty, maintaining a good quality of ERCP also requires a regular minimum number of examinations performed per year. There is extensive evidence that shows a significant correlation between ERCP volumes and primary success rates, lower lengths of hospital stay, fewer unwanted readmissions and fewer complications. The cut-offs for differentiating between high-volume and low-volume centers were chosen inconsistently in the studies, with the highest evidence for a cut-off value of 200 ERCPs/year. The question of specialization in ERCP has been given a relevance by the current developments in german hospital reform. Here, a minimum number of ERCPs should be defined for groups of different specialization. However, a minimum number alone will not be able to achieve good treatment quality. In terms of high-quality patient care, it is necessary to offer ERCPs in specialized gastroenterology center, which, in addition to a sufficient number of ERCPs for training and to maintain competence, offer an on-call service and complementary procedures such as EUS and which are embedded in appropriately accessible clinics that have the necessary resources for complication management., Competing Interests: Alle Autoren und Autorinnen sind Mitglieder der DGVS. Die Autoren und Autorinnen 1–6 und 8–12 arbeiten in leitenden Funktionen in Gastroenterologien in denen auch ERCPs durchgeführt werden., (Thieme. All rights reserved.)

Background and Study Aims: Gastrointestinal adverse reaction to food (GARF) is reported frequently in the general population and even more in patients with disorders of the gut brain axis. However, there is a significant difference between self-reported and objective proven GARF. The aim of the study was to characterize a mucosal correlate of GARF by endoscopic confocal laser endomicroscopy (eCLE) with duodenal food challenge (DFC)., Patients and Methods: In an observational and proof of concept study we evaluated 71 patients with disorders of the gut brain axis without (group I, n=19) and with (group II, n=52) GARF by eCLE and DFC. Spontaneous and food induced transfer of fluorescein into duodenal lumen was detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC., Results: According to Rom IV, the patients (group I/II) could be classified as irritable bowel syndrome (IBS) 32%/31%, functional abdominal pain without changes in bowel movement 47 %/48 %, functional abdominal bloating/distension 0 %/10 %, functional diarrhea 5 %/ 2 %, and unspecified functional bowel disorder 16 %/10 %, respectively. 21 %/27 % of the patients responded with a fluorescein leakage into the duodenal lumen before and 74 %/69 % following to DFC. Frequency rank order of food components that induced a response were soy (55.5 %/60 %), wheat (60 %/45.5 %), egg (35.7 %/8.3), milk (30 %/18.2 %) and yeast (10 %/6.6 %), respectively. Histology of duodenal biopsies, number, form and distribution of intraepithelial lymphocytes and mucosal mast cells as well as mast cell function were normal. Overall, 14 %/79 % reported main symptom benefit following a food exclusion therapy according to eCLE and DFC that was significant different between the groups., Conclusion: The results of our study indicate that eCLE with DFC is a technique to clinically evaluate patients with disorders of the gut brain axis and GARF resulting in a high proportion of patients reporting symptom benefit upon food exclusion dietary advice focussed on the results of eCLE., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: We previously showed enteric nerve activation after application of colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS). The question remains whether this is a region-specific or a generalized sensitization. We tested the nerve-activating properties of supernatants from large and small intestinal regions of IBS patients with diarrhea (IBS-D) in comparison to those from mastocytosis patients with diarrhea (MC-D) or non-IBS/non-MC patients with GI-complaints. MC-D patients were included to test samples from patients with an established, severe mast cell disorder, because mast cells are suggested to play a role in IBS., Methods: Voltage-sensitive dye imaging was used to record the effects of mucosal biopsy supernatants from IBS-D, MC-D, and non-IBS/non-MC on guinea pig submucous neurons. Mast cell density and histamine concentrations were measured in all samples., Results: The median neuroindex (spike frequency × % responding neurons in Hz × %) was significantly (all p < 0.001) increased for IBS-D (duodenum and colon, proximal and distal each, 49.3; 50.5; 63.7; 71.9, respectively) compared to non-IBS/non-MC (duodenum and colon, proximal and distal each, 8.7; 4.9; 6.9; 5.4, respectively) or MC-D supernatants (duodenum and colon, proximal and distal each, 9.4; 11.9; 0.0; 7.9, respectively). Nerve activation by MC-D and non-IBS/non-MC supernatants was comparable ( p >0.05). Mast cell density or histamine concentrations were not different between IBS-D, MC-D, and non-IBS/non-MC samples., Discussion: Nerve activation by biopsy supernatants is an IBS hallmark that occurs throughout the gut, unrelated to mast cell density or histamine concentration. At least as important is our finding that GI complaints per se were not associated with biopsy supernatant-induced nerve activation, which further stresses the relevance of altered nerve behavior in IBS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vignali, Buhner, Greiter, Daniel, Frieling, Schemann and Annahazi.)

