Hannah P. Kim

Burden of Gastrointestinal Disease in the United States: 2012 Update

BACKGROUND & AIMS Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiatives National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was

A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease

32.4 billion. CONCLUSIONS GI diseases are a source of substantial morbidity, mortality, and cost in the United States.

The Prevalence and Diagnostic Utility of Endoscopic Features of Eosinophilic Esophagitis: A Meta-Analysis

BACKGROUND Phenotypes of eosinophilic esophagitis (EoE) are not well-characterized. OBJECTIVE To describe clinical features of patients with EoE with predefined phenotypes, determine predictors of these phenotypes, and make inferences about the natural history of EoE. DESIGN Retrospective study. SETTING Tertiary-care center. PATIENTS Incident EoE cases from 2001 to 2011 that met consensus diagnostic guidelines. INTERVENTION Review of records. MAIN OUTCOME MEASUREMENTS Endoscopic phenotypes, including fibrostenotic, inflammatory, or mixed. Other groups of clinical characteristics examined included atopy, level of esophageal eosinophilia, and age of symptom onset. Multinomial logistic regression assessed predictors of phenotype status. RESULTS Of 379 cases of EoE identified, there were no significant phenotypic differences by atopic status or level of eosinophilia. Those with the inflammatory phenotype were more likely to be younger than those with mixed or fibrostenotic (13 vs 29 vs 39 years, respectively; P < .001) and less likely to have dysphagia, food impaction, and esophageal dilation (P < .001 for all). The mean symptom length before diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; P = .02). After multivariate analysis, age and dysphagia independently predicted phenotype. The odds ratio (OR) for fibrostenosis for each 10-year increase in age was 2.1 (95% CI, 1.7-2.7). The OR for dysphagia was 7.0 (95% CI, 2.6-18.6). LIMITATIONS Retrospective, single-center study. CONCLUSION In this large EoE cohort, the likelihood of fibrostenotic disease increased markedly with age. For every 10-year increase in age, the odds of having a fibrostenotic EoE phenotype more than doubled. This association suggests that the natural history of EoE is a progression from an inflammatory to a fibrostenotic disease.

Intestinal metaplasia recurs infrequently in patients successfully treated for Barrett's esophagus with radiofrequency ablation.

BACKGROUND & AIMS Endoscopic findings such as esophageal rings, strictures, narrow-caliber esophagus, linear furrows, white plaques, and pallor or decreased vasculature might indicate the presence of eosinophilic esophagitis (EoE). We aimed to determine the prevalence and diagnostic utility of endoscopic features of EoE. METHODS We conducted a systematic review and meta-analysis. PubMed, EMBASE, and gastrointestinal meeting abstracts were searched to identify studies that included more than 10 patients with EoE and reported endoscopic findings. Pooled prevalence, sensitivity, specificity, and predictive values were calculated using random- and mixed-effects models. RESULTS The search yielded 100 articles and abstracts on 4678 patients with EoE and 2742 without (controls). In subjects with EoE, the overall pooled prevalence was as follows: esophageal rings, 44%; strictures, 21%; narrow-caliber esophagus, 9%; linear furrows, 48%; white plaques, 27%; and pallor/decreased vasculature, 41%. Substantial heterogeneity existed among studies. Results from endoscopy examinations were normal in 17% of patients, but this number decreased to 7% when the analysis was limited to prospective studies (P < .05). Overall levels of sensitivity were modest, ranging from 15% to 48%, whereas levels of specificity were greater, ranging from 90% to 95%. Positive predictive values ranged from 51% to 73% and negative predictive values ranged from 74% to 84%. CONCLUSIONS There is heterogeneity among studies in the reported prevalence of endoscopic findings in patients with EoE, but in prospective studies at least 1 abnormality was detected by endoscopy in 93% of patients. The operating characteristics of endoscopic findings alone are inadequate for diagnosis of EoE. Esophageal biopsy specimens should be obtained from all patients with clinical features of EoE, regardless of the endoscopic appearance of the esophagus.

Early life exposures as risk factors for pediatric eosinophilic esophagitis.

OBJECTIVES:Radiofrequency ablation (RFA) of Barretts esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA.METHODS:We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence.RESULTS:Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54–1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55–1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence.CONCLUSIONS:In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ∼5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.

Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus.

Objectives: Few etiologic studies of eosinophilic esophagitis (EoE) have been conducted. Early life exposures have been shown to predispose to other allergic disease, but their role has not been assessed in EoE. The present study sought to explore early life exposures as possible risk factors for developing EoE in the pediatric population. Methods: This was a 2-phase case-control study conducted at the University of North Carolina. The first phase consisted of survey development for early life exposures via cognitive interview. In the second phase, a telephone-based questionnaire was administered to cases with EoE (n = 31) and 2 sets of controls, patients with gastroesophageal reflux disease, and siblings of nonsyndromic cleft lip/palate patients (n = 26 in each). Different controls were explored to identify controls reflective of the source population of the cases. Siblings of cleft lip/palate patients were identified as the more suitable control population. Odds ratios were calculated to evaluate the association between early life exposures and the development of pediatric EoE. Results: Early life exposures were associated with increased odds of developing pediatric-onset EoE. Antibiotic use in infancy was associated with 6 times the odds of having EoE (95% confidence interval 1.7–20.8). Cesarean delivery, preterm birth, and formula-only or mixed (infant formula and breast milk) feeding also have trends toward increased odds for developing EoE. Conclusions: A number of early life exposures may be associated with the development of EoE. These are potentially modifiable risk factors that if confirmed would have implications for improved understanding of EoE pathogenesis and disease prevention.

