SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma.

BRCA1/2 mutations are robust biomarkers for platinum-based chemotherapy in epithelial ovarian cancers. However, BRCA1/2 mutations in clear cell ovarian carcinoma (CCC) are less frequent compared with high-grade serous ovarian cancer (HGSC). The discovery of biomarkers that can be applied to CCC is an unmet need in chemotherapy. Schlafen 11 (SLFN11) has attracted attention as a novel sensitizer for DNA-damaging agents including platinum. In this study, we investigated the utility of SLFN11 in HGSC and CCC for platinum-based chemotherapy. SLFN11 expression was analyzed retrospectively by IHC across 326 ovarian cancer samples. The clinicopathologic significance of SLFN11 expression was analyzed across 57 advanced HGSC as a discovery set, 96 advanced HGSC as a validation set, and 57 advanced CCC cases, all of whom received platinum-based chemotherapy. BRCA1/2 mutation was analyzed using targeted-gene sequencing. In the HGSC cohort, the SLFN11-positive and BRCA mutation group showed significantly longer whereas the SLFN11-negative and BRCA wild-type group showed significantly shorter progression-free survival and overall survival. Moreover, SLFN11-positive HGSC shrunk significantly better than SLFN11-negative HGSC after neoadjuvant chemotherapy. Comparable results were obtained with CCC but without consideration of BRCA1/2 mutation due to a small population. Multivariate analysis identified SLFN11 as an independent factor for better survival in HGSC and CCC. The SLFN11-dependent sensitivity to platinum and PARP inhibitors were validated with genetically modified non-HGSC ovarian cancer cell lines. Our study reveals that SLFN11 predicts platinum sensitivity in HGSC and CCC independently of BRCA1/2 mutation status, indicating that SLFN11 assessment can guide treatment selection in HGSC and CCC.

Tumor cell-expressed lipolysis-stimulated lipoprotein receptor negatively regulates T-cell function.

Lipolysis-stimulated lipoprotein receptor (LSR) is known as a lipoprotein receptor. LSR is expressed in various solid tumors, including epithelial ovarian, gastric, and colon cancers. High LSR expression is significantly associated with poor prognosis, but its role in cancer has not been fully elucidated. LSR belongs to the Ig protein superfamily, which is conserved in B7 family. Here, we assessed LSR as a novel immune checkpoint molecule. We developed a novel anti-LSR antibody (#27-6 mF-18) that defects antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. The #27-6 mF-18 cross-reacts with both human and mouse LSR. We found that LSR was expressed on 4T1 murine breast cancer cell line. The #27-6 mF-18 exhibited antitumor effects against the 4T1 syngeneic tumor model, a poor immunogenic model refractory to treatment with anti-PD-1 or anti-CTLA-4 antibodies. Compared with control antibody-treated mice, mice treated with #27-6 mF-18 showed significantly increased numbers of CD8+ T cells and a ratio of activated CD8+ T cells infiltrated in the tumor tissue. This antitumor effect was abrogated by CD8+ T-cell depletion through anti-CD8 antibody treatment, indicating that LSR negatively regulates tumor immunity by repressing CD8+ T cells. These findings show that LSR negatively regulates T-cell immune activity. LSR targeting could provide immune checkpoint inhibitors for cancer immunotherapy.

Intracorporeal colpotomy using the Gutclamper as a novel clamping device to prevent tumor spillage during laparoscopic radical hysterectomy for cervical cancer.

INTRODUCTION: Tumor cell spillage during the colpotomy has been suspected as one reason for poor oncologic outcomes in laparoscopic radical hysterectomy (LRH) for cervical cancer. To prevent such tumor spillage in LRH, we focused on use of a Gutclamper which is a device originally designed to clamp the colon and rectum during colorectal resections. MATERIALS AND SURGICAL TECHNIQUE: A woman with stage IB1 cervical cancer underwent LRH using the Gutclamper. The Gutclamper was inserted into the abdominal cavity via 5-mm trocar, the vagina was clamped, and an intracorporeal colpotomy was performed caudal to this device. DISCUSSION: The Gutclamper can be used to clamp the vaginal canal and avoid the exposure of cervical tumor, regardless of the surgeon's skills or patient conditions. An intracorporeal colpotomy using the Gutclamper can contribute to the standardization of LRH.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Assisted Reproductive Technique and Abnormal Cord Insertion: A Systematic Review and Meta-Analysis.

