Wilson, Timothy O.

BACKGROUND: Increasing numbers of robotic hysterectomies (RH) are being performed. To provide ventilation (with pneumoperitoneum and steep Trendelenburg position) for these procedures, utilization of lung protective strategies with limiting airway pressures and tidal volumes is difficult. Little is known about the effects of intraoperative mechanical ventilation and high peak airway pressures on perioperative complications. We performed a retrospective review to determine whether patients undergoing RH had increased pulmonary complications compared to total abdominal hysterectomy (TAH). METHODS: We performed a single center retrospective review comparing the intraoperative, anesthetic, and immediate and 30-day postoperative course of patients undergoing RH to TAH, including intraoperative ventilatory parameters and respiratory complications. Patients undergoing TAH (201) from 2004 to 2006 were compared to RH (251) from 2009 to 2012. It was our hypothesis that patients undergoing RH would have increased incidence of postoperative pulmonary complications. A secondary hypothesis was that morbid obesity predicts pulmonary complications in patients undergoing RH. Complications were compared between groups using Fisher’s exact test. To account for potential confounders, the primary analysis was performed for a subgroup of patients matched on the propensity for RH. RESULTS: A total of 351 RH and 201 TAH procedures are included. Higher inspiratory pressures were required in ventilation of the RH group (median [25th, 75th] 31 [26, 36] cm H 2 O) than the TAH group (23 [19, 27] cm H 2 O) ( P < .001) at 30 minutes after incision. Peak inspiratory pressures at 30 minutes after incision for RH increased according to increasing body mass index group ( P < .001). There were 163 RH and 163 TAH procedures included in the propensity matched analysis. From this analysis, there were no significant differences in cardiopulmonary complications between RH and TAH (0.6% vs 1.2%; odds ratio = 2.0, 95% confidence interval = 0.2–2.4; P = 1.00). Surgical site infection was significantly lower in the RH compared to TAH group (0.6% vs 8.6%; P < .001). Hospital length of stay was longer for those who underwent TAH versus RH (median [25th, 75th] 2 [2, 3] vs 1 [0, 2] days; P < .001). CONCLUSIONS: There was no significant difference in perioperative complications in obese and morbidly obese women compared to nonobese undergoing RH. Patients undergoing RH had shorter hospital stays, fewer infectious complications, and no increase in overall complications compared to TAH. Higher ventilatory airway pressures (RH versus TAH and obese versus nonobese) did not result in an increase in cardiopulmonary or overall complications. We believe that peritoneal insufflation attenuates the effect of high airway pressures by raising intrapleural pressure and reducing the gradient across terminal bronchioles and alveoli. Thus, we propose that lung protective strategies for patients undergoing RH account for the markedly elevated intraperitoneal and intrapleural pressures, whereas transpulmonary airway pressures remain static. This reduced transpulmonary gradient attenuates the strain on lung tissue that would otherwise be imposed by ventilation at high pressures.

Abstract Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (103–109 TCID50). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54–277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3–38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875–82