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To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS).Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models.Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p 0.05) and neoadjuvant chemotherapy (p 0.001) were associated with worse PFS and OS.In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.

Objectives To identify risk factors for Cesarean delivery and non-reassuring fetal heart tracing (NRFHT) in pregnancies with a small-for-gestational-age (SGA) fetus undergoing induction of labor and to design and validate a prediction model, combining antenatal and intrapartum variables known at the time of labor induction, to identify pregnancies at increased risk of Cesarean delivery. Methods This was a retrospective cohort study of non-anomalous, singleton gestations with a SGA fetus that underwent induction of labor, delivered in a single tertiary referral center between January 2011 and December 2016. SGA was defined as estimated fetal weight (EFW) Results A total of 594 pregnancies were included. Cesarean delivery was performed in 243 (40.9%) pregnancies. Significant risk factors associated with Cesarean delivery, and included in the final model, were maternal age, gestational age at delivery and initial method of labor induction. The bootstrap estimate of the AUC of the final prediction model for Cesarean delivery was 0.82 (95% CI, 0.78-0.86). The model had sensitivity of 64.2%, specificity of 86.9%, positive likelihood ratio (LR) of 4.9 and negative LR of 0.41. The model had good fit (P = 0.617). NRFHT complicated 117 (19.7%) pregnancies. Significant risk factors for NRFHT included EFW 95th percentile or absent/reversed end-diastolic flow) and gestational age at delivery. The final prediction model for NRFHT had an AUC of 0.69 (95% CI, 0.63-0.75) and specificity of 97.0%. Conclusion We identified several significant risk factors for Cesarean delivery and NRFHT among SGA pregnancies undergoing induction of labor. Clinicians may use these risk factors to guide patient counseling and to help anticipate the potential need for operative delivery. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis.An IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed.Of the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24).In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer.This multicenter retrospective study examined women aged50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy.During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged.Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

BackgroundGynecologic oncology surgery is associated with a wide variation in surgical site infection risk. The optimal method for infection prevention in this heterogeneous population remains uncertain.Study DesignA retrospective cohort study was performed to compare surgical site infection rates for patients undergoing hysterectomy over a 1-year period surrounding the implementation of an institutional infection prevention bundle. The bundle comprised pre-operative, intra-operative, and post-operative interventions including a dual-agent antibiotic surgical prophylaxis with cefazolin and metronidazole. Cohorts consisted of patients undergoing surgery during the 6 months prior to this intervention (pre-bundle) versus those undergoing surgery during the 6 months following the intervention (post-bundle). Secondary outcomes included length of stay, readmission rates, compliance measures, and infection microbiology. Data were compared with pre-specified one-sided exact test, Chi-square test, Fisher’s exact test, or Kruskal–Wallis test as appropriate.ResultsA total of 358 patients were included (178 PRE, 180 POST). Median age was 58 (range 23–90) years. The post-bundle cohort had a 58% reduction in surgical site infection rate, 3.3% POST vs 7.9% PRE (−4.5%, 95% CI −9.3% to −0.2%, p=0.049) as well as reductions in organ space infection, 0.6% POST vs 4.5% PRE (−3.9%, 95% CI −7.2% to −0.7%, p=0.019), and readmission rates, 2.2% POST vs 6.7% PRE (−4.5%, 95% CI −8.7% to −0.2%, p=0.04). Gram-positive, Gram-negative, and anaerobic bacteria were all prevalent in surgical site infection cultures. There were no monomicrobial infections in post-cohort cultures (0% POST vs 58% PRE, p=0.04). No infections contained methicillin-resistant Staphylococcus aureus.ConclusionImplementation of a dual antibiotic infection prevention bundle was associated with a 58% reduction in surgical site infection rate after hysterectomy in a surgically diverse gynecologic oncology practice.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may be used to treat peritoneal based malignancies, such as epithelial ovarian cancer (EOC). Despite results of clinical trials supporting an increasing indication for HIPEC in EOC, concerns have existed regarding morbidity and challenges with initiating HIPEC at an institutional level. The objective of this review is to describe evidence-based recommendations to guide implementation of a HIPEC program, following our experience at a high-volume tertiary care center. Establishing a HIPEC program requires building a multi-disciplinary team, including gynecologic oncologists, anesthesia, nursing, perfusionists and pharmacists. Team members require education regarding HIPEC protocols, toxic waste and spill management, and personal protective equipment (PPE). Required equipment includes chemotherapy certified PPE and a HIPEC pump which is connected to inflow and outflow catheters placed within the peritoneal cavity. During the procedure, 3–6 L of a hyperthermic perfusate, composed of a isotonic crystalloid vehicle and the chemotherapy of choice, is infused through the peritoneal cavity with goal temperature of 41–43 °C. Prior to HIPEC infusion, surgical teams must communicate with anesthesia and pharmacy. In patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered one hour prior to chemotherapy to ensure adequate diuresis. Sodium thiosulfate may also be considered for renal protection (van Driel et al., n.d. [3]). We utilize a multi-agent pre-medication protocol prior to HIPEC infusion to reduce hypersensitivity reactions, renal toxicity and post-operative nausea and vomiting. Limited data exists to support the optimal regimen for HIPEC at the time of CRS in women with EOC. From our experience, we favor use of cisplatin 100 mg/m2 alone or in combination with paclitaxel 135–175 mg/m2 with 90 min of total perfusion time. Close attention to temperature and glycemic control is essential during the procedure, as electrolyte derangements including hyperglycemia, lactic acidosis and hypokalemia may occur. Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.

