Pharmacological treatment of ectopic pregnancy: Accuracy, safety and cost-effectiveness of day 1-7 ß-hCG measurements.

OBJECTIVE: The aim of the present study was to compare accuracy, safety and cost-effectiveness of three ß-hCG measurements protocols, applied in managing ectopic pregnancies (EP) with methotrexate (MTX): (1) day 1 to 7 ß-hCG levels, (2) day 1 to 4 ß-hCG levels and (3) day 4 to 7 ß-hCG levels. METHODS: Cost-minimization analysis (CMA) based on a retrospective study of patients treated with single-dose MTX for EP, was evaluated at a single institution between January 2001 to May 2021. Successful MTX treatment was defined as no surgical intervention. We evaluated safety by analyzing cases of day 4 interventions and cases of inconsistency between the different protocols. Predicting accuracy was assessed by the area under the receiver operating characteristic (AUC) curve. RESULTS: A total of 229 patients with single dose MTX treatment were included. Overall, 184 (80.3%) patients were treated successfully with a single dose of MTX. For days 1 and 7 the optimal cutoff point was 7% reduction in ß-hCG levels with sensitivity, specificity and PPV of 76.6% (69.9-82.5, 95% CI), 75.5% (60.5-87.1, 95% CI) and 92.8% (88.4-95.6, 95% CI), respectively. There was no significant difference between the protocols' AUC. None of the patients had any change of management during their day 4 visit in our 20 years of records. The cost for each visit day (day 4 and 7) was calculated with a total cost of 251 USD per patient. CONCLUSION: Patients treated with MTX for EP, measurement of day 1 and day 7 ß-hCG serum levels has a cost minimization advantage and is not inferior to the traditional protocol for predictive accuracy and safety.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Ethnic disparity in cervical cancer stage at diagnosis: A retrospective study in an Israeli referral-center.

OBJECTIVE: To compare stage and survival of cervical cancer between Jewish and Arab women in a tertiary medical center in Israel. METHODS: Retrospective study of consecutive women diagnosed with cervical cancer in a single institution between 2010 and 2021. We compared Jewish and Arab patients using univariate, multivariable, and survival curves analysis. RESULTS: Overall, 207 Jewish women and 45 Arab women were included with a median follow up of 20 months (interquartile range 7-46 months). The groups did not differ in median body mass index, mean age at diagnosis, or menopausal status. Arab women had higher parity. Arab women were at a higher risk to be diagnosed with advanced stage disease (≥2b) (84.4% vs. 57% Arab and Jewish women, respectively, P < 0.001). In a multivariable regression analysis, Arab descent was found to be the only independent factor associated with advanced stage disease (odds ratio 3.95, 95% confidence interval 1.54-10.10). Overall survival and stage-specific survival were not different between the ethnic groups. CONCLUSIONS: Advanced stage at diagnosis was more prevalent in Arab women compared with Jewish women with cervical cancer, whereas stage-specific survival was similar. Further studies addressing possible contributing factors to inequality should be undertaken to find corrective measures.

Sentinel lymph node mapping in endometrial cancer: A comparison of main national and international guidelines.

OBJECTIVES: To compare national and international guidelines regarding sentinel lymph node (SLN) mapping in endometrial cancer. METHODS: A descriptive comparative study of the National Comprehensive Cancer Network (NCCN), the Society of Gynecologic Oncology (SGO), the European Society of Gynecological Oncology (ESGO), the British Gynecological Cancer Society (BGCS), and the Japan Society of Gynecologic Oncology (JSGO) guidelines. RESULTS: There is a broad consensus that SLN mapping is an appropriate alternative to pelvic lymphadenectomy for uterine-confined endometrioid endometrial cancer (five of five guidelines). It is broadly accepted that a full lymphadenectomy should be performed in case of failed SLN mapping (four of five guidelines), and that mapping with the fluorescent dye indocyanine green is superior to other methods (four of five guidelines). It is agreed that the cervix is the preferable site for dye injection (four of five guidelines), and pathology ultrastaging is advocated by most guidelines (three of five guidelines). Regarding high-risk patients (i.e., high-grade histology and non-endometroid carcinomas), some guidelines accept (three of five), but others currently do not advocate (one of five guidelines), SLN mapping as a sole method for lymph node evaluation. There is no consensus regarding para-aortic lymph node evaluation in pelvic SLN-positive patients. CONCLUSION: Guidelines for SLN mapping are comparable with regards to surgical technique, ultrastaging, and management in case of failed mapping. Nevertheless, some variations exist regarding the management of high-grade histology and positive pelvic lymph nodes.

