Immune checkpoint blockade (ICB) with programmed cell death protein-1(PD-1)/programmed death ligand -1(PD-L1) antibodies has revolutionized the management of several cancers, especially non-small cell lung cancer, melanoma, urothelial, and renal cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with high morbidity and mortality. Based on available data, it’s obvious that ICB has limited success in PDACs, which can be explained by the low immunogenicity and immunosuppressive tumor microenvironment of these tumors. In this review article, we focus on PD-L1 expression and microsatellite instability (MSI) in PDAC, and their roles as prognostic and predictive markers. We also discuss data supporting combination therapies to augment cancer immunity cycle. Combining anti-PD-1/PD-L1 agents with other modalities such as vaccines, chemotherapy, and radiation could potentially overcome resistance patterns and increase immune responsiveness in PDAC.

Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains. We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo. We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice. The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice.

Introduction: Patients with paraesophageal hernias often present secondary to chronic symptomatology. Infrequently, acute intestinal ischemia and perforation can occur as a consequence of paraesophageal hernias with potentially dire consequences. Case presentation: An 86-year-old obtunded male presented to the emergency department with hypotension and severe back and abdominal pain. An emergency abdominal CT scan was ordered with a presumptive diagnosis of ruptured abdominal aortic aneurysm. CT topograms revealed extensive free intra-abdominal air and herniated abdominal viscera into the right hemithorax. Prior to completion of the CT study, the patient sustained a cardiopulmonary arrest. Surgery was consulted, but the patient was unable to be revived. Post-mortem examination revealed gross contamination within the abdomen and a giant, incarcerated, hiatal hernia with organoaxial volvulus and ischemic perforation. Conclusion: Current recommendations call for prompt repair of giant hiatal hernias before they become symptomatic due to the increased risk of strangulation. Torsion of the stomach in large hiatal hernias frequently leads to a fatal complication such as this warranting elective repair as soon as possible.

RRH: Rural and Remote Health. Published article number: 2668 - Colorectal cancer outcome inequalities: association between population density, race, and socioeconomic status