PUBLICATIONS

2017

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.

Nayor J, Maniar S, Chan WW. Appointment-keeping behaviors and procedure day are associated with colonoscopy attendance in a patient navigator population.. Preventive medicine. 2017;97:8-12. doi:10.1016/j.ypmed.2016.12.022

BACKGROUND: Patient navigator programs (PNP) have been shown to improve colonoscopy completion with demonstrated cost-effectiveness. Despite additional resources available to these patients, many still do not attend their colonoscopies. The aim of this study was to determine factors associated with colonoscopy attendance amongst patients in whom logistical barriers to attendance have been minimized through enrollment in a PNP.

METHODS: Retrospective case-control study of patients enrolled in a PNP for colonoscopy performed at a tertiary endoscopy center from 2009 to 2014. Cases were defined as patients who did not attend their first scheduled colonoscopy after PNP enrollment. Age- and gender-matched controls completed their first scheduled colonoscopy after PNP enrollment.

RESULTS: 514 subjects (257 cases, mean age 57.1years, 36.6% males) were included. Patients who attended their colonoscopy were less likely to be Spanish-speaking (64.6% vs 78.2%, p=0.0003) and uninsured (0.4% vs 3.9%, p=0.006). Attendance rates were significantly lower for screening colonoscopies compared to an indication of surveillance or diagnostic (45.5% vs 65.3%, p<0.0001). Fewer patients attended colonoscopies scheduled on Monday (39.2% vs 52.1%, p=0.04) and in December (10.7% vs 52.3%, p<0.0001). On multivariate analysis, poor appointment-keeping behaviors, including a prior missed colonoscopy (OR 0.20, 95% CI 0.10-0.39) or missed office visit (OR 0.44, 95% CI 0.26-0.73) and procedures scheduled on Mondays (OR 0.51, 95% CI 0.27-0.94) were negatively associated with attendance.

CONCLUSIONS: Appointment-keeping behaviors, in addition to insurance-status, language-barriers and medical comorbidities, influence colonoscopy attendance in a PNP population. Patients scheduled for colonoscopies on Mondays or in December may require more resources to ensure attendance.

Schulman AR, Chan WW, Devery A, Ryan MB, Thompson CC. Opened Proton Pump Inhibitor Capsules Reduce Time to Healing Compared With Intact Capsules for Marginal Ulceration Following Roux-en-Y Gastric Bypass.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017;15(4):494-500.e1. doi:10.1016/j.cgh.2016.10.015

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.

2016

Fiorenza JP, Tinianow AM, Chan WW. The Initial Management and Endoscopic Outcomes of Dyspepsia in a Low-Risk Patient Population.. Digestive diseases and sciences. 2016;61(10):2942-2948. doi:10.1007/s10620-016-4051-3

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.

Patel A, Sayuk GS, Kushnir VM, Chan WW, Gyawali CP. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation.. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2016;28(4):513-21. doi:10.1111/nmo.12745

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.

Mangla S, Goldin AH, Singal G, et al. Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.. Digestive diseases and sciences. 2016;61(9):2578-84. doi:10.1007/s10620-016-4190-6

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).