The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m2) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.

Pseudoachalasia is a condition in which symptoms, radiologic, endoscopic, and manometric findings mimick idiopathic achalasia. About 4% of patients with a typical constellation for idiopathic achalasia will turn out to have pseudoachalasia, posing a major diagnostic challenge. A large spectrum of underlying causes of pseudoachalasia has been described. However, in about 70% of affected patients, this condition is caused by a malignancy (mostly adenocarcinoma of the esophagogastric junction or cardia). We describe a 16-year-old high school student referred for management of achalasia who turned out to have pseudoachalasia due to adenocarcinoma of the cardia. He was cured with preoperative chemotherapy followed by radical surgery. Therapy of pseudoachalasia secondary to neoplasia is directed against the tumor or may be palliative to keep the lumen open. Other causes of pseudoachalasia include esophageal motility disturbances as a paraneoplastic phenomenon (e.g., with small cell lung cancer), post fundoplication or post bariatric surgery, in association with a thoracic aortic aneurysm, or with sarcoidosis or amyloidosis. Therapy is directed accordingly to eliminate or correct the underlying cause.

Background: Over 90% of patients with systemic sclerosis suffer from gastroesophageal reflux. Esophageal motility disturbances are associated with a reduced life quality and may force interstitial lung disease progression. We wanted to determine whether we can improve gastroesophageal reflux in these patients by esophageal stem-cell injection. Methods: We performed a pilot study including eights patients with systemic sclerosis and symptomatic gastroesophageal reflux. Sampling of adipose tissue was performed by an experienced plastic surgeon under local anesthesia. The collected fat was injected into the submucosa of the distal esophagus, each time 1 ml in all four quadrants starting 2, 4 and 6 cm proximal to the Z line (ending up to a total volume of 12 ml). Before the intervention, 3, 6 and finally 12 months after the procedure, patients answered the Gastroesophageal Reflux Disease Health-Related Quality of Life Questionnaire (GERD HRQL) and a high-resolution manometry was performed to quantify changes in motility function. Results: All patients showed an improvement in the GERD HRQL score after the stem-cell injection and a lower dosage of proton-pump inhibitors. The manometric findings showed no change throughout the time. A serious adverse event occurred, as one patient developed multiple cerebellar embolic infarcts. Conclusion: Because of the favorable effect in all patients, a safe route for esophageal fat injection needs to be developed.

Background The prostaglandin D-2 receptor DP2 has been implicated in eosinophil infiltration and the development of eosinophilic esophagitis (EoE). Aims and Methods In this study, we investigated an involvement of PGE(2) (EP1-EP4) and PGD(2) (DP1) receptors in EoE by measuring their expression in peripheral blood eosinophils and esophageal mucosal biopsies of EoE patients and by performing migration and adhesion assays with eosinophils from healthy donors. Results Expression of EP2 and EP4, but not EP1 and EP3, was decreased in blood eosinophils of patients with EoE vs. control subjects. Adhesion of eosinophils to esophageal epithelial cells was decreased by EP2 receptor agonist butaprost and EP4 agonist ONO-AE1-329, whereas DP1 agonist BW245C increased adhesion. In chemotaxis assays with supernatant from human esophageal epithelial cells, only ONO-AE1-329 but not butaprost or BW245C inhibited the migration of eosinophils. Expression of EP and DP receptors in epithelial cells and eosinophils was detected in sections of esophageal biopsies from EoE patients by immunohistochemistry. qPCR of biopsies from EoE patients revealed that gene expression of EP4 and DP1 was the highest among PGE(2) and PGD(2) receptors. Esophageal epithelial cells in culture showed high gene expression for EP2 and EP4. Activation of EP2 and EP4 receptors decreased barrier integrity of esophageal epithelial cells in impedance assays. Conclusions Activation of EP2 and EP4 receptors may inhibit eosinophil recruitment to the esophageal mucosa. However, their activation could negatively affect esophageal barrier integrity suggesting that eosinophilic rather than epithelial EP2 and EP4 have a protective role in EoE.

A 60-cm endoscopically implantable duodenal–jejunal bypass liner (Endobarrier™, GI Dynamics, Lexington, MA, USA) has been introduced as a therapeutic option to support weight loss for a selected group of obese subjects with type 2 diabetes mellitus (T2DM). The sleeve prevents contact between chyme and the intestinal mucosa of the upper gastrointestinal tract. The primary aim of this study is to elucidate the changes in insulin sensitivity and beta-cell function after EndoBarrier™ implantation in obese patients with T2DM; changes in gut permeability and gut microbiome are also to be examined.

