Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Outcomes from a single tertiary center.

BACKGROUND: Multivisceral resection as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) may be required in order to achieve optimal debulking. This study aimed to assess perioperative and long-term outcomes of the most extensive CRS/HIPEC procedures. METHODS: All patients who underwent CRS/HIPEC at our institution between March 2007 and July 2014 were retrospectively reviewed. Patients undergoing extreme cytoreduction (n = 50), defined as a resection of ≥5 organs or ≥3 bowel anastomoses, were compared with patients who underwent less extensive procedures (n = 219). RESULTS: Complete cytoreduction (CC score ≤1) was achieved in 76% of the extreme CRS/HIPEC group, which included patients with colorectal cancer (CRC, n = 17), appendiceal adenocarcinoma (n = 20), gastric cancer (n = 6), and low-grade appendiceal neoplasm (n = 3). When compared with other patients undergoing CRS/HIPEC, the extreme CRS/HIPEC group had higher median PCI score, increased intraoperative blood loss, longer duration of surgery and longer hospital stay (all p values < 0.001). Major 30-day morbidity was significantly higher among the extreme CRS/HIPEC group (34% vs. 17.4%, p = 0.008) and there was also a trend towards higher 90-day mortality (12% vs. 5.1%, p = 0.07). Median disease free survival and overall survival in CRC patients undergoing extreme CRS/HIPEC was poorer (4.1 vs. 14.3 months, p = 0.01 and 10.1 vs. 43.8 months, p < 0.001, respectively). Extreme CRS/HIPEC was found to independently predict decreased overall survival in CRC patients. CONCLUSIONS: Extreme multivisceral resection as part of CRS/HIPEC is associated with higher major morbidity and inferior oncologic outcomes; therefore CRS/HIPEC provides the best outcomes in patients with fewer organs involved.

Intratumoral delivery of adenovirus-mediated interleukin-12 gene in mice with metastatic cancer in the liver.

Clinical trials of recombinant human interleukin-12 (rhIL-12) delivered by intravenous administration have shown dose-limiting toxicities with limited tumor responses at the doses tested. We have previously reported that intratumoral injection of an adenovirus vector expressing murine interleukin-12 (Adv.RSV-mIL-12) was effective in inducing antitumor immune responses, tumor regression, and long-term survival in mice with established metastatic cancer in the liver. We now report additional studies in the same murine tumor model to assess the safety of intratumoral Adv.RSV-mIL-12 injection. At vector doses that were previously shown to be therapeutically effective, no inflammation in the liver or lungs, and no significant elevations in serum creatinine and aminotransferases were seen after vector injection. Serum elevations of IL-12 and interferon-gamma (IFN-gamma) were 17- and 19-fold lower than peak levels after intravenous recombinant IL-12 at the maximal tolerated dose in clinical trials. No elevations in serum proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha) were noted up to 2 weeks after vector injection. No systemic dissemination of the vector was detected on polymerase chain reaction (PCR) assays at therapeutically effective vector doses. At higher supratherapeutic vector doses of Adv.RSV-mIL-12, however, inflammation in the liver and lungs with elevation in serum aminotransferases were seen, but not in controls injected with the equivalent particle number of an empty adenoviral vector. These results support the cautious testing in patients with hepatic metastases of adenovirus mediated IL-12 gene delivery by intratumoral injection.

Comparative outcomes of elderly stage I lung cancer patients treated with segmentectomy via video-assisted thoracoscopic surgery versus open resection.

INTRODUCTION: Video-assisted thorcacic surgery (VATS) is considered an alternative to open lobectomy for the treatment of non-small-cell lung cancer (NSCLC). Limited data are available, however, regarding the equivalence of open versus VATS segmental resections, particularly among elderly patients. METHODS: From the Surveillance, Epidemiology, and End Results-Medicare database we identified 577 stage I NSCLC patients aged more than 65 years treated with VATS or open segmentectomy. We used propensity score methods to control for differences in the baseline characteristics of patients treated with VATS versus open segmentectomy. Outcomes included perioperative complications, need for intensive care unit, extended hospital stay, perioperative mortality, and survival. RESULTS: Overall, 27% of patients underwent VATS. VATS-treated patients had lower rates of postoperative complications (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.37-0.83), intensive care unit admissions (OR: 0.18, 95% CI: 0.12-0.28), and decreased length of stay (OR: 0.41, 95% CI: 0.21-0.81) after adjusting for propensity scores. Postoperative outcomes were not significantly different across groups after adjusting for surgeon characteristics. Overall (hazard ratio: 0.80, 95% CI: 0.60-1.06) and lung cancer-specific (hazard ratio: 0.71, 95% CI: 0.45-1.12) survival was similar across groups. CONCLUSIONS: VATS segmentectomy can be safely performed among elderly NSCLC patients and is associated with equivalent postoperative and oncologic outcomes.