Impact of prior hysterectomy on surgical outcomes for laparoscopic adnexal surgery.

BACKGROUND: Adnexal surgery is believed to be more complex in patients with prior hysterectomy; however, there is little data regarding surgical outcomes. Understanding of individualized risks improves counseling, informed consent, and preoperative planning. METHODS: We performed a retrospective cohort study with a control group; we evaluated 744 patients undergoing laparoscopic adnexal surgery at an academic tertiary care center from 2011 to 2015. Comparisons were made using Chi square, Fisher's exact, or Wilcoxon-rank sum tests. We used log-binomial regression to calculate risk ratio and 95% confidence interval. RESULTS: Patients with prior hysterectomy were more likely to have intraoperative or postoperative complications at the time of laparoscopic adnexal surgery when compared to patients without prior hysterectomy [17.7% vs. 10.2%, p = 0.02, risk ratio (RR) 1.7, 95% confidence interval (CI) 1.1-2.7]. Patients with prior hysterectomy were four times more likely to have intraoperative complications (3.2% vs. 0.8%, p = 0.047, RR 4.0, 95% CI 1.1-14.7), and five times more likely to have conversion to laparotomy (5.6% vs. 1.1%, p = 0.004, RR 5.0, 95% CI 1.8-14.0). Patients with prior hysterectomy were more likely to need additional procedures, including lysis of adhesions (69.4% vs. 26.0%, p < 0.001), ureterolysis (15.3% vs. 4.8%, p < 0.001), and cystoscopy (28.2% vs. 8.1%, p < 0.001). They had longer operative time [101.5 min (IQR 59.5-135.0) vs. 78.0 min (IQR 53.0-109.0, p < 0.001)], and were less likely to have outpatient surgery (56.5% vs. 84.8%, p < 0.01). Postoperative complications were also more common (15.3% vs. 9.4%, p = 0.046). CONCLUSIONS: Patients with prior hysterectomy were 70% more likely to have a complication at the time of laparoscopic adnexal surgery than patients without hysterectomy. Increased risk of complications in subsequent adnexal surgery may influence the informed consent process or decisions regarding ovarian conservation. Awareness of potential need for additional surgical procedures may guide availability of equipment, choice of operating site, or referral to an advanced pelvic surgeon.

Adoption of enhanced recovery after laparotomy in gynecologic oncology.

INTRODUCTION: Enhanced recovery after surgery (ERAS) pathways combine a comprehensive set of peri-operative practices that have been demonstrated to hasten patient post-operative recovery. We aimed to evaluate the adoption of ERAS components and assess attitudes towards ERAS among gynecologic oncologists. METHODS: We developed and administered a cross-sectional survey of attending, fellow, and resident physicians who were members of the Society of Gynecologic Oncology in January 2018. The χ2 test was used to compare adherence to individual components of ERAS. RESULTS: There was a 23% survey response rate and we analyzed 289 responses: 79% were attending physicians, 57% were from academic institutions, and 64% were from institutions with an established ERAS pathway. Respondents from ERAS institutions were significantly more likely to adhere to recommendations regarding pre-operative fasting for liquids (ERAS 51%, non-ERAS 28%; p<0.001), carbohydrate loading (63% vs 16%; p<0.001), intra-operative fluid management (78% vs 32%; p<0.001), and extended duration of deep vein thrombosis prophylaxis for malignancy (69% vs 55%; p=0.003). We found no difference in the use of mechanical bowel preparation, use of peritoneal drainage, or use of nasogastric tubes between ERAS and non-ERAS institutions. Nearly all respondents (92%) felt that ERAS pathways were safe. DISCUSSION: Practicing at an institution with an ERAS pathway increased adoption of many ERAS elements; however, adherence to certain guidelines remains highly variable. Use of bowel preparation, nasogastric tubes, and peritoneal drainage catheters remain common. Future work should identify barriers to the implementation of ERAS and its components.

Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor.

A 42-year-old woman with a germline BRCA2 mutation and recurrent low-grade endometrioid endometrial adenocarcinoma experienced clinical and radiographic response to the poly (ADP ribose) polymerase (PARP) inhibitor, olaparib. Molecular and treatment factors are discussed.

Immunohistochemical loss of BRCA1 protein in uterine serous carcinoma.

