BACKGROUND & AIMS: Marginal ulceration, or ulceration at the gastrojejunal anastomosis, is a common complication of Roux-en-Y gastric bypass (RYGB). Acidity likely contributes to the pathophysiology, and proton pump inhibitors (PPIs) frequently are prescribed for treatment. However, patients with gastric bypass only have a small gastric pouch and rapid small-bowel transit, which limits the opportunity for capsule breakdown and PPI absorption. Soluble PPIs (open capsules [OCs]) might be absorbed more easily than intact capsules (ICs). We compared time to ulcer healing, number of endoscopic procedures, and use of health care for patients with marginal ulceration who received PPIs in OC vs IC form.

METHODS: We performed a retrospective study of 164 patients diagnosed with marginal ulceration who underwent RYGB at the Brigham and Women's Hospital from 2000 through 2015. Patients received high-dose PPIs and underwent repeat endoscopy every 3 months until ulcer healing was confirmed. We used time-to-event analysis with a Cox proportional hazards model to evaluate the association between mode of PPI administration and time to ulcer healing, in addition to Cox multivariate regression analysis. Total charge (procedural and maintenance) was determined by comparison of categorized charges incurred from time of ulcer diagnosis to resolution. The primary outcome was time to healing of marginal ulceration in RYGB patients receiving high-dose PPIs in OC vs IC form.

RESULTS: A total of 162 patients were included (115 received OC and 49 received IC). All patients were followed up until ulcer healing was confirmed. The median time to ulcer healing was 91.0 days for the OC group vs 342.0 days for the IC group (P < .001). OC was the only independent predictor of time to ulcer healing (P < .001) when we controlled for known risk factors. The number of endoscopic procedures (P = .02) and overall health care utilization (P = .05) were lower in the OC than the IC group.

CONCLUSIONS: Patients with marginal ulceration after RYGB who receive OC PPIs have shorter ulcer healing times, fewer endoscopic procedures, and use less health care resources compared with patients who receive IC PPIs. Given these results and the high prevalence of marginal ulceration in this patient population, the use of OC PPIs is a low-risk, low-cost alternative that should be considered.

BACKGROUND AND AIMS: Dyspepsia is frequently encountered by primary care providers (PCP) and gastroenterologists (GI). While esophagogastroduodenoscopy (EGD) may be useful, current guidelines suggest a proton pump inhibitor (PPI) trial and H. pylori (HP) test-and-treat before EGD for low-risk patients. This study aimed to evaluate pre-EGD management and endoscopic outcomes in this population.

METHODS: This was a retrospective cohort study of low-risk dyspepsia patients (age ≤55, no alarm features) undergoing EGD at an ambulatory endoscopy center from January 2011 to March 2012. Adherences to initial management guidelines (PPI trial and HP test-and-treat strategy before EGD) were compared between PCP and GI. Endoscopic and pathologic outcomes were assessed for all patients. Statistical analyses were performed using Chi-squared test (categorical variables) and Student's t test (continuous variables). This study received IRB approval (2011P001715).

RESULTS: A total of 309 low-risk patients underwent EGD for dyspepsia. Only 202 (65.4 %) had HP testing, and 220 (71.2 %) were trialed on any dose/length PPI pre-EGD, with no differences between PCP and GI. PPI exposure was similar between groups for all dose/duration except for trials ≥8 weeks of any dose (46.9 % GI vs 34.3 % PCP, p = 0.03) and high dose (32 % GI vs 18.7 % PCP, p = 0.01). Overall, only 178 (57.6 %) patients had both HP testing and any PPI exposure pre-EGD (56.6 % GI vs 59 % PCP, p = 0.73). Significant pathology was rare, with gastritis (46.6 %) and HP (17.2 %) being most common. No malignancy was found.

CONCLUSIONS: A significant proportion of low-risk dyspepsia patients did not receive any PPI trial or HP testing before EGD. Within this population, significant finding on EGD was rare, supporting the current noninvasive initial management guidelines for dyspepsia.

BACKGROUND: Combinations of reflux parameters (acid exposure time, AET; symptom association probability, SAP) on pH-impedance monitoring describe varying confidence in reflux evidence. We compared outcomes between phenotypes with distinct pre-identified reflux parameters.

METHODS: In this observational cohort study, patients undergoing pH-impedance testing over a 5-year period were phenotyped by strength of reflux evidence as strong (abnormal AET, positive SAP), good (abnormal AET, negative SAP), reflux hypersensitivity (RH, normal AET, positive SAP), and equivocal evidence of reflux, and compared to two historical institutional pH monitoring cohorts. Symptom burden (dominant symptom intensity, DSI; global symptom severity, GSS) was assessed by questionnaire at baseline and on prospective follow-up and compared between phenotypes.