Impact of robotic surgery on patient flow and resource use intensity in ovarian cancer.

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.

Ovarian cancer risk management in BRCA-mutation carriers: A comparison of six international and national guidelines.

OBJECTIVE: Germline mutations in the BRCA gene account for most hereditary ovarian and breast cancer. Management of healthy carriers aims to prevent and allow early detection of breast and ovarian cancer. This study compares six different hereditary ovarian cancer management guidelines, highlighting areas of controversy between different societies. We aim to compare international and national guidelines regarding BRCA carriers' management. STUDY DESIGN: A comparative study. We retrieved, reviewed, and compared the most recent guidelines of BRCA mutation carriers from the specializing societies NCCN (National Comprehensive National network) and ESMO (European society of medical oncology), and national societies of the United States (American College of Obstetricians and Gynecologists), England (the Royal College of Obstetricians and Gynecologists), Canada (the Society of Obstetricians and Gynaecologists of Canada) and Spain (Sociedad Española de Oncología Médica). RESULTS: There is a broad consensus regarding the limited role of screening for early ovarian cancer detection (4 out of 6) (4/6) and regarding the recommendation for implementation of Risk-reducing salpingo-oophorectomy (RRSO) (6/6), some variations exist for age at RRSO. It is widely accepted that risk reducing salpingectomy should be performed only as part of research (5/6), and that the addition of risk-reducing hysterectomy should be individualized (3/6). Not all guidelines address fertility issues, and controversy exists regarding hormone replacement therapy (HRT) recommendations in unaffected young BRCA-mutation carriers following RRSO. CONCLUSION: BRCA carrier's management guidelines consist of well-agreed topics such as the ineffective screening for early detection of ovarian cancer and the recommendation of RRSO. HRT remains controversial. Conforming unified recommendations is needed for providing evidence-based recommendations.

Surgical and oncological outcomes of sentinel lymph node sampling in elderly patients with intermediate to high-risk endometrial carcinoma.

OBJECTIVE: We aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy. METHODS: We conducted a retrospective study of elderly (>65-year-old) patients diagnosed with endometrial cancer between December 2007 and August 2017. These patients had been treated at a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) lymphadenectomy, 2) lymphadenectomy and SLN sampling, 3) SLN sampling alone. Using life tables, Kaplan-Meier survival curves and log-rank tests, we analyzed 2-year progression-free survival, overall survival, and disease-specific survival. RESULTS: Our study included 278 patients with a median age of 73 years (range; 65-91): 84 (30.2%) underwent lymphadenectomy, 120 (43.2%) underwent SLN sampling with lymphadenectomy, and 74 (26.6%) had SLN sampling alone. The SLN sampling alone group had shorter operative times with a median duration of 199 minutes (range, 75-393) compared with 231 (range, 125-403) and 229 (range, 151-440) minutes in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts; respectively (p<0.001). The SLN sampling alone group also had lower estimated blood loss with a median loss of 20 mL (range, 5-150) vs 25 mL (range, 5-800) and 40 mL (range, 5-400) in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts, respectively (p=0.002). The 2 year overall survival and progression-free survival were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, American Society of Anesthesiologists (ASA) score, stage, grade, and lymphovascular space invasion, adding SLN sampling was associated with better overall survival, (HR 0.2, CI [0.1 to 0.6], p=0.006) and progression-free survival (HR 0.5, CI [0.1 to 1.0], p=0.05). CONCLUSION: Sentinel lymph node-based surgical staging is feasible and associated with better surgical outcomes and comparable oncological outcomes in elderly patients with intermediate and high-risk endometrial cancer.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study.

