Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote infection and spread of OVs, and significantly enhances anti-tumor immunity and improves the therapeutic index. Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8+ T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. In summary, OVs properly armed or in rational combinations are potent therapeutic cancer vaccines.

C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.

Background Surgical management of incidental Meckel’s diverticulum (MD) is a highly debated controversial issue that has never been discussed from the oncological standpoint. Objective To describe the epidemiology and risk of Meckel’s diverticulum cancer (MDC) and compare it with other ileal malignancies. Methods Data were obtained from 163 cases of MDC and 6214 cases of non-Meckelian ileal cancer, between 1973 and 2006, from the Surveillance, Epidemiology, and End Results database. Results Mean annual incidence was 1.44 (± 1.12) per 10 million population, with a 5-fold increase in the last few decades. Incidence increases with age, with a mean age at diagnosis of 60.6 (±15.1) years. Adjusted risk of cancer in the MD was at least 70 times higher than any other ileal site. Disease was localized in 67% at presentation and malignant carcinoids constituted the major histologic type (77%). One-third of patients have had lifetime occurrence of other malignancies and in 13% of these patients, MDC was the first malignancy. Median tumor size was 7 mm. Median overall survival was 173 months (95% confidence interval [CI], 124–221 months), with 1- and 5-year relative survival rates of 85.8% (95% CI, 76.9%-91.4%) and 75.8% (95% CI, 64.9%-83.8%), respectively. Cox proportional hazards model revealed that age, histologic type, and metastatic disease were independent factors affecting survival. Conclusions MD is a “hot-spot” or high-risk area for cancer in the ileum. With risk that increases with age and high possibility of curative resection with negligible operative mortality, incidental MD is best treated with resection.