Kelly E. Hathorn

Durability and Predictors of Successful Radiofrequency Ablation for Barrett's Esophagus

BACKGROUND & AIMS After radiofrequency ablation (RFA), patients may experience recurrence of Barretts esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication have been poorly described. METHODS We used the US RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of intestinal metaplasia (IM). We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. RESULTS Among 5521 patients, 3728 had biopsies 12 months or more after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. The average follow-up period was 2.4 years after CEIM. IM recurred in 334 (20%) and was nondysplastic or indefinite for dysplasia in 86% (287 of 334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared with patients without recurrence, patients with recurrence were more likely, based on bivariate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, the likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. CONCLUSIONS BE recurred in 20% of patients followed up for an average of 2.4 years after CEIM. Most recurrences were short segments and were nondysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.

Administrative coding is specific, but not sensitive, for identifying eosinophilic esophagitis.

The use of administrative databases to conduct population-based studies of eosinophilic esophagitis (EoE) in the United States is limited because it is unknown whether the International Classification of Diseases, Ninth Revision (ICD-9) code for EoE, 530.13, accurately identifies those who truly have the disease. The aim of this retrospective study was to validate the ICD-9 code for identifying cases of EoE in administrative data. Confirmed cases of EoE as per consensus guidelines (symptoms of esophageal dysfunction and ≥15 eosinophils per high-power field on biopsy after 8 weeks of twice daily proton pump inhibitor therapy) were identified in the University of North Carolina (UNC) EoE Clinicopathologic Database from 2008 to 2010; 2008 was the first year in which the 530.13 code was approved. Using the Carolina Data Warehouse, the administrative database for patients seen in the UNC system, all diagnostic and procedure codes were obtained for these cases. Then, with the EoE cases as the reference standard, we re-queried the Carolina Data Warehouse over the same time frame for all patients seen in the system (n=308,372) and calculated the sensitivity and specificity of the ICD-9 code 530.13 as a case definition of EoE. To attempt to refine the case definition, we added procedural codes in an iterative fashion to optimize sensitivity and specificity, and restricted our analysis to privately insured patients. We also conducted a sensitivity analysis with 2011 data to identify trends in the operating parameters of the code. We identified 226 cases of EoE at UNC to serve as the reference standard. The ICD-9 code 530.13 yielded a sensitivity of 37% (83/226; 95% confidence interval: 31-43%) and specificity of 99% (308,111/308,146; 95% confidence interval: 98-100%). These operating parameters were not substantially altered if the case definition required a procedure code for endoscopy or if cases were limited to those with commercial insurance. However, in 2011, the sensitivity of the code had increased to 61%, while the specificity remained at 99%. The ICD-9 code for EoE, 530.13, had excellent specificity for identifying cases of EoE in administrative data, although this high specificity was achieved at an academic center. Additionally, the sensitivity of the code appears to be increasing over time, and the threshold at which it will stabilize is not known. While use of this administrative code will still miss a number of cases, those identified in this manner are highly likely to have the disease.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett’s Esophagus

BACKGROUND & AIMS Complete eradication of Barretts esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Role of gastroesophageal reflux disease in lung transplantation

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.

A Multicenter Study Into Causes of Severe Acute Liver Injury

&NA; The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug‐induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single‐center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) to determine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.

106 Random Biopsies in Endoscopically Normal Esophagus Improve Yield of Recurrent Intestinal Metaplasia After Successful Radiofrequency Ablation

Background: Radiofrequency ablation (RFA) treatment for dysplastic Barretts Esophagus (BE) is associated with high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence of intestinal metaplasia (IM) in the esophagus is seen in approximately 25% of patients. The endoscopic findings associated with recurrence of IM are poorly described. Methods: We conducted a retrospective study of patients who underwent RFA for BE at University of North Carolina Hospitals between 2006 and 2013. Patients who achieved CEIM with at least two subsequent surveillance endoscopies were included. Patients were excluded if treated for non-dysplastic BE or invasive esophageal adenocarcinoma. Among patients with histologic evidence of recurrent BE during surveillance, we assessed the endoscopic findings associated with the recurrence. All patients had assessment of the distal esophagus by high-resolution white light and narrow band imaging, and all underwent regular biopsies according to a standard four-quadrant, q1cm procedure, as well as biopsy of endoscopically suspicious lesions. Endoscopic signs recorded included esophageal nodules (Paris classifications 0-Ip, 0-Is, 0-IIa), and areas suspicious for recurrent BE based on mucosal color changes. Statistical analysis was performed using SAS (version 9.3). Results: Of 302 patients, 178 met criteria for inclusion. These patients had 673 biopsy sessions (mean 3.8 sessions/pt). In total, 19 patients had histological recurrence of IM in the tubular esophagus (11%). Of these 19, only 5 (26%) had any endoscopic abnormality suggesting recurrence on endoscopy (table). The remaining 14/19 (74%, 95% confidence interval (CI): 49-91%) were found on routine surveillance biopsies. Of the 17 patients biopsied for a raised lesion or mucosal change suspicious for recurrent IM, only 5 (29%) actually had recurrence; 12 such biopsies were negative for recurrent IM. The median location for recurrent IM in targeted biopsies was 1 cm (Mean 2.5, S.D. 4.3) proximal to the top of the gastric folds; most (75%) specimens indicative of recurrence were from within 2 cm of the top of the gastric folds (figure). The odds ratio for recurrent disease in the setting of endoscopic signs was 17.7 (p < 0.001). Histologic grade was significantly higher for recurrence accompanied by endoscopic signs compared to those found on random biopsy (p = 0.016 for trend). Subsquamous recurrence was not identified in any biopsies regardless of endoscopic signs (95% CI: 0-23%). Conclusion: Histologic recurrence of IM following RFA was most common near the gastroesophageal junction. Subsquamous recurrence was not an important factor in recurrence. Most recurrences were found on routine, non-targeted biopsies, but endoscopic signs of recurrence including nodularity or apparent columnar-lined esophagus are associated with improved biopsy yield. Histology of Apparent and Non-Apparent Recurrence or Progression