OBJECTIVE: To compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. STUDY DESIGN: A retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. RESULTS: Over a median follow-up period of 3 years (interquartile range, 1.5-6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV - respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19-4.20). Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). CONCLUSIONS: In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Inhibition of Poly ADP-Ribose Glycohydrolase Sensitizes Ovarian Cancer Cells to Poly ADP-Ribose Polymerase Inhibitors and Platinum Agents.

BACKGROUND: Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin. METHODS: PARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle. RESULTS: PARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction. CONCLUSIONS: PARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects.

Identification of Predictive Biomarkers for Lymph Node Involvement in Obese Women With Endometrial Cancer.

Obesity, an established risk factor for endometrial cancer (EC), is also associated to increased risks of intraoperative and postoperative complications. A reliable tool to identify patients at low risk for lymph node (LN) metastasis may allow minimizing the surgical staging and omit lymphadenectomy in obese patients. To identify molecular biomarkers that could predict LN involvement in obese patients with EC we performed gene expression analysis in 549 EC patients using publicly available transcriptomic datasets. Patients were filtrated according to cancer subtype, weight (>30 kg/m2) and LN status. While in the LN+ group, NEB, ANK1, AMIGO2, LZTS1, FKBP5, CHGA, USP32P1, CLIC6, CEMIP, HMCN1 and TNFRSF10C genes were highly expressed; in the LN- group CXCL14, FCN1, EPHX3, DDX11L2, TMEM254, RNF207, LTK, RPL36A, HGAL, B4GALNT4, KLRG1 genes were up-regulated. As a second step, we investigated these genes in our patient cohort of 35 patients (15 LN+ and 20 LN-) and found the same correlation with the in-silico analysis. In addition, immunohistochemical expression was confirmed in the tumor tissue. Altogether, our findings propose a novel panel of genes able to predict LN involvement in obese patients with endometrial cancer.

Absence of prognostic value of lymphovascular space invasion in patients with endometrial cancer and negative sentinel lymph nodes.

OBJECTIVE: To evaluate if the prognostic value of lymphovascular space invasion (LVSI) is different in endometrial cancer patients with negative lymph nodes following sentinel lymph node (SLN) mapping or lymph node dissection (LND) as staging procedure. MATERIAL AND METHODS: A retrospective study of 510 patients diagnosed with endometrial carcinoma in our institution between 2007 and 2014. We excluded patients that were diagnosed with positive nodes (Stage IIIc). We compared patients' characteristics and survival outcomes as function of their LVSI status (positive LVSI vs negative LVSI subgroups) in each cohort separately. RESULTS: 413 patients met the inclusion criteria, out of whom 239 underwent SLN and 174 patients underwent LND only. In the SLN group, life table analysis showed 5-year OS and PFS of 80% and 72% in patients with LVSI compared to 96%, and 93% without LVSI. Same trend was observed among patients with LND with 5-year OS and PFS of 74% and 64% in patients with LVSI compared to 97%, and 90% without LVSI. On multivariable analysis, adjusted for age, FIGO stage, grade and maximal tumor size, the favorable survival of negative LVSI remained only in the LND cohort (SLN cohort: HR 1.2, CI [0.3-4.0], P = 0.8 and HR 1.7, CI [0.7-4.3], p = 0.2 for OS and PFS, respectively; LND cohort: HR 3.1, CI [1.4-6.5], p < 0.001 and HR 2.5, CI [1.2-4.9], p = 0.01 for OS and PFS, respectively). CONCLUSIONS: The prognostic value of LVSI disappears when patients undergo staging with SLN and are found to have negative nodes in contrast to those who have undergone LND. Future studies should confirm our observation on patients with negative sentinel nodes, and plan on tailoring adjuvant treatment to this specific subgroup.

Sentinel Lymph Node Sampling as an Alternative to Lymphadenectomy in Patients With Endometrial Cancer and Obesity.

