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Figure S1. Stable expression of SOCS-1 suppressed IFN-γ-induced expression of PD-L1 in vitro and tumor growth in vivo; Figure S2. AdSOCS-1 directly inhibits tumor growth of ovarian cancer cell lines in vitro.

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Difference of treatment procedures for localized of cervical cancer, by age group (1976-2012)

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Difference of tumor stage of cervical cancer, by age group (1976-2012)

Thsi figure shows low expression of hLSR and no toxicity of newly developed anti-hLSR mAb in normal human and mouse tissues.

Changes in number of cervical cancer cases, by treatment procedure

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This Figure shows lipid droplets in LSR-positive OVCAR3 xenograft tissues by electron microscopy

This figure shows binding of newly developed anti-hLSR monoclonal antibody to cell surface LSR.

This article shows how to product anti-LSR antibody

This table shows no toxicity of anti-hLSR mAb in mice

This table shows the list of all the proteins identified by iTRAQ analysis including LSR.

5-years relative survival rate, by stage and age group (1976-2010, SCC and adenocarcinoma of the cervix)

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These tables shows LSR immunostaining distribution of patients with ovarian serous carcinoma (Table S2) and clear cell carcinoma (Table S3)

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This Figure shows anti-tumor activity of anti-hLSR mAb (#1-25) in EOC xenografts using SCID mice

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, but it still lacks effective treatment options. In this study, we utilized proteomic technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction with survival analysis of EOC patients showed that high expression of LSR is associated with poor prognosis. High LSR expression also occurred in tumor metastases including to the lymph node and omentum. To evaluate the possible benefits of blocking this antigen in EOC, we raised a new monoclonal antibody (mAb) to human LSR (hLSR). In mouse xenograft models of hLSR+ EOC (cell lines or patient-derived tumors), we found that administration of anti-hLSR mAb inhibited tumor growth in a manner independent of both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Mechanistic investigations showed that hLSR expression increased incorporation of very-low-density lipoprotein (VLDL) into EOC cells and that anti-hLSR mAb inhibited lipid uptake in vitro and in vivo. Moreover, VLDL promoted cell proliferation in hLSR-positive EOC cells in vitro, and this effect was inhibited by anti-hLSR mAb. While the anti-hLSR mAb studied cross reacted with the mouse antigen, we observed no adverse effects on normal organs and lipid metabolism in murine hosts. Our findings suggest that hLSR plays a key functional role in EOC development and that this antigen can be therapeutically targeted by specific mAb to improve EOC treatment.Significance: These findings offer preclinical evidence of the therapeutic efficacy of a novel targeted antibody therapy against deadly epithelial ovarian cancers. Cancer Res; 78(2); 516–27. ©2017 AACR.

Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC ≥0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection.Significance:This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.

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Cervical cancer screening rate is extremely low and the governmental recommendation of HPV vaccine has been suspended for 5 years in Japan. Here, we utilized data from the Osaka Cancer Registry, collected between 1976 and 2012, to evaluate cervical cancer trends in Japan. Age-adjusted incidence, relative survival, and conditional survival rates were calculated using multiple imputation methods and period analyses in 25,826 cervical cancer cases. Association of survival rates and clinical factors, including patients' age, clinical stage, and treatment procedures, were also analyzed. A trend for significantly decreasing age-adjusted incidence of cervical cancer (per 100,000) began in 1976 but reversed after 2000, increasing significantly to date (annual percent change = 3.8, 95% confidence interval, 2.7–4.8; age-adjusted rate: 28.0 in 1976, 9.1 in 2000, 14.1 in 2012). The 10-year relative survival rate improved significantly after 2002, especially in cases of “localized” and “adjacent organs” disease; this was likely due to the introduction of concurrent chemotherapy and radiation. The conditional 5-year relative survival rate improved significantly yearly until the fourth survival year. In the surgery-based group, we observed no age-dependent differences in outcomes. Unexpectedly, however, prognosis for younger age groups was poorer in the radiation-based treatment group. These results indicate that although relative survival rates have recently increased, treatment for more advanced cases with distant metastasis requires further improvement. In addition, this study is the first to suggest that age might be an important predictor of radiotherapy resistance in cervical cancer.Significance: A large-cohort analysis of cervical cancer cases reveals that age-adjusted incidence in Japan has increased since 2000 and that age may negatively correlate with resistance to radiotherapy.

