PUBLICATIONS

2017

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).

Lo WK, Goldberg HJ, Wee J, Fisichella M, Chan WW. Both Pre-Transplant and Early Post-Transplant Antireflux Surgery Prevent Development of Early Allograft Injury After Lung Transplantation.. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2016;20(1):111-8; discussion 118.

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.

Ahuja NK, Chan WW. Assessing Upper Esophageal Sphincter Function in Clinical Practice: a Primer.. Current gastroenterology reports. 2016;18(2):7. doi:10.1007/s11894-015-0480-y

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.

Lo WK, Goldberg HJ, Burakoff R, Feldman N, Chan WW. Increased proximal acid reflux is associated with early readmission following lung transplantation.. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2016;28(2):251-9. doi:10.1111/nmo.12720

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.