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Placenta Accreta Spectrum (PAS) is an invasive placental disorder characterized by significant maternal and fetal morbidity. Utilization of multidisciplinary teams has been shown to optimize patient outcomes. Our objective was to assess the impact of cesarean hysterectomy performed by gynecologic oncologists versus Ob/Gyn specialists in maternal morbidity.A retrospective cohort study was performed of singleton, non-anomalous pregnancies complicated by PAS University of Texas Health San Antonio Placenta Accreta program from 2010 to 2021. Our primary outcome was a maternal morbidity composite of any of the following: estimated blood loss2 L, ICU admission, intraoperative acidosis and post-operative length of stay4 days. In addition, demographic and pregnancy data were obtained. Univariate and multivariate analyses were performed to identify the individual impact of variables such as general anesthesia, episodes of vaginal bleeding, uterine artery embolization, emergent delivery and placenta percreta pathology.122 pregnancies complicated by PAS who underwent cesarean hysterectomy were identified from 2010 to 2021. Gynecologic oncologists were the primary surgeons for 62 (50.8%) of these cases. The involvement of gynecologic oncologists increased over the time period from 16% to 80%. Gynecologic oncologists were more like to be involved in cases with an antenatal diagnosis of placenta percreta (11.7 vs 37.1%, p = 0.001) and these cases were characterized by increased composite maternal morbidity (65 vs 83.9%, p = 0.02). These cases were also significantly longer (151 vs 271 min, p0.0001), involved greater usage of urinary stents (36.7 vs 66.1%, p = 0.002) and had longer post-operative lengths of stay (3 vs 4 days, p0.0001). PAS cesarean hysterectomies by gynecologic oncologists were less likely to be supracervical (25 vs 3.2%, p = 0.0005). Multivariate analysis controlling for placenta percreta, uterine artery embolization, vaginal bleeding and emergent delivery showed no difference in composite maternal morbidity (aOR = 0.95, 95%CI [0.35-2.52]) and lower rates of intraoperative acidosis (aOR = 0.36, 95%CI [0.14-0.93]) or post-operative length of stay4 days (aOR = 0.37, 95%CI [0.15-0.91]).Gynecologic oncologists play a critical role in the surgical management of PAS cesarean hysterectomies. When compared to Ob/Gyn specialists, gynecologic oncologists are more likely to act as primary surgeons in complex cases similar morbidity and greater post-operative outcomes.

Study Objective To evaluate the effect of expert guided mentorship on technical score and time for a set of robotic training drills. Design Prospective randomized controlled trial (Canadian Task Force classification I). Setting Academic institution. Subjects Fifty trainees in robotic surgery. Intervention Inexperienced trainees underwent either a 20-minute expert guided mentorship session or no intervention. The primary outcomes were technical score and time-to-drill completion for a set of dry lab robotic training drills evaluated at an initial and final skills assessment. The t-test, including paired analyses, was used to evaluate outcomes. Measurements and Main Results Forty-nine of 50 trainees (98%) completed the study. There were no significant differences in participant characteristics or initial performance between the 2 groups. During the final skills assessment, the intervention group demonstrated significantly better performance on 1 of 8 objective measures. They had a higher mean score for the bead transfer drill when compared with the control group (21.6 vs 19.9; p = .03). No differences in time-to-drill completion were noted between the 2 groups. Regardless of randomization, all participants had significantly improved scores for each of the drills on the final compared with the initial skills assessment (p

Objective Constitutive activation of STAT3 is a hallmark of various human cancers, however an increased pSTAT3 expression in high grade human endometrial cancer has not been reported. In the present study, we examine the expression of STAT family of proteins in endometrial cancer cell lines and the efficacy of HO-3867, a novel STAT3 inhibitor designed in our lab. Methods Expression of STAT family proteins was evaluated via Western blot. The cell viability, post-treatment with HO-3867, was assessed using MTT, cell-cycle profile and Annexin assay. In vivo efficacy of HO-3867 was evaluated using xenograft mice. Results Expression of activated STATs was inconsistent among the cell lines and 18 human endometrial cancer specimens tested. While pSTAT3 Tyr705 was not expressed in any of the cell lines, pSTAT3 Ser727 was highly expressed in endometrial cancer cell lines and tumor specimens. HO-3867 decreased the expression of pSTAT3 Ser727 while total STAT3 remained constant; cell viability decreased by 50–80% and induced G2/M arrest in 55% of Ishikawa cells at the G2/M cell cycle checkpoint. There was an increase in p53, a decrease in Bcl2 and Bcl-xL, and cleavage of caspase-3, caspase-7 and PARP. HO-3867 mediated a dosage-dependent inhibition of the growth of xenografted endometrial tumors. Conclusions HO-3867 treatment decreases the high levels of pSTAT3 Ser727 in endometrial cancer cells by inducing cell cycle arrest and apoptosis. This suggests a specific role of serine-phosphorylated STAT3, independent of tyrosine phosphorylation in the oncogenesis of endometrial cancer. HO-3867 could potentially serve as an adjunctive targeted therapy.

