Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Relationship between Abnormal Placenta and Obstetric Outcomes: A Meta-Analysis.

The placenta has several crucial physiological functions that help maintain a normal pregnancy. Although approximately 2-4% of pregnancies are complicated by abnormal placentas, obstetric outcomes remain understudied. This study aimed to determine the outcomes and prevalence of patients with abnormal placentas by conducting a systematic review of 48 studies published between 1974 and 2022. The cumulative prevalence of circumvallate placenta, succenturiate placenta, multilobed placenta, and placenta membranacea were 1.2%, 1.0%, 0.2%, and 0.004%, respectively. Pregnancies with a circumvallate placenta were associated with an increased rate of emergent cesarean delivery, preterm birth (PTB), and placental abruption compared to those without a circumvallate placenta. The succenturiate lobe of the placenta was associated with a higher rate of emergent cesarean delivery, whereas comparative results were observed in terms of PTB, placental abruption, and placenta previa in comparison to those without a succenturiate lobe of the placenta. A comparator study that examined the outcomes of multilobed placentas found that this data is usually unavailable. Patient-level analysis (n = 15) showed high-rates of abortion (40%), placenta accreta spectrum (40%), and a low term delivery rate (13.3%) in women with placenta membranacea. Although the current evidence is insufficient to draw a robust conclusion, abnormal placentas should be recognized as a high-risk factor for adverse outcomes during pregnancy.

Current Evidence on Vasa Previa without Velamentous Cord Insertion or Placental Morphological Anomalies (Type III Vasa Previa): Systematic Review and Meta-Analysis.

Vasa previa carries a high risk of severe fetal morbidity and mortality due to fetal hemorrhage caused by damage to unprotected fetal cord vessels upon membrane rupture. Vasa previa is generally classified into types I and II. However, some cases are difficult to classify, and some studies have proposed a type III classification. This study aimed to review the current evidence on type III vasa previa. A systematic literature search was conducted, and 11 articles (2011-2022) were included. A systematic review showed that type III vasa previa accounts for 5.7% of vasa previa cases. Thirteen women with type III vasa previa were examined at a patient-level analysis. The median age was 35 (interquartile range [IQR] 31.5-38) years, and approximately 45% were assisted reproductive technology (ART) pregnancies. The median gestational week of delivery was 36 (IQR 34-37) weeks; the antenatal detection rate was 84.6%, and no cases reported neonatal death. The characteristics and obstetric outcomes (rate of ART, antenatal diagnosis, emergent cesarean delivery, gestational age at delivery, and neonatal mortality) were compared between types I and III vasa previa, and all outcomes of interest were similar. The current evidence on type III vasa previa is scanty, and further studies are warranted.

The Characteristics and Obstetric Outcomes of Type II Vasa Previa: Systematic Review and Meta-Analysis.

Vasa previa is a rare fetal life-threatening obstetric disease classified into types I and II. This study aimed to examine the characteristics and obstetric outcomes of type II vasa previa. A systematic review was performed, and 20 studies (1998-2022) were identified. The results from six studies showed that type II vasa previa accounted for 21.3% of vasa previa cases. The characteristics and obstetric outcomes (rate of assisted reproductive technology (ART), antenatal diagnosis, emergent cesarean delivery, maternal transfusion, gestational age at delivery, and neonatal mortality) were compared between type I and II vasa previa, and all outcomes of interest were similar. The association between ART and abnormal placenta (bilobed placenta or succenturiate lobe) was examined in three studies, and the results were as follows: (i) increased rate of succenturiate lobes (ART versus non-ART pregnancy; OR (odds ratio) 6.97, 95% confidence interval (CI) 2.45-19.78); (ii) similar rate of abnormal placenta (cleavage-stage versus blastocyst embryo transfer); (iii) increased rate of abnormal placenta (frozen versus fresh embryo transfer; OR 2.97, 95%CI 1.10-7.96). Although the outcomes of type II vasa previa appear to be similar to those of type I vasa previa, the current evidence is insufficient for a robust conclusion.

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.

