Pooja R. Patel

Clinical and Biological Significance of Vascular Endothelial Growth Factor in Endometrial Cancer

Purpose: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer is not fully known. Therefore, we examined the clinical and therapeutic significance of VEGF in endometrial carcinoma using patient samples and an endometrioid orthotopic mouse model. Experimental Design: Following Institutional Review Board approval, VEGF expression and microvessel density (MVD) counts were evaluated using immunohistochemistry in 111 invasive endometrioid endometrial cancers by two independent investigators. Results were correlated with clinicopathologic characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were injected directly into the uterine horn. Therapy experiments with bevacizumab alone or in combination with docetaxel were done and samples were analyzed for markers of angiogenesis and proliferation. Results: Of 111 endometrial cancers, high expression of VEGF was seen in 56% of tumors. There was a strong correlation between VEGF expression and MVD (P < 0.001). On multivariate analysis, stage (P = 0.04), grade (P = 0.003), VEGF levels (P = 0.03), and MVD (P = 0.037) were independent predictors of shorter disease-specific survival. In the murine model, whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth inhibition over controls, combination therapy had the greatest efficacy (85-97% inhibition over controls; P < 0.01) in both models. In treated tumors, combination therapy significantly reduced MVD counts (50-70% reduction over controls; P < 0.01) and percent proliferation (39% reduction over controls; P < 0.001). Conclusions: Increased levels of VEGF and angiogenic markers are associated with poor outcome in endometrioid endometrial cancer patients. Using a novel orthotopic model of endometrioid endometrial cancer, we showed that combination of antivascular therapy with docetaxel is highly efficacious and should be considered for future clinical trials.

Trends in the National Distribution of Laparoscopic Hysterectomies From 2003 to 2010

STUDY OBJECTIVE The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010. DESIGN Retrospective study (Canadian Task Force classification II-3). SETTING National sample of hospital admissions after hysterectomy. PATIENTS Health Cost and Utilization Project-Nationwide Inpatient Sample database was used to review records of women who underwent hysterectomy for either menorrhagia or leiomyoma from 2003-2010. INTERVENTION The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories. MAIN RESULTS A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003-2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01). CONCLUSIONS There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies.

Clinical stage after preoperative chemoradiation is a better predictor of patient outcome than the baseline stage for localized gastric cancer

For patients with localized gastric cancer (LGC) who are receiving preoperative chemoradiation (CTRT), the postsurgical pathologic stage predicts overall survival (OS) better than the baseline stage. The authors hypothesized that presurgical (postCTRT) stage would also correlate better with patient outcome than the baseline stage.

Sources of HPV vaccine hesitancy in parents.

Despite strong national recommendations to vaccinate adolescents against the human papillomavirus (HPV), only 14% of teenage girls completed all 3 doses in 2010. Parental hesitancy may be one of the strongest reasons behind this low uptake rate. This review investigates sources of parental hesitancy including parental concerns associated with vaccinations in general, parental knowledge as a basis of HPV vaccine hesitancy, social qualms parents may have with regards to the HPV vaccine, and parental attitudes toward allowing their sons to be vaccinated against HPV. By better understanding these sources of hesitancy, we can focus research efforts towards addressing them in an attempt to improve HPV vaccine uptake.

Effect of timing of metastasis/disease recurrence and histologic differentiation on survival of patients with advanced gastric cancer

Patients with advanced gastric cancer have a median survival (MS) of <9 months. It is unclear whether the MS of patients who have advanced cancer at the time of diagnosis (synchronous, Group A) is different from that for patients who develop advanced cancer after curative surgery (metachronous, Group B). It was hypothesized that survival would be similar.

Impact of cardiovascular comorbidity on ovarian cancer mortality

Background: A retrospective cohort study utilizing prospectively collected data was conducted from August 2003 until March 2008 at M.D. Anderson Cancer Center. It is unknown whether cardiovascular comorbidity and chronic stress impact ovarian cancer outcome, which remains poor despite advances in therapy. The purpose of this study was to determine whether cardiovascular disease and markers that may be associated with stress are also associated with survival in patients with ovarian cancer. Methods: Participants with newly diagnosed epithelial ovarian cancer were followed until time of death or truncation of study period (median follow-up = 4.2 years; n = 271). Tumor characteristics (stage, tumor grade, histology, debulking status), demographic variables, and cardiovascular comorbidity were documented and compared to overall survival. Results: Of the nine cardiovascular events tracked during follow-up, venous thromboembolism [VTE; HR, 3.2; 95% confidence interval (CI), 1.8–5.5] and pulmonary hypertension (HR, 8.5; 95% CI, 3.9–18.7) were associated with shorter survival in multivariate analysis. In addition, high tumor grade, suboptimal cytoreduction, and baseline heart rate (HR, 1.02; 95% CI, 1.01–1.04) were related to decreased survival. Conclusion: Careful management of certain cardiovascular comorbidities may extend survival in patients with ovarian cancer. Our findings suggest that increased baseline heart rate and the development of VTE and pulmonary hypertension after cancer diagnosis may be significant predictors of survival in women with ovarian cancer. Impact: Our study emphasizes the importance of identifying and optimally treating tachycardia, VTE, and pulmonary hypertension in conjunction with cancer therapy. Cancer Epidemiol Biomarkers Prev; 22(11); 2102–9. ©2013 AACR.

Intraocular pressure and steep trendelenburg during minimally invasive gynecologic surgery: Is there a risk?