The objective of this study was to evaluate gynecologic oncology provider (GOP) practices regarding weight loss (WL) counseling, and to assess their willingness to initiate weight loss interventions, specifically bariatric surgery (WLS).Members of the Society of Gynecologic Oncology were invited to complete an online survey of 49 items assessing knowledge, attitudes, and behaviors related to WL counseling.A total of 454 participants initiated the survey, yielding a response rate of 30%. The majority of respondents (85%) were practicing GOP or fellows. A majority of responders reported that50% of their patient population is clinically obese (BMI ≥ 30). Only 10% reported having any formal training in WL counseling, most often in medical school or residency. Providers who feel adequate about WL counseling were more likely to offer multiple WL options to their patients (p.05). Over 90% of responders believe that WLS is an effective WL option and is more effective than self-directed diet and medical management of obesity. Providers who were more comfortable with WL counseling were significantly more likely to recommend WLS (p.01). Approximately 75% of respondents expressed interest in clinical trials evaluating WLS in obese cancer survivors.The present study suggests that GOP appreciate the importance of WL counseling, but often fail to provide it. Our results demonstrate the paucity of formal obesity training in oncology. Providers seem willing to recommend WLS as an option to their patients but also in clinical trials examining gynecologic cancer outcomes in women treated with BS.

STAT3 is well corroborated preclinically as a cancer therapeutic target, but tractable translational strategies for its blockade by small molecule inhibitors have remained elusive. In this study, we report the development of a novel class of bifunctional STAT3 inhibitors, based on conjugation of a diarylidenyl-piperidone (DAP) backbone to an N-hydroxypyrroline (–NOH) group, which exhibits minimal toxicity against normal cells and good oral bioavailability. Molecular modeling studies of this class suggested direct interaction with the STAT3 DNA binding domain. In particular, the DAP compound HO-3867 selectively inhibited STAT3 phosphorylation, transcription, and DNA binding without affecting the expression of other active STATs. HO-3867 exhibited minimal toxicity toward noncancerous cells and tissues but induced apoptosis in ovarian cancer cells. Pharmacologic analysis revealed greater bioabsorption and bioavailability of the active (cytotoxic) metabolites in cancer cells compared with normal cells. The selective cytotoxicity of HO-3867 seemed to be multifaceted, eliciting differential activation of the Akt pathway in normal versus cancer cells. RNAi attenuation experiments confirmed the requirement of STAT3 for HO-3867–mediated apoptosis in ovarian cancer cells. In vivo testing showed that HO-3867 could block xenograft tumor growth without toxic side effects. Furthermore, in primary human ovarian cancer cells isolated from patient ascites, HO-3867 inhibited cell migration/invasion and survival. Our results offer preclinical proof-of-concept for HO-3867 as a selective STAT3 inhibitor to treat ovarian cancer and other solid tumors where STAT3 is widely upregulated. Cancer Res; 74(8); 2316–27. ©2014 AACR.

Importance Poly(adenosine diphosphate-ribose) polymerase inhibitor and anti-programmed death receptor-1 inhibitor monotherapy have shown limited clinical activity in patients with advanced triple-negative breast cancer (TNBC). Objective To evaluate the clinical activity (primary) and safety (secondary) of combination treatment with niraparib and pembrolizumab in patients with advanced or metastatic TNBC. Design, setting, and participants This open-label, single-arm, phase 2 study enrolled 55 eligible patients with advanced or metastatic TNBC irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression at 34 US sites. Data were collected from January 3, 2017, through October 29, 2018, and analyzed from October 29, 2018, through February 27, 2019. Interventions Patients were administered 200 mg of oral niraparib once daily in combination with 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle. Main outcomes and measures The primary end point was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points were safety, disease control rate (DCR; complete response plus partial response plus stable disease), duration of response (DOR), progression-free survival (PFS), and overall survival. Results Within the full study population of 55 women (median age, 54 years [range, 32-90 years]), 5 patients had confirmed complete responses, 5 had confirmed partial responses, 13 had stable disease, and 24 had progressive disease. In the efficacy-evaluable population (n = 47), ORR included 10 patients (21%; 90% CI, 12%-33%) and DCR included 23 (49%; 90% CI, 36%-62%). Median DOR was not reached at the time of the data cutoff, with 7 patients still receiving treatment at the time of analysis. In 15 evaluable patients with tumor BRCA mutations, ORR included 7 patients(47%; 90% CI, 24%-70%), DCR included 12 (80%; 90% CI, 56%-94%), and median PFS was 8.3 months (95% CI, 2.1 months to not estimable). In 27 evaluable patients with BRCA wild-type tumors, ORR included 3 patients (11%; 90% CI, 3%-26%), DCR included 9 (33%; 90% CI, 19%-51%), and median PFS was 2.1 months (95% CI, 1.4-2.5 months). The most common treatment-related adverse events of grade 3 or higher were anemia (10 [18%]), thrombocytopenia (8 [15%]), and fatigue (4 [7%]). Immune-related adverse events were reported in 8 patients (15%) and were grade 3 in 2 patients (4%); no new safety signals were detected. Conclusions and relevance Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations. The combination therapy was safe with a tolerable safety profile, warranting further investigation. Trial registration ClinicalTrials.gov identifier: NCT02657889.

