Food-Specific IgG4 Is Elevated Throughout the Upper Gastrointestinal Tract in Eosinophilic Esophagitis.

BACKGROUND: Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus. AIMS: To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms. METHODS: We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg. RESULTS: Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate. CONCLUSIONS: Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia.

Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis.

INTRODUCTION: We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge (CS) samples in eosinophilic esophagitis (EoE). METHODS: Esophageal biopsy (BX) samples from adult subjects with EoE were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE histologic scoring system. EPX staining and eos/hpf were compared (BX vs CS). RESULTS: CS EPX positivity correlated with eos/hpf (CS [ r = 0.82, P < 0.0001]; BX [ r = 0.65, P < 0.0001]) and EoE histologic scoring system (grade [ r = 0.62, P < 0.00001]; stage [ r = 0.61, P < 0.0001]). CS EPX identified subjects with active EoE (area under the curve = 0.86, P < 0.0001). DISCUSSION: The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Image Analysis of Eosinophil Peroxidase Immunohistochemistry for Diagnosis of Eosinophilic Esophagitis.

BACKGROUND: Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation. AIMS: The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE. METHODS: We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized, and EPX staining area/mm2 was quantified using image analysis. Paired samples were compared for changes in EPX staining in treatment responders and non-responders. RESULTS: Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm2 was significantly increased in EoE subjects and decreased in treatment responders. EPX quantification correlated strongly with eos/hpf (r = 0.84, p < 0.0001) and identified EoE subjects with high diagnostic accuracy (AUC 0.95, p < 0.0001). The optimal diagnostic EPX-positive pixel/area threshold was 17,379 EPX/mm2. Several controls (5/49) with < 15 eos/hpf on H&E staining exceeded this cutoff. CONCLUSIONS: EPX/mm2 correlates strongly with eos/hpf, accurately identifies subjects with EoE, and decreases in treatment responders. Automated quantification of intact eosinophils and their degranulation products may enhance pathologic assessment. Future studies are needed to correlate EPX/mm2 with symptoms, endoscopic findings, and esophageal distensibility.

Eosinophilic esophagitis: updates on key unanswered questions.

Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. In the last decade, there has been a dramatic increase in its prevalence for reasons that are not completely understood. The underlying pathophysiology involves an antigen-mediated TH 2 immune response that draws eosinophils to the esophagus, causing mucosal inflammation, esophageal remodeling, and fibrosis. This ultimately leads to esophageal dysfunction that most commonly manifests as dysphagia. In this review, we will discuss updates on key questions regarding the diagnosis and treatment of EoE.

Opioids Interfere With Deglutitive Inhibition Assessed by Response to Multiple Rapid Swallows During High-Resolution Esophageal Manometry.

INTRODUCTION: Normal response to multiple rapid swallows (MRS) during high-resolution esophageal manometry is deglutitive inhibition; opioids may interfere with this. The aim of this study was to evaluate the response to MRS in patients on opioids, not on opioids, and healthy controls. METHODS: Response to MRS was evaluated for complete vs impaired inhibition in 72 chronic opioid users, 100 patients not on opioids, and 24 healthy controls. RESULTS: Impaired deglutitive inhibition was significantly more frequent in chronic opioid users compared with patients not on opioids and healthy controls (54% vs 14% vs 0%; P < 0.0001). DISCUSSION: Impaired deglutitive inhibition during MRS is frequent in opioid users, supporting that opioids interfere with esophageal inhibitory signals.

Effect of bowel preparation volume in inpatient colonoscopy. Results of a prospective, randomized, comparative pilot study.

BACKGROUND: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy. METHODS: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). RESULTS: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01. CONCLUSION: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings. TRIAL REGISTRATION: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies. TRIAL REGISTRATION: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

Mucosal impedance for esophageal disease: evaluating the evidence.

Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies.

Response to multiple rapid swallows shows impaired inhibitory pathways in distal esophageal spasm patients with and without concomitant esophagogastric junction outflow obstruction.

Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. The normal response to multiple rapid swallows (MRS) is deglutitive inhibition of the esophageal body during the MRS sequence. Our aim was to compare the response to MRS in DES patients and healthy control subjects. Response to MRS during HRM was evaluated in 19 DES patients (8 with and 11 without concomitant esophagogastric junction outflow obstruction [EGJOO]) and 24 asymptomatic healthy controls. Patients with prior gastroesophageal surgery, peroral endoscopic myotomy, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, opioid medication use, and esophageal stricture were excluded. Response to MRS was evaluated for complete versus impaired inhibition (esophageal body contractility with distal contractile integral [DCI] > 100 mmHg-sec-cm during MRS), presence of post-MRS contraction augmentation (DCI post MRS greater than single swallow mean DCI), and integrated relaxation pressure (IRP). Impaired deglutitive inhibition during MRS was significantly more frequent in DES compared to controls (89% vs. 0%, P < 0.001), and frequency was similar for DES with versus without concomitant EGJOO (100% vs. 82%, P = 0.48). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs. 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3360.0 vs. 1238.9, P = 0.009). IRP was lower during MRS compared to single swallows in all patients, and IRP during MRS was normal in 5 of 8 patients with DES and EGJOO. Our study suggests that impaired deglutitive inhibition during MRS is present in the majority of patients with DES regardless of whether they have concomitant EGJOO, and future studies should explore the usefulness of incorporating response to MRS in the diagnosis of DES.

Removal of a Large Stone in the Upper Thoracic Esophagus.

