Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

CONTEXT: - Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. OBJECTIVES: - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. DESIGN: - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical records from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. RESULTS: - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. CONCLUSIONS: - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

Utility of Intraoperative Frozen Sections during Thyroid Surgery.

Objective. To describe the usefulness of intraoperative frozen section in the diagnosis and treatment of thyroid nodules where fine needle aspirate biopsies have evidence of follicular neoplasm. Study Design. Retrospective case series. Methods. All patients have a fine needle aspirate biopsy, an intraoperative frozen section, and final pathology performed on a thyroid nodule after initiation of the Bethesda System for Reporting Thyroid Cytopathology in 2009 at a single tertiary referral center. Sensitivity, specificity, positive predictive value, and negative predictive value are calculated in order to determine added benefit of frozen section to original fine needle aspirate data. Results. The sensitivity and specificity of the frozen section were 76.9% and 67.9%, respectively, while for the fine needle aspirate were 53.8% and 74.1%, respectively. The positive and negative predictive values for the fine needle aspirates were 25% and 90.9%, respectively, while for the frozen sections were 27.8% and 94.8%, respectively. There were no changes in the operative course as a consequence of the frozen sections. Conclusion. Our data does not support the clinical usefulness of intraoperative frozen section when the fine needle aspirate yields a Bethesda Criteria diagnosis of follicular neoplasm, suspicious for follicular neoplasm, or suspicious for malignancy at our institution.

Targeting eNOS in pancreatic cancer.

Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in the pathogenesis of PDACs. In this study, we used genetically engineered mouse and human xenograft models to evaluate the consequences of targeting eNOS in PDACs. Genetic deficiency in eNOS limited the development of preinvasive pancreatic lesions and trended toward an extended lifespan in mice with advanced pancreatic cancer. These effects were also observed upon oral administration of the clinically evaluated NOS small molecule inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME). Similarly, other transgenic models of oncogenic KRas-driven tumors responded to l-NAME treatment. Finally, these results were recapitulated in xenograft models of human pancreatic cancer, in which l-NAME was found to broadly inhibit tumorigenic growth. Taken together, our findings offer preclinical proof-of-principle to repurpose l-NAME for clinical investigations in treatment of PDACs and possibly other KRas-driven human cancers.