OBJECTIVES: This study aimed to assess the association between hormone replacement therapy and the incidence of subsequent malignancies in patients who underwent risk-reducing salpingo-oophorectomy and had mutations predisposing them to Müllerian cancers. METHODS: This Institutional Review Board-approved retrospective study was performed at five academic institutions. Women were included if they were age 18-51 years, had one or more confirmed germline highly penetrant pathogenic variants, and underwent risk-reducing salpingo-oophorectomy. Patients with a prior malignancy were excluded. Clinicodemographic data were collected by chart review. Patients with no documented contact for one year prior to study termination were called to confirm duration of hormone use and occurrence of secondary outcomes. Hormone replacement therapy included any combination of estrogen or progesterone. RESULTS: Data were analyzed for 159 women, of which 82 received hormone replacement therapy and 77 did not. In both groups an average of 6 years since risk reduction had passed. The patients treated with hormone replacement therapy did not have a higher risk of subsequent malignancy than those not treated with hormone replacement therapy (6 out of 82 vs. 7 out of 77, P=0.68). Patients who received hormone replacement therapy were younger than those who did not receive hormone replacement therapy (39.0 vs. 43.9 years, P

Objectives: Chemotherapy dose capping in overweight and obese advanced ovarian cancer patients remains controversial in regard to its effect on oncologic outcomes and toxicity. Methods: Women with stage III or IV ovarian cancer receiving carboplatin and paclitaxel as primary therapy in combination with surgical resection between 1/2007-12/2016 were included in this retrospective study evaluating the interaction between body mass index (BMI) and chemotherapy dose capping on progression free survival (PFS) and toxicity. A calculated carboplatin dose based on the planned AUC and actual body weight (ABW) at the time of the first chemotherapy cycle following debulking surgery was compared to the dose received at this time based on the electronic medical record. A 5% or greater difference in treatment plan dosing received compared to actual weight-based dose was considered clinically significant. Results: 263 ovarian cancer patients were included in analysis (233 serous, 7 endometrioid, 14 clear cell, 8 carcinosarcoma, 1 NOS). Median age was 64 years (35-86). 62 (23.6%) received neoadjuvant chemotherapy prior to debulking surgery and 236 (88.2%) of all patients had an optimal cytoreductive surgery of Download : Download high-res image (75KB) Download : Download full-size image Conclusions: Carboplatin dose modification using adjusted body weight over a BMI of 25 may have a negative effect on PFS in ovarian cancer patients receiving primary therapy. Toxicity does not appear to be increased in this population when actual body weight is used for carboplatin dosing.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare and commonly characterized as benign tumors, with infrequent reports of metastasis and recurrence. Treatment recommendations have not been well established, particularly for more advanced cases. We present the first reported death from a metastatic UTROSCT, summarize the available literature, and describe characteristics common to UTROSCTs with aggressive features. In this case, a 49-year-old woman presented with abdominal distension and pain; initial imaging and diagnostic workup suggested metastatic epithelial ovarian cancer to be the cause. The patient subsequently underwent neoadjuvant chemotherapy followed by optimal cytoreductive surgery and adjuvant chemotherapy. Final pathology revealed UTROSCT with omental and peritoneal metastases. She then underwent adjuvant chemotherapy with subsequent recurrence and died 15 months after her initial diagnosis. Our analysis of this case and the available literature led us to identify pathologic risk factors that may help predict aggressive UTROSCT behavior., Highlights • Uterine tumors resembling ovarian sex cord tumors are rare and generally considered benign. • Few aggressive/metastatic cases have been reported, and we report on the first death from this disease. • Analysis of the literature allowed for identification of potential pathologic risk factors of aggressive disease. • Better identifying these risk factors could help guide treatment recommendations for this tumor type.