Focal endoscopic mucosal resection before radiofrequency ablation is equally effective and safe compared with radiofrequency ablation alone for the eradication of Barrett's esophagus with advanced neoplasia

BACKGROUND & AIMS The goal of radiofrequency ablation (RFA) for patients with Barretts esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely. METHODS We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia, total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation. RESULTS CEIM was achieved in 80% of patients, and complete eradication of dysplasia was achieved in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%; P = .045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm; P = .03), had incomplete healing between treatment sessions (45% vs 15%; P = 0.004), and underwent more treatment sessions (4 vs 3; P = .007). Incomplete healing was associated independently with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), postprocedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients who developed strictures were more likely to use nonsteroidal anti-inflammatory drugs than those without strictures (70% vs 45%; P = .04), have undergone antireflux surgery (15% vs 3%; P = .04), or had erosive esophagitis (35% vs 12%; P = .01). CONCLUSIONS RFA is highly effective and safe for treatment of BE with dysplasia or early stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. Nonsteroidal anti-inflammatory drug use, prior antireflux surgery, and a history of erosive esophagitis predicted stricture formation.

Vedolizumab treatment may reduce steroid burden and improve histology in patients with eosinophilic gastroenteritis

BACKGROUND EMR is commonly performed before radiofrequency ablation (RFA) for nodular dysplastic Barretts esophagus (BE). OBJECTIVE To determine the efficacy and safety of EMR before RFA for nodular BE with advanced neoplasia (high-grade dysplasia [HGD] or intramucosal carcinoma [IMC]). DESIGN Retrospective study. SETTING University of North Carolina Hospitals, from 2006 to 2011. PATIENTS 169 patients with BE with advanced neoplasia: 65 patients treated with EMR and RFA for nodular disease and 104 patients treated with RFA alone for nonnodular disease. INTERVENTIONS EMR, RFA. MAIN OUTCOME MEASUREMENTS Efficacy (complete eradication of dysplasia, complete eradication of intestinal metaplasia, total treatment sessions, RFA treatment sessions), safety (stricture formation, bleeding, and hospitalization). RESULTS EMR followed by RFA achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia in 94.0% and 88.0% of patients, respectively, compared with 82.7% and 77.6% of patients, respectively, in the RFA-only group (P = .06 and P = .13, respectively). The complication rates between the 2 groups were similar (7.7% vs 9.6%, P = .79). Strictures occurred in 4.6% of patients in the EMR-before-RFA group. compared with 7.7% of patients in the RFA-only group (P = .53). LIMITATIONS Retrospective study at a tertiary-care referral center. CONCLUSION In patients treated with EMR before RFA for nodular BE with HGD or IMC, no differences in efficacy and safety outcomes were observed compared with RFA alone for nonnodular BE with HGD or IMC. EMR followed by RFA is safe and effective for patients with nodular BE and advanced neoplasia.

Su1847 Decreasing Frequency of the Fibrostenotic Phenotype of Eosinophilic Esophagitis: Time Trends Over the Past Decade

Eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) are rare diseases characterized by marked eosinophilic infiltration of the gastrointestinal (GI) tract and symptoms which typically reflect the location(s) of GI involvement.1,2 Knowledge of these conditions is limited, and treatments, which are largely based on case series, most frequently involve corticosteroids. As long-term steroid treatment is fraught with complications, novel treatment options are needed. Vedolizumab is a humanized monoclonal antibody to the α4β7 integrin that blocks leukocyte migration into GI mucosa.3 Vedolizumab is approved for treatment of moderate to severe inflammatory bowel disease (IBD), and provides benefit via inhibition of gastrointestinal-homing of T lymphocytes.4 However, there is evidence that increased levels of eosinophils can be associated with IBD and may play a role in IBD pathogenesis, that the α4β7 integrin may play an important role in eosinophil localization in IBD, and that blocking α4β7 may inhibit eosinophil recruitment to intestinal mucosa.5,6 Based on this eosinophil effect, there is a strong rationale that vedolizumab may benefit patients with EG/EGE, but it has not yet been assessed in these conditions. Therefore, this study aimed to assess whether vedolizumab therapy is associated with improved clinical symptoms, endoscopic features, and histologic findings in patients with EG/EGE who failed to respond to prior therapies.

Tu1122 Predictors of “Difficult to Ablate” Barrett's Esophagus Among 244 Patients With Dysplasia or Early Cancer

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.