Development of information dissemination methods that contribute to improving maternal and child healthcare using social networking sites: a community-based cross-sectional study in Japan.

BACKGROUND: In recent years, feelings of isolation among mothers caring for small children has become a significant social issue in Japan. The purpose of this study is to develop a message to alleviate their loneliness, to evaluate the impact of social networking sites (SNS) for delivering such messages, and to propose means of more effective information transmission to promote health for mothers raising small children. METHODS: Our study was conducted in two stages, first an interview and then a cross-sectional study of the mothers involving a questionnaire survey. The interview was targeted two public-health nurses caring for mothers. Based on these interviews, we developed six messages intended to alleviate the mothers' sense of loneliness, which were vetted by seven mothers. The second stage was to conduct a questionnaire survey of mothers both before and after our selected message as advertisement on Instagram and analyzed the effect. The surveys were collected during routine child health check-ups in the City of Takatsuki, Japan. RESULTS: From the six draft messages created based on interviews with public health nurses, we selected the message that most relieves the feeling of loneliness of the mothers who are raising small children. The survey questionnaire was taken by 494 mothers prior to our posting of Instagram advertisements (ads), and afterwards by 419 mothers. The percentage of mothers feeling loneliness tended to decrease after reading the messages (before ads.:8.1%, after ads.:5.8%). 8.6% of the mothers (36/419) remembered seeing the Instagram ads. Mothers with financial anxiety were significantly more likely to have remembered seeing the Instagram ads (p < 0.01). CONCLUSIONS: Our results indicate that usefulness of SNS messaging for mothers raising small children may reduce their feeling of loneliness. Among the SNS, disseminating child-rearing information on Instagram may be more effective for people with financial instability.

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.

Maternal and Fetal Outcomes after Prior Mid-Trimester Uterine Rupture: A Systematic Review with Our Experience.

Background and Objectives: Since spontaneous uterine rupture in the mid-trimester is rare, maternal and fetal outcomes in subsequent pregnancies remain unclear. Therefore, this study aimed to examine the maternal and fetal outcomes of subsequent pregnancies after prior mid-trimester uterine rupture. Materials and Methods: A systematic review using PubMed, the Cochrane Central Register of Controlled Trials, and Scopus until 30 September 2021, was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The studies that clarified the maternal and fetal outcomes after prior mid-trimester uterine rupture and our case (n = 1) were included in the analysis. Results: Among the eligible cases, there were five women with eight subsequent pregnancies after prior mid-trimester uterine rupture. The timing of prior mid-trimester uterine rupture ranged from 15 to 26 weeks of gestation. The gestational age at delivery in subsequent pregnancies was 23-38 gestational weeks. Among the included cases (n = 8), those involving prior mid-trimester uterine rupture appeared to be associated with an increased prevalence of placenta accreta spectrum (PAS) (n = 3, 37.5%) compared with those involving term uterine rupture published in the literature; moreover, one case exhibited recurrent uterine rupture at 23 weeks of gestation (12.5%). No maternal deaths have been reported in subsequent pregnancies following prior mid-trimester uterine rupture. Fetal outcomes were feasible, except for one pregnancy with recurrent mid-trimester uterine rupture at 23 weeks of gestation, whose fetus was alive complicated by cerebral palsy. Conclusions: Our findings suggest that clinicians should be aware of the possibility of PAS and possible uterine rupture in pregnancies after prior mid-trimester uterine rupture. Further case studies are warranted to assess maternal and fetal outcomes in pregnancies following prior mid-trimester prior uterine rupture.

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.

Minimally Invasive Surgery and Surgical Volume-Specific Survival and Perioperative Outcome: Unmet Need for Evidence in Gynecologic Malignancy.

