No abstract

Oncolytic viruses cause direct cytolysis and cancer-specific immunity in preclinical models. The goal of this study was to demonstrate induction of functional anticancer immunity that can lyse target cancer cells in humans. Pexa-Vec (pexastimogene devacirepvec; JX-594) is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte-macrophage colony-stimulating factor (GM-CSF). Pexa-Vec demonstrated replication, GM-CSF expression, and tumor responses in previous phase 1 trials. We now evaluated whether Pexa-Vec induced functional anticancer immunity both in the rabbit VX2 tumor model and in patients with diverse solid tumor types in phase 1. Antibody-mediated complement-dependent cancer cell cytotoxicity (CDC) was induced by intravenous Pexa-Vec in rabbits; transfer of serum from Pexa-Vec-treated animals to tumor-bearing animals resulted in tumor necrosis and improved survival. In patients with diverse tumor types treated on a phase 1 trial, CDC developed within 4 to 8 weeks in most patients; normal cells were resistant to the cytotoxic effects. T lymphocyte activation in patients was evidenced by antibody class switching. We determined that patients with the longest survival duration had the highest CDC activity, and identified candidate target tumor cell antigens. Thus, we demonstrated that Pexa-Vec induced polyclonal antibody-mediated CDC against multiple tumor antigens both in rabbits and in patients with diverse solid tumor types.

Background/AimsThe bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactorial scoring system. As more data are needed before clinical application, we compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously.MethodsFifty consecutive acute pancreatitis patients were enrolled prospectively. Blood samples were obtained at admission and after 48 hours and imaging studies were performed within 48 hours of admission. The BISAP score was compared with the serum PCT, Ranson's score, and the acute physiology and chronic health examination (APACHE)-II, Glasgow, and Balthazar computed tomography severity index (BCTSI) scores. Acute pancreatitis was graded using the Atlanta criteria. The predictive accuracy of the scoring systems was measured using the area under the receiver-operating curve (AUC).ResultsThe accuracy of BISAP (≥ 2) at predicting severe acute pancreatitis was 84% and was superior to the serum PCT (≥ 3.29 ng/mL, 76%) which was similar to the APACHE-II score. The best cutoff value of BISAP was 2 (AUC, 0.873; 95% confidence interval, 0.770 to 0.976; p < 0.001). In logistic regression analysis, BISAP had greater statistical significance than serum PCT.ConclusionsBISAP is more accurate for predicting the severity of acute pancreatitis than the serum PCT, APACHE-II, Glasgow, and BCTSI scores.

The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.

An aortoesophageal fistula (AEF) is uncommon but is frequently fatal. Most cases are attributable to a thoracic aortic aneurysm. Other common causes include malignant intrathoracic neoplasm, foreign body ingestion, endovascular stent graft repair for thoracic aortic disease, and esophageal surgery. We report a case of an AEF that developed after chemo-irradiation and subsequent esophageal stent implantation in patient with non-small cell lung cancer. The patient underwent self expanding metallic esophageal stent implantation for an esophageal stricture after chemotherapy and radiotherapy. However, 1 month later, he presented with hematemesis. Chest computed tomography and aortography revealed a fistula from the descending thoracic aorta to the stented esophagus. The patient expired 36 hours after initial hematemesis. To our knowledge, this is the first confirmed report of an AEF in patient with a nonesophageal malignancy that had undergone chemo-irradiation and subsequent esophageal stent implantation. We recommend that special caution be exercised when performing esophageal stent implantation in patients who have received prior radiotherapy to the thorax including the esophagus.