Morbid obesity increases the failure rate of sentinel lymph node mapping for endometrial carcinoma.

The goal of this study was to examine the relationship between body mass index (BMI) and the success rate of sentinel lymph node (SLN) mapping using indocyanine green and near-infrared imaging. Sentinel lymph node mapping is recommended for patients with endometrial carcinoma to reduce the rate of full lymphadenectomy and its associated morbidity such as lymphedema. A retrospective review was conducted of robotic hysterectomy procedures for patients with a coded diagnosis of endometrial cancer and a cost code for indocyanine green discharged between March, 2016 and August, 2019. Preoperative characteristics included age, BMI, and number of prior abdominal surgeries (includes cervical, adnexal, uterine or rectal procedures, caesarian section, or appendectomy). Intra and postoperative characteristics included procedure time (incision to close), estimated blood loss, the American Society of Anesthesiologists (ASA) physical status classification, uterine weight, uterine diameter, FIGO Grade, myometrial depth, and depth of myometrial invasion. SLN and non-SLN number, location, and pathology were recorded. The primary outcome was the bilateral success rate for SLN mapping. Patients with class III obesity (BMI > 40) were found to have a significantly lower success rate for SLN mapping when compared with all other BMI categories (54.1% vs. 76.1%, respectively, p < 0.01).

Clinical comparison of robotic, laparoscopic, and open hysterectomy procedures for endometrial cancer patients.

The goal of this study was to compare outcomes for robotic, laparoscopic, and open hysterectomy procedures for endometrial cancer as well as to investigate whether specific patient demographic, comorbidity, and severity variables were associated with the type of hysterectomy performed. A retrospective review was conducted of hysterectomy procedures for patients discharged from October 1, 2008 and September 30, 2012. Preoperative characteristics included age, BMI, number of past abdominal surgeries, and comorbidities. Intraoperative and postoperative characteristics included uterine weight and diameter, American Society of Anesthesiologists physical status classification, lymph-vascular space involvement, FIGO stage and tumor grade. Outcomes included operative time, estimated blood loss, length of stay, conversion to open, other intraoperative and postoperative complications, readmissions within 30 days and lymph node yield. The robotic and laparoscopic cohorts show no significant differences in patient or tumor characteristics, while the open cases represent patients with increased complexity. In general, laparoscopic cases were shorter than robotic and open cases. Laparoscopic cases had fewer conversions to open than robotic cases. Robotic and open cases had significantly higher lymph node yield than laparoscopic cases. The reduction in surgical time and conversion rates in the laparoscopic cohort may be related to the reduction in node dissection performed.

Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer.

PURPOSE: To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. PATIENTS AND METHODS: Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). RESULTS: One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. CONCLUSION: Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.

Body mass index, conversion rate and complications among patients undergoing robotic surgery for endometrial carcinoma.

A retrospective cohort study was performed to evaluate the relationship of BMI to conversion rate in patients undergoing robotic surgery for endometrial cancer. Secondary outcomes were operative times, number of lymph nodes retrieved, and complications. Women with endometrial cancer scheduled for robotic surgery from September 2008 to September 2012 were included. Women were divided into three groups based on BMI, and conversion rates to laparotomy were compared. Descriptive and comparative analyses were performed among non-obese, obese, and morbidly obese women who completed robotic surgery. 298 women were scheduled for robotic surgery for endometrial carcinoma: 87 non-obese (BMI 19-29, µ 25.23), 110 obese (BMI 30-39, µ 34.21), and 101 morbidly obese (BMI 40-71, µ 47.38). Conversion to laparotomy occurred in 18 patients (6%), with no difference in conversion rate between BMI categories. Direct comparison between converted and completed robotic patients showed no significant differences in preoperative characteristics, except that patients who required conversion had a higher number of previous abdominal surgeries. Patients completing robotic surgery underwent node dissections at similar rates in all three BMI categories. Operating room time, but not surgical time, was increased in morbidly obese patients. There were no significant differences in complications, performance of lymphadenectomy, or lymph node yields between BMI categories. Increase in BMI was not associated with an increase in rate of conversion to laparotomy or complication rate in patients undergoing robotic surgery for endometrial carcinoma. Node dissections were pathologically equivalent between BMI categories.

