Implementation and outcomes of a uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum disorders are a continuum of placental pathologies with significant maternal morbidity and mortality. Morbidity is related to the overall degree of placental adherence, and thus patients with placenta increta or percreta represent a high-risk category of patients. Hemorrhage and transfusion of blood products represent 90% of placenta accreta spectrum morbidity. Both tranexamic acid and uterine artery embolization independently decrease obstetrical hemorrhage. OBJECTIVE: This study aimed to provide an evidence-based intraoperative protocol for placenta accreta spectrum management. STUDY DESIGN: This study was a pre- and postimplementation analysis of concomitant uterine artery embolization and tranexamic acid in cases of patients with antenatally suspected placenta increta and percreta over a 5-year period (2018-2022). For comparison, a 5-year (2013-2017) preimplementation group was used to assess the impact of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum. Patient demographics and clinically relevant outcomes were obtained from electronic medical records. RESULTS: A total of 126 cases were managed by the placenta accreta spectrum team, of which 66 had suspected placenta increta/percreta over the 10-year time period. Two patients were excluded from the postimplementation cohort because they did not undergo both interventions. Thus, 30 (30/64; 47%) were treated after implementation of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum, and 34 (34/64; 53%) preimplementation patients did not undergo uterine artery embolization or tranexamic acid infusion. With the uterine artery embolization and tranexamic acid protocol, operative times were longer (416 vs 187 minutes; P<.01), and patients were more likely to receive general anesthesia (80% vs 47%; P<.01). However, blood loss was reduced by 33% (2000 vs 3000 cc; P=.03), overall blood transfusion rates decreased by 51% (odds ratio, 0.05 [95% confidence interval, 0.001-0.20]; P<.01), and massive blood transfusion (>10 units transfused) was reduced 5-fold (odds ratio, 0.17 [95% confidence interval, 0.02-0.17]; P=.02). Postoperative complication rates remained unchanged (4 vs 10 events; P=.14). Neonatal outcomes were equivalent. CONCLUSION: The uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum is an effective approach to the standardization of complex placenta accreta spectrum cases that results in optimal perioperative outcomes and reduced maternal morbidity.

Importance of the gynecologic oncologist in management of cesarean hysterectomy for Placenta Accreta Spectrum (PAS).

OBJECTIVE: 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. METHODS: 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 loss >2 L, ICU admission, intraoperative acidosis and post-operative length of stay >4 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. RESULTS: 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, p < 0.0001), 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, p < 0.0001). 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 stay >4 days (aOR = 0.37, 95%CI [0.15-0.91]). CONCLUSIONS: 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.

Risk factors predicting the loss of functional independence after obliterative procedures for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: To determine the risk factors associated with loss of functional independence after obliterative procedures for pelvic organ prolapse (POP). METHODS: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database was used to collect data on women who underwent obliterative vaginal procedures from 2011 to 2016, using current procedural terminology (CPT) codes for LeFort colpocleisis (57120) and vaginectomy (57110). The criterion for loss of functional independence was a transition from a functionally independent status to a dependent status (discharge to a post-care facility) or death within the 30-day postoperative period. Multivariate regression analysis was utilized to determine factors associated with loss of functional independence. RESULTS: A total of 1847 women were included in the analysis. A loss of functional independence was noted in 50 of the 1847 women (2.6%). The women who suffered loss of functional independence were older than those who were independent postoperatively (mean age 79.3 years, SD 7.47 vs. 76.7 years, SD 8.1, respectively). On multiple logistic regression analysis, age ≥ 80 years (OR 2.8, 95% CI 1.4-5.5), American Society of Anesthesiologists (ASA) classification ≥ 3 (OR 2.3, CI 1.1-4.7) and length of stay ≥ 5 days (OR 15.2, 95% CI 6.2-37.1) remained significantly associated with an increased risk of loss of functional independence. CONCLUSIONS: Age ≥ 80 years, ASA classification ≥ 3 and longer length of stay are associated with an increased risk of loss of functional independence after an obliterative procedure for pelvic organ prolapse. Consideration of these factors during the preoperative decision-making process may help improve outcomes in this cohort.

