Swathi Eluri

Burden of Gastrointestinal, Liver, and Pancreatic Diseases in the United States

BACKGROUND & AIMS Gastrointestinal (GI), liver, and pancreatic diseases are a source of substantial morbidity, mortality, and cost in the United States. Quantification and statistical analyses of the burden of these diseases are important for researchers, clinicians, policy makers, and public health professionals. We gathered data from national databases to estimate the burden and cost of GI and liver disease in the United States. METHODS We collected statistics on health care utilization in the ambulatory and inpatient setting along with data on cancers and mortality from 2007 through 2012. We included trends in utilization and charges. The most recent data were obtained from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. RESULTS There were 7 million diagnoses of gastroesophageal reflux and almost 4 million diagnoses of hemorrhoids in the ambulatory setting in a year. Functional and motility disorders resulted in nearly 1 million emergency department visits in 2012; most of these visits were for constipation. GI hemorrhage was the most common diagnosis leading to hospitalization, with >500,000 discharges in 2012, at a cost of nearly

Outcomes of Esophageal Dilation in Eosinophilic Esophagitis: Safety, Efficacy, and Persistence of the Fibrostenotic Phenotype

5 billion dollars. Hospitalizations and associated charges for inflammatory bowel disease, Clostridium difficile infection, and chronic liver disease have increased during the last 20 years. In 2011, there were >1 million people in the United States living with colorectal cancer. The leading GI cause of death was colorectal cancer, followed by pancreatic and hepatobiliary neoplasms. CONCLUSIONS GI, liver and pancreatic diseases are a source of substantial burden and cost in the United States.

Increased Risk of Esophageal Eosinophilia and Eosinophilic Esophagitis in Patients With Active Celiac Disease on Biopsy

Objectives:Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases, and to determine the frequency and predictors of requiring multiple dilations.Methods:We conducted a retrospective cohort study in the University of North Carolina EoE Clinicopathological Database from 2002 to 2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, and total number of dilations) and complications. Patients with EoE who had undergone dilation were compared with those who did not and also stratified by whether they required single or multiple dilations.Results:Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms before diagnosis (11.1 vs. 5.4 years, P<0.001). Ninety-five patients (58%) required >1 dilation (417 dilations total, mean of 4.4±4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58% or 95/164) required a second dilation. Of these individuals, 75% required repeat dilation within 1 year.Conclusions:Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms before diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within 1 year. These findings can be used to counsel patients with fibrostenotic complications of EoE.

Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: more similarities than differences.

BACKGROUND & AIMS The possible association between eosinophilic esophagitis (EoE) and celiac disease is controversial because prior results have been contradictory. We aimed to determine the relationship between EoE and celiac disease among patients with concomitant esophageal and duodenal biopsies. METHODS We conducted a cross-sectional study in a U.S. national pathology database by using data from January 2009 through June 2012. Our primary case definition was defined by the presence of esophageal eosinophilia with ≥15 eosinophils per high-power field. The crude and adjusted (for age and sex) odds of esophageal eosinophilia for patients with active celiac disease were compared with those without celiac disease. Sensitivity analyses were performed by using more stringent case definitions and by estimating the associations between celiac disease and reflux esophagitis and celiac disease and Barretts esophagus. RESULTS Of 292,621 patients in the source population, 88,517 with both esophageal and duodenal biopsies were studied. Four thousand one hundred one (4.6%) met criteria for EoE, and 1203 (1.4%) met criteria for celiac disease. Odds of EoE were 26% higher in patients with celiac disease than in patients without celiac disease (adjusted odds ratio [aOR], 1.26; 95% confidence interval [CI], 0.98-1.60). The magnitude of association varied according to EoE case definition, but all definitions showed a weak positive association between the 2 conditions. There was no association between celiac disease and reflux esophagitis (aOR, 0.95; 95% CI, 0.85-1.07) or Barretts esophagus (aOR, 0.89; 95% CI, 0.69-1.14) and celiac disease. CONCLUSIONS There is a weak increase in EoE in patients with celiac disease. This association strengthened with increasingly stringent definitions of EoE and was not observed for other esophageal conditions. In patients with celiac disease, concomitant EoE should be considered in the correct clinical setting.