Uterine serous carcinoma is a uncommon aggressive variant of endometrial cancer whose biologic origin is unclear. Mutations in p53 and BRCA1 genes play a key role in ovarian serous carcinogenesis. We investigated whether the loss of BRCA1 expression plays a similar role in uterine serous carcinoma. Loss of BRCA1 expression and Wilms tumor 1 (WT-1) overexpression were detected by immunohistochemical analysis. Depth of myometrial invasion, the presence of precursor lesions or polyps, and clinical parameters (age, history of breast cancer, and germline BRCA1 mutation status) were recorded. A total of 27 cases were available for evaluation. Three tumors (11.1%, 95% confidence interval, 2%-29%) showed the loss of BRCA1 expression. Two of these had known germline mutation in BRCA1, and the third had not been analyzed. Two of these cases expressed WT-1 or showed some morphologic features suggestive of drop metastasis from the adnexa, but no case showed detectable serous tubal intraepithelial carcinoma or features of an ovarian primary tumor. Overall, 5 women in the group had a personal history of breast cancer, and the finding was significantly associated with BRCA1 staining (P=0.049). A subset of uterine serous carcinomas shows the loss of BRCA1 protein and is associated with germline mutation.

Safety and outcome of patients treated with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer.

BACKGROUND: Despite the survival benefit of intraperitoneal (IP) chemotherapy observed in GOG172, significant toxicity and poor treatment completion rates have prevented the widespread acceptance of this regimen. Here, we report our experience with a modified outpatient GOG172 regimen. METHODS: Eligible patients had stage III, optimally debulked epithelial ovarian, fallopian tube or primary peritoneal cancer that underwent IP port placement for administration of a modified GOG172 regimen consisting of: (i) intravenous paclitaxel 135 mg/m² on day 1 over 3 h; (ii) intraperitoneal cisplatin 75 mg/m² on day 2, and (iii) intraperitoneal paclitaxel 60 mg/m² on day 8. Day 8 IP paclitaxel was omitted until tolerance of the first cycle of IP cisplatin had been established. RESULTS: Four or more cycles of IP chemotherapy were completed by 72.5% (29) of 40 eligible patients; 20% of patients exhibited catheter-related complications requiring port removal and discontinuation of IP chemotherapy. Grade 3-4 hematologic, metabolic and gastrointestinal toxicities occurred in 36, 8 and 21% of the patients, respectively. With a median follow-up of 47.7 months, progression-free and overall survival was comparable to GOG172. CONCLUSIONS: This modified outpatient GOG172 regimen is associated with less toxicity and improved completion rates compared to the original GOG172 regimen.

Management of ovarian cancer: a 75-year-old woman who has completed treatment.

Ovarian cancer includes primary tumors of epithelial, sex cord-stromal, or germ cell origin as well as metastatic tumors that frequently originate in the gastrointestinal tract. Approximately 90% of ovarian cancer is epithelial in origin and constitutes a major therapeutic challenge because of its advanced stage of presentation in most patients. Epithelial ovarian cancer is the most lethal gynecologic malignancy and the fifth most common cause of female cancer death in the United States, with approximately 1 in 70 women developing this disease in their lifetime. Several important advances in surgical and medical management of this disease have led to prolongation of survival and improvement of quality of life of patients with ovarian cancer. Using the case of Ms W, we discuss the signs, symptoms, risk factors, and prognostic factors of epithelial ovarian cancer; review the evidence for surgical and postoperative medical management; and present the current recommendations for screening and follow-up.

Laparoscopic intraperitoneal port placement for optimally cytoreduced advanced ovarian cancer.

STUDY OBJECTIVE: To evaluate complications of intraperitoneal ports placed laparoscopically as a separate procedure after initial debulking surgery for ovarian, fallopian tube, or primary peritoneal cancer. DESIGN: A retrospective case series (Canadian Task Force Classification III). SETTING: Inpatient, academic teaching institution. PATIENTS: Female patients of any age, at a single institution, undergoing laparoscopically-assisted intraperitoneal port placement after initial surgery for ovarian, fallopian tube, or primary peritoneal cancer from January 2001 through December 2009. INTERVENTIONS: Laparoscopically assisted intra-peritoneal port placement. MEASUREMENTS/MAIN RESULTS: Thirty-three ports were successfully placed, with no conversions to laparotomy. Only 2 patients were unable to receive intraperitoneal chemotherapy, and there was 1 major complication (enterotomy) related to port placement. There were 6 cases of port dysfunction (17%); however, in 3 cases the port was replaced and subsequently functioned well. There were 2 cases of port infection necessitating port removal. The majority (81.8%) of patients were able to complete all planned cycles of intraperitoneal chemotherapy. CONCLUSION: Based on the data from our institution, laparoscopic placement of an intraperitoneal port may be safely performed as a second procedure after initial surgery for stage III ovarian, fallopian tube, or primary peritoneal cancer and provides access for post-operative therapy.

