Opioid Exposure Differentially Impacts Esophageal Body Contraction Over the Lower Esophageal Sphincter.

BACKGROUND & AIMS: Studies with limited sample sizes have investigated association of chronic opioid use with motility disorders of esophagogastric junction and esophageal body peristalsis. Our aims were to use a large cohort of patients to assess (1) the impact of opioid exposure on clinical and manometric characteristics, and (2) the association of opioid exposure with higher long-term symptom burden. METHODS: Patients recruited from a tertiary medical center who underwent high-resolution manometry (HRM) between 2007 and 2018 were included. Demographics, opiate exposure, clinical symptoms, and HRM parameters were compared. Patient-Reported Outcomes Measurement Information System-Gastrointestinal swallowing domain (PROMIS-GI swallowing domain) and Eckardt score were administered via phone interviews in patients with hypercontractile esophagus (HE) or distal esophageal spasm (DES) to determine long-term symptom burden between opioid and nonopioid users. RESULTS: Our cohort included 4075 patients (869 with opiate exposure with median morphine milligram equivalent [interquartile range] of 30 [10-45]). Patients in the opioid group were significantly more likely to have dysphagia (65% vs 51%, P < .01) and diagnosis of DES (11% vs 5%, P < .01) and HE (9% vs 3%, P < .01). Partial opioid agonists were not associated with motility abnormalities. Patients on opioids had significantly higher symptom burden on median (interquartile range) follow-up of 8.9 years (5.8-10.4) post manometric diagnosis with median PROMIS-GI swallowing domain score of 21.5 (17-25) compared with the nonopioid group at 15 (9.8-21, P = .03). CONCLUSIONS: Nearly 2 of 3 patients with opioid exposure undergoing HRM have dysphagia and more than 25% of them with dysphagia as the primary symptom have a diagnosis of either DES or HE. Opioid users with spastic disorders have higher symptom burden long-term compared with nonopioid users.

Impedance and Histologic Characteristics of the Sub-Laryngeal Esophagus Distinguish Eosinophilic Esophagitis From Other Esophageal Disorders.

BACKGROUND & AIMS: The region of the esophagus 15-17 cm below the incisors, called the sub-upper esophageal sphincter (sub-UES), has not been characterized in adults with eosinophilic esophagitis (EoE) but appears different during endoscopy. We investigated how the sub-UES differs from the remaining esophagus in patients with EoE and aimed to determine whether these differences be used to distinguish patients with EoE from those with lichen planus. METHODS: We performed a prospective study of 14 patients with EoE, 7 patients with lichen planus (based on presence of Civatte bodies, dysphagia, and/or narrow esophagus with thin esophageal mucosa without signs of EoE), and 20 patients undergoing upper endoscopy for upper gastrointestinal or with dysphagia but without features of EoE (controls) at a single medical center from 2015 through 2018. Biopsies from the distal, middle, and sub-UES regions of the esophagus were analyzed by histology, quantitative PCR, and immunohistochemistry. We measured mucosal impedance (MI) in all subjects at the sub-UES and 2 cm, 5 cm, and 10 cm from the gastro-esophageal junction. RESULTS: Patients with EoE had significantly fewer eosinophils (median, 2 eosinophils/high-powered field [HPF]; range, 0-8 eosinophils/HPF) in sub-UES tissues compared with distal esophagus (median, 50 eosinophils/HPF; range, 22.5-60.8 eosinophils/HPF; P < .0001) or middle esophagus (median, 32 eosinophils/HPF; range, 19.3-60; P < .0001). Sub-UES tissues from patients with EoE had significantly less basal cell hyperplasia (P < .01), papillary elongation (P < .01), and dilated intercellular spaces (P < .01) than middle or and distal esophagus. MI in the sub-UES did not differ significantly between patients with EoE vs controls (P = .24), but was significantly lower in patients with lichen planus (median, 1344 ohms; range, 1046-1488) than patients with EoE (median, 2880 ohms; range, 2149-4858) (P < .001). mRNA and protein expression patterns did not differ significantly in the sub-UES of patients with EoE vs controls, except for expression of desmoglein-1, which was increased in sub-UES tissues from patients with EoE. CONCLUSIONS: Sub-UES tissues from patients with EoE differ in numbers of eosinophils, histologic features, and MI compared to controls or patients with lichen planus. These features might help to distinguish these 2 diseases.

Over-the-scope clip-assisted method for resection of full-thickness submucosal lesions of the gastrointestinal tract.

BACKGROUND AND STUDY AIMS: The over-the-scope clip (OTSC; Ovesco Endoscopy, Tübingen, Germany) is deployed after suctioning tissue into the cap. The tissue may then be resected endoscopically. The aim of this study was to evaluate the efficacy and safety of the OTSC for the endoscopic resection of gastrointestinal tumors. PATIENTS AND METHODS: This was a retrospective, observational cohort study of patients undergoing endoscopic resection of submucosal lesions. RESULTS: Eight patients underwent endoscopic resection of neuroendocrine tumors (NETs) of the duodenum (n = 4), rectum (n = 1), or stomach (n = 2), or granular cell tumor (GCT) of the esophagus (n = 1). The mean size of the lesions was 13.4 mm (range 9 - 20 mm). Application of the clip was successful in all patients. A successful endoscopic resection was accomplished in all. A complete resection (R0) was accomplished in 7/8 patients (87.5 %). A full-thickness resection was achieved in 2/8 (25.0 %), one in a patient with a gastric NET and the other in a patient with GCT of the esophagus. There were no complications. CONCLUSIONS: This case series suggests that the OTSC system may be a valuable tool for the resection of submucosal lesions, but further prospective and randomized studies are necessary to assess the indications and outcome.

