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The violation of the U(1) axial symmetry in QCD is stricter than the chiral SU(2) breaking simply because of the presence of the quantum axial anomaly. If the QCD gauge coupling is sent to zero (the asymptotic free limit, where the U(1) axial anomaly does not exist), the strength of the U(1) axial breaking coincides with that of the chiral SU(2) breaking, which we, in short, call an axial–chiral coincidence. This coincidence is trivial since QCD then becomes a non-interacting theory. Actually, there exists another limit in the QCD parameter space, where an axial–chiral coincidence occurs even with nonzero QCD gauge coupling, which can be dubbed a nontrivial coincidence: it is the case with the massive light quarks (ml≠0) and the massless strange quark (ms=0) due to the flavor-singlet nature of the topological susceptibility. This coincidence is robust and tied to the anomalous chiral Ward–Takahashi identity, which is operative even at hot QCD. This implies that the chiral SU(2) symmetry is restored simultaneously with the U(1) axial symmetry at high temperatures. This simultaneous restoration is independent of ml(≠0) and, hence, is irrespective of the order of the chiral phase transition. In this paper, we discuss how the real-life QCD can be evolved from the nontrivial chiral–axial coincidence limit by working on a Nambu–Jona–Lasinio model with the U(1) axial anomaly contribution properly incorporated. It is shown that, at high temperatures, the large differences between the restorations of the chiral SU(2) symmetry and the U(1) axial symmetry for two light quarks and a sufficiently large current mass for the strange quark are induced by a significant interference of the topological susceptibility. Thus, the deviation from the nontrivial coincidence, which is monitored by the strange quark mass controlling the topological susceptibility, provides a new way of understanding the chiral SU(2) and U(1) axial breaking in QCD.

The aim of the current study is to investigate the survival outcome of stage IVB SCNEC of the uterine cervix in comparison to major histological subtypes of cervical cancer. A population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. All FIGO 2009 stage IVB cervical cancer patients who displayed squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small-cell neuroendocrine carcinoma (SCNEC) were first identified. The patients were classified into groups according to the types of primary treatment. Then, their survival rates were examined using the Kaplan–Meier method. Overall, in a total of 1158 patients, clearly differential survival rates were observed according to the histological subtypes, and SCNEC was associated with shortest survival. When examined according to the types of primary treatments, SCNEC was associated with significantly decreased survival when compared to SCC or A/AS, except for those treated with surgery. In patients with FIGO 2009 stage IVB cervical cancer, SCNEC was associated with decreased survival when compared to SCC or A/AS. Although current treatments with either surgery, chemotherapy or radiotherapy have some therapeutic efficacies, to improve the prognosis, novel effective treatments specifically targeting cervical SCNEC need to be developed.

We find that a big gap between indicators for the breaking strengths of the global chiral SU(2) and U(1) axial symmetries in the QCD of the standard model (SM) can be interpreted as a new fine-tuning problem. This may thus imply calling for a class beyond the SM, which turns out to favor having a new chiral symmetry, and the associated massless new quark is insensitive to the chiral SU(2) symmetry for the lightest up and down quarks so that the fine-tuning is relaxed. Our statistical estimate shows that QCD of the SM is by more than 300 standard deviations off the parameter space free from fine-tuning, and the significance will be greater as the lattice measurements on the QCD hadron observables become more accurate. We briefly address a dark QCD model with massless new quarks as one viable candidate.

In early-stage cervical cancer, ovarian metastasis is relatively rare, and ovarian transposition is often performed during surgery. Although rare, the diagnosis and surgical approach for recurrence at transposed ovaries are challenging. This study focused on the diagnosis and surgical management of transposed ovarian recurrence in cervical cancer patients. A 45-year-old premenopausal woman underwent radical hysterectomy, bilateral salpingectomy, and pelvic lymphadenectomy following postoperative concurrent chemoradiotherapy for stage IB1 cervical cancer. During the initial surgery, the ovary was transposed to the paracolic gutter, and no postoperative complications were observed. Ovarian recurrence was diagnosed using positron emission tomography–computed tomography, and a laparoscopic bilateral oophorectomy was performed. A systematic review identified nine women with transposed ovarian recurrence with no other metastases of cervical cancer, and no studies have discussed the optimal surveillance of transposed ovaries. Of those (n = 9), four women had died of the disease within 2 years of the second surgery, and the prognosis of transposed ovarian cervical cancer seemed poor. Nevertheless, three women underwent laparoscopic oophorectomies, none of whom experienced recurrence after the second surgery. Few studies have examined the surgical management of transposed ovarian recurrence. The optimal surgical approach for transposed ovarian recurrence of cervical cancer requires further investigation.

