PUBLICATIONS

2019

Allegretti JR, Kassam Z, Fischer M, Kelly C, Chan WW. Risk Factors for Gastrointestinal Symptoms Following Successful Eradication of Clostridium difficile by Fecal Microbiota Transplantation (FMT). Journal of clinical gastroenterology. 2019;53(9):e405-e408. doi:10.1097/MCG.0000000000001194

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridioides difficile infection (CDI). Many patients report altered bowel habits including constipation, bloating, gas and loose stool post-FMT despite resolution of CDI, and the etiology remains unclear.

METHODS: This was a prospective cohort study of adult patients with recurrent CDI who underwent FMT (1) via colonoscopy with patient-selected donor stool, (2) via colonoscopy from a universal stool bank donor, or (3) via capsules from a universal stool bank. Reassessment occurred 8 weeks post-FMT. Those cured were assessed for gastrointestinal symptoms (bloating, loose stools, constipation). Multivariate logistic regression was performed to assess predictors of post-FMT gastrointestinal symptoms.

RESULTS: A total of 150 subjects underwent FMT for recurrent CDI, of which 68.7% (103) were female, mean age was 61.5 years±18.1 and 31 patients (20.7%) had preexisting irritable bowel syndrome. Thirty-six had FMT via colonoscopy with a patient-selected donor, 67 via colonoscopy with stool bank donors, and 47 via FMT capsules from stool bank donors. Among those cured, 41 (31.2%) had gastrointestinal symptoms post-FMT. The factors associated with symptoms included younger age (57.2 vs. 64.1 y, P=0.03), a baseline history of irritable bowel syndrome (36.6% vs. 13.3%, P=0.002) and preexisting inflammatory bowel disease (31.7% vs. 10%, P=0.002). Small bowel exposure to donor stool was not related to symptoms (63.4% vs. 62.2%, P=0.89).

CONCLUSIONS: Altered bowel habits are a consequence of CDI and are common after FMT. This study suggests that donor type and FMT delivery modality are not related to the presence of irregular gastrointestinal symptoms after FMT.

Hathorn KE, Bazarbashi AN, Sack JS, et al. EUS-guided biliary drainage is equivalent to ERCP for primary treatment of malignant distal biliary obstruction: a systematic review and meta-analysis. Endoscopy international open. 2019;7(11):E1432-E1441. doi:10.1055/a-0990-9488

Background and study aims  Although endoscopic retrograde cholangiopancreatography (ERCP) is standard of care for malignant biliary obstruction, endoscopic ultrasound-guided biliary drainage (EUS-BD) as a primary treatment has become increasingly utilized. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness and safety of EUS-BD for primary treatment of malignant biliary obstruction and comparison to traditional ERCP. Methods  Individualized search strategies were developed through November 2018 using PRISMA and MOOSE guidelines. A cumulative meta-analysis was performed by calculating pooled proportions. Subgroup analysis was performed for studies comparing EUS-BD versus ERCP. Heterogeneity was assessed with Cochran Q test or I 2 statistics, and publication bias by funnel plot and Egger's tests. Results  Seven studies (n = 193 patients; 57.5 % males) evaluating primary EUS-BD for malignant biliary obstruction were included. Mean age was 67.4 years (2.3) followed an average of 5.4 months (1.0). For primary EUS-BD, pooled technical success, clinical success, and adverse event (AE) rates were 95 % (95 % CI 91 - 98), 97 % (95 % CI 93 - 100), and 19 % (95 % CI 11 - 29), respectively. Among EUS-BD and ERCP comparator studies, technical and clinical success, and total AEs were not different with lower rates of post-ERCP pancreatitis and reintervention among the EUS-BD group. Conclusion  Primary EUS-BD is an effective treatment with few AE. Comparing EUS-BD versus ERCP, EUS-BD has comparable efficacy and improved safety as a primary treatment for malignant biliary obstruction. Further randomized trials should be performed to identify patient populations and clinical scenarios in which primary EUS-BD would be most appropriate.