Acute abdominal pain may relate to specific organ systems and needs an interdisciplinary approach with close collaboration between internal and surgical disciplines. Main objective is to shorten the diagnostic work-up between the beginning of the symptoms and their therapy. After clarifying of the five w-questions: when, how, how long, why, and where, abdominal ultrasound, ECG, laboratory diagnostics and early application of computed tomography should be performed.For the most part, chronic abdominal pain is caused by disorders of the gut-brain-axis such as the irritable bowel syndrome. Because of the synaptic plasticity, the processing of pain is dynamic and cannot be related to a single organ system. This problem is obvious in patients with irritable bowel syndrome and colonic diverticula, which may be interpreted as symptomatic uncomplicated diverticular disease (SUDD, type 3a). However, a reliable clinical differentiation between both groups is not possible. The establishment of SUDD (type 3a) considerable widened the application area of mesalazine., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Endoscopic confocal laser endomicroscopy (eCLE) is an established technique that allows clinical evaluation of mucosal integrity by fluorescein leaking through the mucosa upon duodenal food challenge (DFC). Analysis of eCLE with DFC in eosinophilic esophagitis (EoE) would be interesting to evaluate epithelial barrier dysfunction also in other regions of the gastrointestinal tract and to characterize potential individual food allergens that trigger the esophageal inflammation., Methods: In an observational and proof of concept study we evaluated 9 patients with histologically proven EoE by eCLE and DFC. Severity of symptoms were graduated according to the validated symptom-based EoE activity index. The endoscopic appearance of the esophagus was described according to the Endoscopic Reference Score System (ERERS). Spontaneous and food induced transfer of fluorescein into duodenal lumen were detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. Food allergens were yeast, egg, soy, milk, and wheat, respectively. Local application of sodium chloride solution 10 % to the duodenal mucosa before DFC served as a control. Patients responding to DFC received a dietary exclusion therapy according to the results of DFC., Results: We investigated 9 patients with EoE (8 men, 49.7±13.8, 36-76 years). Symptom-based EoE activity index was 79±27.4, 33-100. In all patients EoE was confirmed by histology with number of esophageal mucosal eosinophilic granulocytes > 15/HPF, (91.4±77.4, 42-263). Mean ERERS score was 4.5±1.3, 3-7. None of the patients was aware of any food intolerance. eCLE revealed one patient with spontaneous transfer of i. v. fluorescein into duodenal lumen before DFC ("leaky gut"). 40 DFC were performed in the remaining 8 patients of whom 5 patients (61 %) responded to DFC. Rank order of fluorescein leakage upon DFC was wheat and milk in 37.5 % each, soy in 25 %, and egg in 12.5 %. The patients were treated by PPI (n=9), esophageal bouginage (n=5) and/or local corticoid therapy (n=3). The 5 patients responding to DFC received an additional food exclusion dietary advice focussed on the results of DFC. All patients reported a reduction of their symptoms. EoE activity indexes of patients with positive DFC were 73.7+28.6, 33-100 before and 22.7+37.9, 0-79 four weeks after food exclusion., Conclusion: The findings of our proof of concept study suggest that eCLE with DFC may be an interesting tool to further evaluate patients with EoE. This technique has the potential to identify patients who may benefit from an additional individual dietary therapy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: The removal of bolus impaction within the esophagus is an indication for emergency endoscopy. The current guideline of the European Society of Gastrointestinal Endoscopy (ESGE) recommends gently pushing the bolus into the stomach. This view is discerned by many endoscopists because of the increased risk of complications. In addition, the use of an endoscopic cap for bolus removal is not mentioned., Material and Methods: In a retrospective analysis from 2017 to 2021 we investigated 66 adults and 11 children with acute bolus impaction within the esophagus., Results: Eosinophilic esophagitis, reflux esophagitic /peptic stenosis and Schatzki Ring caused 57.6%, esophageal and bronchial carcinoma 18%, esophageal motility disorders 4.5%, Zenkers diverticulum 1.5% and radiation esophagitis 1.5% of the bolus obstructions. The reason remained unclear in 16.7% of the cases. The spectrum was comparable in children with additional 2 cases with esophageal atresia and stenosis. The