Background: A 60cm endoscopically implantable, duodeno-jejunal bypass liner (Endobarrier®) has been introduced as a therapeutic option for obese subjects with type 2 diabetes (T2DM). The aim of the study was to explore short and mid-term metabolic effects in the clamp setting. Materials and Methods: This open, single-center trial investigated 10 obese, T2DM subjects with suboptimal glycemic control (HbA1c >48mmol/mol). Prior to the implantation of the gastrointestinal liner (baseline), 4 weeks and 9 months (explantation) after, all subjects underwent Dual-energy X-ray absorptiometry (DXA) measurement, assessment of beta cell function and insulin sensitivity by a Botnia clamp procedure and a mixed-meal tolerance test. Results: We investigated 10 patients with a mean age of 48±9 years and mean diabetes duration of 7±6 years. Detailed results and changes over the time are given in Table. No device has been removed prematurely. Conclusion: Treating obese T2DM subjects by an endoluminally implanted Endobarrier® leads to moderate weight reduction with large inter-individual variation. Significant improvements in insulin sensitivity occurred already 4 weeks after the Endobarrier® implantation, which were maintained until the explantation of the device, accompanied by reductions in blood pressure.Baseline (mean±SD)4 Weeks (mean±SD)9 Monhts (mean±SD)p-value (Group comparison baseline vs. 4 weeks)p-value (Group comparison baseline vs. 9 months)Body weight (kg)121.2 ± 18.5116.3 ± 18.2115.7± 22.5<0.0010.016Fat-Mass (kg)58.1 ± 12.055.0 ± 12.553.3 ± 16.10.0010.014HbA1c (mmol/mol)61 ± 1056 ± 955 ± 120.0160.139Blood pressure systolic (mmHg)143 ± 16129 ± 24125 ± 210.0590.007Blood pressure diastolic (mmHg)94 ± 1085 ± 1579 ± 160.1070.021Glucose infusion rate (mg/kg/min)0.50 ± 1.020.86 ± 0.990.81 ± 1.28<0.0010.034C-peptide AUC (ng/mL/min)8.10 ± 3.017.27 ± 3.765.81 ± 2.090.4400.046 Disclosure N.J. Tripolt: None. F. Aberer: None. J. Url: None. P.N. Pferschy: None. C. Högenauer: None. F. Schreiber: None. A. Eherer: None. E. Svehlikova: None. C. Sourij: None. A.M. Obermayer: None. V. Stadlbauer: None. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc..

Background and Aims: The GI tract is rarely affected by secondary tumors. Patients often present at an advanced stage of the disease, and prognosis is dismal. This study aimed to analyze the clinical, endoscopic, and pathologic features of secondary tumors that had been diagnosed endoscopically. Methods: We conducted a retrospective database analysis of 217 patients with secondary tumors of the GI tract. Endoscopic findings and histologic diagnoses were systematically re-evaluated. Results: Malignant melanoma (n=33, 15%), breast cancer (n=32, 15%), and pancreatic cancer (n=27, 12%) were the most common corresponding primaries. About one-third of secondary tumors were detected in the stomach (n=76, 35%), followed by small intestine (n=54, 25%) and rectum (n=53, 24%). The median time between the diagnoses of primary and secondary tumors was 19 months (mean, 31; range, 0-251), and this time was particularly long for renal cell carcinoma and breast cancer (median, 38 and 45 months, respectively). Direct invasion from extra-GI malignancies was more common (56%) than vascular cancer spread (44%) and depended on both sites of tumor involvement and corresponding primary. The lesions presented with various endoscopic patterns. In patients for whom a definitive diagnosis of cancer was known before the examination (n=168), a secondary tumor was included in the differential diagnosis in only 48% of lesions. It is of note that the remaining cases were diagnosed endoscopically as primary tumors and rarely also as nonneoplastic change. Conclusions: Secondary tumors may affect all parts of the GI tract. Malignant melanoma and breast and pancreatic cancer represent the most common primaries. Diagnosis based on examination of biopsy specimens is crucial to avoid misclassification.