2018

Gyawali P, Azagury DE, Chan WW, et al. Nonerosive reflux disease: clinical concepts. Annals of the New York Academy of Sciences. 2018;1434(1):290-303. doi:10.1111/nyas.13845

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.

Schulman AR, Lin M V, Rutherford A, Chan WW, Ryou M. A Prospective Blinded Study of Endoscopic Ultrasound Elastography in Liver Disease: Towards a Virtual Biopsy. Clinical endoscopy. 2018;51(2):181-185. doi:10.5946/ce.2017.095

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.

Borges LF, Jagadeesan V, Goldberg H, et al. Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis. Journal of neurogastroenterology and motility. 2018;24(3):395-402. doi:10.5056/jnm18023

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.

Jirapinyo P, Thompson AC, Kröner PT, Chan WW, Thompson CC. Metabolic Effect of Foregut Exclusion Demonstrated by the Impact of Gastrogastric Fistula on Recurrence of Diabetes. Journal of the American College of Surgeons. 2018;226(3):259-266.e1. doi:10.1016/j.jamcollsurg.2017.12.015

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.

Allegretti JR, Kassam Z, Chan WW. Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre-fecal Microbiota Transplantation Evaluation?. Digestive diseases and sciences. 2018;63(1):193-197. doi:10.1007/s10620-017-4864-8

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.

Lo WK, Goldberg HJ, Boukedes S, Burakoff R, Chan WW. Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation. Digestive diseases and sciences. 2018;63(2):403-410. doi:10.1007/s10620-017-4827-0

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.

2017

Patel RV, Winter RW, Chan WW, Sparks JA. Isolated gastric sarcoidosis: a rare entity. BMJ case reports. 2017;2017. doi:10.1136/bcr-2017-219682

We present a case of isolated granulomatous gastritis in a 21-year-old woman. Initial symptoms included nausea, vomiting and inability to tolerate oral intake. An upper oesophagogastroduodenoscopy revealed nodular and thickened mucosa with histological findings of granulomatous gastritis. Infectious, inflammatory and malignant causes were excluded prior to making a diagnosis of gastric sarcoidosis.

Nayor J, Rotman SR, Chan WW, Goldberg JE, Saltzman JR. Endoscopic Localization of Colon Cancer Is Frequently Inaccurate. Digestive diseases and sciences. 2017;62(8):2120-2125. doi:10.1007/s10620-017-4591-1

BACKGROUND: Colonoscopic location of a tumor can influence both the surgical procedure choice and overall treatment strategy.

AIMS: To determine the accuracy of colonoscopy in determining the location of colon cancer compared to surgical localization and to elucidate factors that predict discordant colon cancer localization.

METHODS: We conducted a retrospective cross-sectional study of colon cancers diagnosed on colonoscopy at two academic tertiary-care hospitals and two affiliated community hospitals from 2012 to 2014. Colon cancer location was obtained from the endoscopic and surgical pathology reports and characterized by colon segment. We collected data on patient demographics, tumor characteristics, endoscopic procedure characteristics, surgery planned, and surgery performed. Univariate analyses using Chi-squared test and multivariate analysis using forward stepwise logistic regression were performed to determine factors that predict discordant colon cancer localization.

RESULTS: There were 110 colon cancer cases identified during the study period. Inaccurate endoscopic colon cancer localization was found in 29% (32/110) of cases. These included 14 cases (12.7%) that were discordant by more than one colonic segment and three cases where the presurgical planned procedure was significantly changed at the time of surgery. On univariate analyses, right-sided colon lesions were associated with increased inaccuracy (43.8 vs 24.4%, p = 0.04). On multivariate analysis, right-sided colon lesions remained independently associated with inaccuracy (OR 1.74, 95% CI 1.03-2.93, p = 0.04).

CONCLUSIONS: Colon cancer location as determined by colonoscopy is often inaccurate, which can result in intraoperative changes to surgical management, particularly in the right colon.