Ingestion of a foreign body is a common occurrence. Flexible endoscopy is most commonly used for treatment, but certain large foreign bodies are more easily retrieved with rigid endoscopy. We present a technically challenging case of intentional ingestion of a large stone that required retrieval from the upper thoracic esophagus using rigid endoscopy. This case highlights the importance of alternative methods to manage large foreign bodies and of collaboration of medical subspecialties.

Eosinophilic esophagitis: imaging features with endoscopic and pathologic correlation.

OBJECTIVE: We aim to review the imaging features of eosinophilic esophagitis on fluoroscopy and present how they can correlate with endoscopic and pathologic findings. RESULTS: Eosinophilic esophagitis is a chronic immune-mediated disease that results in esophageal dysfunction. Upper esophagogastroduodenoscopy is high yield and required for biopsies to demonstrate the hallmark histologic findings of eosinophil-predominant inflammation. While esophagogastroduodenoscopy is currently mandatory for diagnosis, imaging findings can provide valuable information regarding the structural and functional properties of the esophagus. In addition, fluoroscopic studies may be very helpful in the setting of subtle findings and to evaluate fibrotic remodeling changes. CONCLUSION: Radiologic examinations are a valuable tool in the assessment of eosinophilic esophagitis and can highlight changes of fibrostenotic disease, as overall narrowing can be more conspicuous fluoroscopically than endoscopically. As the disease increases in prevalence, it is critical that physicians recognize this condition and facilitate diagnosis and treatment.

Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

Peppermint Oil to Improve Visualization in Screening Colonoscopy: A Randomized Controlled Clinical Trial.

BACKGROUND: Screening colonoscopy has been associated with reduced mortality from colorectal cancer by means of early detection and timely treatment. However, visualization during colonoscopy is often impaired since the colon is naturally prone to peristalsis and spasm. There is evidence to suggest benefit of topical peppermint oil in causing smooth muscle relaxation, thereby decreasing peristalsis. The aim of our study was to determine if peppermint oil helps reduce colonic spasticity so as to allow for better visualization during screening colonoscopy. METHODS: We performed a randomized controlled, double-blinded, clinical trial where patients undergoing screening colonoscopy were assigned to receive either peppermint oil or placebo. Once cecum was reached, 50 mL of either solution was directly injected via the working channel of the colonoscope. Colonic peristalsis, spasticity and bowel visibility were documented. Bowel preparation quality, withdrawal time and adenoma detection rate (ADR) were also assessed. Continuous variables were analyzed using t-test or Wilcoxon rank-sum test while categorical variables were compared using the two-way Chi-square test. RESULTS: Forty-eight patients were included, of whom 24 patients received peppermint oil and 24 received placebo. Mean Boston bowel preparation score (BBPS) was excellent for both groups (8 points vs. 7.9 points; P = 0.98). Both mean total colonoscopy time (17.8 min vs. 21.9 min; P = 0.07) and mean cecal intubation time (7.2 min vs. 10.3 min; P = 0.04) were shorter with peppermint oil as compared to placebo. Complete absence of bowel spasticity was observed among 58.3% patients in the peppermint oil group as compared to 45.8% patients in the placebo group (P = 0.05). More than 75% of bowel was visualized in 83% of patients in both groups (P = 0.56). Mean ADR was higher in the peppermint group as compared to the placebo group (45.8% vs. 37.5%; P = 0.56). CONCLUSION: Our study suggests that topical peppermint oil reduces bowel wall spasticity, which could lead to better visualization of the bowel during screening colonoscopy. Although use of peppermint oil was associated with better ADRs, these results did not achieve statistical significance. Larger sample size and use of alternative methods of peppermint oil administration allowing for more absorption time may establish stronger results.

Association of Total Fluid Intake and Output with Duration of Hospital Stay in Patients with Acute Pancreatitis.

BACKGROUND/AIMS: The aim of this study was to evaluate the association of fluid balance with outcomes in patients hospitalized with acute pancreatitis (AP). METHODS: This was a retrospective study of patients hospitalized between May 2008 and June 2016 with AP and a clinical order for strict recording of intake and output. Data collected included various types of fluid intake and output at 24 and 48 hours after admission. The primary outcome was length of stay (LOS). Analysis was performed using single-variable and multivariable negative binomial regression models. RESULTS: Of 1256 patients hospitalized for AP during the study period, only 71 patients (5.6%) had a clinical order for strict recording of intake and output. Increased urine output was associated with a decreased LOS at 24 and 48 hours in univariable analysis. An increasingly positive fluid balance (total intake minus urine output) at 24 hours was associated with a longer LOS in multivariable analysis. CONCLUSIONS: Few patients hospitalized for AP had a documented order for strict monitoring of fluid intake and output, despite the importance of monitoring fluid balance in these patients. Our study suggests an association between urine output and fluid balance with LOS in AP.

New Therapies for Hepatitis C Virus Infection.

Approximately 350 million people worldwide are infected with hepatitis C virus (HCV), which is associated with morbidity and mortality related to cirrhosis, hepatocellular carcinoma, or liver failure. Recently, vast improvements have been made with the development of direct-acting antiviral (DAA) agents, which are all-oral, are better tolerated than interferon-based treatment, and provide a sustained virologic response in more than 90% of treated patients. This article reviews the new therapies available for HCV infection, with a focus on patients who have chronic HCV with and without compensated cirrhosis. As DAA development continues, more attention will need to be given to special patient populations, specifically to patients who fail treatment due to emerging resistant strains. Considerable challenges yet to be overcome are incremental diagnosis of unidentified patients and linkage to care that is affordable and available to all patients.