Although laser vaporization is a popular minimally invasive treatment for cervical intraepithelial neoplasia (CIN), factors influencing CIN recurrence are understudied. Moreover, the effect of surgeon volume on patients’ prognosis after laser vaporization for CIN is unknown. This single-center retrospective study evaluated the predictive value of surgeon volume and patient characteristics for laser vaporization outcomes in women with pathologically confirmed CIN2. Histologically confirmed CIN2 or higher grade after laser vaporization was defined as persistent or recurrent. Various patient characteristics were compared between women with and those without recurrence to examine the predictive factors for laser vaporization. There were 270 patients with a median age of 36 (18–60) years. The median follow-up period was 25 (6–75.5) months and the median period between treatment and persistence or recurrence was 17 (1.5–69) months. The median annual number of procedures for all seven surgeons was 7.8. There were 38 patients (14.1%) with persistent or recurrent lesions—24 had CIN2, 13 had CIN3, and one had adenocarcinoma in situ. Patient age, body mass index, surgeon volume, and history of prior CIN treatment or invasive cervical cancer were not significantly correlated with lesion persistence or recurrence. In conclusion, laser vaporization has comparable success rates and is a feasible treatment for both low- and high-volume surgeons.

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.

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.

We aimed to compare the oncological outcomes between Japanese women with uterine-confined and node-negative cervical cancer who underwent open surgery and those who underwent minimally invasive surgery (MIS). A population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry that ranged from 2011 to 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (group one, 2011–2014; group two, 2015–2018). The oncologic outcomes were compared between the MIS and open groups. When the MIS group (n = 225) was compared with open group (n = 2054), overall, there was no significant between-group difference in terms of overall survival. Based on Kaplan–Meier estimates, the probability of overall survival at four years was 99.5% in the MIS group and 97.2% in the open group (p = 0.1110). When examined according to the year of diagnosis, there were no significant between-group differences in the overall survival in both groups one and two. In this population-based cohort study, MIS did not compromise survival outcomes when compared with conventional open surgery in Japanese patients with uterine-confined and node-negative (FIGO 2018 stage I) cervical cancer.

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.

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.

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.

Primary fallopian tube carcinoma (PFTC) has characteristics similar to those of ovarian carcinoma. The typical course of PFTC metastasis includes peritoneal dissemination and pelvic and paraaortic lymph node metastasis, while inguinal lymph node metastasis is rare. Moreover, the initial presentation of PFTC with an inguinal tumor is extremely rare. A 77-year-old postmenopausal woman presented with a massive 12-cm inguinal subcutaneous tumor. After tumor resection, histopathological and immunohistochemical analysis showed that the tumor was a high-grade serous carcinoma of gynecological origin. Subsequent surgery for total hysterectomy with bilateral salpingo-oophorectomy revealed that the tumor developed in the fallopian tube. She received adjuvant chemotherapy with carboplatin and paclitaxel, followed by maintenance therapy with niraparib. There has been no recurrence or metastasis 9 months after the second surgery. We reviewed the literature for cases of PFTC and ovarian carcinoma that initially presented with an inguinal tumor. In compliance with the Preferred Reporting Items for Systematic Reviews guidelines, a systematic literature search was performed through 31 January 2022 using the PubMed and Google scholar databases and identified 14 cases. In half of them, it was difficult to identify the primary site using preoperative imaging modalities. Disease recurrence occurred in two cases; thus, the prognosis of this type of PFTC appears to be good.

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.

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.

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.

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.

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.

Background: Targeting DNA repair and immune checkpoint pathways has been the focus of multiple clinical trials. In this study, we explore the association between DNA repair proteins, immune response markers, and clinical outcome in women with EOC. Methods: Immunohistochemical analysis of TMA with 181 EOC samples was used to determine expression levels for DNA repair proteins (PARP, PTEN, p53, H2Ax, FANCD2, and ATM) and immune-markers (CD4, CD8, CD68, PD-L2, PD-L1, and FOXP3). Biomarker expression was correlated to clinical data. Prognostic discriminatory ability was assessed per the combination of biomarkers. Results: Tumor immunity biomarkers correlated with HRD biomarkers. High PD-L2 was significantly associated with high expression of CD8 (r = 0.18), CD68 (r = 0.17), and FOXp3 (r = 0.16) (all, p < 0.05). In a multivariate analysis, PD-L2 (hazard ratio (HR) 1.89), PARP (HR 1.75), and PTEN (HR 1.96) expressions were independently associated with decreased progression-free survival (PFS), whereas PD-L1 (HR 0.49) and CD4 (HR 0.67) were associated with improved PFS (all, p < 0.05). In 15 biomarker combinations, six combinations exhibited a discriminatory ability of >20% for the 4.5-year PFS rate, with four based on PD-L2 (PARP, PTEN, CD4, and PD-L1, 20.5–30.0%). Conclusions: Increased PD-L2 expression is a prognostic marker of decreased survival in EOC. Interaction between tumor DNA repair and microenvironment determines tumor progression and survival.