Abnormal cord insertion (ACI) is associated with adverse obstetric outcomes; however, the relationship between ACI and assisted reproductive technology (ART) has not been examined in a meta-analysis. This study examines the association between ACI and ART, and delivery outcomes of women with ACI. A systematic review was conducted, and 16 studies (1990-2021) met the inclusion criteria. In the unadjusted pooled analysis (n = 10), ART was correlated with a higher rate of velamentous cord insertion (VCI) (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.64-2.79), marginal cord insertion (n = 6; OR 1.58, 95%CI 1.26-1.99), and vasa previa (n = 1; OR 10.96, 95%CI 2.94-40.89). Nevertheless, the VCI rate was similar among the different ART types (blastocyst versus cleavage-stage transfer and frozen versus fresh embryo transfer). Regarding the cesarean delivery (CD) rate, women with VCI were more likely to have elective (n = 3; OR 1.13, 95%CI 1.04-1.22) and emergent CD (n = 5; OR 1.93, 95%CI 1.82-2.03). In conclusion, ART may be correlated with an increased prevalence of ACI. However, most studies could not exclude confounding factors; thus, further studies are warranted to characterize ART as a risk factor for ACI. In women with ACI, elective and emergent CD rates are high.

Anti-lipolysis-stimulated lipoprotein receptor monoclonal antibody as a novel therapeutic agent for endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken-mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. METHODS: We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. RESULTS: High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35-9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm3 versus 726.3 mm3, p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2. CONCLUSIONS: Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC.

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan.

BACKGROUND: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. METHODS: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. RESULTS: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. CONCLUSION: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.

Placenta Accreta Spectrum Disorder Complicated with Endometriosis: Systematic Review and Meta-Analysis.

This study aimed to assess the relationship between placenta accreta spectrum disorder (PASD) and endometriosis. The relationships among pregnancy, assisted reproductive technology (ART), placenta previa, ART-conceived pregnancy and PASD were also determined. A systematic literature review was conducted using multiple computerized databases. Forty-eight studies (1990-2021) met the inclusion criteria. According to the adjusted pooled analysis (n = 3), endometriosis was associated with an increased prevalence of PASD (adjusted odds ratio [OR] 3.39, 95% confidence interval [CI] 1.96-5.87). In the included studies, the ART rate ranged from 18.2% to 37.2% for women with endometriosis. According to the adjusted pooled analysis, women who used ART were more likely to have placenta previa (n = 13: adjusted OR 2.96, 95%CI, 2.43-3.60) and PASD (n = 4: adjusted OR 3.54, 95%CI 1.86-6.76) than those who did not use ART. According to the sensitivity analysis using an unadjusted analysis accounting for the type of ART, frozen embryo transfer (ET) was associated with an increased risk of PASD (n = 4: OR 2.79, 95%CI, 1.22-6.37) compared to fresh ET. Endometriosis may be associated with an increased rate of PASD. Women with placenta previa complicated with endometriosis who conceived using frozen ET may be a high risk for PASD.

Association between Endometriosis and Delivery Outcomes: A Systematic Review and Meta-Analysis.

