Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD.

BACKGROUND: Type 2 diabetes mellitus (T2DM) resolves in >80% of patients after Roux-en-Y gastric bypass (RYGB). It has been hypothesized that foregut exclusion is mechanistically important to this observation. This study aimed to determine whether gastrogastric (GG) fistula, with a loss of foregut exclusion, is associated with T2DM relapse, and to assess whether closure of GG fistula is associated with T2DM resolution.

STUDY DESIGN: A matched cohort study of patients who experienced T2DM remission after RYGB. Cases (patients with GG fistula) were matched to controls (patients without GG fistula) based on age, BMI, weight regain, and duration from RYGB. Primary end point was T2DM relapse. Time-to-event analysis was performed to identify an association between GG fistula and time to T2DM resolution.

RESULTS: One hundred and twenty-six patients (42 cases and 84 controls) were included. Cases experienced a higher rate of T2DM relapse than controls (48% vs 13%; odds ratio 18; p < 0.0001). On multivariable analysis, GG fistula remained a significant predictor of T2DM relapse after controlling for sex and insulin use (odds ratio 6.3; p = 0.02). Of the 42 cases, 20 experienced T2DM relapse, with 1 spontaneous resolution. Of 19, thirteen underwent fistula revision and experienced a higher rate of T2DM resolution than the nonrevision group (69% vs 0%; odds ratio 27; p = 0.036). Time to T2DM resolution was shorter in the revision group compared with the nonrevision group (p = 0.006).

CONCLUSIONS: The RYGB patients with GG fistula have a higher rate of T2DM relapse, compared with those without GG fistula with similar BMI and weight regain. Successful fistula revision is associated with resolution of T2DM.

BACKGROUND/AIMS: Liver biopsy has traditionally been used for determining the degree of fibrosis, however there are several limitations. Endoscopic ultrasound (EUS) real-time elastography (RTE) is a novel technology that uses image enhancement to display differences in tissue compressibility. We sought to assess whether liver fibrosis index (LFI) can distinguish normal, fatty, and cirrhotic liver tissue.

METHODS: A total of 50 patients undergoing EUS were prospectively enrolled. RTE of the liver was performed to synthesize the LFI in each patient. Univariate and multivariable analyses were performed. Chi-square and t-tests were performed for categorical and continuous variables, respectively. A p-value of <0.05 was considered significant.

RESULTS: Abdominal imaging prior to endoscopic evaluation suggested normal tissue, fatty liver, and cirrhosis in 26, 16, and 8 patients, respectively. Patients with cirrhosis had significantly increased mean LFI compared to the fatty liver (3.2 vs. 1.7, p<0.001) and normal (3.2 vs. 0.8, p<0.001) groups. The fatty liver group showed significantly increased LFI compared to the normal group (3.8 vs. 1.4, p<0.001). Multivariable regression analysis suggested that LFI was an independent predictor of group features (p<0.001).

CONCLUSIONS: LFI computed from RTE images significantly correlates with abdominal imaging and can distinguish normal, fatty, and cirrhotic-appearing livers; therefore, LFI may play an important role in patients with chronic liver disease.

BACKGROUND/AIMS: Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in prelung transplant IPF patients.

METHODS: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes.

RESULTS: Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380).

CONCLUSION: Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients.

BACKGROUND: Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms.

METHODS: This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm within 90 min. The presence of GI symptoms and CDI resolution were assessed 8 weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical analyses.

RESULTS: Twenty recipients (58.3 years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p = 0.09).

CONCLUSIONS: FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.

BACKGROUND: Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain.

AIMS: To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation.

METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use.

RESULTS: A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications.

CONCLUSIONS: Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.