Objective This systematic review aimed to evaluate oncologic and reproductive outcomes after fertility-sparing surgery (FSS) for early-stage cervical cancer (early CC). Data Sources Ovid MEDLINE, Ovid EMBASE, and Cochrane CENTRAL were searched from 1980 to the present using Medical Subject Headings terms; other controlled vocabulary terms; and keywords related to fertility, cervical cancer, and surgical techniques. Methods of Study Selection A total of 2415 studies were screened, with 53 studies included. Studies reporting recurrences with a median follow-up of 12 months in early CC (International Federation of Gynecology and Obstetrics 2009 stages IA with lymphovascular space invasion, IB, or IIA) of traditional histologic type undergoing FSS were included. Tabulation, Integration, and Results The studies were grouped by intervention, including vaginal radical trachelectomy (VRT), abdominal radical trachelectomy (ART), minimally invasive radical trachelectomy (MIS-RT), and conization or simple trachelectomy (ST), and studies involving neoadjuvant chemotherapy (NACT). Combined rates of recurrence (RR), cancer death (CDR), pregnancy (PR), and live birth (LBR) were calculated per procedure on the basis of all included studies that reported outcomes on that procedure. The results were as follows: VRT: RR 4%, CDR 1.7%, PR 49.4%, and LBR 65.0% ART: RR 3.9%, CDR 1.4%, PR 43.2%, and LBR 44.0% MIS-RT: RR 4.2%, CDR 0.7%, PR 36.2%, and LBR 57.1% Cone or ST: RR 4.2%, CDR 0.8%, PR 55.1%, and LBR 71.9% NACT: RR 7.5% and CDR 2.0% Conclusion FSS of early CC with VRT, ART, or MIS-RT have comparable oncologic outcomes in carefully selected patients, with reproductive outcomes favoring VRT. Data on nonradical FSS with cone or ST are less robust but support similar oncologic outcomes to radical trachelectomy with fewer reproductive complications. NACT in this setting requires more investigation before routine implementation into practice.

Highlights • Previously treated gynecologic clear cell tumors had a CPI response rate of 57% despite MSI stable status. • Immune related adverse events occurred in 40.3% of patients. • Patients who developed immune toxicity had higher ORR, PFS and OS. • In chemo-naïve MSI-H recurrent endometrial carcinoma ORR to CPI was 83%., Prognostic factors for immune checkpoint inhibitor (CPI) response in gynecologic cancer are limited. This retrospective study aimed to identify prognostic factors associated with improved overall response rate (ORR) and progression free survival (PFS) in gynecologic cancer patients receiving at least two cycles of CPI. PFS was compared by univariate cox regressions. Univariate and multivariable analyses were used for prognostic factors of PFS and ORR. 72 patients were identified (20 ovarian, 36 endometrial, 13 cervix, 1 vaginal, 2 others). Immune related adverse events (IRAE) occurred in 40.3% of patients (29/72). IRAE was associated with higher ORR (44.8% IRAE vs 20.9% no IRAE, OR 3.1, p = 0.024), improved PFS (12.9 m IRAE vs 4.7 m no IRAE, HR 0.43, p = 0.004) and improved OS (22.9 m IRAE vs 12.2 m no IRAE, HR 0.47, p = 0.021). Additionally, Clear cell histology had superior ORR compared to MSI stable endometrial and ovarian cancers (ORR 57.1% vs 11.8%, OR 10.0, p = 0.032). Responders more often had ARIDIA mutation, PI3K/PTEN alteration and less often had a P53 mutation. In a subset of six MSI-H, recurrent, chemo-naive endometrial cancer ORR was 83.3%. Overall, we found favorable outcomes after CPI for clear cell tumors and patients who developed IRAE. Additionally, first-line systemic therapy with CPI in recurrent MSI-H endometrial cancer had encouraging ORR with durable responses.