Camille C. Gunderson

Oncologic and Reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 Adenocarcinoma: A systematic review

OBJECTIVE The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy. METHODS A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fishers exact test was used to calculate statistical differences. RESULTS Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p=.002). The median time to complete response was 6 months (range, 1-18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p=.03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p=.02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p=.39), with 117 live births reported. CONCLUSION Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts.

The impact of obesity on surgical staging, complications, and survival with uterine cancer: A Gynecologic Oncology Group LAP2 ancillary data study

OBJECTIVE To determine the association of body mass index (BMI) on complications, recurrence, and survival in GOG LAP2, a randomized comparison of laparoscopic versus open staging in clinically early stage uterine cancer (EC). METHODS An ancillary data analysis of GOG LAP2 was performed. Categorical variables were compared using Pearson chi-square test and continuous variables using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests by BMI group. Survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate independent prognostic factors on survival. Statistical tests were two-tailed with α=0.05, except where noted. Statistical analyses utilized R programming language. RESULTS 2596 women were included. BMI (kg/m(2)) groups were <25 (29.5%), 25-30 (28.2%), 30-35 (21%), 35-40 (10.9%), and ≥40 (10.4%). Stage (p=0.021), grade (p<0.001), and histology (p=0.005) differed by BMI. Obese women were less likely to have high risk (HR) disease (+lymph nodes/ovaries/cytology) or tumor features that met GOG99 high intermediate risk (HIR) criteria (p<0.001). Adjuvant therapy (p=0.151) and recurrence (p=0.46) did not vary by BMI. Hospitalization >2days, antibiotic use, wound infection, and venous thrombophlebitis were higher with BMI ≥40. BMI (p=0.016), age (p<0.0001), race (p=0.033), and risk group (p<0.0001) predicted all-cause mortality. BMI was not predictive of disease-specific survival (p=0.79), but age (p=0.032) and risk group (p<0.0001) were significant factors. CONCLUSION Obese women have greater surgical risk and lower risk of metastatic disease. BMI is associated with all-cause but not disease-specific mortality, emphasizing the detrimental effect of obesity (independent of EC), which deserves particular attention.

Laparoendoscopic single-site surgery in gynecology

Purpose of review To review the contemporary literature on laparoendoscopic single-site surgery (LESS) advances in gynecology. Recent findings Minimally invasive surgery has become a standard of care for the treatment of many benign and malignant gynecologic conditions. Both conventional laparoscopy and robotic assisted surgery have impacted the entire spectrum of gynecologic surgery. Ongoing efforts to improve upon the morbidity and cosmetic sequelae of laparoscopic surgery have led to minimization of size and number of ports required for these procedures. LESS surgery is a recently coined surgical term used to describe various techniques that aim at performing laparoscopic surgery through a single, small skin incision concealed within the umbilicus. LESS surgery is not a new endeavor but recent developments in surgical technology and techniques have resulted in an exponential increase in utilization of LESS across many surgical subspecialties. Recently published outcome data demonstrate feasibility, safety and reproducibility for LESS in gynecology. The contemporary LESS literature, gamut of gynecologic procedures and limitations of current technology will be reviewed in this article. Summary LESS represents the latest innovation in minimally invasive surgery but comparative data and prospective trials are required to determine the clinical impact of LESS in treatment of gynecologic conditions.

Laparoendoscopic single-site surgery in gynaecology: A new frontier in minimally invasive surgery

UNLABELLED REVIEW OBJECTIVE: To review the recent developments and published literature on laparoendoscopic single-site (LESS) surgery in gynaecology. RECENT FINDINGS Minimally invasive surgery has become a standard of care for the treatment of many benign and malignant gynaecological conditions. Recent advances in conventional laparoscopy and robotic-assisted surgery have favorably impacted the entire spectrum of gynaecological surgery. With the goal of improving morbidity and cosmesis, continued efforts towards refinement of laparoscopic techniques have lead to minimization of size and number of ports required for these procedures. LESS surgery is a recently proposed surgical term used to describe various techniques that aim at performing laparoscopic surgery through a single, small-skin incision concealed within the umbilicus. In the last 5 years, there has been a surge in the developments in surgical technology and techniques for LESS surgery, which have resulted in a significant increase in utilisation of LESS across many surgical subspecialties. Recently published outcomes data demonstrate feasibility, safety and reproducibility for LESS in gynaecology. The contemporary LESS literature, extent of gynaecological procedures utilising these techniques and limitations of current technology will be reviewed in this manuscript. CONCLUSIONS LESS surgery represents the newest frontier in minimally invasive surgery. Comparative data and prospective trials are necessary in order to determine the clinical impact of LESS in treatment of gynaecological conditions.