A 48-year-old woman with known menopausal depression was referred to the hospital because of watery non-bloody diarrhea, abdominal pain, and weight loss of 4 kg within the last 3 months. Physical examination was unremarkable. Laboratory analysis showed mild leukocytosis (13,600/μL; normal, 4400–11,300), and C-reactive protein was elevated (101 mg/L; normal, <5). Stool testing was negative for viral and bacterial pathogens, including Clostridium difficile, which was assessed by the C. Diff Quik Chek Complete test (Techlab, Blacksburg, VA), which is a rapid membrane enzyme immunoassay for the simultaneous detection of both C difficile glutamate dehydrogenase antigen and toxins A and B. Colonoscopy showed coherent yellowish pseudomembranes covering large parts of the mucosa within the right colon (Figure A). By using the closed biopsy forceps, the membranes could easily be removed from the mucosal surface. The cleared mucosa revealed minute erosions but was otherwise largely normal on gross inspection (Video), as was the left-sided colonic mucosa. Biopsies were taken from the right and left colon and submitted for analysis in separate containers. Histology shows preserved crypt architecture, with diffusely increased mononuclear inflammation of the lamina propria. There is marked surface epithelial injury with vacuolization and detachment, which are visible already on low power (Figure B). The subepithelial collagen band is significantly thickened (>10 μm), as illustrated by trichrome staining (Figure C). Immunoreactivity for tenascin confirms diagnosis of collagenous colitis (Figure D). In accordance with the endoscopic picture, eruptive fibrinopurulent pseudomembranes emerge from superficial erosions in the right colon (Figure E), prompting final diagnosis of pseudomembranous collagenous colitis. Treatment with budesonide was initiated and resulted in clinical remission within 8 weeks. Collagenous colitis is a major subtype of so-called microscopic colitis, which has emerged as a major cause of chronic watery non-bloody diarrhea, particularly in elderly women. Diagnosis rests on histologic analysis of biopsies sampled from the right and left colon, with close clinical correlation.1Münch A. Langner C. Microscopic colitis: clinical and pathologic perspectives.Clin Gastroenterol Hepatol. 2015; 13: 228-236Abstract Full Text Full Text PDF Scopus (54) Google Scholar Rare incomplete and variant forms have been reported. These include pseudomembranous collagenous colitis, which seems to be exceedingly rare; only a few case reports and small case series are available in the literature.2Treanor D. Gibbons D. O'Donoghue D.P. et al.Pseudomembranes in collagenous colitis.Histopathology. 2001; 38: 83-84Google Scholar, 3Yuan S. Reyes V. Bronner M.P. Pseudomembranous collagenous colitis.Am J Surg Pathol. 2003; 27: 1375-1379Google Scholar, 4Buchman A.L. Rao S. Pseudomembranous collagenous colitis.Dig Dis Sci. 2004; 49: 1763-1767Google Scholar The etiology of microscopic colitis is likely to be multifactorial, and drug intake may play a central role. Our patient was under long-term therapy with serotonin antagonists and reuptake inhibitors, which is of note because this type of antidepressant medication has been identified as a possible cause.5Masclee G.M. Coloma P.M. Kuipers E.J. et al.Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs.Am J Gastroenterol. 2015; 110: 749-759Google Scholar Still, the formation of pseudomembranes in otherwise typical collagenous colitis is extremely uncommon, and the pathogenesis is entirely unclear. It may be related to the severity of mucosal injury. As in our patient, C difficile toxin does not seem to play a major role.2Treanor D. Gibbons D. O'Donoghue D.P. et al.Pseudomembranes in collagenous colitis.Histopathology. 2001; 38: 83-84Google Scholar, 3Yuan S. Reyes V. Bronner M.P. Pseudomembranous collagenous colitis.Am J Surg Pathol. 2003; 27: 1375-1379Google Scholar In summary, pseudomembranous collagenous colitis is a distinct type of colitis that occurs in patients with chronic watery diarrhea. The disease should be considered in the differential diagnosis of colitis with pseudomembrane formation, including ischemic, toxin-induced, and infective etiologies. The easy detachment of the membranes that leaves mucosa behind, which is largely normal on gross inspection, may serve as a clue to accurate endoscopic diagnosis. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1NjdkZGM0Y2U4Nzk1ZmJlMTYzMjhmNWRmNmVjZDY1OSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NTQ5OTQ4fQ.QH9HzwNpEPF-lO8sHSHw4d9DSbq1fFeCnezv8EwoS881Wa226OUDO6d2PaBJ38OlbtiSXdquY7r4UzA9nZ9Lis24GZKKMmKvNKfmtUcOpSMrDupHekKnDZp6foj9tyv4n3COvwIVnLri53WgU63f2e2IZRG11ys7JWTuNXyDdZ8ceqrI-pc7hdJx4uoLwJ_G1DHtLR9WnMGopUBpSZoI9IiFrhmCsDMKv380eDkRYN6k-Rjk7SW5EPdmal-6wL-PJoT3O35k6RmrKUE8JeXQZHAlsJ4t2MxxlCDT96qoznhgsADuW_YTZ-pwOIAFm0exc-wx3RFjBKY0_LrPW9E8pA Download .mp4 (2.5 MB) Help with .mp4 files Video 1