reason was unclear in 2 cases. Removal of bolus impaction was successful in 92.4% in adults and 100% in children. Bolus obstruction in adults was successfully removed solely by endoscopic cap in 57.6% and 75% in children. Pushing the bolus into the stomach without disintegration was possible in only 9% of cases., Conclusion: Flexible endoscopy is an effective ermergency intervention for removal of bolus obstruction within the esophagus. Uncontrolled pushing the bolus into the stomach without view cannot be recommended. An endoscopic cap is a good extension for safe bolus removal., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Intestinal epithelial barrier dysfunction ("leaky gut syndrome", LGS) is thought to play a major role in the pathogenesis of disorders of the gut brain axis. Endoscopic confocal laser endomicroscopy (eCLE) is an objective measure to test duodenal permeability. We applied this technique in patients with functional gastrointestinal symptoms and food intolerance to characterize the proportion of patients with LGS., Material and Methods: In an observational study, we evaluated 85 patients with functional gastrointestinal symptoms and food intolerance. Gastrointestinal symptoms were classified according to Rom IV into functional abdominal pain (FAP), irritable bowel syndrome (IBS), irritable bowel syndrome diarrhea dominant (IBS-D), irritable bowel syndrome constipation dominant (IBS-C), irritable bowel syndrome with mixed stool (IBS-M), functional abdominal bloating (FAB), functional diarrhea (FD) and unclassified (NC). During eCLE, spontaneous transfer of intravenously applied fluorescein into duodenal lumen (LGS) and following duodenal food challenge (DFC) were analyzed. Blood analysis comprised parameters of mast cell function, histology of duodenal mucosal biopsies analysis of mucosal inflammation, intraepithelial lymphocytes (IELs) as well as number, distribution and morphology of mast cells., Results: 24 patients (9 IBS, 9 FAP, 3 FAB, 1 FD, 2 NC), showed LGS, 50 patients (14 IBS-D, 4 IBS-C, 3 IBS-M, 23 FAP, 3 FAB, 3 NC) had no LGS but responded to DFC and 11 patients (6 NC, 3 FAP, 1 FAB, 1 FD) had no LGS and no response to DFC. The proportion of subgroups with/or without spontaneous leakage of fluorescein (+LGS/-LGS) were IBS-LGS/IBS+LGS 67%/33%, FAP-LGS/FAP+LGS 72%/28%,FAB-LGS/FAB+LGS 50%/50%, NC-LGS/NC+LGS 60%/40%. Subgroup analysis revealed no significant differences for all parameters tested., Conclusion: As a proof of concept, the results of our study indicate that eCLE is a clinical useful tool to evaluate patients with disorders of the gut brain axis and those suspicious of LGS. However, the clinical significance of LGS remains unclear. The study should be an incentive to perform a randomized study including healthy controls., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Neurogastroenterological disorders (NGDs) are highly prevalent and substantially impact patients' quality of life. Effective treatment of NGDs depends on the competence and training of medical caregivers. Students' perceived competence in neurogastroenterology and its place in medical school curricula are assessed in this study., Methods: A multi-center digital survey among medical students was conducted at five universities. Self-ratings of competence regarding basic mechanisms, diagnosis, and treatment of six chronic medical conditions were assessed. These included irritable bowel syndrome (IBS), gastroesophageal reflux disease, and achalasia. Ulcerative colitis, hypertension, and migraine were included as references., Key Results: Of 231 participants, 38% remembered that neurogastroenterology was covered in their curriculum. Highest competence ratings were stated for hypertension and the lowest for IBS. These findings were identical for all institutions irrespective of their curricular model and demographic parameters. Students who remembered neurogastroenterology as a part of their curriculum reported higher competence ratings. According to 72% of students, NGDs should be highlighted more prominently in the curriculum., Conclusions & Inferences: Despite its epidemiological relevance, neurogastroenterology is only weakly represented in medical curricula. Students report low levels of subjective competence in handling NGDs. In general, assessing the learners' perspective on an empirical basis may enrichen the process of national standardization of medical school curricula., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Competing Interests: LL, UD, TF, RJ, SF, HL, JM, JO, UT, BT, HW und JA sind in ehrenamtlicher Tätigkeit für die DGVA an dem Manuskript beteiligt, PL als Geschäftsführerin der DGVS. Es liegen keine weiteren Interessenskonflikte vor.