A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia

OBJECTIVE The purpose of this study was to review a large cohort of patients with vaginal intraepithelial neoplasia (VAIN) and to analyze the epidemiology and outcomes with various treatment modalities. STUDY DESIGN A retrospective chart review was performed that encompassed patients who were treated for VAIN at a single center from 1990-2007. Demographics, disease characteristics, referring cytology, and histologic information were recorded. Primary outcome was recurrence or progression to carcinoma. Statistical analyses were performed with statistical software. RESULTS One hundred sixty-three women were included in the study: median age, 50 years (range, 21-84 years); white, 87%; current or previous smokers, 35%. At the time of diagnosis, 23% of the women had VAIN1; 37% of the women had VAIN2, and 35% of the women had VAIN3. Referral Papanicolaou smear results of high-grade squamous intraepithelial lesion or atypical glandular cells revealed VAIN2 or VAIN3 in 89% of cases (P = .0019) vs 53% of cases with low-grade squamous intraepithelial lesion. The median follow-up period was 18 months (range, 1-194 months). VAIN1 was observed in 70% of cases; 71% of patients who were treated for VAIN1 had recurrence or progression. VAIN2 was treated in 77% of patients; 53% of those who were treated had recurrence or progression. VAIN3 was treated in 94% of cases; 31% of them had recurrence or progression. Risk of recurrence was not correlated to VAIN type (P = .3). Six carcinomas were discovered in patients with VAIN2 and VAIN3. Median time to progression was 17 months for VAIN1, 11 months for VAIN2, and 11 months for VAIN3 (P = .036). CONCLUSION Despite the subtype, VAIN often recurs but does so more quickly with higher grade dysplasia.

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer

Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drugs mechanism of action.

The survival detriment of venous thromboembolism with epithelial ovarian cancer.

OBJECTIVE The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC). METHODS An IRB approved, retrospective review was performed of patients treated for Stage I-IV EOC from 1996 to 2011. Cox proportional hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses. RESULTS 586 patients met study criteria. Median age was 63 years (range, 17-94); median BMI was 27.1 kg/m(2) (range, 13.7-67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6-6.1, p=0.001) but not PFS (p=0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04-2.02, p=0.03) and OS (HR 1.8, 95% CI: 1.3-2.6, p=0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8-6.9, p<0.001) and postoperative VTE after primary therapy (HR 2.3, 95% CI: 1.4-3.6, p=0.001) were predictive of OS. CONCLUSION Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events.

Primary uterine cancer in maryland impact of distance on access to surgical care at high-volume hospitals

Objective To evaluate the influence of distance on access to high-volume surgical treatment for patients with uterine cancer in Maryland. Methods The Maryland Health Services Cost Review Commission database was retrospectively searched to identify primary uterine cancer surgical cases from 1994 to 2010. Race, type of insurance, year of surgery, community setting, and both surgeon and hospital volume were collected. Geographical coordinates of hospital and patient’s zip code were used to calculate primary independent outcomes of distance traveled and distance from nearest high-volume hospital (HVH). Logistic regression was used to calculate odds ratios and confidence intervals. Results From 1994 to 2010, 8529 women underwent primary surgical management of uterine cancer in Maryland. Multivariable analysis demonstrated white race, rural residence, surgery by a high-volume surgeon and surgery from 2003 to 2010 to be associated with both travel 50 miles or more to the treating hospital and residence 50 miles or more from the nearest HVH (all P < 0.05). Patients who travel 50 miles or more to the treating hospital are more likely to have surgery at a HVH (odds ratio, 6.03; 95% confidence interval, 4.67–7.79) In contrast, patients, who reside ≥50 miles from a HVH, are less likely to have their surgery at an HVH. (odds ratio, 0.37; 95% confidence interval, 0.32–0.42). Conclusion In Maryland, 50 miles or more from residence to the nearest HVH is a barrier to high-volume care. However, patients who travel 50 miles or more seem to do so to receive care by a high-volume surgeon at an HVH. In Maryland, Nonwhites are more likely to live closer to an HVH and more likely to use these services.

