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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.)

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.)

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 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: Patient and public involvement (PPI) in quality improvement of oncological care pathways for older patients are rare., Objectives: Improve the care pathway experience of older cancer patients and explore lessons learned regarding how to engage this vulnerable group., Design: Experience-Based Co-Design., Setting and Participants: Older cancer patients, their caregivers and healthcare professionals within colorectal and breast cancer care pathways., Interventions: Co-design quality improvement teams., Main Outcome Measures: Colorectal cancer care pathway touchpoints were (a) availability of a contact person during diagnostic, treatment and aftercare phases; (b) collaboration between physicians and different hospital departments; (c) continuous relationship with same physician; (d) respectful treatment; (e) and information transfer with primary care. Breast cancer care pathway touchpoints were (a) comprehensive information package and information provision, (b) care planning based on patient preferences, (c) continuity of patient-professional relationship and (d) specialized care in case of vulnerability. Challenges related to PPI included (a) ability of older cancer patients to be reflective, critical and think at a collective level; (b) gaining support and commitment of professionals; (d) overcoming cultural differences and power inequalities; and (e) involving researchers and facilitators with appropriate expertise and position., Conclusion: This multidisciplinary quality improvement project revealed several challenges of PPI with older cancer patients and their caregivers. Research teams themselves need to assume the role of facilitator to enable meaningful PPI of older cancer patients., Patient or Public Contribution: Patient and caregiver representatives and advocates were involved in the design, conduct, analysis, interpretation of the data and preparation of this manuscript., (© 2020 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Cultural values are crucial to the practice and impact of patient and public involvement (PPI) in research., Objective: To understand different PPI cultures among research teams and the impacts of PPI associated with each culture type., Design: A participatory action research design., Setting and Participants: The setting was 10 palliative care research projects. Seventeen patients and members of the public and 31 researchers participated., Intervention: A programme consisting of four components: (1) training and coaching of patients and the public to prepare them for participation in research, (2) tailored coaching of the 10 research teams over 12-18 months, (3) a community of practice, and (4) a qualitative evaluation., Results: We identified three cultures types: relationship cultures, task cultures, and control cultures. We identified four areas of impact: the project aim became more relevant to the target audience, methodological reliability increased, the research products were better able to reach the public, and the awareness increased, associated with behavioural changes, among researchers regarding PPI., Discussion: A relationship culture appears to be long-lasting due to impacting the behaviours of the researchers during future projects. Different cultural types require different types of patients and researcher participants, assigned to different tasks., Conclusions: Further research remains necessary to investigate the support required by researchers to enable relationship- and task-oriented PPI cultures., Patient or Public Contribution: Patient advocates and representatives contributed to our research team throughout the entire research process, as well as within the 10 implementation projects., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background:  Intramural pseudodiverticulosis of the esophagus (EIPD) is a rare disease leading to dysphagia, chest pain, and weight loss. The diagnosis is difficult, and the disease can be confounded with eosinophilic esophagitis (EoE). We present a patient with esophageal intramural pseudodiverticulosis and a literature review., Case Report:  The 45-year-old white caucasian woman with a history of nicotine and alcohol abuse had progressive hoarseness and severe dysphagia for solid food. Esophagogastroduodenoscopy (EGD) showed proximal esophageal stenosis, thrush esophagitis, and mucosal alteration with trachealization suspicious of EoE. However, repeated bouginage EGD and barium swallow revealed typical signs of esophageal intramural pseudodiverticulosis (EIPD). The patient was treated successfully by bougingage, acid suppression, and antifungal therapy. The literature analysis revealed the characteristics of EIPD according to age, sex, risk factors, and therapy modalities., Conclusion:  The case report and the literature overview suggest that EIPD can be confounded with EoE., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background:  Verrucous carcinoma of the esophagus is a rare disease leading to dysphagia, chest pain, and weight loss. The diagnosis is difficult because even repeated biopsies are often without tumor evidence. We present a patient with verrucous carcinoma of the esophagus and a literature review., Case Report:  A 64-year-old patient with dysphagia and sore throat received esophagogastroduodenoscopy illustrating segmental circumferential verrucous inflammation and Candida esophagitis in the middle part of the esophagus. Repeated mucosal biopsies revealed reactive hyperkeratosis of the squamous epithelium with minimal atypia but without ulcera, eosinophilic esophagitis, or suspicion of cancer. Mucosal infection with adenovirus, herpes simplex virus 1, human papilloma virus types, and cytomegaly virus was ruled out. Veruccous carcinoma was detected finally by endoscopic mucosal resection. The patient was successfully treated by esophageal resection. Tumor stage was G1, pT1b, pN0, L0, V0, Pn0, R0., Conclusion:  The results suggest that macroscopic suspicion of verrucous esophageal carcinoma should lead to resections of larger tissue specimens by EMR to confirm the diagnosis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background:  Neurological autoimmune disorders (NAD) are caused by autoimmune inflammation triggered by specific antibody subtypes. NAD may disturb the gut-brain axis at several levels including brain, spinal cord, peripheral, or enteric nervous system., Case Report:  We present a case with antinuclear neuronal Hu (ANNA-1)- and antiglial nuclear (SOX-1) autoimmune antibody-positive limbic encephalitis and significant gastrointestinal dysmotility consisting of achalasia type II, gastroparesis, altered small intestinal interdigestive motility, and severe slow transit constipation. The autoantibodies of the patient's serum labeled enteric neurons and interstitial cells of Cajal but no other cells in the gut wall. Achalasia was treated successfully by pneumatic cardia dilation and gastrointestinal dysmotility successfully with prucalopride., Conclusion:  NAD may disturb gastrointestinal motility by altering various levels of the gut-brain axis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The implementation of oncology care pathways that standardize organizational procedures has improved cancer care in recent years. However, the involvement of "authentic" patients and caregivers in quality improvement of these predetermined pathways is in its infancy, especially the scholarly reflection on this process. We, therefore, aim to explore the multidisciplinary challenges both in practice, when cancer patients, their caregivers, and a multidisciplinary team of professionals work together on quality improvement, as well as in our research team, in which a social scientist, health care professionals, health care researchers, and experience experts design a research project together., Methods and Design: Experience-based co-design will be used to involve cancer patients and their caregivers in a qualitative research design. In-depth open discovery interviews with 12 colorectal cancer patients, 12 breast cancer patients, and seven patients with cancer-associated thrombosis and their caregivers, and focus group discussions with professionals from various disciplines will be conducted. During the subsequent prioritization events and various co-design quality improvement meetings, observational field notes will be made on the multidisciplinary challenges these participants face in the process of co-design, and evaluation interviews will be done afterwards. Similar data will be collected during the monthly meetings of our multidisciplinary research team. The data will be analyzed according to the constant comparative method., Discussion: This study may facilitate quality improvement programs in oncologic care pathways, by increasing our real-world knowledge about the challenges of involving "experience experts" together with a team of multidisciplinary professionals in the implementation process of quality improvement. Such co-creation might be challenging due to the traditional paternalistic relationship, actual disease-/treatment-related constraints, and a lack of shared language and culture between patients, caregivers, and professionals and between professionals from various disciplines. These challenges have to be met in order to establish equality, respect, team spirit, and eventual meaningful participation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation., Methodology/principal Findings: Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency., Conclusion: The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.