ObjectiveThe optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB).MethodsWe conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included.ResultsForty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P= 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P= 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P= 0.72). The median PFS for patients in the CWOB group was 2.6 months (95% confidence interval [CI], 1.3–5 months), compared with 5.0 months (95% CI, 3.5–7.3 months) for patients in the BAB group (P= 0.01). Overall survival was similar, 9.4 months (95% CI, 5.0–12.0 months) for CWOB versus 8.6 months (95% CI, 5.8–15.5 months) for BAB (P= 0.19). One patient in the BAB group died of a bowel perforation.ConclusionsIn patients previously treated with Bev for recurrent ovarian cancer, the subsequent addition of Bev to cytotoxic chemotherapy increased the PFS compared with patients not receiving a second course of Bev, but did so without an impact on overall survival. The response to the first Bev regimen did not predict whether a patient would respond again to the next Bev regimen. Randomized, larger studies will have to be performed to confirm this observation.

Highlights • We describe bilateral groin reconstruction with a single anterolateral thigh flap. • Anatomy and surgical technique of the anterolateral thigh flap are discussed.

Objectives The objective of this review is to discuss alternatives to commonly used methods of soft tissue reconstruction in patients with gynecologic malignancies, and in particular alternatives to skin grafts, local skin flaps, and rectus abdominis/gracilis flaps. Methods A review of the literature was performed on soft tissue reconstruction in patients with gynecologic malignancies. Results Soft tissue reconstruction is often necessary to achieve successful wound healing, minimize complications, and to restore anatomic form and function. Commonly used methods such as skin grafts, local skin flaps, and rectus abdominis/gracilis flaps are effective, but many scenarios exist where they may be suboptimal or unavailable for use. Situations faced by the gynecologic oncologist where this may be the case include patients in whom prior treatments and/or tumor involvement have affected the vascular supply and tissues of commonly used options, those with disease recurrence who have previously undergone tumor extirpation and reconstruction, and patients undergoing radical surgery where commonly used options alone are inadequate. Under these circumstances, there are several alternative options, and an understanding of the full spectrum of reconstructive techniques is essential. Conclusions Many clinical scenarios exist where commonly used options for soft tissue reconstruction are suboptimal or unavailable. Current evidence supports use of alternative methods of reconstruction in these situations. However, further larger scale and comparative studies are needed to refine surgical decision-making.

BRCA1 plays an important role in DNA damage and repair, homologous recombination, cell-cycle regulation and apoptosis. BRCA-mutated ovarian cancer often presents at an advanced stage, however, tend to have better response to platinum-based chemotherapy as compared with sporadic cases of epithelial ovarian cancer (EOC). In spite of this, most patients will develop a recurrence and eventually succumb to the disease. Preclinical studies are currently investigating natural compounds and their analogs for tumor-directed targets in ovarian cancer. The aim of this study is to investigate whether the STAT3 inhibitor HO-3867, a novel curcumin analog, has a therapeutic effect on BRCA1-mutated ovarian cancer. Our novel agent, HO-3867 and a commercial STAT3 inhibitor, STATTIC, significantly inhibited BRCA-mutated ovarian cancer cells in vitro in a dose- and time-dependent manner. BRCA-mutated ovarian cancer cells treated with HO-3867 exhibited a significant degree of apoptosis with elevated levels of cleaved caspase-3, caspase-7 and PARP. HO-3867 treatment induced more reactive oxygen species (ROS) in BRCA-mutated cells compared with wild-type cells, however, there was no increased ROS when benign ovarian surface epithelial cells were treated with HO-3867. BRCA1-mutated cancer cells had higher expression of Tyrosine-phosphorylated STAT3 (pTyr705) as compared with other STAT proteins. Furthermore, treatment of these cells with HO-3867 resulted in decreased expression of pTyr705 and its downstream targets cyclin D1, Bcl-2 and survivin. In addition, overexpression of STAT3 cDNA provided resistance to HO-3867-induced apoptosis. Our results show that HO-3867, a potent STAT3 inhibitor, may have a role as a biologically targeted agent for BRCA1-mutated cancers either as an adjunct to cytotoxic chemotherapy or as a single agent.