Epithelial ovarian cancer remains a leading cause of death amongst all gynecologic cancers despite advances in surgical and medical therapy. Historically, patients with ovarian cancer underwent primary tumor reductive surgery followed by postoperative chemotherapy; however, neoadjuvant chemotherapy followed by interval tumor reductive surgery has gradually become an alternative approach for patients with advanced-stage ovarian cancer for whom primary tumor reductive surgery is not feasible. Decision-making about the use of these approaches has not been uniform. Hence, it is essential to identify patients who can benefit most from neoadjuvant chemotherapy followed by interval tumor reductive surgery. Several prospective and retrospective studies have proposed potential models to guide upfront decision-making for patients with advanced ovarian cancer. In this review, we summarize important decision-making models that can improve patient selection for personalized treatment. Models based on clinical factors (clinical parameters, radiology studies and laparoscopy scoring) and molecular markers (circulating and tumor-based) are useful, but laparoscopic staging is among the most informative diagnostic methods for upfront decision-making in patients medically fit for surgery. Further research is needed to explore more reliable models to determine personalized treatment for advanced epithelial ovarian cancer.

(1) Background: This study examined the use of a two-tier system in grouping cervical adenocarcinoma for survival discrimination. (2) Methods: A nationwide retrospective observational cohort study was conducted using the Japan Society of Gynecologic Oncology tumor registry database from 2001 to 2015 (n = 86,754). Adenocarcinoma subtypes were grouped as type 1 (endocervical usual type and endometrioid) or type 2 (serous, clear, mucinous, and not otherwise specified), based on their relative survival compared with that of squamous tumors. (3) Results: The majority of the adenocarcinoma cases were type 1 (n = 10,121) versus type 2 tumors (n = 5157). Type 2 tumors were more likely to be old and have stage IV disease than those with squamous tumors. The number of type 2 tumors increased from 2001 to 2014 (106.1% relative increase, p < 0.001). Type 2 tumors had disproportionally poorer survival compared to other types (5-year survival rates: 68.9% for type 2, 75.4% for type 1, and 78.0% for squamous; p < 0.001). On multivariate analysis, type 2 tumors remained an independent prognostic factor associated with decreased survival compared with squamous (adjusted hazard ratio 2.00, 95% CI 1.84–2.15, p < 0.001). (4) Conclusion: The survival of cervical adenocarcinoma varies largely across the histological subtypes, and the proposed two-tier grouping may be useful for survival discrimination.

Non-epithelial ovarian tumors are heterogeneous and account for approximately 10% of ovarian malignancies. The most common subtypes of non-epithelial ovarian tumors arise from germ cells or sex cord and stromal cells of the gonads. These tumors are usually detected at an early stage, and management includes surgical staging and debulking. When indicated for advanced disease, most respond to chemotherapy; however, options for patients with refractory disease are limited, and regimens can be associated with significant toxicities, including permanent organ dysfunction, secondary malignancies, and death. Targeted therapies that potentially decrease chemotherapy-related adverse effects and improve outcomes for patients with chemotherapy-refractory disease are needed. Here, we review the molecular landscape of non-epithelial ovarian tumors for the purpose of informing rational clinical trial design. Recent genomic discoveries have uncovered recurring somatic alterations and germline mutations in subtypes of non-epithelial ovarian tumors. Though there is a paucity of efficacy data on targeted therapies, such as kinase inhibitors, antibody–drug conjugates, immunotherapy, and hormonal therapy, exceptional responses to some compounds have been reported. The rarity and complexity of non-epithelial ovarian tumors warrant collaboration and efficient clinical trial design, including high-quality molecular characterization, to guide future efforts.

This study examined the association between peritoneal cytology and survival in early-stage cervical cancer. This is a nationwide multicenter retrospective study, examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy with available peritoneal cytology results from 2004−2008. Propensity score inverse probability of treatment weighting was used to assess the impact of malignant peritoneal cytology on survival. Among 1409 analyzed cases, 88 (6.2%) had malignant peritoneal cytology. On weighted models, malignant peritoneal cytology was associated with decreased disease-free survival (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.36−2.32) and overall survival (OS, HR 1.93, 95% CI 1.44−2.59). On sensitivity analyses, malignant peritoneal cytology was associated with decreased OS in adenocarcinoma/adenosquamous carcinoma, high-risk early-stage disease and those who received concurrent chemo-radiotherapy. However, among women who received postoperative systemic chemotherapy, malignant peritoneal cytology was not associated with OS (HR 1.21, 95% CI 0.72−2.04). A systematic review, including our results, showed that malignant peritoneal cytology was associated with decreased OS (HR 4.03, 95% CI 1.81−8.99) and increased recurrence in squamous carcinoma (odds ratio 1.89, 95% CI 1.05−3.39) and adenocarcinoma (odds ratio 4.30, 95% CI 2.30−8.02). In conclusion, the presence of malignant cells in peritoneal cytology is associated with decreased survival in early-stage cervical cancer. The possible benefit of systemic chemotherapy in this subgroup merits further investigation.

Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and perinatal morbidity and mortality. Maternal endothelial dysfunction caused by placental factors has long been accepted with respect to the pathophysiology of preeclampsia. Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunction. This review summarizes the recent advances in understanding the molecular mechanisms of endothelial dysfunction caused by placental antiangiogenic factors, and the novel clinical strategies based on these discoveries.