OBJECTIVE: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes. METHODS: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease. RESULTS: Out of 223 patients with a median BMI of 40.6 kg/m2, 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively). CONCLUSIONS: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years.

Surgical Technique for Sentinel Lymph Node Sampling in Presumed Early-stage Ovarian Cancer.

STUDY OBJECTIVE: Surgical staging for apparent early-stage ovarian cancer includes systematic pelvic and para-aortic lymph node evaluation to detect occult stage III disease [1]. Although, lymphadenectomy procedure is associated with increased duration of surgery and a 13% risk of lymphocyst formation [2]. Sentinel lymph node (SLN) biopsy is still investigational, and no standardized approach has been studied. Recent mounting evidence has approved the applicability of SLN technique in early-stage ovarian cancer [3,4]. The objective of this video is to demonstrate a surgical technique for robotic performance of SLN biopsy in presumed early-stage ovarian cancer. DESIGN: Stepwise demonstration of the robotic technique for SLN sampling in presumed early-stage ovarian cancer. This video report is part of an institutional, investigational review board-approved study. SETTING: Academic tertiary referral center. INTERVENTIONS: This video presents our team's robotic technique for SLN sampling in a 37-year-old woman who presented to our center with a 10-cm right complex adnexal mass, suspicious for malignancy. A 27-gauge spinal needle was inserted through the abdominal wall under direct visualization. We injected 0.5 mL of dilute indocyanine green solution (Novadaq Technologies, Mississauga, Ontario, Canada) (1.25 mg/mL) subperitoneally into the utero-ovarian ligament. The SLN was checked with the fluorescence-guided camera of the Xi DaVinci robotic system (Sunnyvale, CA). Eight to 10 minutes after the injection, a right para-aortic SLN was identified, and dissection was performed. After dissection, the node was extracted and sent to pathology for evaluation by ultra-staging. The final pathology revealed a stage IA low-grade serous ovarian cancer. CONCLUSION: SLN sampling appears to be feasible in presumed early-stage ovarian cancer and may allow the avoidance of systematic lymph node dissection in this set of patients.

Endometrial Cancer in Germline BRCA Mutation Carriers: A Systematic Review and Meta-analysis.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software. METHODS OF STUDY SELECTION: Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous results from each of the studies eligible for the meta-analysis were expressed as the proportion of patients with EC or UPSC per total number of BRCA mutation carriers, with 95% confidence interval (CI). The Mantel-Haenszel statistical method was used. TABULATION, INTEGRATION, AND RESULTS: Eleven studies reported the outcome of interest and were included in the final meta-analysis. In total, 13 871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutation carriers were 82/13 827 (0.59%) and 19/11 582 (0.16%), respectively. The EC prevalence was 46/7429 (0.62%) in BRCA1 mutation carriers and 17/3546 (0.47%) in BRCA2 mutation carriers, with relative risk of 1.18 (95% CI, 0.7-2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (relative risk 1.39; 95% CI, 0.5-3.7). CONCLUSION: Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.

Short- and Long-Term Complications of Intraoperative Benign Ovarian Cyst Spillage: A Systematic Review and Meta-analysis.

OBJECTIVE: To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts. DATA SOURCES: The Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched using the following terms and their combinations: "spillage," "rupture," "leakage," "ovarian cyst," "teratoma," "dermoid," "operative," "surgery," "outcome." METHODS OF STUDY SELECTION: Randomized controlled and observational studies evaluating the operative outcomes of surgical treatment of ovarian cysts with intraoperative spillage compared with those of surgical treatment of ovarian cysts without spillage were included. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. TABULATION, INTEGRATION, AND RESULTS: A total of 28 studies were included in the qualitative analysis and 12 in the quantitative analysis. Ovarian cyst diameter was not found to be associated with the risk for spillage (relative risk [RR] 0.75; 95% confidence interval [CI], -0.33 to 1.82). Intraoperative benign ovarian cyst rupture was not associated with adverse short- and long-term outcomes such as reoperation (RR 1.16; 95% CI, 0.39-3.48), infertility (RR 0.73; 95% CI, 0.15-3.63), transient fever (RR 3.22; 95% CI, 0.83-12.51), and readmission (RR 1.00; 95% CI, 0.33-2.98). However, intraoperative spillage was found to be associated with increased risk for benign recurrence (RR 3.1; 95% CI, 1.05-9.14). A subgroup analysis of the studies that included only dermoid cysts showed an association between intraoperative cyst rupture and postoperative chemical peritonitis (RR 9.36; 95% CI, 1.20-73.28). CONCLUSION: Intraoperative ovarian cyst spillage of a benign cyst is associated with limited adverse clinical outcomes. Although the surgical approach (minimally invasive vs open) should not be affected by the concern regarding an intraoperative cyst rupture, maximal efforts should be made to prevent intra-abdominal spillage.

