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Sepehr, Alireza

Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.

Background: Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC). Methodology/Principal Findings: We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17–2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63–1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure. Conclusions/Significance: Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.