Mirk kinase inhibition targets ovarian cancer ascites.

The Mirk/dyrk1B gene is commonly amplified or upregulated in ovarian cancers, and Mirk is an active kinase in these cancers. Mirk mediates cancer cell survival by decreasing toxic ROS levels through maintaining expression of a series of antioxidant genes, possibly through its transcriptional activator functions. Mirk has the unusual property of being most active in quiescent cancer cells because of marked transcriptional downregulation by Akt/mTOR signaling and by MEK/erk signaling in cycling cells. Metastatic ovarian cancer cells form ascites, non-adherent multicellular aggregates floating within the peritoneal fluid. Most ascites cancer cells are in a reversible quiescent, dormant state, suggesting that Mirk might be expressed in these quiescent cells and thus a therapeutic target. The current studies show that ovarian cancer cell line spheroids that mimic ascites cancer spheroids were largely quiescent in G0/G1, and enriched in Mirk and the quiescence proteins, p130/Rb2 and the CDKI p27. Mirk kinase inhibition in spheroids made from established cell lines and in patient-derived ascites cancer cell spheroids reduced spheroid volume, disrupted spheroid structure to single cells, increased apoptosis, and decreased cell numbers. Earlier studies had shown that the mTOR inhibitor RAD001 increased transcription of the Mirk/dyrk1B gene, so treatments combined RAD001 with the most active Mirk kinase inhibitor. The number of ascites cells from 9 patients was reduced a similar amount by cisplatin, Mirk kinase inhibition or RAD001, but reduced substantially more, about 90%, by concurrent treatment with both the Mirk kinase inhibitor EHT5372 and RAD001. Addition of RAD001 increased the amount of toxic ROS induced by Mirk kinase inhibition. Two ascites samples taken one month apart gave similar drug responses, showing reproducibility of the techniques. Thus Mirk/dyrk1B kinase may be a therapeutic target in ovarian cancer ascites.

Kinetics of cisplatin binding to cellular DNA and modulations by thiol-blocking agents and thiol drugs.

DNA platination by cisplatin (CDDP) was investigated in peripheral blood mononuclear cells and ovarian cancer cells using atomic absorption spectroscopy. Plots showing the amount of platinum (Pt) bound to DNA versus the molar concentration of cisplatin in the incubation medium ([CDDP]) were nonlinear. For [CDDP] < about 5 microM, the amount of Pt bound to DNA increased slowly with added drug. However, for larger [CDDP], the slope of the plot increased significantly. To study the role of thiols in affecting cisplatin binding to DNA, cells were treated with N-ethylmaleimide, which modifies thiol groups, rendering them incapable of binding cisplatin. Analysis using high-pressure liquid chromatography showed that approximately 99% of cellular glutathione was modified by N-ethylmaleimide. A plot of the amount of Pt bound to DNA versus [CDDP] for thiol-blocked cells is linear, with a slope similar to that of unblocked cells at high [CDDP]. Neither S-2-(3 aminopropylamino)ethanethiol (WR-1065) nor mesna, when added at clinically achievable concentrations (i.e., < approximately 300 microM), affected DNA platination. However, DNA platination was totally abolished by millimolar concentrations of the drug thiols (approximately 1.25 mM WR-1065 or approximately 5 mM mesna). Thus, the data show that endogenous thiols intercept cellular cisplatin, but this mechanism is less important at high [CDDP]. Moreover, therapeutic concentrations of drug thiols do not significantly affect DNA platination. A simple model that reproduces the experimental results of the amount of cisplatin binding to DNA as a function of [CDDP], time, and thiol content is proposed. The model takes into account passage of cisplatin and thiols through the cell membrane, binding of cisplatin to cellular thiols, and platination of DNA.