Controlled decompression of large ovarian cystic tumors via mini-laparotomy using Dermabond Advanced™.

Large cystic ovarian tumors usually require surgical removal because of symptoms and the possibility of malignancy. The ideal surgical approach would minimize the risk of spillage of tumor contents while minimizing surgical morbidity. The present study aims to demonstrate a novel technique to drain large cystic ovarian tumors without spillage. A mini-laparotomy is performed and the tumor surface is exposed. Dermabond Advanced™ (USA Medical and Surgical Supplies 2019a) is applied to the tumor and a surgical glove (USA Medical and Surgical Supplies 2019b) is applied to the glue area. A small incision is made in the center of the portion of the glove that is adherent to the tumor. The cyst fluid is allowed to drain into the glove where it is suctioned away, collapsing the tumor. Once the tumor is sufficiently decompressed, it is exteriorized and resected with the glove still attached. The technique was initially developed in a pig model and subsequently successfully performed by mini-laparotomy on two patients with >20 cm ovarian masses. This novel technique uses inexpensive and readily available materials for draining large cystic ovarian tumors without spillage so that they can be removed via mini-laparotomy.

Hysterectomy Practice Patterns in the Postmorcellation Era.

OBJECTIVE: To characterize long-term national trends in surgical approach for hysterectomy after the U.S. Food and Drug Administration (FDA) warning against power morcellation for laparoscopic specimen removal. METHODS: This was a descriptive study using data from the American College of Surgeons National Surgical Quality Improvement Program from 2012 to 2016. We identified hysterectomies using Current Procedural Terminology codes. We used an interrupted time-series analysis to evaluate abdominal and supracervical hysterectomy trends surrounding The Wall Street Journal article first reporting morcellation safety concerns and the FDA safety communication. We compared categorical and continuous variables using χ, t, and Wilcoxon rank sum tests. RESULTS: We identified 179,950 hysterectomies; laparoscopy was the most common mode of hysterectomy in every quarter. Before The Wall Street Journal article, there was no significant change in proportion of abdominal hysterectomies (0.3% decrease/quarter, P=.14). After The Wall Street Journal article, use of abdominal hysterectomy increased 1.1% per quarter for two quarters through the FDA warning (P<.001), plateaued for three quarters until March 2015 (P=.65), then decreased by 0.8% per quarter through 2016 (P<.001). Supracervical hysterectomy volume continuously decreased after the FDA warning (1.0% decrease per quarter, P<.001) and after three quarters (0.7% decrease per quarter, P=.01), then plateaued from April 2015 through 2016 (0.05% decrease per quarter, P=.40). Mode of supracervical hysterectomy was unchanged from 2012 to 2013 (P=.43), followed by two quarters of significant increase in proportion of supracervical abdominal hysterectomies (11.7%/quarter, P<.001). This change in mode of supracervical hysterectomy then plateaued through 2016 (P=.06). CONCLUSION: Despite early studies suggesting that minimally invasive hysterectomy decreased in response to safety concerns regarding power morcellation, we found that this effect reversed 1 year after the FDA safety communication. However, there was a sustained decline in supracervical hysterectomy, and the remaining supracervical hysterectomies were more likely to be performed using laparotomy.

Nomogram for survival after primary surgery for bulky stage IIIC ovarian carcinoma.

OBJECTIVE: Nomograms have been developed for numerous malignancies to predict a specific individual's probability of long-term survival based on known prognostic factors. To date, only one prediction model has been reported for patients with epithelial ovarian carcinoma (EOC). The objective of this study was to develop a more accurate survival nomogram for patients with bulky stage IIIC EOC. PATIENTS AND METHODS: Nomogram predictor variables included age, tumor grade, histologic type, preoperative platelet count, ascites, and residual disease after primary cytoreduction. Disease-specific survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression was used for multivariate analysis, which was the basis for the nomogram. The concordance index was used as an accuracy measure with bootstrapping to correct for optimistic bias. RESULTS: A total of 424 evaluable patients with bulky stage IIIC EOC underwent primary surgery at our institution during the study period of 1/89 to 12/03. All patients received postoperative platinum-based systemic chemotherapy. EOC-specific survival at 5 years was 51%. Using the six predictor variables, a nomogram was constructed and internally validated using bootstrapping. It was shown to have excellent calibration with a bootstrap corrected concordance index of 0.67, which was more accurate in predicting survival at this stage than the previously published model (concordance index=0.53). CONCLUSION: Utilizing six readily accessible predictor variables, our nomogram more accurately predicted 5-year disease-specific survival for bulky stage IIIC EOC than the previously published model. This tool may be useful for patient counseling, determination of clinical trial eligibility, and postoperative management.