Endometriosis is a common benign gynecological disorder; however, delivery outcomes concerning pregnancies with endometriosis remain understudied. This study aimed to assess the effect of endometriosis on delivery outcomes, including the rate of instrumental delivery, cesarean delivery (CD), postpartum hemorrhage (PPH), and perioperative complications during CD. A systematic literature review was conducted using multiple computerized databases, and 28 studies met the inclusion criteria. Pooled analysis showed that histologically diagnosed endometriosis was associated with an increased rate of instrumental delivery (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.02-1.56) and an increased risk of CD (adjusted OR 2.59, 95%CI 1.32-5.07). In our analysis, histologically diagnosed endometriosis was not associated with an increased rate of PPH; however, one retrospective study reported that endometriosis increased the rate of PPH during CD (adjusted OR 1.7, 95%CI 1.5-2.0). Two studies examined perioperative complications during CD, and women with deep endometriosis had a higher rate of bowel resection or bladder injury than those without endometriosis. Our findings suggest that endometriosis is a significant risk factor for instrumental delivery and CD and may be associated with a higher rate of PPH and intraoperative complications during CD.

Placenta Previa Complicated with Endometriosis: Contemporary Clinical Management, Molecular Mechanisms, and Future Research Opportunities.

Endometriosis is a common gynecological disease characterized by chronic inflammation, with an estimated prevalence of approximately 5-15% in reproductive-aged women. This study aimed to assess the relationship between placenta previa (PP) and endometriosis. We performed a systematic review of the literature until 30 June 2021, and 24 studies met the inclusion criteria. Using an adjusted pooled analysis, we found that women with endometriosis had a significantly increased rate of PP (adjusted odds ratio (OR) 3.17, 95% confidence interval (CI) 2.58-3.89) compared to those without endometriosis. In an unadjusted analysis, severe endometriosis was associated with an increased prevalence of PP (OR 11.86, 95% CI 4.32-32.57), whereas non-severe endometriosis was not (OR 2.16, 95% CI 0.95-4.89). Notably, one study showed that PP with endometriosis was associated with increased intraoperative bleeding (1.515 mL versus 870 mL, p < 0.01) compared to those without endometriosis. Unfortunately, no studies assessed the molecular mechanisms underlying PP in patients with endometriosis. Our findings suggest that there is a strong association between endometriosis and a higher incidence of PP, as well as poor surgical outcomes during cesarean delivery. Therefore, the development of novel therapeutic agents or methods is warranted to prevent PP in women with endometriosis.

A systematic review and meta-analysis of obstetric and maternal outcomes after prior uterine artery embolization.

This study aimed to review the obstetric complications during subsequent pregnancies after uterine artery embolization (UAE) for postpartum hemorrhage (PPH) by exploring the relationship between prior UAE and obstetric complications through a meta-analysis. We conducted a systematic literature review through March 31, 2021, using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials in compliance with the PRISMA guidelines and determined the effect of prior UAE for PPH on the rate of placenta accreta spectrum (PAS), PPH, placenta previa, hysterectomy, fetal growth restriction (FGR), and preterm birth (PTB). Twenty-three retrospective studies (2003-2021) met the inclusion criteria. They included 483 pregnancies with prior UAE and 320,703 pregnancies without prior UAE. The cumulative results of all women with prior UAE indicated that the rates of obstetric complications PAS, hysterectomy, and PPH were 16.3% (34/208), 6.5% (28/432), and 24.0% (115/480), respectively. According to the patient background-matched analysis based on the presence of prior PPH, women with prior UAE were associated with higher rates of PAS (odds ratio [OR] 20.82; 95% confidence interval [CI] 3.27-132.41) and PPH (OR 5.32, 95% CI 1.40-20.16) but not with higher rates of hysterectomy (OR 8.93, 95% CI 0.43-187.06), placenta previa (OR 2.31, 95% CI 0.35-15.22), FGR (OR 7.22, 95% CI 0.28-188.69), or PTB (OR 3.00, 95% CI 0.74-12.14), compared with those who did not undergo prior UAE. Prior UAE for PPH may be a significant risk factor for PAS and PPH during subsequent pregnancies. Therefore, at the time of delivery, clinicians should be more attentive to PAS and PPH when women have undergone prior UAE. Since the number of women included in the patient background-matched study was limited, further investigations are warranted to confirm the results of this study.