Gastroenterology has made crucial advances in diagnostic and interventional endoscopic procedures, opening up improvements in the treatment of many patients. Thus, organ-preserving treatments are increasingly being made possible, replacing more invasive organ resecting surgical procedures. At the same time, the degree of complexity and risks varies widely between different endoscopic procedures. In many cases, simpler endoscopic procedures are now offered on an outpatient basis. Further potential for cross-sectoral performance of endoscopic procedures exists in the case of complex endoscopic procedures, which, however, require special structural, procedural and personnel requirements in order to provide quality-assured treatment, enable post-interventional monitoring and, if necessary, take measures to ensure the success of the treatment. We summarize the essential prerequisites and limitations for cross-sector performance of endoscopic procedures in gastroenterology., Competing Interests: LL, UD, TF, RJ, SF, HL, JM, JO, UT, BT, HW und JA sind in ehrenamtlicher Tätigkeit für die DGVA an dem Manuskript beteiligt, PL als Geschäftsführerin der DGVS. Es liegen keine weiteren Interessenskonflikte vor., (Thieme. All rights reserved.)

Background and study aims  Gastrointestinal symptoms assumed to be caused by food intolerance are reported frequently in the general population. There is a significant difference between self-reported and objective proven food intolerance, as shown by placebo-controlled, double-blind, randomized trials. This discrepancy may be overcome by endoscopic confocal laser endomicroscopy (eCLE). Patients and methods  In an observational study we evaluated 34 patients with functional abdominal pain and adverse reaction to food by eCLE and local duodenal food challenge for the first time. Spontaneous and food-induced transfer of fluorescein into the duodenal lumen was detected 10 minutes after intravenously application of fluorescein and 10 minutes after duodenal food challenge (DFC). Results  Of the patients, 67.6 % responded with a fluorescein leakage into the duodenal lumen. Frequency rank order of food antigens that induced a response were soy (50 %), wheat (46.1 %), milk (20 %), egg (12 %), and yeast (11.5 %), respectively. Of the patients, 23.5 % showed spontaneous leakage of fluorescein, suggesting leaky gut syndrome. Histology of duodenal biopsies and mast cell function were normal. Overall, 69.5 % of patients improved with food exclusion therapy and 13 % were symptom-free according to eCLE. Conclusions  The results of our study indicate that eCLE is a clinically useful tool to evaluate patients with functional abdominal pain and adverse reaction to food and to create individualized dietary therapy with clinical benefit for patients., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: 2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up., Methods: We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score >3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed., Findings: Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p<0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group., Interpretation: Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made., Funding: Fonds NutsOhra and European Society of Gastrointestinal Endoscopy., Competing Interests: Declaration of interests PFo received consultancy fees from Olympus and Cook Endoscopy. HN declares the following financial relationships with a commercial interest: consulting for Boston Scientific, Olympus, Medtronic, Cook, and Microtech; and grant or research support from Pentax and Erbe. TB declares the following financial relationships with a commercial interest: consulting for Olympus and Erbe. TF received speaker or consulting fees from Dr Wilmar Schwab, Sanofi-Aventis Deutschland, Takeda Pharma Vertriebs, Falk Foundation, Medizinisches Forum, Forum Medizinische Fortbildung, Promedia Medizintechnik A Ahnfeldt, MEDICE Arzneimittel Pütter, ABOCA Group, Reckitt Benckiser Deutschland, Bayer Vital. PWYC declares the following financial relationships with a commercial interest: board membership for Cornerstone Robotics; advisory committees or review panels for EndoVision and EndoMaster; and consulting for Boston Scientific. GC reported the following financial relationships with a commercial interest: advisory committees or review panels for Olympus and Cook Endoscopy; and grant or research support from Boston Scientific. JEP received research funding from National Institutes of Health National Institute of Diabetes and Digestive and Kidney Disease, and declares the following financial relationships with a commercial interest: consulting for Medtronic, ethicon, diversatek, Ironwood, Phathom, and Neurogastrx; patent held or filed (FLIP-AI) for Medtronic; and speaking and teaching for Medtronic and ethicon. AJB received research funding from Nutricia, Dr Falk Pharma, Thelial, Side Sleep Technologies and Bayer and received speaker or consulting fees from Laborie, Medtronic, Dr Falk Pharma, Alimentiv, Sanofi/Regeneron, and AstraZeneca. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT 3 receptor family. 5-HT 3 Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT 3 R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D., (© 2022. The Author(s).)