Participation in global health delivery: Survey results from the Society of Gynecologic Oncology.

•Gynecologic oncologists face multiple barriers in participating in global health.•Several barriers may be addressed at the institutional level.•Most global health experiences involved direct patient care, while only a small proportion involved research.•Gynecologic oncologists receive little structured training in global health.

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.

Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers.

PURPOSE: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma. EXPERIMENTAL DESIGN: Gene expression profiles were generated from 21 primary chemosensitive tumors and 24 primary chemo-resistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy ("post-chemotherapy" tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance. RESULTS: Comparison of primary chemosensitive and chemo-resistant tumors revealed differential expression of 85 genes (P < 0.001). Comparison of gene expression profiles of primary chemosensitive tumors and post-chemotherapy tumors revealed more robust differences with 760 genes differentiating the two groups (P < 0.001). In contrast, only 230 genes were differentially expressed between primary chemo-resistant and post-chemotherapy groups (P < 0.001). Common to both gene lists were 178 genes representing transcripts differentially expressed between post-chemotherapy tumors and all primary tumors irrespective of intrinsic chemosensitivity. The gene expression profile of post-chemotherapy tumors compared with that of primary tumors revealed statistically significant overrepresentation of genes encoding extracellular matrix-related proteins. CONCLUSIONS: These data show that gene expression profiling can discriminate primary chemo-resistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions.

Choice of normal ovarian control influences determination of differentially expressed genes in ovarian cancer expression profiling studies.

PURPOSE: As with many cancers thought to be of epithelial origin, expression profiling studies of ovarian cancer have relied on a variety of sources of normal cells for comparison with tumors, including whole ovary samples (WO), ovarian surface epithelium (OSE) exposed to short-term culture, and immortalized OSE cell lines (IOSE). Our purpose was to assess the impact of the use of different types of normal controls on the determination of gene expression alterations in ovarian cancer studies. EXPERIMENTAL DESIGN: We compared the gene expression profiles generated on an 11,000-element cDNA microarray of OSE brushings, whole ovary samples, short-term cultures of normal OSE, SV40 large T antigen-immortalized OSE cell lines, and telomerase-immortalized OSE cell lines. The function of the groups as normal controls was then assessed by separate comparisons of each group to a set of 24 serous ovarian carcinoma samples. RESULTS: The normal groups formed robust, distinct clusters in hierarchical clustering and multidimensional scaling. The Pearson correlation coefficient for all combinations of any two of the groups ranged from 0.04 to 0.54, emphasizing the disparity of the groups. In the gene lists produced by comparing each normal group with the ovarian cancer samples, the majority of genes were unique to that normal-cancer comparison, with no gene appearing on all five lists. CONCLUSIONS: These results suggest that the selection of a normal control to compare with epithelial ovarian cancer samples in microarray studies strongly influences the genes that are identified as differentially expressed and complicates comparison with studies using a different normal control.

Urinary incontinence, depression, and economic outcomes in a cohort of women between the ages of 54 and 65 years.

OBJECTIVE: To estimate the association between urinary incontinence (UI) and probable depression, work disability, and workforce exit. METHODS: The analytic sample consisted of 4,511 women enrolled in the population-based Health and Retirement Study cohort. The analysis baseline was 1996, the year that questions about UI were added to the survey instrument, and at which time study participants were 54-65 years of age. Women were followed-up with biennial interviews until 2010-2011. Outcomes of interest were onset of probable depression, work disability, and workforce exit. Urinary incontinence was specified in different ways based on questions about experience and frequency of urine loss. We fit Cox proportional hazards regression models to the data, adjusting the estimates for baseline sociodemographic and health status variables previously found to confound the association between UI and the outcomes of interest. RESULTS: At baseline, 727 participants (survey-weighted prevalence, 16.6%; 95% confidence interval [CI] 15.4-18.0) reported any UI, of which 212 (survey-weighted prevalence, 29.2%; 95% CI 25.4-33.3) reported urine loss on more than 15 days in the past month; and 1,052 participants were categorized as having probable depression (survey-weighted prevalence, 21.6%; 95% CI 19.8-23.6). Urinary incontinence was associated with increased risks for probable depression (adjusted hazard ratio, 1.43; 95% CI 1.27-1.62) and work disability (adjusted hazard ratio, 1.21; 95% CI 1.01-1.45), but not workforce exit (adjusted hazard ratio, 1.06; 95% CI 0.93-1.21). CONCLUSION: In a population-based cohort of women between ages 54 and 65 years, UI was associated with increased risks for probable depression and work disability. Improved diagnosis and management of UI may yield significant economic and psychosocial benefits.

