Publications

2018

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.

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.

Hathorn KE, Chan WW, Lo WK. Role of gastroesophageal reflux disease in lung transplantation.. World journal of transplantation. 2017;7(2):103-116. doi:10.5500/wjt.v7.i2.103

Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques.

Gavini S, Borges LF, Finn RT, et al. Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2017;29(5). doi:10.1111/nmo.13001

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF.

METHODS: This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic.

KEY RESULTS: Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction.

CONCLUSIONS & INFERENCES: MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF.

Schulman AR, Ryou M, Chan WW. A Novel Hands-Free Abdominal Compression Device for Colonoscopy Significantly Decreases Cecal Intubation Time: A Prospective Single-Blinded Pilot Study.. Journal of laparoendoscopic & advanced surgical techniques. Part A. 2017;27(6):564-570. doi:10.1089/lap.2016.0649

BACKGROUND: Colonoscopy outcome is limited by endoscope looping, which leads to patient discomfort, prolonged procedure, and increased sedation requirement. Traditional manual abdominal pressure is imprecise and manually intensive. A hands-free abdominal compression device (ACD) may improve colonoscopy outcome. We aimed to assess the effect of a novel ACD on colonoscopy outcomes compared to manual pressure.

MATERIALS AND METHODS: This was a prospective single-blinded study of patients undergoing outpatient colonoscopy. The ACD (N-Doe Pillow™) was applied on 50 consecutive patients. Endoscopists were blinded to device usage. Control cases using manual pressure were randomly selected in a 2:1 manner. Primary outcome was cecal intubation time. Secondary outcomes included sedation requirement and complications. Subgroup analyses evaluated ACD effect on endoscopists with different experiences and patients at higher risk of difficult colonoscopy. Fisher's exact and Student's t-tests were performed for univariate analyses. Multivariate analysis was performed using generalized linear regression.

RESULTS: Fifty patients undergoing colonoscopy with ACD assistance were compared to 100 matched controls. Mean cecal intubation time was significantly reduced in the ACD group compared to controls (6.38 minutes versus 11.8 minutes, P < .0001). Multivariate analysis showed that ACD use was independently associated with reduction in cecal intubation time (β-coeff: -4.11, P = .007). Subgroup analyses revealed a trend toward increased improvement in cecal intubation time among junior endoscopists and obese patients.

CONCLUSIONS: A novel, hands-free ACD significantly decreased cecal intubation time in this prospective, single-blinded, match-controlled study. A trend toward more improvement was seen among junior faculty, suggesting an application for trainees and/or endoscopists with smaller case volumes.

Schulman AR, Thompson CC, Odze R, Chan WW, Ryou M. Optimizing EUS-guided liver biopsy sampling: comprehensive assessment of needle types and tissue acquisition techniques.. Gastrointestinal endoscopy. 2017;85(2):419-426. doi:10.1016/j.gie.2016.07.065

BACKGROUND AND AIMS: EUS-guided liver biopsy sampling using FNA and, more recently, fine-needle biopsy (FNB) needles has been reported with discrepant diagnostic accuracy, in part due to differences in methodology. We aimed to compare liver histologic yields of 4 EUS-based needles and 2 percutaneous needles to identify optimal number of needle passes and suction.

METHODS: Six needle types were tested on human cadaveric tissue: one 19G FNA needle, one existing 19G FNB needle, one novel 19G FNB needle, one 22G FNB needle, and two 18G percutaneous needles (18G1 and 18G2). Two needle excursion patterns (1 vs 3 fanning passes) were performed on all EUS needles. Primary outcome was number of portal tracts. Secondary outcomes were degree of fragmentation and specimen adequacy. Pairwise comparisons were performed using t tests, with a 2-sided P < .05 considered to be significant. Multivariable regression analysis was performed.

RESULTS: In total, 288 liver biopsy samplings (48 per needle type) were performed. The novel 19G FNB needle had significantly increased mean portal tracts compared with all needle types. The 22G FNB needle had significantly increased portal tracts compared with the 18G1 needle (3.8 vs 2.5, P < .001) and was not statistically different from the 18G2 needle (3.8 vs 3.5, P = .68). FNB needles (P < .001) and 3 fanning passes (P ≤ .001) were independent predictors of the number of portal tracts.

CONCLUSIONS: A novel 19G EUS-guided liver biopsy needle provides superior histologic yield compared with 18G percutaneous needles and existing 19G FNA and core needles. Moreover, the 22G FNB needle may be adequate for liver biopsy sampling. Investigations are underway to determine whether these results can be replicated in a clinical setting.