Gastric granulomas and Helicobacter pylori: An incidental relationship.

AIMS: Studies investigating the relationship between granulomatous gastritis (GG) and Helicobacter pylori infection have been largely inconclusive. This study was designed to determine whether the analysis of a very large number of patients would provide clearer answers evaluate the association between H. pylori infection and gastric granulomas. METHODS: We used a large national database of clinicopathological data to extract 1,673,086 patients who underwent esophagogastroduodenoscopy with gastric biopsies between 2008 and 2020. In a case-control study, we evaluated the occurrence of H. pylori infection in patients with and without gastric granulomas. We also explored other clinical and histopathological associations. RESULTS: H. pylori infection was present in 44 of 496 (8.9%) patients with gastric granulomas, compared to 158,949 (9.5%) in the control group (OR = 0.93, 95% CI = 0.68-1.26). Of the 129 patients with gastric granulomas, 50 had documented inflammatory bowel disease. CONCLUSIONS: The results of this study show that the prevalence of H. pylori infection in patients with gastric granulomas is essentially identical to that of controls with no evidence of granulomas or granulomatous disease. When patients with and without a plausible-known association for gastric granulomas were analyzed separately, the prevalence of H. pylori infection remained remarkably similar in GG patients and controls. Considering the very large numbers of patients with gastric biopsies analyzed in this study, we submit that there is no basis for suggesting that H. pylori is etiologically related to GG.

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

Inverse association of esophageal eosinophilia and Barrett esophagus.

BACKGROUND: The high frequency of gastroesophageal reflux symptoms reported in patients with eosinophilic esophagitis has suggested that the two disorders may be associated; however, few studies have systematically addressed this issue. GOALS: To determine the frequency of the simultaneous occurrence of esophageal eosinophilia and Barrett esophagus and define the clinical characteristics of patients with both conditions. STUDY: From a national pathology database of patients who had esophagogastroduodenoscopy with mucosal biopsies we extracted patients with a diagnosis of Barrett mucosa, eosinophilic esophagitis pattern of injury [(≥15 eosinophils/high-power field (HPF)], or both. We then evaluated their respective clinicopathologic associations. RESULTS: Among 233,662 unique patients evaluated during the study period, Barrett mucosa without increased eosinophils was diagnosed in 29,733 patients (12.7%; median age 63 y; 67.6% male); eosinophil counts of ≥15/HPF were recorded in 9509 patients without Barrett mucosa (4.1%; median age 44 y; 63.9% male). A simultaneous diagnosis of Barrett mucosa and ≥15 eosinophils/HPF in the squamous epithelium and was made in 404 unique patients (0.17%; median age 56 y; 79.5% male). The observed prevalence of the simultaneous occurrence of the two conditions was one third of that expected if they occurred independently (odds ratio 0.29; 95% confidence interval, 0.27-0.33; P<0.0001). CONCLUSIONS: These data suggest a strong inverse relationship between Barrett metaplasia and eosinophilic infiltrates in the esophageal mucosa. Although the influence of diagnostic bias cannot be excluded, the possibility that eosinophilic infiltrates in the esophageal mucosa prevent subsequent metaplastic changes may deserve to be explored.

Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with variable patient survival and few known prognostically relevant genomic biomarkers. To identify survival-associated genomic biomarkers, we performed high-resolution array-based comparative genomic hybridization (aCGH) on a large set of MPNSTs. EXPERIMENTAL DESIGN: Candidate gene alterations identified by aCGH in 38 MPNSTs were validated at the DNA, RNA, and protein levels on these same tumors and an independent set of 87 MPNST specimens. RESULTS: aCGH revealed highly complex copy number alterations, including both previously reported and completely novel loci. Four regions of copy number gain were associated with poor patient survival. Candidate genes in these regions include SOX5 (12p12.1), NOL1 and MLF2 (12p13.31), FOXM1 and FKBP1 (12p13.33), and CDK4 and TSPAN31 (12q14.1). Alterations of these candidate genes and several others of interest (ERBB2, MYC and TP53) were confirmed by at least 1 complementary methodology, including DNA and mRNA quantitative real-time PCR, mRNA expression profiling, and tissue microarray-based fluorescence in situ hybridization and immunohistochemistry. Multivariate analysis showed that CDK4 gain/amplification and increased FOXM1 protein expression were the most significant independent predictors for poor survival in MPNST patients (P < 0.05). CONCLUSIONS: Our study provides new and independently confirmed candidate genes that could serve as genomic biomarkers for overall survival in MPNST patients.