Value of additional level sections in the evaluation of lymph nodes for endometrial carcinoma staging.

OBJECTIVES: To evaluate the value of deeper sections for conventional (non-sentinel) lymph node dissections in high-risk endometrial carcinoma (EC). METHODS: We conducted a retrospective review of all ECs with high-grade or serous histology, more than 50% myometrial invasion or International Federation of Gynecology and Obstetrics (FIGO) pathologic stage greater than 2, and conventional complete pelvic lymph node dissections. No sentinel lymph node (SLN) biopsies were performed. Nodes were originally processed entirely in 3-mm slices, with residual fatty tissue submitted separately. When lymph nodes were negative on original H&E sections, paraffin blocks were sectioned to produce 1 additional H&E slide at approximately 0.8 mm deep. With positive nodes, we examined the relationship between micrometastases, staging parameters, and recurrence. RESULTS: Fifty-one high-risk cases were identified, with a median of 15 pelvic lymph nodes per case. Fifteen (29%) cases contained positive nodes. Review of the original slides and additional sections of all blocks from the remaining 36 cases failed to reveal metastases. Statistically significant associations were found between node status and depth of myometrial invasion, lymphovascular invasion, and FIGO stage. We found no significant relationship between lymph node status and serous histology. CONCLUSIONS: Our results suggest that enhanced detection of metastasis by SLN biopsies may be related to targeted lymph node selection rather than additional histologic sectioning.

Assessment of long-term knowledge retention following single-day simulation training for uncommon but critical obstetrical events.

OBJECTIVE: The objectives were to determine (i) whether simulation training results in short-term and long-term improvement in the management of uncommon but critical obstetrical events and (ii) to determine whether there was additional benefit from annual exposure to the workshop. METHODS: Physicians completed a pretest to measure knowledge and confidence in the management of eclampsia, shoulder dystocia, postpartum hemorrhage and vacuum-assisted vaginal delivery. They then attended a simulation workshop and immediately completed a posttest. Residents completed the same posttests 4 and 12 months later, and attending physicians completed the posttest at 12 months. Physicians participated in the same simulation workshop 1 year later and then completed a final posttest. Scores were compared using paired t-tests. RESULTS: Physicians demonstrated improved knowledge and comfort immediately after simulation. Residents maintained this improvement at 1 year. Attending physicians remained more comfortable managing these scenarios up to 1 year later; however, knowledge retention diminished with time. Repeating the simulation after 1 year brought additional improvement to physicians. CONCLUSION: Simulation training can result in short-term and contribute to long-term improvement in objective measures of knowledge and comfort level in managing uncommon but critical obstetrical events. Repeat exposure to simulation training after 1 year can yield additional benefits.

Description and validation of the Pelv-Sim: a training model designed to improve gynecologic minimally invasive suturing skills.

STUDY OBJECTIVE: To describe and validate the Pelv-Sim trainer, an innovative training model for gynecologic laparoscopic suturing with 4 laparoscopic exercises: closing an open vaginal cuff, transposing an ovary to the pelvic sidewall, ligating an infundibulopelvic ligament, and closing a port-site fascial incision. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: Academic medical center. PARTICIPANTS: Obstetrics and gynecology residents (n = 19) and third-year medical students (n = 10). INTERVENTIONS: To test the Pelv-Sim model for construct validity, all participants were timed as they completed the 4 tasks, and their performances were compared. The residents were then randomized to a study group asked to train with the Pelv-Sim for 1 hour/week for 10 weeks, or to a control group. To evaluate the effectiveness of training with the Pelv-Sim model, both groups of residents were retested at the end of the 10-week study period. Pretraining and posttraining performances were compared within each group. MEASUREMENTS AND MAIN RESULTS: Before the intervention, the residents completed all 4 tasks in significantly less time than the medical students (all p values