Barrett's esophagus and its association with hiatal hernia, cigarette smoking and colonic tumors

Introduction and Aims Barrett's esophagus (BE) is a premalignant condition to esophageal adenocarcinoma involving metaplasia of the esophageal epithelium. Since BE was first identified and described, it has been closely associated with hiatal hernia. The strength of the relationship has never been quantified, nor has the association, adjusted for confounders such as obesity and reflux, been examined. Male gender, obesity and reflux are well recognized risk factors for BE, however it is less certain what role environmental factors such as cigarette smoking play in the development of the condition. The association of BE with colonic tumors has also been speculated on but not clearly established. The aim of this thesis was to further explore the epidemiology of BE, specifically the relationship between BE and hiatal hernia, cigarette smoking and colonic tumors, through meta-analyses. Methods Three meta-analyses and systematic reviews were conducted, quantifying the relationship between BE and hiatal hernia, cigarette smoking and colonic tumors, respectively. Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched for observational studies of BE patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model for the association BE with hiatal hernia, cigarette smoking and colonic tumors. Results A positive relationship was observed between BE and hiatal hernia, which remained even after adjusting for reflux. Cigarette smoking was associated with an increased risk of BE. This was reflected in subgroup analyses of ever-, current- and former-smokers. BE was also associated with colonic tumors. The relationship was observed with both benign adenomatous tumors as well as with colorectal cancer, though it was stronger for colorectal cancer. Conclusions The association between BE and hiatal hernia is stronger for long segment BE when compared with short segment BE, and it appears to be independent of reflux. BE patients are also more likely to have ever smoked cigarettes. BE is associated with colonic tumors, with the association being stronger with colorectal cancer than with benign lesions

Tissue biomarkers detected by immunohistochemistry as diagnostic and prognostic indicators in human malignancies

Immunohistochemistry involves the use of labelled antobodies to detect and visualise the presence of selected antigens. It is widely used in the doagnosis of cancers in which specific antigens are either up-regulated or absent.«br /» We are studying newly-discovered biomarkers such as BAP1, and are suggesting novel uses for them in the diagnosis of cancers such as malignant mesothelioma, cholangiocarcinoma, and gynecological malignancies.«br /» We are also examining the role of microsatellite instability in the diagnosis of colorectal cancer and adrenocortical cancer

Somatostatin receptor SSTR-2a expression is a stronger predictor for survival than Ki-67 in pancreatic neuroendocrine tumors

Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18-87 years) and median tumor size was 25 mm (range 8-160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1-0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1-5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs.6 page(s

Immunoregulatory Forkhead box protein p3-positive lymphocytes are associated with overall survival in patients with pancreatic neuroendocrine tumors

Background: Forkhead box protein p3-positive (FoxP3⁺) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. Study design: This study aims to identify the prognostic significance of FoxP3⁺ Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3⁺ Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis. Results: A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3⁺ Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3⁺ tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3⁺ expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality. Conclusions: FoxP3⁺ Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3⁺ Tregs in PNETs.7 page(s

Fatal Powassan Encephalitis (Deer Tick Virus, Lineage II) in a Patient With Fever and Orchitis Receiving Rituximab.

Importance:Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective:To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants:Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure:Infection with Powassan virus. Main Outcomes and Measures:Results of individual assays compared retrospectively. Results:In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance:Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios

Clinical and pathological characteristics of 306 pancreatic adenocarcinoma patients.

<p>Clinical and pathological characteristics of 306 pancreatic adenocarcinoma patients.</p

Kaplan-Meier survival curve for 306 pancreatic ductal adenocarcinoma patients.

<p>Kaplan-Meier survival curve for 306 pancreatic ductal adenocarcinoma patients.</p