Autonomic and Enteric Profiling May Help Predict Response to Diverse Obesity Therapies.

PURPOSE: Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies. MATERIAL AND METHODS: We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45 years, weight 129.7 kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1 year and in some up to 5 years; classified as < or > /= 20% for each group. ANS testing included sympathetic adrenergic function by measuring reflex vasoconstriction and postural adjustment ratio. ENS was measured non-invasively using cutaneous low-resolution electrogastrogram. RESULTS: Percent weight loss was greater with the invasive (28.5%) than semi-invasive (9.1%) or non-invasive low-calorie diet (4.4%) (p < .001). Percent weight loss at 1 year (and up to 5 years) corresponded to the adrenergic measure of postural adjustment ratio (r = .42, p = .012), total pulse amplitude at rest (r = .56, p < .001), and electrogastrogram standing-to-rest difference (r = .33, p = .056). CONCLUSION: Baseline autonomic and enteric function measures correspond to percentage with loss in this pilot study using diverse weight loss methods. Autonomic and enteric profiling has potential clinical use for evaluation and treatment of obesity but needed larger controlled trials.

Inflammatory Markers and Mortality in Diabetic Versus Idiopathic Gastroparesis.

INTRODUCTION: Markers of systemic inflammation have been shown to be elevated in patients with gastroparesis (Gp). We hypothesized the presence of elevated markers of inflammation and/or coagulation can predict death in gastroparesis. METHODS: Retrospective evaluation of 396 patients with symptoms of gastroparesis with baseline measures of inflammation and coagulation, using a database of patients from 2001 through 2011 followed for an additional 5 plus years. Patients were divided into two groups; diabetic (DM; n=137) and non-diabetic (non-DM; n=259). Inflammation, evaluated by C-reactive protein (CRP), and coagulation by fibrinogen by factor VIII assays, was compared to patient mortality, reported as death during the follow-up period. RESULTS: Six DM and 13 non-DM patients died during the study period. DM patients had higher fibrinogen, CRP, and factor VIII levels of 454.0±135.2, 4.0±6.3, and 168±63.5, versus non-DM whose levels were 410.4±127.9, 2.6±4.9, 140.4±127.9, p=0.03, 0.001, and <0.001 respectively. Hypercoagulability risk differed by DM status (37% Vs. 29%, p=0.08). Compared to living non-DM, deceased non-DM/idiopathic patients had lower factor VIII (142.3±51.2 vs 117.7±40.3, p=0.07). The majority of deceased non-DM patients had abnormal fibrinogen (62%) but CRP and factor VIII were normal (80% and 85% respectively). CONCLUSIONS: In this sample of 396 patients with symptoms of gastroparesis, systemic inflammation and coagulopathy appear related to diabetes mellitus. Patients who died had markers of inflammation and coagulation that differed from those still alive. Further analysis may suggest a link between inflammation, hypercoagulability, and the mechanism for mortality in gastroparesis or as a marker of disease severity.

Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications.

BACKGROUND AND AIMS: Advanced liver fibrosis is an important predictor of liver disease progression and mortality, and current guidelines recommend screening for complications of cirrhosis once patients develop F3 fibrosis. Our study compared liver disease progression and survival in patients with stage 3 (F3) and stage 4 (F4) fibrosis on liver biopsy. METHODS: Retrospective study of patients with F3 or F4 on liver biopsy followed for development of liver disease complications (variceal bleeding, ascites, and hepatic encephalopathy); hepatocellular carcinoma, and survival (overall and transplant free survival). RESULTS: Of 2488 patients receiving liver biopsy between 01/02 and 12/12, a total of 294 (171 F3) were analyzed. Over a median follow up period of 3 years, patients with F4 (mean age 53 years, 63% male) compared to F3 (mean age 49 years, 43% male) had higher five year cumulative probability of any decompensation (38% vs. 14%, p<0.0001), including variceal bleed (10% vs. 4%, p = 0.014), ascites (21% vs. 9%, p = 0.0014), and hepatic encephalopathy (14% vs. 5%, p = 0.003). F4 patients also had lower overall 5-year survival (80% vs. 93%, p = 0.003) and transplant free survival (80% vs. 93%, p = 0.002). Probability of hepatocellular carcinoma in 5 years after biopsy was similar between F3 and F4 (1.2% vs. 2%, p = 0.54). CONCLUSIONS: Compared to F4 stage, patients with F3 fibrosis have decreased risk for development of liver disease complications and better survival. Prospective well designed studies are suggested with large sample size and overcoming the limitations identified in this study, to confirm and validate these findings, as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.

Correction: Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications.

[This corrects the article DOI: 10.1371/journal.pone.0197117.].