This study examined the effect of hospital surgical volume on oncologic outcomes in minimally invasive surgery (MIS) for gynecologic malignancies. The objectives were to assess survival outcomes related to hospital surgical volume and to evaluate perioperative outcomes and examine non-gynecologic malignancies. Literature available from the PubMed, Scopus, and the Cochrane Library databases were systematically reviewed. All surgical procedures including gynecologic surgery with hospital surgical volume information were eligible for analysis. Twenty-three studies met the inclusion criteria, and nine gastro-intestinal studies, seven genitourinary studies, four gynecological studies, two hepatobiliary studies, and one thoracic study were reviewed. Of those, 11 showed a positive volume-outcome association for perioperative outcomes. A study on MIS for ovarian cancer reported lower surgical morbidity in high-volume centers. Two studies were on endometrial cancer, of which one showed lower treatment costs in high-volume centers and the other showed no association with perioperative morbidity. Another study examined robotic-assisted radical hysterectomy for cervical cancer and found no volume-outcome association for surgical morbidity. There were no gynecologic studies examining the association between hospital surgical volume and oncologic outcomes in MIS. The volume-outcome association for oncologic outcome in gynecologic MIS is understudied. This lack of evidence calls for further studies to address this knowledge gap.

A questionnaire survey on a feeling of loneliness of the mothers raising children.

AIM: A feeling of isolation childcare mothers' face is a serious social problem in Japan because the relationships with mothers and local communities have grown sparser. The purpose of this study was to clarify the feelings of isolation of mothers during childcare and the factors related to it. METHODS: We conducted a questionnaire survey in Yao City, Osaka. We mailed out a questionnaire survey of 1293 mothers with infants who had either a 4-month or 42-month routine health checkup during the period from September to December of 2018. RESULTS: There was no association between "feeling lonely while raising my child" and the absence of "people who helped raise my children." On the other hand, it was found that the mothers' inner feelings, such as "I wasn't satisfied with my childcare environment" (OR: 2.55, 95% CI: 1.32-4.91, p = 0.0052) or "I lacked confidence in my own childcare abilities" (OR: 6.21, 95% CI: 4.31-8.95, p < 0.0001), were associated with their sense of loneliness. CONCLUSIONS: Mothers' "sense of loneliness" was shown to be best correlated with their dissatisfaction with the environment of their childcare and with their lack of confidence in raising their own children.

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.

CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

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.

Clinico-pathological significance of suspicious peritoneal cytology in endometrial cancer.

BACKGROUND AND OBJECTIVES: Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. METHODS: A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. RESULTS: Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution-hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29-2.20, p < 0.001) and all-cause mortality (adjusted-HR: 1.55, 95% CI: 1.27-1.90, p < 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72-0.99, p = 0.049). CONCLUSION: Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.

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.

Surgical and oncologic outcomes of hyperthermic intraperitoneal chemotherapy for uterine leiomyosarcoma: A systematic review of literature.

OBJECTIVE: To examine the perioperative and survival outcomes in women with disseminated peritoneal uterine leiomyosarcoma (uLMS) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A comprehensive systematic review of literature was conducted using multiple public search engines, PubMed, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. Women with disseminated peritoneal uLMS treated with CRS-HIPEC were analyzed. Perioperative morbidity and mortality rate as well as oncologic outcomes related to CRS-HIPEC were assessed. RESULTS: Ten studies met the inclusion criteria from 2004 to 2020, including 8 case series (n=28) and 2 original articles (n=47). Of the 75 patients, 68 (90.7%) were women with uLMS whereas 7 women were non-uLMS. Of these, 64 (85.3%) had recurrent disease, and 39 (52.0%) received chemotherapy or radiotherapy prior to CRS-HIPEC. The perioperative mortality rate was 4.0% (intraoperative 1.3%, and postoperative 2.7%), and postoperative complications (grade ≥3) rate ranged 21.4-22.2%. With regard to HIPEC regimens (n=75), cisplatin was most frequently used (n=55, 73.3%) followed by melphalan (n=17, 22.7%) and others (n=3, 4.0%). Among the two observational studies, the median overall survival after CRS-HIPEC treatment was 29.5-37 months. In one limited comparative effectiveness study (n=13), albeit statistically non-significant CRS-HIPEC was associated with higher progression-free survival versus CRS alone (3-year rates, 71.4% versus 0%, P=0.10). When the HIPEC regimens were compared, melphalan use was associated with decreased uLMS-related mortality compared to a cisplatin-based regimen, but the association was not statistically significant (hazard ratio 0.35, 95% confidence interval 0.04-3.05, P=0.35). CONCLUSION: Effectiveness of CRS-HIPEC for disseminated peritoneal uLMS is yet to be determined. As interpretation of the available data on survival is limited due to small sample sizes or the lack of an active comparator, further study is warranted to examine the safety and survival effect of CRS-HIPEC in disseminated peritoneal uLMS.