Distance traveled for treatment of cervical cancer who travels the farthest, and does it impact outcome?

Objective To evaluate the impact of distance from residence to treatment center on disease characteristics and recurrence of cervical cancer. Materials and Methods A single-institution retrospective chart review of patients treated for cervical cancer during 2006–2011 was performed. Demographic, socioeconomic, and clinicopathologic characteristics were recorded. Distance traveled from home to treatment facility was calculated and categorized. Recurrence and follow-up data were extracted; progression-free survival and overall survival were calculated. SAS version 9.2 was used for statistical analysis. Results Two hundred nineteen patients met the study criteria; 75% were Caucasian. Forty-nine percent used tobacco. Twenty-five percent had stage III/IV disease. Insurance type was 46% private, 25% Medicaid, 20% Medicare, and 9% uninsured. Distance between residence and hospital was less than 15 miles (29%), 15 to 30 miles (21%), 30 to 50 miles (17%), and more than 50 miles (33%). Median follow-up period was 23 months (range, 1–65). Caucasians were more likely to travel more than 30 miles to a treatment center (P = 0.018) Non-Caucasians were less likely to have private insurance (P = 0.0005) and more likely to recur (P = 0.0045). Recurrence was highest (50%) in African Americans. Travel of more than 30 miles was not associated with age, stage, histology, tobacco abuse, employment, clinical trial enrollment, primary chemoradiation for stage IB disease, or delayed radiation. Travel of more than 30 miles was associated with government insurance (P = 0.029) and a trend toward unemployment (P = 0.059). Four-year progression-free survival (53% vs 52%; P = 0.992) and overall survival (57% vs 62%; P = 0.73) were similar between less than or more than 30-mile travel. Conclusions Fifty percent of the patients reside more than 30 miles from treating hospital. Despite farther travel, stage of disease, clinical trial enrollment, treatment type, radiation completion, and recurrence rates were similar among patients with cervical cancer. Non-Caucasians are less likely to travel more than 30 miles.

Laparoscopic-Assisted Vaginal Hysterectomy vs Laparoscopic Supracervical Hysterectomy for Treatment of Nonprolapsed Uterus

STUDY OBJECTIVE To compare perioperative outcomes between laparoscopic-assisted vaginal hysterectomy (LAVH) and laparoscopic supracervical hysterectomy (LSH) for the nonprolapsed uterus. DESIGN Retrospective chart analysis (Canadian Task Force classification II-2). SETTING Three university-affiliated community hospitals. PATIENTS Women undergoing LAVH or LSH because of benign indications without concomitant pelvic organ prolapse. INTERVENTION Laparoscopic hysterectomy with or without adnexectomy. MEASUREMENTS AND MAIN RESULTS Data from 265 LAVH procedures and 181 LSH procedures performed at 3 university-affiliated community hospitals were included in the analysis from January 2001 to December 2007. The cases were successive. Exclusion criteria included surgery performed to treat malignancy or pelvic organ prolapse, and procedures that were converted to laparotomy. Two hundred forty-eight LAVH procedures and 173 LSH procedures were completed successfully. There was no significant difference in mean (SD) operating time between the 2 groups (145.1 [45.6] minutes for LAVH vs 143 [51.7] minutes for LSH; p = .66). Hospital stay was significantly shorter in the LSH group (1.6 [0.6] days vs 1.2 [0.5] days; p = .001). Patients in the LAVH group had significantly larger uterine weight (147.7 [84.8] g vs 121.5 [105.5] g; p = .005). Postoperative hemoglobin change and febrile morbidity were similar between the groups, as were overall perioperative complications (19% vs 15%, respectively; p = .36) and conversion rate to laparotomy (6.9% vs 4.6%; p = .27). CONCLUSION Compared with LAVH, LSH offers the benefits of a shorter hospital stay when performed in patients without uterine prolapse. Other perioperative outcomes studied were not significantly different between groups.