Similar Overall Survival Using Neoadjuvant Chemotherapy or Primary Debulking Surgery in Patients Aged Over 75 Years with High-Grade Ovarian Cancer.

OBJECTIVE: To perform a hypothesis-generating evaluation of patient outcomes following neoadjuvant chemotherapy (NACT) compared with those following primary debulking surgery (PDS) in patients over age 75 with high-grade ovarian cancer. METHODS: This was a retrospective cohort study of consecutive patients aged 75 years and older, with high-grade ovarian cancer. Data were analyzed in SPSS 25.0 using descriptive statistics to characterize groups based on primary treatment modality, Kaplan-Meier survival curves to estimate overall and progression-free survival, and Cox proportional hazards to analyze confounders. RESULTS: Of 429 patients with stages III and IV high-grade ovarian cancer (endometrioid and serous), 71 were aged older than 75 years and met our criteria for inclusion; 58 were treated with NACT while 13 underwent primary debulking. Sixteen patients did not undergo interval debulking following NACT. There were no significant differences in demographic characteristics between the groups. Following NACT, more patients were completely debulked-36.2% versus 21% (P = 0.000)-and had a shorter length of stay (5 vs. 7 d; P = 0.018). Overall survival was similar between the NACT and PDS groups (58.7 vs. 59.7 mo; LR -0.836; P = 0.361) despite lower progression-free survival in the NACT group (25.9 vs. 47.1 mo; P = 0.042; LR 4.31). Both progression-free and overall survival were significantly higher when patients undergoing NACT achieved complete debulking (21.7 and 102.3 mo, respectively) compared with suboptimal debulking (12.03 and 14.2 mo, respectively). CONCLUSION: In this select group older patients with stage III and IV high-grade ovarian cancers, neoadjuvant chemotherapy may be considered without compromising outcomes and contributes to complete debulking.

The added value of sentinel node mapping in endometrial cancer.

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.

The impact of wait times on oncological outcome in high-risk patients with endometrial cancer.

OBJECTIVE: To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer. METHODS: All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. RESULTS: A total of 136 patients with grade 3 endometrial cancer were followed for a median of 5.6 years. Fifty-one women (37.5%) waited more than 12 weeks for surgery. Prolonged surgical wait times were not associated with advanced stage at surgery, positive lymph nodes, increased lymphovascular space invasion, and tumor size (P = .8, P = 1.0, P = .2, P = .9, respectively). In multivariable analysis adjusted for clinical and pathological factors, wait times did not significantly affect disease-specific survival (adjusted hazard ratio [HR]: 1.2, 95% confidence interval [CI], 0.6-2.5, P = .6), overall survival (HR: 1.1, 95% CI, 0.6-2.1, P = .7), or progression-free survival (HR: 0.9, 95% CI, 0.5-1.7, P = .8). CONCLUSION: Prolonged surgical wait time for poorly differentiated endometrial cancer seemed to have a limited impact on clinical outcomes compared to biological factors.

CA-125 reduction during neoadjuvant chemotherapy is associated with success of cytoreductive surgery and outcome of patients with advanced high-grade ovarian cancer.

INTRODUCTION: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. MATERIAL AND METHODS: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. RESULTS: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05). CONCLUSIONS: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.