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.

Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity.

Uterine carcinosarcoma (UCS) is a biphasic aggressive high-grade endometrial cancer in which the sarcoma element has de-differentiated from the carcinoma element. UCS is considered a rare tumor, but its incidence has gradually increased in recent years (annual percent change from 2000 to 2016 1.7%, 95% confidence interval 1.2-2.2) as has the proportion of UCS among endometrial cancer, exceeding 5% in recent years. UCS typically affects the elderly, but in recent decades patients became younger. Notably, a stage-shift has occurred in recent years with increasing nodal metastasis and decreasing distant metastasis. The concept of sarcoma dominance may be new in UCS, and a sarcomatous element >50% of the uterine tumor is associated with decreased survival. Multimodal treatment is the mainstay of UCS. Lymphadenectomy, chemotherapy, and brachytherapy have increased in the past few decades, but survival outcomes remain dismal: the median survival is less than two years, and the 5-year overall survival rate has not changed in decades (31.9% in 1975 to 33.8% in 2012). Carboplatin/paclitaxel adjuvant chemotherapy improves progression-free survival compared with ifosfamide/paclitaxel, particularly in stages III-IV disease (GOG-261 trial). Twenty-six clinical trials previously examined therapeutic effectiveness in recurrent/metastatic UCS. The median response rate and progression-free survival were 37.5% and 5.9 months, respectively, after first-line therapy, but after later therapies, the outcomes were far worse (5.5% and 1.8 months, respectively). One significant discovery was that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of sarcomatous dedifferentiation in UCS and that heterologous sarcoma is associated with a higher EMT signature compared with homologous sarcoma. Furthermore, next-generation sequencing has revealed that UCS tumors are serous-like and that common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, and ARID1A. This contemporary review highlights recent clinical and molecular updates in UCS. A possible therapeutic target of EMT in UCS is also discussed.

Obstetric Outcomes of Pregnancy After Uterine Artery Embolization.

BACKGROUND: Uterine artery embolization (UAE) is used to treat severe postpartum hemorrhage (PPH). According to a few studies, UAE for PPH was associated with preterm birth, fetal growth restriction (FGR), and placenta accreta spectrum (PAS) in subsequent pregnancies. These previous studies, however, lacked controls, and to the best of our knowledge, no systematic literature reviews have been conducted thus far. We report the results of our retrospective case-control study of pregnancies after UAE at a single center and include a literature review to evaluate the risk of PAS in pregnancies after UAE. METHODS: We retrospectively reviewed data from deliveries at our hospital between January 2012 and October 2017. We divided the delivery data into cases with previous UAEs performed for PPH (the post-UAE group) and those without UAEs (the non-UAE group, which included women without previous PPH). We defined PAS as cases in which hysterectomy was performed and pathological examination confirmed the diagnosis. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We used data from 3155 patients in this study, of whom 16 patients had undergone UAE (post-UAE group) and 3139 had not (non-UAE group). We found no differences between the groups in terms of frequency of preterm births (12.5% versus 14.2%, respectively; OR, 0.863; 95% CI, 0.218 to 3.414; P = 0.84) or FGR (6.2% versus 10.0%, respectively; OR, 0.602; 95% CI, 0.104 to 3.584; P = 0.61). However, cases of PAS were significantly more common in the post-UAE group (37.5%) than in the non-UAE group (1.2%; OR, 50.303; 95% CI, 17.38 to 145.592; P < 0.01). CONCLUSION: Our results suggest that previous UAE is a significant risk factor for PAS.