STUDY OBJECTIVE Steep Trendelenburg position is frequently used during gynecologic minimally invasive surgery (MIS). However, little attention has been given to the potential impact of this nonphysiologic positioning on patients, specifically intraocular pressure (IOP). The purpose of our study was to evaluate IOP changes during laparoscopic or robotic hysterectomy conducted in the steep Trendelenburg position. DESIGN Prospective cohort study (Canadian Task Force classification II-2). SETTING John Sealy Hospital at the University of Texas Medical Branch, Galveston, TX. PATIENTS Female patients with no history of ocular pathology who underwent elective robotic or laparoscopic hysterectomy. INTERVENTIONS The anesthesia protocol was standardized for all study patients. IOP and mean arterial pressure (MAP) were obtained before anesthesia, after general anesthesia and intubation were achieved, after 1 hour of steep Trendelenburg positioning, after 2 hours of steep Trendelenburg positioning, and after the patient was returned to the supine position. Ocular perfusion pressure (OPP) was calculated using the following equation: OPP = MAP - IOP. MAIN RESULTS A total of 10 patients were included in this prospective study. A significant increase in IOP from baseline was observed after 1 hour and 2 hours of steep Trendelenburg positioning (p = .005 and .002, respectively). There was a statistically significant trend of increasing the IOP from baseline to the second hour of steep Trendelenburg positioning (p < .001). The IOP remained significantly elevated once the patient was returned to the supine position when compared with the baseline IOP (p = .006). OPP significantly decreased from baseline after 2 hours of steep Trendelenburg positioning (p = .03). CONCLUSIONS IOP increases significantly when patients are placed in the steep Trendelenburg position. Although further studies are needed to better characterize this process, given the aging population of our MIS patients in whom risk for glaucoma is significant, preoperative ocular health assessment should be considered in certain cases.

Assessment of minimally invasive surgical skills of pre-medical students: What can we learn from future learners?

OBJECTIVE Knowledge of baseline laparoscopic and robotic surgical skills of future learners is essential to develop teaching strategies that best fit them. The objectives of this study are to determine baseline laparoscopic and robotic skills of high school and college students and compare them to those of current obstetrics and gynecology residents. MATERIAL AND METHODS A cross-sectional (Class II-2) pilot study. Laparoscopic and robotic surgical skills of college and high (secondary) school students were evaluated using simulators and compared to those of obstetrics and gynecology residents. In addition, questionnaire data were collected regarding video game playing and computer use. RESULTS A total of 17 students, both high school (n=9) and college (n=8), in addition to 11 residents, completed the study. Overall, students performed comparably to the residents in simple exercises (p>.05). However, students took significantly longer time to complete complex exercises (p=.001). Finally, students played video games significantly more than residents (p<.001). CONCLUSION Future learners may have a different background skill set. This difference may be related to improved hand-eye coordination, possibly due to playing video games. The results of this pilot study should spur more research into surgical teaching strategies.

Outpatient robotic hysterectomy: clinical outcomes and financial analysis of initial experience

Robotic surgery is associated with several advantages but also high costs. This study evaluates clinical outcomes and financial feasibility of outpatient robotic hysterectomy.

Modular Comparison of Laparoscopic and Robotic Simulation Platforms in Residency Training: A Randomized Trial

STUDY OBJECTIVE To compare minimally invasive surgery (MIS) skills acquired using laparoscopic and robotic simulation training platforms. DESIGN Randomized trial (Canadian Task Force classification I). SETTING University residency training program. SUBJECTS PGY1 and PGY2 resident physicians in Obstetrics and Gynecology. INTERVENTIONS All residents completed prestudy questionnaires (demographic data and previous experience in MIS) followed by simulation pretesting to assess baseline laparoscopic and robotic skills. Residents were then randomized to laparoscopic or robotic training cohorts in which they completed proctored training of 4 basic laparoscopic or 4 matching robotic modules (1 hour per module, 4 hours total). Thereafter, residents repeated the timed assessment of all skills. Finally, they completed poststudy questionnaires about the training experience. The primary outcome measure was the percentage of improvement in skill completion time. Secondary outcome measures were answers to poststudy questionnaires. MEASUREMENTS AND MAIN RESULTS Sixteen residents completed the study. The laparoscopic and robotic training groups did not differ substantially on demographic measures, previous experience in MIS, or baseline laparoscopic and robotic completion times. Median improvement for individual laparoscopic modules was, respectively, 37.76%, 46.43%, 53.29%, and 66.48% in the laparoscopic cohort vs 21.84%, 21.80%, 38.15%, and 32.98% in the robotic cohort. Median improvement for individual robotic modules was, respectively, 35.42%, 26.08%, 22.33%, and 47.48% in the laparoscopic cohort vs 52.70%, 62.02%, 67.64%, and 71.62% in the robotic cohort. Median improvement in combined laparoscopic, robotic, and overall skills was, respectively, 50.56%, 34.83%, and 45.52% in the laparoscopic group vs 36.18%, 64.12%, and 49.86% in the robotic group. Residents predicted greater comfort performing surgical procedures using the platform in which they trained; however, the robotic training cohort liked their training more. CONCLUSIONS Laparoscopic and robotic simulation platforms each demonstrated improved performance in the same and other platform. The robotic platform seems to have an edge over the laparoscopic platform. Larger studies are required in addition to studies to compare the effectiveness of both platforms in more advanced skills and to compare their effect on proficiency in the operating room.