Genetics of Motility Disorders: Gastroesophageal Reflux, Triple A Syndrome, Hirschsprung Disease, and Chronic Intestinal Pseudo-obstruction

Context.— Published reports have suggested an association of lymphocytic esophagitis (LyE) with gastroesophageal reflux disease (GERD) and primary motility disorders and have also shown that GERD and motility disorders frequently overlap. These findings make it difficult to determine the true relationship between LyE and GERD, which may be confounded by the presence of motility disorders with LyE. Objective.— To characterize patterns of lymphocytic inflammation in patients with GERD that have no motility abnormalities. Design.— We identified 161 patients seen at our institution from 1998 to 2014, who were diagnosed with GERD, had normal esophageal motility, and available esophageal biopsies. LyE was defined as peripapillary lymphocytosis with rare or absent granulocytes. CD4 and CD8 immunophenotype of lymphocytes was evaluated using immunohistochemistry. Results.— We found increased intraepithelial lymphocytes in 13.7% of patients with GERD. Two major patterns and 1 minor pattern of lymphocytic inflammation were observed as follows: (1) LyE (in 6.8% [11 of 161] of patients and typically focal), (2) dispersed lymphocytes in an area of reflux esophagitis (in 5.6% [9 of 161] and typically diffuse), and (3) peripapillary lymphocytes in an area of reflux esophagitis (in 1.2% [2 of 161]). CD8 T cells significantly outnumbered CD4 T cells in 91% of patients with lymphocytic esophagitis and 100% of patients with dispersed lymphocytes (9 of 9) or peripapillary lymphocytes (2 of 2) in the area of reflux esophagitis. Conclusions.— These findings suggest that LyE is one of the major patterns of lymphocytic inflammation in GERD. CD8 T-cell–predominant immunophenotype may be useful as a marker of GERD in the differential diagnosis of LyE.

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Silent Gastroesophageal Reflux Disease in Patients with Morbid Obesity Prior to Primary Metabolic Surgery

Obesity Surgery ◽

10.1007/s11695-020-04959-6 ◽

2020 ◽

Vol 30 (12) ◽

pp. 4885-4891

Author(s):

Ivan Kristo ◽

Matthias Paireder ◽

Gerd Jomrich ◽

Daniel M. Felsenreich ◽

Mario Fischer ◽

...

Keyword(s):

Morbid Obesity ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Metabolic Surgery ◽

Reflux Disease ◽

Esophageal Motility ◽

Esophageal Motility Disorders ◽

Objective Testing ◽

Motility Disorders ◽

Asymptomatic Patients

Abstract Purpose Long-term follow-up after sleeve gastrectomy (SG) revealed a high incidence of gastroesophageal reflux disease (GERD) frequently caused by preoperative silent pathologic reflux. We aimed to evaluate prevalence and phenotypes of GERD in asymptomatic patients with morbid obesity prior to metabolic surgery according to modern objective testing. Material and Methods Prospective collection of data including consecutive patients with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) prior to metabolic surgery was applied for this study between 2014 and 2019. Patients underwent clinical examinations, endoscopy, pH metry, and high-resolution manometry and were analyzed according to the Lyon consensus. Results Of 1379 patients undergoing metabolic surgery, 177 (12.8%, females = 105) asymptomatic individuals with a median age of 42.6 (33.8; 51.6) years and a median BMI of 44.6 (41.3; 50.8) kg/m2 completed objective testing and were included during the study period. GERD was diagnosed in 55 (31.1%), whereas criteria of borderline GERD were met in another 78 (44.1%). GERD was mediated by a structural defective lower esophageal sphincter (p = 0.004) and highlighted by acidic (p = 0.004) and non-acidic (p = 0.022) reflux episodes. Esophageal motility disorders were diagnosed in 35.6% (n = 63) of individuals with a novel hypercontractile disorder found in 7.9% (n = 14) of patients. Conclusion GERD affects a majority of asymptomatic patients with morbid obesity prior to primary bariatric surgery. Future longitudinal trials will have to reveal the clinical significance of esophageal motility disorders in patients with morbid obesity.

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Submucosal Supernumerary Smooth Muscle Coat: A Common Histologic Finding in Mowat–Wilson Syndrome With or Without Hirschsprung Disease

Pediatric and Developmental Pathology ◽

10.1177/1093526620925960 ◽

2020 ◽

Vol 23 (5) ◽

pp. 372-379

Author(s):

Mariko Suchi ◽

Casey M Calkins ◽

Ashish Chogle ◽

Jesse Steffan Bond ◽

Raj P Kapur

Keyword(s):

Smooth Muscle ◽

Circular Muscle ◽

Hirschsprung Disease ◽

Clinical Information ◽

Pathological Feature ◽

Glass Slides ◽

Intestinal Pseudo Obstruction ◽

System Disorder ◽

Rectal Biopsies ◽

Muscle Coat

Background Mowat–Wilson syndrome (MWS) is a multiorgan system disorder caused by ZEB2 (zinc finger E-box-binding homeobox 2) mutations or deletions. One common manifestation is constipation, and approximately half of the patients have Hirschsprung disease (HSCR). In addition to classic histologic features of HSCR, an unusual supernumerary intestinal muscle coat was recently reported in a patient of MWS with HSCR. A similar smooth muscle alteration, segmental additional circular muscle coat, had been described in the specimens from patients with intestinal pseudo-obstruction without MWS or HSCR. Method Rectal biopsies and rectosigmoidectomy specimens from MWS patients were identified by retrospective reviews of surgical pathology records. Routinely prepared glass slides were examined to determine whether any smooth muscle structural alteration was present. Clinical information was obtained by chart review. Results Six MWS patients were identified. A supernumerary smooth muscle coat in the submucosa was present in 3 of them, including 2 of the 4 patients with HSCR. Conclusion The structural anomaly, termed submucosal supernumerary smooth muscle coat, is not a syndrome-specific pathological feature. However, it appears to be more common than expected in MWS and is consistent with contemporary models for the roles of ZEB2 and related cell signaling pathways in the patterning of intestinal musculature during embryonic development.

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