The association of endometriosis with placenta previa and postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to review the effect of endometriosis on the prevalence of placenta previa and postpartum hemorrhage in pregnant patients and the surgical outcomes of pregnant patients with endometriosis developing placenta previa. DATA SOURCES: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the literature was conducted on December 31, 2020, using PubMed, Scopus, and the Cochrane Library. STUDY ELIGIBILITY CRITERIA: Comparative studies between pregnant women with and without endometriosis and studies that investigated the surgical outcomes of patients with and without endometriosis developing placenta previa were included. METHODS: Here, 2 reviewers independently screened the titles and abstracts, completed data extraction, and assessed the reporting quality using the Risk of Bias in Nonrandomized Studies of Interventions tool. RESULTS: Overall, 19 studies (from 2010 to 2020) met the inclusion criteria (98,463 pregnancies with endometriosis and 7,184,313 pregnancies without endometriosis). In the adjusted pooled analysis, endometriosis was associated with a higher rate of placenta previa (adjusted odds ratio, 3.17; 95% confidence interval, 2.58-3.89), whereas the incidence of postpartum hemorrhage was similar between pregnant women with and without endometriosis (adjusted odds ratio, 1.15; 95% confidence interval, 0.99-1.34). When the analysis was restricted to histologically confirmed endometriosis cases, the relationship of endometriosis with placenta previa (adjusted odds ratio, 4.23; 95% confidence interval, 1.74-10.30) and postpartum hemorrhage (adjusted odds ratio, 1.29; 95% confidence interval, 0.50-3.34) was consistent with results from the nonrestricted analysis. There was no study that examined the surgical outcomes of patients with endometriosis developing placenta previa patients. However, there are 3 studies that examined the effect of endometriosis on surgical outcomes during cesarean delivery: 1 study showing that endometriosis was associated with increased intraoperative bleeding during emergent cesarean delivery; the other study showing that endometriosis was associated with an increased incidence of postpartum hemorrhage during cesarean delivery (adjusted odds ratio, 1.1; 95% confidence interval, 1.0-1.2), especially in primiparous women with singleton pregnancies (adjusted odds ratio, 1.7; 95% confidence interval, 1.5-2.0); and another study suggesting a significantly higher rate of hysterectomy (7.1%) and bladder injury (7.1%) in patients with endometriosis than in those without endometriosis. CONCLUSION: Endometriosis can potentially be associated with adverse surgical outcomes during cesarean delivery. Although there is a correlation between endometriosis and increased rate of placenta previa, the surgical outcomes of patients with endometriosis developing placenta previa remain understudied.

Antenatal diagnosis of placenta accreta spectrum after in vitro fertilization-embryo transfer: a systematic review and meta-analysis.

Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011-2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34-7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42-6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12-10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle.

Placenta previa with posterior extrauterine adhesion: clinical features and management practice.

BACKGROUND: A diagnostic sign on magnetic resonance imaging, suggestive of posterior extrauterine adhesion (PEUA), was identified in patients with placenta previa. However, the clinical features or surgical outcomes of patients with placenta previa and PEUA are unclear. Our study aimed to investigate the clinical characteristics of placenta previa with PEUA and determine whether an altered management strategy improved surgical outcomes. METHODS: This single institution retrospective study examined patients with placenta previa who underwent cesarean delivery between 2014 and 2019. In June 2017, we recognized that PEUA was associated with increased intraoperative bleeding; thus, we altered the management of patients with placenta previa and PEUA. To assess the relationship between changes in practice and surgical outcomes, a quasi-experimental method was used to examine the difference-in-difference before (pre group) and after (post group) the changes. Surgical management was modified as follows: (i) minimization of uterine exteriorization and adhesion detachment during cesarean delivery and (ii) use of Nelaton catheters for guiding cervical passage during Bakri balloon insertion. To account for patient characteristics, propensity score matching and multivariate regression analyses were performed. RESULTS: The study cohort (n = 141) comprised of 24 patients with placenta previa and PEUA (PEUA group) and 117 non-PEUA patients (control group). The PEUA patients were further categorized into the pre (n = 12) and post groups (n = 12) based on the changes in surgical management. Total placenta previa and posterior placentas were more likely in the PEUA group than in the control group (66.7% versus 42.7% [P = 0.04] and 95.8% versus 63.2% [P < 0.01], respectively). After propensity score matching (n = 72), intraoperative blood loss was significantly higher in the PEUA group (n = 24) than in the control group (n = 48) (1515 mL versus 870 mL, P < 0.01). Multivariate regression analysis revealed that PEUA was a significant risk factor for intraoperative bleeding before changes were implemented in practice (t = 2.46, P = 0.02). Intraoperative blood loss in the post group was successfully reduced, as opposed to in the pre group (1180 mL versus 1827 mL, P = 0.04). CONCLUSIONS: PEUA was associated with total placenta previa, posterior placenta, and increased intraoperative bleeding in patients with placenta previa. Our altered management could reduce the intraoperative blood loss.

CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. OBJECTIVE: This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma. STUDY DESIGN: Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). RESULTS: CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001). CONCLUSION: Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

Proposing the 3-tier staging system for improving prognostication in Stage I uterine leiomyosarcoma.

BACKGROUND AND OBJECTIVES: To examine the utility of a 3-tier schema (≤5 cm, 5.1-10 cm, and > 10 cm) in determining characteristics and survival in Stage I uterine leiomyosarcoma. METHODS: This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 1988 to 2016. Surgically treated stage I uterine leiomyosarcomas with known tumor size were examined (N = 2217). Trends, characteristics, and survival were assessed based on tumor size. RESULTS: The most common tumor size was 5.1-10 cm (45.7%) followed by >10 cm (35.0%) and ≤5 cm (19.4%). Tumor size-shift occurred during the study period; the percentage of tumor size >10 cm increased from 12.9% to 44.5% and the groups with smaller tumor sizes decreased (p < .001). In weighted models, 5-year overall survival rates ranged from 49.9% to 71.6% in the 3-tier system and 55.2%-70.6% in the 2-tier system: the absolute difference was larger in the 3-tier system (21.7% vs. 15.4%). In the 3-tier system, all-cause mortality risk of tumor size >10 cm versus ≤5 cm nearly doubled (hazard ratio 1.96, 95% confidence interval 1.78-2.16). CONCLUSION: In the past decades, tumors of stage I uterine leiomyosarcoma have become larger. Our study suggests that a tumor size-based 3-tier staging system may be useful to differentiate survival in stage I uterine leiomyosarcoma.

Malignant peritoneal cytology and decreased survival of women with stage I endometrioid endometrial cancer.

BACKGROUND: To examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. FINDINGS: Malignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56-2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16-1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high-intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20-2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01-2.68). In the high-intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14-0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53-1.14). INTERPRETATION: Malignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.

Efficacy of Prophylactic Antibiotics in Bakri Intrauterine Balloon Placement: A Single-Center Retrospective Analysis and Literature Review.

Objective Bakri intrauterine balloon (BIUB) placement is an effective treatment for postpartum hemorrhage (PPH). This study aims to evaluate the risk of infection during BIUB placement. Study Design Data for all deliveries ( n = 2,144) at our institution between January 2014 and March 2018 were retrospectively reviewed. Patients diagnosed with PPH ( n = 758) were included in our analysis, further divided into BIUB ( n = 80) and non-BIUB groups ( n = 678), and subdivided into vaginal delivery (VD), elective cesarean delivery (CD), and emergency CD groups. Postpartum endometritis rate was compared in each group. A single dose of prophylactic antibiotics was administered for BIUB placement in the VD group. In the CD groups, antibiotics were administered preoperatively once, and no additional antibiotics for BIUB placement were administered. To obtain an antibiotics administration protocol to be applied during BIUB placement, we electronically searched the PubMed and Scopus databases. Results No significant differences were observed in endometritis rates between BIUB and non-BIUB groups of all groups. In the literature review, of 27 suitable publications identified, multiple doses of antibiotics were administered in 17 (62.9%) studies and none investigated the efficacy of a protocol for antibiotic. Conclusion Our protocol might be effective and sufficient in preventing postpartum BIUB placement-related endometritis.