KEY RESULTS: Of 94 patients tested off proton pump inhibitor (PPI) therapy, baseline symptom burden was highest with strong reflux evidence and lowest when equivocal (DSI: p = 0.01; GSS: p = 0.03 across groups). After 3.1 ± 0.2 years follow-up, symptomatic improvement with surgical or medical therapy was highest with strong or good evidence, and lowest when equivocal (DSI: p = 0.008; GSS: p = 0.005 across groups). This was most pronounced for typical symptoms (DSI: p = 0.001; GSS: 0.016 across groups), but not atypical symptoms (DSI: p = 0.6; GSS: p = 0.2). For testing on PPI therapy, only GSS followed a similar trend (GSS: p = 0.057, DSI: p = 0.3). Compared to historical cohorts with pH monitoring alone, equivocal evidence for reflux was partly replaced by RH, especially off PPI (p < 0.0001).

CONCLUSIONS & INFERENCES: Phenotyping gastroesophageal reflux disease by the strength of reflux evidence on pH-impedance testing off PPI efficiently stratifies symptomatic outcome, especially for typical symptoms, and could be useful in planning management.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia.

METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate).

RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (β-coefficient = 0.01, p = 0.04) remained associated with food impaction.

CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

BACKGROUND: Antireflux surgery (ARS) has been associated with improved lung transplant outcomes. Pre-transplant ARS has been shown in small studies to improve pulmonary function among transplant candidates with gastroesophageal reflux disease (GERD). Although early post-transplant ARS has been shown to be effective in reducing chronic rejection, the optimal timing of ARS in transplant recipients remains unclear. The aim of this study is to evaluate the time to early allograft injury among lung transplant recipients by timing of ARS.

METHODS: This was a retrospective cohort study of lung transplant recipients undergoing ARS before or after transplantation at a tertiary care center since 2007, with at least 1-year follow-up. Early allograft injury was defined clinically and histologically as acute rejection or lymphocytic bronchiolitis, occurring within the first year after transplantation. In accordance with prior studies, the cutoff between early and late post-transplant ARS was set at 6 months. Time-to-event analysis using the Cox proportional hazards model was applied to assess the relationship between timing of surgery and early allograft injury. Subjects not meeting this outcome were censored at 1 year in the time-to-event analysis. Fisher’s exact test for binary variables and Student’s t test for continuous variables were performed to assess for differences among the three groups: ARS pre-transplant, ARS early post-transplant, and ARS late post-transplant.

RESULTS: Forty-eight subjects (60% men, mean age 55) met the inclusion criteria for the study. Patient demographics, pre-transplant cardiopulmonary function, BMI, CMV status, and PPI exposure were similar between groups. Kaplan-Meier analysis demonstrated significantly increased early allograft injury in late post-transplant ARS patients compared with both pre-transplant (log-rank p = 0.007) and early post-transplant (log-rank p = 0.05) patients, as well as a significant trend across groups (log-rank p = 0.005). No significant difference between pre- and early post-transplant groups was noted. Three ARS failures were noted in the pre- and late post-transplant groups. Complications included one death due to aspiration pneumonia in a late post-transplant ARS recipient. No early post-transplant ARS patients experienced ARS failure or complications.

CONCLUSION: Late post-lung transplant ARS resulted in increased risk of early allograft injury compared to pre-transplant and early post-transplant ARS. Both pre- and early post-transplant ARS appear equally safe and effective in improving lung transplant outcomes. These findings support consideration of aggressive reflux testing and application of antireflux measures before or soon after transplantation to minimize the impact of reflux on allograft injury.

The upper esophageal sphincter constitutes an important anatomic and functional landmark in the physiology of pharyngeal swallowing. A variety of clinical circumstances may call for a dedicated evaluation of this mechanism, from the etiologic evaluation of indeterminate symptoms to the generation of complex locoregional therapeutic strategies. Multiple diagnostic tools exist for the assessment of pharyngeal swallowing generally and of upper esophageal sphincter function specifically, some well established and others not yet settled into routine practice. This report reviews five specific modalities for use in making this assessment, outlining the strengths, weaknesses, and logistical considerations of each with respect to its potential use in clinical settings. In many cases, these studies will provide complementary information regarding pharyngeal function, suggesting the relative advantage of a multimodal evaluation.

BACKGROUND: Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed.

METHODS: This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring.

KEY RESULTS: Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis.

CONCLUSIONS & INFERENCES: Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered.

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury.

METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time.

RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone.

CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis.

METHODS: This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders.

KEY RESULTS: A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF.

CONCLUSIONS & INFERENCES: Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients.