Johnathan Hollyfield

Optimal Histologic Cutpoints for Treatment Response in Patients With Eosinophilic Esophagitis: Analysis of Data From a Prospective Cohort Study

BACKGROUND AND AIMS: No prospective studies substantiate 15 eos/hpf as an appropriate endpoint for treatment of eosinophilic esophagitis (EoE). We aimed to determine a histologic cutpoint that identifies successful treatment of EoE by assessing symptomatic and endoscopic improvement. METHODS: We performed a prospective cohort study of 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy at the University of North Carolina from 2009 through 2014. At diagnosis of EoE and after 8 weeks of standard treatment, symptom and endoscopic responses were measured using a visual analogue scale and an endoscopic severity score (ESS), and eosinophil counts were assessed. Receiver operator curves and logistic regression models evaluated the histologic threshold that best predicted symptomatic and endoscopic response. For symptoms, analysis was limited to patients without baseline esophageal dilation. RESULTS: The mean eosinophil count at diagnosis was 124 eos/hpf, falling to 35 eos/hpf after treatment. The mean visual analogue scale decreased from 3.4 at baseline to 1.7 after treatment, and the mean ESS decreased from 3 to 1.6. Twenty‐nine patients had symptom responses (47%) and 34 had endoscopic responses (55%). Post‐treatment eosinophil count thresholds of 8, 15, and 5 eos/hpf best predicted symptom, endoscopic and combined responses, respectively. On logistic regression, decreasing eosinophil count was significantly associated with the probability of symptomatic (P = .01) and endoscopic response (P < .001). CONCLUSIONS: In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold.

Palladin expression is a conserved characteristic of the desmoplastic tumor microenvironment and contributes to altered gene expression

The stroma surrounding solid tumors contributes in complex ways to tumor progression. Cancer‐associated fibroblasts (CAFs) are the predominant cell type in the tumor stroma. Previous studies have shown that the actin‐binding protein palladin is highly expressed in the stroma of pancreas tumors, but the interpretation of these results is complicated by the fact that palladin exists as multiple isoforms. In the current study, the expression and localization of palladin isoform 4 was examined in normal specimens and adenocarcinomas of human pancreas, lung, colon, and stomach samples. Immunohistochemistry with isoform‐selective antibodies revealed that expression of palladin isoform 4 was higher in adenocarcinomas versus normal tissues, and highest in CAFs. Immunohistochemistry staining revealed that palladin was present in both the cytoplasm and the nucleus of CAFs, and this was confirmed using immunofluorescence staining and subcellular fractionation of a pancreatic CAF cell line. To investigate the functional significance of nuclear palladin, RNA Seq analysis of palladin knockdown CAFs versus control CAFs was performed, and the results showed that palladin regulates the expression of genes involved in the biosynthesis and assembly of collagen, and organization of the extracellular matrix. These results suggested that palladin isoform 4 may play a conserved role in establishing the phenotype of CAFs in multiple tumor types.

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS Few factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response. METHODS We collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (<15 eos/hpf) and non‐responders (≥15 eos/hpf). We performed sensitivity analyses for alternative histologic response definitions. Multivariate logistic regression was performed to identify predictive factors associated with response to therapy, which were assessed with area under the receiver operator characteristic (AUROC) curves. RESULTS Baseline dilation was the only independent predictor of non‐response (odds ratio [OR], 0.30; 95% CI, 0.10–0.89). When an alternate response (<1 eos/hpf) and non‐response (<50% decrease in baseline eos/hpf) definition was used, independent predictors of response status were age (OR, 1.08; 95% CI, 1.02–1.14), food allergies (OR, 12.95; 95% CI, 2.20–76.15), baseline dilation (OR, 0.17; 95% CI, 0.03–0.88), edema or decreased vascularity (OR, 0.20; 95% CI, 0.04–1.03), and hiatal hernia (OR, 0.07; 95% CI, 0.01–0.66). Using these 5 factors, we developed a predictive model that discriminated complete responders from non‐responders with an AUROC of 0.88. Baseline gene expression patterns were not associated with treatment response and did not change with different histologic response thresholds. CONCLUSIONS In an analysis of 97 patients with EoE, we found dilation to be the only baseline factor associated with non‐response to steroid treatment (<15 eos/hpf). However, a model comprising 5 clinical, endoscopic, and histologic factors identified patients with a complete response (<1 eos/hpf). A baseline gene expression panel was not predictive of treatment response at any threshold.

Northern Italy in the American South: Assessing interobserver reliability within the Milan System for Reporting Salivary Gland Cytopathology: Interobserver Reliability Within Milan System

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been proposed to standardize salivary gland fine‐needle aspiration (FNA) diagnoses. This study assessed salivary gland FNA results and risk of malignancy (ROM) rates at the University of North Carolina as well as the interobserver reliability (IOR) of the atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP) categories.

Association of mast cells with clinical, endoscopic, and histologic findings in adults with eosinophilic esophagitis

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