Su1496 Esophageal Endoscopic Mucosal Resection: Efficacy and Safety At a Tertiary Care Center

liquid lifting and by stretching the mucosa. We report our experience of esophageal ESD comparing tunnel method versus a standard approach (circumferential incision first). Patients and Methods: We reviewed all the consecutive esophageal ESD performed in the unit between the 1St January, 2010 and July 31, 2012. These patients presented with a superficial neoplastic lesion of the esophagus, adenocarcinoma or squamous cell carcinoma from the middle and lower third, UT1N0 at EUS . Two techniques were used: the standard technique of ESD initially and then the technique of the “Tunnel” (10 patients). Results: 34 patients (mean age: 65.5 years) had an esophageal ESD in the period of time. Standard ESD was performed in 24 patients and Tunnel technique in 10 patients. In the “Standard” group, the mean dissected surface (calculated as the area of an ellipse) was 5.30 square cm versus 13.89 square cm in the group “Tunnel”. The average speed of dissection was faster for the “Tunnel” group with 17.2 square mm/min versus 5.5 square mm/min in the standard group (p 0.005). The ESD was the only technique used in “Tunnel” mode whereas mucosectomy was necessary to finalize standard ESD in 2 cases. Esophageal ESD was en bloc in 100% of cases in the “Tunnel” group versus 95.8% (one case in piece meal) in the standard approach. R0 resection (in depth and lateral margins in sano) was obtained in 90% of the “Tunnel” group versus 83.7% with the standard technique. Complications resolved conservatively: 2 immediate bleedings in the standard group, and one sub cutaneous emphysema in the “Tunnel” group without visible perforation. Conclusion: ESD with “Tunnel” method is an interesting option in the endoscopic management of superficial neoplastic lesions of the esophagus. It is faster than usual technique without more complications.

Su1022 What Is the Histology of Subsquamous Intestinal Metaplasia (SSIM) in Patients With Prior Radiofrequency Ablation (RFA) for Treatment of Barrett's Esophagus (BE)? Results From the U.S. RFA Registry

What Is the Histology of Subsquamous Intestinal Metaplasia (SSIM) in Patients With Prior Radiofrequency Ablation (RFA) for Treatment of Barretts Esophagus (BE)? Results From the U.S. RFA Registry Kelly E. Hathorn, William J. Bulsiewicz, Ronald E. Pruitt, Gary W. Chmielewski, Ryan D. Madanick, F Scott Corbett, Richard I. Rothstein, Charles J. Lightdale, George Triadafilopoulos, Nicholas J. Shaheen

Su1849 Is Low Body Mass Index a Risk Factor for Eosinophilic Esophagitis

Background: Separate phenotypes of eosinophilic esophagitis (EoE) based on an inflammatory, fibrotic, or mixed appearance have recently been described, but the trends in these phenotypes over time is unknown. Aim: To describe the number of EoE patients with inflammatory, fibrostenotic, and mixed phenotypes over the past decade, determine time trends, and explore reasons for any change. Methods: This was a retrospective study of the University of North Carolina EoE Clinicopathologic database over the past decade, from 2001-2011. Subjects with an incident diagnosis of EoE who met consensus guidelines were included. All had symptoms of esophageal dysfunction, ≥15 eos/hpf (hpf area=0.24 mm2), and did not respond to a PPI trial. The phenotypes were defined as fibrostenotic if there were esophageal rings, narrowing, or strictures and no evidence of linear furrows or white plaques; as inflammatory if there were furrows, plaques, or a normal esophagus and no evidence of fibrostenotic changes; and as mixed if there were a combination of findings. The proportions of phenotypes per year were calculated. Results: Of 374 EoE cases (mean age 25, range 6 mos-82 yrs; 73% male; 81% white; mean eosinophil count 86, range 15609), 134 (36%) had an inflammatory phenotype, 163 (43%) were mixed, and 77 (21%) were fibrostenotic. There was a significant change in the proportion of phenotypes over time (Figure). In 2001, 50% of patients were fibrostenotic, 50% were inflammatory, and none were mixed. In 2011, just 12% were fibrostenotic with 29% inflammatory and 59% mixed (p=0.002). There was no significant change in duration of symptoms prior to the diagnosis of EoE over this time frame (mean 8 yrs in 2001, 6 years in 2006, and 10 years in 2011; p=0.15). The proportion of patients with a endoscopically normal appearing esophagus decreased over this time frame (50% normal in 2001-2002, 16% normal in 2006, and 10% normal in 2001; p=0.05). The age at diagnosis of EoE did not change substantially between 2006 and 2011 (mean 27.7 vs 27.6 yrs; p=0.36). Conclusions: Over the past decade, the proportion of patients with a purely fibrostenotic phenotype of EoE has significantly decreased. This trend does not appear to be explained by a decrease in the length of symptoms prior to diagnosis of EoE or with EoE diagnosed in younger patients. It may be due to increased awareness of the endoscopic findings of EoE and recognition of subtle furrows and plaques with higher resolution endoscopes.