Norepinephrine Reduces Reactive Oxygen Species (ROS) and DNA Damage in Ovarian Surface Epithelial Cells.

OBJECTIVE: To determine the role of norepinephrine (NE) on DNA damage and reactive oxygen species (ROS) generation in ovarian surface epithelial cells. METHOD: Non-tumorigenic, immortalized ovarian surface epithelial cells were treated with NE, bleomycin, and bleomycin followed by NE. The comet assay was performed on each treatment group to determine the amount of single and double-strand breaks induced by treatments. ROS levels for each treatment group were measured using the H2DCF-DA fluorescence assay. Finally, RNA transcripts were measured for each treatment group with regards to the expression of DNA repair and oxidative stress genes. RESULTS: The mean tail moment of untreated cells was significantly greater than that of cells treated with NE (p=0.02). The mean tail moment of cells treated with bleomycin was significantly greater than that of cells treated with bleomycin followed by NE (p<0.01). Treatment with NE resulted in significantly less ROS generation than in untreated cells (p<0.01). NE treatment after hydrogen peroxide treatment resulted in a noticeable decrease in ROS generation. Genes associated with oxidative stress were upregulated in cells treated with bleomycin, however this upregulation was blunted when bleomycin-treated cells were treated subsequently with NE. CONCLUSION: NE is associated with decreased DNA damage and ROS production in ovarian surface epithelial cells. This effect is protective in the presence of the oxidative-damaging agent bleomycin. These results suggest an additional physiologic role for the stress hormone NE, in protecting ovarian surface epithelial cells from oxidative stress.

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.

The internet's role in HPV vaccine education.

The internet is the second most popular source, after healthcare providers, of information regarding human papillomavirus (HPV). These online searches usually begin with the user entering generic terms in the search engine, and then reading the first few results that the engine returns. Unfortunately, research shows that much of this information obtained about the HPV vaccine is inaccurate and incomplete. In this review, we summarize the literature pertaining to online information concerning the HPV vaccine and review concerns related to obtaining online medical information. Finally, we propose possible solutions medical providers can employ in their everyday practice to help their patients obtain accurate information through their online searches.

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.

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

BACKGROUND: Robotic surgery is associated with several advantages but also high costs. This study evaluates clinical outcomes and financial feasibility of outpatient robotic hysterectomy. METHODS: Retrospective cohort study (Class II-2) of patients who underwent robotic hysterectomy for benign conditions by the same surgeon (M.A.B.) at the University of Texas Medical Branch, Galveston, TX, USA, during November 2010-February 2013. The study only included cases considered appropriate for outpatient management. Clinical outcomes and costs for patients discharged the same day (outpatients) were compared to those electively admitted (hospitalized). RESULTS: Twenty-nine cases (14 outpatient and 15 hospitalized) were analysed. Demographic, pre-, peri- and postoperative characteristics and payer types were not different among the groups (p > 0.05). Outpatient hysterectomy was associated with $4968 hospital savings (p < 0.001), $410 payer savings (p = 0.775) and $4558 improvement in net profit/loss (p = 0.01). CONCLUSIONS: In well-selected patients, adopting a well-designed programme, outpatient robotic hysterectomy seems to be safe and financially feasible.

Outcomes of robotic sacrocolpopexy using barbed delayed absorbable sutures.

STUDY OBJECTIVE: To evaluate 1-year outcomes of robotic sacrocolpopexy (RSC) for pelvic organ prolapse using barbed delayed absorbable sutures. DESIGN: Retrospective cohort study (Class II-3). SETTINGS: University-based hospital in Southeast Texas. PATIENTS: Patients with symptomatic apical pelvic organ prolapse who underwent RSC using barbed delayed absorbable sutures between January 2011 and August 2012. Patients were examined postoperatively at least twice (after 6 weeks and 1 year). INTERVENTIONS: RSC procedure. MEASUREMENTS AND MAIN RESULTS: The study included a total of 20 patients, of them 15 had grades 3 or 4 whereas 5 had grade 2 apical defects according to the Baden-Walker classification system. Fourteen patients (70%) underwent concomitant hysterectomy while 9 (45%) underwent concomitant anti-incontinence surgery. Mesh suturing times were 46.9 ± 12.6 and 20.5 ± 9.3 minutes in the first 10 versus the last 10 cases, respectively (p < .001). The mean follow-up duration was 17.3 months (range, 12-24 months). There were no recurrences of apical defects or mesh/suture exposure/erosion. However, 1 patient developed a grade 2 cystocele, and another developed new-onset urinary incontinence, both after 1 year. A third patient's urine leakage did not improve postoperatively. Lastly, a fourth patient developed port site incisional hernia and underwent repair 5 months later. CONCLUSION: Our study suggests that barbed delayed absorbable sutures are safe and effective in RCS procedures over 1 year. Larger, comparative, and randomized trials are recommended for definitive conclusions.