Inhibition of LIFR Blocks Adiposity-Driven Endometrioid Endometrial Cancer Growth.

Endometrial cancer (EC) is the fourth most common cancer in women, and half of the endometrioid EC (EEC) cases are attributable to obesity. However, the underlying mechanism(s) of obesity-driven EEC remain(s) unclear. In this study, we examined whether LIF signaling plays a role in the obesity-driven progression of EEC. RNA-seq analysis of EEC cells stimulated by adipose conditioned medium (ADP-CM) showed upregulation of LIF/LIFR-mediated signaling pathways including JAK/STAT and interleukin pathways. Immunohistochemistry analysis of normal and EEC tissues collected from obese patients revealed that LIF expression is upregulated in EEC tissues compared to the normal endometrium. Treatment of both primary and established EEC cells with ADP-CM increased the expression of LIF and its receptor LIFR and enhanced proliferation of EEC cells. Treatment of EEC cells with the LIFR inhibitor EC359 abolished ADP-CM induced colony formation andcell viability and decreased growth of EEC organoids. Mechanistic studies using Western blotting, RT-qPCR and reporter assays confirmed that ADP-CM activated LIF/LIFR downstream signaling, which can be effectively attenuated by the addition of EC359. In xenograft assays, co-implantation of adipocytes significantly enhanced EEC xenograft tumor growth. Further, treatment with EC359 significantly attenuated adipocyte-induced EEC progression in vivo. Collectively, our data support the premise that LIF/LIFR signaling plays an important role in obesity-driven EEC progression and the LIFR inhibitor EC359 has the potential to suppress adipocyte-driven tumor progression.

A rectovaginal septum mass in a BRCA1 positive patient years after risk reducing surgery: A case report.

•Rectovaginal septum mass in BRCA1 positive patient after risk reducing BSO years prior.•Papillary serous carcinoma presenting as a rectovaginal septum mass.•PAOLA-1 trial discussion for rectovaginal septum mass in BRCA1 positive patient.

LIF/LIFR oncogenic signaling is a novel therapeutic target in endometrial cancer.

Endometrial cancer (EC) is the fourth most common cancer in women. Advanced-stage EC has limited treatment options with a poor prognosis. There is an unmet need for the identification of actionable drivers for the development of targeted therapies in EC. Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a major role in cancer progression, metastasis, stemness, and therapy resistance. However, little is known about the functional significance of the LIF/LIFR axis in EC progression. In this study using endometrial tumor tissue arrays, we identified that expression of LIF, LIFR is upregulated in EC. Knockout of LIFR using CRISPR/Cas9 in two different EC cells resulted in a significant reduction of their cell viability and cell survival. In vivo studies demonstrated that LIFR-KO significantly reduced EC xenograft tumor growth. Treatment of established and primary patient-derived EC cells with a novel LIFR inhibitor, EC359 resulted in the reduction of cell viability with an IC50 in the range of 20-100 nM and induction of apoptosis. Further, treatment with EC359 reduced the spheroid formation of EC cancer stem cells and reduced the levels of cancer stem cell markers SOX2, OCT4, NANOG, and Axin2. Mechanistic studies demonstrated that EC359 treatment attenuated the activation of LIF-LIFR driven pathways, including STAT3 and AKT/mTOR signaling in EC cells. Importantly, EC359 treatment resulted in a significant reduction of the growth of EC patient-derived explants ex vivo, EC cell line-derived xenografts, and patient-derived xenografts in vivo. Collectively, our work revealed the oncogenic potential of the LIF/LIFR axis in EC and support the utility of LIFR inhibitor, EC359, as a novel targeted therapy for EC via the inhibition of LIF/LIFR oncogenic signaling.