Adherence to biopsy guidelines for Barrett's esophagus surveillance in the community setting in the United States.

BACKGROUND & AIMS: Current surveillance guidelines for Barrett's esophagus (BE) recommend extensive biopsies to minimize sampling error. Biopsy practice patterns for BE surveillance in the community have not been well-described. We used a national community-based pathology database to analyze adherence to guidelines and to determine whether adherence was associated with dysplasia detection. METHODS: We identified 10,958 cases of established BE in the Caris Diagnostics pathology database from January 2002-April 2007. Demographic, pathologic, and endoscopic data were recorded. Dysplasia was categorized as low grade, high grade, or adenocarcinoma. Adherence was defined as > or =4 esophageal biopsies per 2 cm BE or a ratio > or =2.0. Generalized estimating equation multivariable analysis was performed to assess factors associated with adherence, adjusted for clustering by individual gastroenterologist. RESULTS: A total of 2245 BE surveillance cases were identified with linked endoscopy reports that recorded BE length and could be assessed for adherence. Adherence to guidelines was seen in 51.2% of cases. In multivariable analysis, longer segment BE was associated with significantly reduced adherence (3-5 cm, odds ratio [OR] 0.14, 95% confidence interval [CI] 0.10-0.19; 6-8 cm, OR 0.06, 95% CI 0.03-0.09; > or =9 cm, OR 0.03, 95% CI 0.01-0.07). Stratified by BE length, nonadherence was associated with significantly decreased dysplasia detection (summary OR 0.53, 95% CI 0.35-0.82). CONCLUSIONS: Adherence to BE biopsy guidelines in the community is low, and nonadherence is associated with significantly decreased dysplasia detection. Future studies should identify factors underlying nonadherence as well as mechanisms to increase adherence to guidelines to improve early detection of dysplasia.

A case of herpes esophagitis after fluticasone propionate for eosinophilic esophagitis.

BACKGROUND: A 19-year-old white woman presented with a 6-month history of progressively worsening dysphagia. INVESTIGATIONS: Esophagogastroduodenoscopy, esophageal biopsies followed by histological evaluation of biopsy samples including immunohistochemical staining for herpes simplex virus. DIAGNOSIS: Herpes esophagitis with concurrent eosinophilic esophagitis. MANAGEMENT: Valaciclovir and fluconazole.

Innate immunity genes influence the severity of acute appendicitis.

OBJECTIVE: Using acute appendicitis as a model, we tested the hypothesis that polymorphisms in genes involved in host defense can be associated with the severity of local infection-inflammation in humans. SUMMARY BACKGROUND DATA: Innate immunity is the body's front-line system for antimicrobial host defense. Local inflammation is a major innate immune mechanism for containing and destroying microbes, but it may also contribute to tissue injury. METHODS: We studied 134 patients with acute appendicitis treated at an urban hospital. We looked for associations between the severity of appendicitis (uncomplicated vs. perforated or gangrenous), plasma and peritoneal cytokine concentrations, and single nucleotide polymorphisms in genes involved in recognizing bacterial molecules [CD14 (-159 C-->T); TLR4 (896 A-->G)] and in mounting an inflammatory response [IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), IL-1beta (-31 C -->T)]. RESULTS: Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1beta, and TNF-alpha genes were not associated with the severity of appendicitis. A strong association was found between C-allele carriage at -174 in the IL-6 gene and decreased risk of complicated disease (adjusted odds ratio = 0.24, 95% CI = 0.07-0.76). Lower plasma and peritoneal fluid IL-6 concentrations in the IL-6 -174 C-carriers than in the GG homozygotes suggest that this polymorphism contributes to decreased IL-6 production in vivo. CONCLUSIONS: Polymorphism in the IL-6 gene was associated with the severity of appendicitis, even after adjustment for duration of symptoms. The risk for developing appendiceal perforation or gangrene may be determined, in part, by variation in the IL-6 gene.