Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.

Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

Transperitoneal repair of a juxtarenal abdominal aortic aneurysm and co-existent horseshoe kidney with division of the renal isthmus.

The co-existence of abdominal aortic aneurysm (AAA) and horseshoe kidney (HSK) is rare. We report a 67-year-old man with an expanding juxtarenal AAA associated with a HSK. The aneurysm had a severely angulated neck and contained a significant amount of mural thrombus. The isthmus of HSK closely lied over the aneurysm, making its exposure extremely difficult. The aneurysm was successfully repaired using transperitoneal approach with division of the renal isthmus and without any need for the renal artery reconstruction. Despite the potential complications, particularly renal insufficiency, associated with division of the renal isthmus and suprarenal cross-clamping of the abdominal aorta, in our case, post-operative period was uneventful and the patient's recovery was satisfactory.