A 71-year-old woman with primary myelofibrosis and esophageal varices was admitted for her first rubber band ligation procedure (platelet count, 58 000/mm3; partial thromboplastin time, 33.4 seconds; international normalized ratio, 1.28). At endoscopy, the esophageal mucosa was extremely fragile and difficult to aspirate into the ligation device. Three of the six rubber bands placed at the gastroesophageal junction slipped off, leaving oozing blood. This was treated by injecting 3.5 mL of polidocanol (Aethoxysklerol; Base Pharma, Gordon, NSW, Australia). During withdrawal of the endoscope, several areas with bluish bullous lesions (each < 1 cm in diameter) were observed in the upper two-thirds of the esophagus ([Fig. 1]). One of these lesions, which showed slight oozing of blood, was injected with 1 mL of polidocanol.

Histologic examination of gastric biopsies is crucial for determining the cause of gastritis. This prospective multicenter study was undertaken to investigate different histologic parameters arguing in favor or against the diagnosis of reactive gastropathy and to correlate findings with patient's symptoms and endoscopic findings. A total of 1123 individuals aged 15–93 years participated in a prospective multicenter study (histoGERD trial). Diagnosis of Helicobacter gastritis was made following the Updated Sydney System. Diagnosis of reactive gastropathy was based upon Dixon's parameters of foveolar hyperplasia, smooth muscle fibers in the lamina propria and vasodilatation and congestion of mucosal capillaries. Including paucity of acute and chronic inflammatory cells in analysis, a new score with visual analog scales for the diagnosis of reactive gastropathy was developed. All three histologic parameters in favor of the diagnosis of reactive gastropathy were positively associated with the endoscopic diagnosis of gastritis (p<0.001), yet negatively with Helicobacter infection (p<0.001). In contrast, presence of acute and chronic inflammatory cells in lamina propria was positively associated with Helicobacter infection (p<0.001), yet not with the endoscopic diagnosis of gastritis. Our score demonstrated strong association between histologic and endoscopic diagnoses (p<0.001), yet not with patient's symptoms. In conclusion, our data prove foveolar hyperplasia, smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy. The proposed score may enhance the diagnostic accuracy. It should be validated in future studies.

Multilayered epithelium is defined as hybrid epithelium with characteristics of both squamous and columnar epithelia. Our aim was to evaluate the clinicopathological significance of the lesion by relating its presence to various histological and clinical and/or endoscopic features indicating gastroesophageal reflux disease (GERD). A total of 1,071 individuals participated in a prospective cross-sectional study (576 females and 495 males; median age 53 years). Biopsy material was systematically sampled from the gastroesophageal junction. The histological diagnosis of esophagitis was made according to the Esohisto consensus guidelines. The endoscopic diagnosis of esophagitis was made according to the modified Los Angeles classification and the diagnosis of Barrett's esophagus according to Prague's C & M criteria, respectively. Multilayered epithelium was identified in 103 (9.6 %) individuals, frequently within or adjacent to the ducts of esophageal glands. Its presence was associated with increasing age (p < 0.001), high BMI (p = 0.026), hiatal hernia (p < 0.001), and the endoscopic diagnoses of esophagitis (p = 0.002) and Barrett's esophagus (p < 0.001). Upon histology, multilayered epithelium was associated with features of the squamous epithelium indicating GERD, particularly intercellular space dilation (p = 0.005), and presence of cardiac mucosa (< 0.001). For intestinal metaplasia, a trend was noted (p = 0.094). In conclusion, multilayered epithelium was observed in about every tenth individual undergoing upper gastrointestinal endoscopy. The association with histological and clinical features indicating GERD advocates the lesion as a promising new marker for reflux esophagitis. The association with cardiac mucosa and Barrett's esophagus suggests multilayered epithelium to be an intermediate step in the development of columnar metaplasia and, ultimately, Barrett's esophagus.