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Background & Aims Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap; because they cannot be differentiated based on eosinophil counts alone, it can be a challenge to distinguish between these disorders. We aimed to characterize the clinical, endoscopic, and histologic features of EoE and GERD and identify factors that might be used to differentiate them. Methods We performed a retrospective case-control study on data collected from 2000 to 2007. Cases were patients of any age with EoE, as defined by recent consensus guidelines; controls were patients of any age with GERD. Clinical and endoscopic data were collected and all esophageal biopsy specimens were reassessed by gastrointestinal pathologists. Cases and controls were compared, unconditional logistic regression was performed to develop a model to predict EoE, and receiver operator characteristic curves were constructed. Results Data from 151 patients with EoE and 226 with GERD were analyzed. Compared to GERD, features that independently predicted EoE included younger age; symptoms of dysphagia; documented food allergies; observations of esophageal rings, linear furrows, white plaques, or exudates by upper endoscopy; an absence of a hiatal hernia, observed by upper endoscopy; a higher maximum eosinophil count; and the presence of eosinophil degranulation, observed in biopsy specimens. The area under the curve for this model was 0.934. Conclusions We identified a set of readily available and routinely measured variables that differentiate EoE from GERD. Use of this type of analysis with patients suspected to have EoE might lead to more accurate diagnoses.

Background Phenotypes of eosinophilic esophagitis (EoE) are not well characterized. Objective To describe clinical features of EoE patients 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 2001–2011 who met consensus diagnostic guidelines. Interventions n/a 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. Multinominal 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<0.001), and less likely to have dysphagia, food impaction, and esophageal dilation (p<0.001 for all). The mean symptom length prior to diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; p=0.02). After multivariate analysis, age and dysphagia independently predicted phenotype. The OR for fibrostenosis for each 10-year increase in age was 2.1 (1.7–2.7). The OR for dysphagia was 7.0 (2.6–18.6). Limitations Retrospective, single-center study. Conclusions In this large EoE cohort, the likelihood of fibrostenosing disease increased markedly with age. For every ten 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.

We performed a randomized trial to compare nebulized and viscous topical steroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n=25) received budesonide 1 mg twice daily—either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB)—for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P=.62). Post-treatment counts were 89 and 11 (P=.02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P<.005) and was inversely correlated with eosinophil count (R= −0.67; P=.001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.

Objectives Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy, and determine features that distinguish the two groups. Methods This prospective study conducted at University of North Carolina from 2009–2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-powered field (eos/hpf; hpf = 0.24mm2). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared. Results Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male, and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, while some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis. Conclusions Esophageal eosinophilia is common among patients undergoing EGD for dysphagia. While EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE prior to the PPI trial.

The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-A (TNF-A) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-A in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-A were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between known risk factors for colorectal neoplasia and circulating levels of inflammatory cytokines and associations between inflammatory cytokines and colorectal adenomas. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines, including older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-A and, to a lesser degree, with CRP. For IL-6, adjusted odds ratios (OR) for colorectal adenomas were 1.79 [95% confidence interval (CI), 1.19-2.69] for the second highest plasma level and 1.85 (95% CI, 1.24-2.75) for the highest level compared with the reference level. A similar association was found with TNF-A, with adjusted ORs of 1.56 (95% CI, 1.03-2.36) and 1.66 (95% CI, 1.10-2.52), respectively. Our findings indicate that systemic inflammation might be involved in the early development of colorectal neoplasia. [Cancer Res 2008;68(1):323-8]

Significant variability in diagnostic criteria for eosinophilic esophagitis exists, and in a large proportion of studies, criteria are not reported. Because of this lack of a common disease definition, conclusions drawn from the cumulative EoE literature should be viewed with caution. A consensus research-quality standard for diagnosis of eosinophilic esophagitis is needed.

The importance of antibody-mediated rejection (AMR) in ABO-compatible liver transplantation is controversial. Here we report a prospective series of liver recipients with a preoperative positive crossmatch. To establish the diagnosis of AMR in liver recipients, the criteria described for kidney allografts were adopted. In approximately 10% of 197 liver transplants, we observed a positive T and B cell flow crossmatch before transplantation. Fifteen of 19 patients converted to negative crossmatches early after transplantation and displayed normal liver function while they were on routine immunosuppression. Four patients maintained positive crossmatches. Three of the 4 met the criteria for AMR and showed evidence of graft dysfunction, the presence of donor-specific antibodies (DSAs), morphological tissue destruction with positive C4d linear staining on the graft sinusoidal endothelium, and improved function with attempts to eliminate DSAs. A persistently positive crossmatch after liver transplantation may lead to early, severe AMR and liver failure. C4d staining in the liver sinusoidal endothelium should alert one to the possibility of AMR. In our experience, patients with a positive crossmatch should have it repeated at 2 weeks and, if it is positive, again at 3 to 5 weeks. Recipients with an unknown preoperative crossmatch who develop early cholestasis of unclear etiology should be crossmatched or tested for the presence of DSAs to evaluate for AMR. Liver