INTRODUCTION Pancreaticoduodenectomy (PD) performed for pancreatic ductal adenocarcinoma (PDA) has a postoperative morbidity of 40–50%. In this study, we analyzed the impact of high grade complications after PD for PDA on overall survival. METHODS 596 patients that underwent PD for PDA between 2001–2009 were identified from a prospective database. Complications were defined and graded (1–5) as per our Institutional Surgical Secondary Events Program. High grade complications were defined as ≥ grade 3. Postoperative mortality (≤ 90 days) was excluded. Univariate and multivariate analyses were performed to identify factors associated with overall survival. RESULTS Median survival was 24 months. Overall complication rate was 51% (301/596). Low grade complications were recorded in 266 patients (45%) and high grade complications in 22% (n= 129). Our 90 day mortality was 3.7% (n= 22). Anastomotic fistula/ leak/abscess rate was 14% (n= 82). Multivariate Cox-Regression analysis identified node positivity, estimated blood loss (EBL) > 600 ml, length of stay (LOS) > 10 days, margin positivity and vascular procedures as predictors of decreased overall survival (p < 0.05). High grade complications were not associated with overall survival (p = 0.948). CONCLUSION In this study, the occurrence of high grade postoperative complications was not associated with overall survival.

BACKGROUND In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-induced hepatic injury is associated with increased splenic volume, thrombocytopenia, and decreased long-term survival. The current study investigates the relationship between change in splenic volume after preoperative chemotherapy and development of postoperative complications. STUDY DESIGN The study group consisted of 80 patients who underwent resection of CRCLM; half received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the other half did not (n = 40). The study group was compared with two control groups: a normal group composed of patients undergoing cholecystectomy for benign disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC) patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study group, the nontumoral liver was graded for steatosis and sinusoidal injury; operative and outcomes characteristics were also analyzed. RESULTS Before chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 ± 1.1 mL/kg, significantly higher than normal (2.5 ± 0.8 mL/kg; p < 0.001) and nonmetastatic CRC (2.6 ± 1.3 mL/kg; p < 0.05) patients, with higher splenic volume after 6 months of chemotherapy (4.2 ± 1.7 mL/kg; p < 0.01). After chemotherapy, splenic volume increase was associated with any perioperative complication (p < 0.01) and major complications (p < 0.05). Patients with ≥39% splenic volume increase (maximal chi-square test) were significantly more likely to have major complications (p < 0.01). Spleen volume changes were not correlated with change in platelet count (R2 = 0.03; p = 0.301). CONCLUSIONS In patients with CRCLM, the presence of liver metastases and chemotherapy are associated with higher splenic volume. Percent splenic volume increase after 6 months of chemotherapy can aid preoperative risk stratification, as it was an independent predictor of major postoperative complications.

While the spleen is an uncommon site of metastatic disease, in patients with a history of cancer, splenic masses selected for resection are frequently malignant.

Although early stage cholangiocarcinoma (CC) can be cured by surgical extirpation, the options for treatment of advanced stage CC are very few and suboptimal. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ability of oncolytic VACV GLV-1h68 to infect, replicate in, and lyse three human CC cell lines was assayed in vitro and in subcutaneous flank xenografts in athymic nude mice. In this study, we have demonstrated that GLV-1h68 effectively infects and lyses three CC cell lines (KMC-1, KMBC, and KMCH-1) in vitro. Expression of the viral marker gene ruc-gfp facilitated real-time monitoring of infection and replication. Furthermore in athymic nude mice, a single dose of GLV-1h68 significantly suppressed tumor growth. The treatment was well tolerated in all animals. Recombinant VACV GLV-1h68 has significant oncolytic ability against CC both in vitro and in vivo. GLV-1h68 has the potential to be used clinically as a therapeutic agent against CC.

Background Sorafenib is the standard systemic therapy for un-resectable or recurrent hepatocellular carcinoma (HCC) with minimal increase in survival. Therefore, there is a great need to develop novel therapies for advanced or recurrent HCC. One emerging field of cancer treatment involves oncolytic viruses that specifically infect, replicate within, and kill cancer cells. In this study we look at the ability of GLV-1h68, a recombinant vaccinia virus derived from the vaccine strain that was used to eradicate smallpox, to kill sorafenib-resistant HCC. Methods Four sorafenib-resistant HCC cell lines were generated by repeated passage in the presence of sorafenib. Median inhibitory concentration was determined for all cell lines. The infectivity, viral replication and cytotoxicity of GLV-1h68 were assayed for both parental and sorafenib-resistant HCC cells. Results Infectivity increased in a time and concentration dependent manner in all cell lines. All cell lines supported efficient replication of virus. No significant difference between the rates of cell death between the parental and sorafenib-resistant cell lines was observed. Conclusions Our results demonstrate that oncolytic vaccinia virus GLV-1h68 efficiently kills both parental and sorafenib-resistant HCC cell lines. This study indicates that patients who have failed treatment with sorafenib remain viable candidates for oncolytic therapy.