The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus

Purpose of review The purpose of this study is to discuss the clinical, endoscopic and histologic features, pathogenesis and disease mechanisms of proton pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-REE), and to highlight similarities and differences with eosinophilic oesophagitis (EoE). Recent findings PPI-REE is a condition in which patients have clinical and histologic findings similar to EoE, but achieve complete remission with PPI treatment. More than one-third of patients who have oesophageal symptoms associated with oesophageal eosinophilia respond to PPI treatment. Emerging data elucidating the pathogenesis of PPI-REE have shown that Th2-related inflammatory factors such as interleukin (IL)-13, IL-5, eotaxin-3 and major basic protein (MBP) are elevated in PPI-REE, similar to EoE. PPI-REE also shares a genetic expression signature with EoE that reverses with PPI treatment. Mechanisms proposed to explain the PPI response include an acid-independent, anti-inflammatory action of PPIs and PPI-induced restoration of oesophageal barrier function. Summary Multiple features of PPI-REE overlap extensively with EoE. This raises the question of whether PPI-REE is merely a subtype of EoE rather than an independent condition. This similarity may have future implications for algorithms informing evaluation and treatment of oesophageal eosinophilia.

Diminishing Effectiveness of Long-Term Maintenance Topical Steroid Therapy in PPI Non-Responsive Eosinophilic Esophagitis

OBJECTIVES:Risk stratification in Barrett’s esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).METHODS:In this case–control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created.RESULTS:There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95.CONCLUSIONS:ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.Am J Gastroenterol advance online publication, 26 May 2015; doi:10.1038/ajg.2015.152

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression

OBJECTIVES: While topical corticosteroids are first‐line therapy for eosinophilic esophagitis (EoE), the data regarding long‐term effectiveness are lacking. We aimed to determine long‐term histologic and endoscopic outcomes of maintenance therapy in EoE steroid responders. METHODS: We performed a retrospective study of adults with EoE at UNC Hospitals who had initial histologic response (<15 eos/hpf) after 8 weeks of topical steroids, and maintained on therapy. Endoscopic and the histologic data were recorded at baseline and follow‐up endoscopies. Multivariable logistic regression was performed to assess loss of treatment response by steroid dose at recurrence, and Kaplan–Meier analysis to calculate durability of disease remission. RESULTS: Of 55 EoE patients with initial response to swallowed/topical fluticasone or budesonide over a median 11.7 months, 33 had at least two follow‐up EGDs. Of these patients, 61% had histologic loss of response and worse endoscopic findings. There was no difference in baseline steroid dose (P=0.55) between the groups, but those maintained on their initial dose had lower odds (OR: 0.10; 95% CI: 0.01, 0.90) of loss of response compared to those who had subsequent dose reduction. On survival analysis, 50% had loss of response to steroids by 18.5 months and 75% by 29.6 months. CONCLUSIONS: In adult EoE steroid responders, loss of treatment response is common, and is associated with a steroid dose reduction. Routinely lowering doses for maintenance steroids may provide inferior outcomes.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis

BackgroundTopical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE).AimsWe aimed to summarize published manuscripts that report outcomes of these therapies for EoE.MethodsWe performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis.ResultsSystematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2–96.0%] for fluticasone, 76.8% (95% PL 36.1–95.1%) for budesonide, and 69.0% (95% PL 31.9–91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0–56.7), 62.5 (95% PL 125.6 to −0.67, and 44.6 (95% PL 26.5–62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1–91.1%), 87.9% (95% PL 42.7–98.6%), and 87.3% (95% PL 64.5–96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations’ baseline eosinophil count and age.ConclusionsThe literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

Family history of inflammatory bowel disease among patients with ulcerative colitis: a systematic review and meta-analysis.

Background & Aims Topical corticosteroids or dietary elimination are recommended as first‐line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6‐food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. Methods We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort‐member level. Simulation parameters were defined by systematic review and meta‐analysis to determine the base‐case estimates and bounds of uncertainty for sensitivity analysis. Meta‐regression models included adjustment for differences in study and cohort characteristics. Results In the base‐case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5‐year time horizon (

Esophageal dilation with either bougie or balloon technique as a treatment for eosinophilic esophagitis: a systematic review and meta-analysis

9261.58 vs