Is administration of the HPV vaccine during pregnancy feasible in the future?

Despite the strong evidence supporting the efficacy of the HPV vaccine, the uptake rate remains low. One reason for this is that young females do not interact frequently with the healthcare system. In fact, pregnancy is often the first time young women experience multiple scheduled visits to a health provider. We review the data regarding safety of administering the HPV vaccine during pregnancy and consider the possibility of incorporating vaccination into prenatal care. Although the optimal time for vaccination is prior to sexual debut, this does not always occur, and as such, a broader approach to HPV vaccination may be necessary. Increasing the vaccine uptake rate among young women who did not initiate or complete the series earlier may significantly contribute to the decline in HPV-associated diseases.

Disparities in use of laparoscopic hysterectomies: a nationwide analysis.

STUDY OBJECTIVE: To determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy. DESIGN: Canadian Task Force Classification II-3. METHODS: In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included based on International Classification of Diseases, Ninth Revision coding. A linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach. MAIN RESULTS: A total of 32 436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies, and 67% underwent abdominal hysterectomies. With regard to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared with each of the other age categories (p < .001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women, or women classified as "other" races (p < .001 for all comparisons). With regard to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared with each of the other 3 national quartiles for income (p = .01, p < .001, p = .001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared with payment by Medicare or payment by insurance category "other" (p < .001 for both). With regard to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p < .001 for both comparisons); urban hospitals were more likely than rural hospitals (p < .001); teaching hospitals were more likely than nonteaching hospitals (p < .001); and government-owned hospitals were less likely than private, nonprofit or private, investor owned (p < .001 for both comparisons). CONCLUSIONS: Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regard to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it.

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.

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.

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.

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.

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

BACKGROUND: 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. METHODS: The medical records of all patients treated at the University of Texas M. D. Anderson Cancer Center who were in either Group A or Group B were reviewed. Survival of patients was assessed by the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate hazards ratios that were adjusted for the effects of location of recurrence, histologic differentiation, patient sex and age, the location of the primary tumor, and timing of disease recurrence (Group A or Group B) on survival. RESULTS: In all, 773 consecutive patients qualified for the analysis. The distribution of age, race, histologic differentiation, and primary tumor location was similar in both groups. The MS of Group A (n = 603 patients) and Group B (n = 170 patients) was the same (7.6 months). Similarly, the location of the primary tumor and patient sex were found to have no impact on survival. Patients with poorly differentiated tumors (World Health Organization grade 3 or 4) were found to have a shorter survival compared with those with well-differentiated or moderately differentiated tumors (grade 1 or 2; P = .004). Patients with distant metastases had a shorter survival (P = .01) than those with locoregional disease recurrence. CONCLUSIONS: The data show that MS is similarly poor in patients with advanced gastric cancer with synchronous metastasis (Group A) or those with metachronous metastasis/disease recurrence (Group B). Poor differentiation and anatomically distant site of metastasis were found to impact MS adversely.

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

BACKGROUND: 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. METHODS: The authors analyzed 74 LGC patients treated with preoperative CTRT receiving similar treatment. Patients were staged with baseline endoscopic ultrasonography (EUS) and laparoscopy. Patients received induction chemotherapy, then CTRT (45 Gy), and had an attempted surgery. After CTRT, patients had complete preoperative staging including EUS in 35 patients. RESULTS: Thirty-five had all 3 sets of staging, baseline, presurgical, and postsurgical. Baseline stage did not associate with OS (P = .16) nor disease-free survival (DFS; P = .13). However, presurgical stage was associated with OS (P = .01), and DFS (P = .05). OS was also associated with postsurgical stage and was longer for stages 0 and I than for stages III and IV (P = .01 and .04, respectively). Similarly, DFS was longer in postsurgical pathologic stages 0, I, and II than in stage III or IV (P < .001, <.001, and <.01, respectively). Baseline staging did not correlate with the proportion of patients alive at 4 years; however, presurgical staging did. Patients with stage I or II survived longer than those with stage III or IV (81% vs 25%; P < .01). CONCLUSIONS: Heterogeneity in clinical biology of LGC is best reflected after CTRT in presurgical and postsurgical pathologic stages rather than by the baseline stage. Correlation of outcome with presurgical staging may facilitate strategies to individualize therapy for LGC.