10-years relative survival rate, by period and by stage (1976-2010, invasive cervical cancer)

To examine characteristics and outcomes of cesarean delivery (CD) in women with a history of vertical hysterotomy.This is a comparative study that retrospectively queried the National Inpatient Sample from October 2016 to December 2018. Pregnancy characteristics and surgical outcomes of CD among 18 575 women with prior vertical uterine incision were compared to 1 072 949 women with prior low-transverse incision, assessed by multivariable generalized estimating equation model and propensity score weighting.In a multivariable analysis, women who had prior vertical uterine incision were more likely to have placenta percreta (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.87-6.20), pre-labor uterine rupture (OR 2.70, 95% CI 1.52-4.80), in-labor uterine rupture (OR 2.33, 95% CI 1.55-3.51), and extreme preterm delivery28 weeks (OR 17.8, 95% CI 15.2-20.7) in the current pregnancy, compared to those who had prior low-transverse uterine incision. In a weighted model, prior vertical hysterotomy was associated with increased surgical morbidity in current CD compared to prior low-transverse hysterotomy (10.6% vs. 4.8%, OR 2.02, 95% CI 1.81-2.26), including hemorrhage (OR 1.99, 95% CI 1.74-2.27) and hysterectomy (OR 3.67, 95% CI 2.97-4.53).Prior vertical uterine incision at CD was associated with increased risk of placenta percreta, uterine rupture, particularly before labor, and adverse outcomes in the subsequent pregnancy.

OBJECTIVE To examine the association between hospital surgical volume of caesarean hysterectomy and surgical morbidity in women with placenta accreta spectrum (PAS). DESIGN Population-based retrospective cohort study. SETTING National Inpatient Sample, January 2016 to December 2018. POPULATION Six thousand and ten women with PAS who underwent caesarean hysterectomy in 738 centres. METHODS (1) Comprehensive modelling for relative hospital surgical volume cut-point selection, (2) multinomial regression analysis for characterising hospital surgical volume, and (3) binary logistic regression analysis to examine the volume-outcome relationship. MAIN OUTCOME MEASURES Surgical morbidity (haemorrhage, coagulopathy, shock, urinary tract injury, and death). RESULTS The majority of centres had five surgeries over the 3-year period (468 centres, 63.4%) and were grouped as the low-volume group. Surgical morbidity decreased after a relative hospital surgical volume of 25 cases (24 centres, 3.3%) was reached, grouped as the high-volume group. The remaining centres were grouped as the mid-volume group (246 centres, 33.3%). In multivariable analysis, women in the high-volume group were more likely to be Black, have lower median household income, medical comorbidity, previous caesarean delivery, placenta praevia or placenta percreta, and to have undergone surgeries at large urban teaching hospitals compared with those in the low-volume group (all, P

Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.

INTRODUCTION This study examined national-level trends, characteristics, and perioperative outcomes of women who had intra-arterial balloon occlusion at cesarean hysterectomy for placenta accreta spectrum (PAS). MATERIAL AND METHODS This was a population-based retrospective observational study that queried the National Inpatient Sample from October 2015 to December 2018. Study population was women who underwent hysterectomy at cesarean delivery for PAS (n = 6440 in 806 centers). Exposure allocation was the use of intra-arterial balloon occlusion. Main outcome measures were (a) characteristics associated with intra-arterial balloon occlusion use, and (b) perioperative outcome including hemorrhage, blood transfusion, coagulopathy, shock, urinary tract injury, intra-arterial balloon occlusion-related complication (arterial injury, arterial thrombosis, and lower extremities ischemia), and death, assessed in multivariable analysis. RESULTS Intra-arterial balloon occlusion was used in 420 (6.5%) women in 64 (7.9%) centers. Utilization of intra-arterial balloon occlusion during cesarean hysterectomy for placenta accreta decreased significantly over time (from 6.3% to 3.1%, p

Placenta accreta spectrum (PAS) encompasses a range of disorders of placental trophoblastic tissue that is morbidly adherent to the underlying gravid uterus. Women with PAS commonly undergo surgical treatment with hysterectomy at cesarean delivery that is associated with significant surgical morbidity and mortality. Increased vascularity due to gestational change and the abnormally enlarged lower uterine segment due to the location of placenta make the surgery complex and morbid. Here, we propose a simple 2-hand technique that can be used to improve surgical outcomes of cesarean hysterectomy for PAS. Unlike the ordinary hysterectomy where the transection of the cardinal ligament is started at the isthmus below the low uterine segment, the proposed 2-hand technique allows transection of the cardinal ligament at the level of the lower uterine segment below the placental bed. This minimizes blood loss that may be associated with serial transection of cardinal ligament which occurs when it is transected at or above the placenta level. This surgical approach starts with demarcation of 3 anatomical landmarks [rectum (posterior aspect), ureters (lateral aspect), and bladder (anterior aspect)] in postero-anterior progression. Complete de-serosalization of posterior low uterine segment allows lateralization of the ureter and enables the uterus to be mobilized antero-caudally where the surgeon’s hand can reach below the placental bed. After the bladder flap creation to the level of endopelvic fascia, the surgeon’s two hands are placed antero-posteriorly at low uterine segment below the placental bed. The fingertips of both hands meet at the cardinal ligament below placenta at the level of the upper cervix. At this point the two hands are gently moved upwards, carrying the placenta-containing low uterine segment. This step enables creation of a safe anatomical distance from surrounding structures and isolation of the cardinal ligament where surgical clamp can be applied to transect the cardinal ligament.

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.

The first-order nature of the chiral phase transition in QCD-like theories can play crucial roles to address a dark side of the Universe, where the created out-of equilibrium is essential to serve as cosmological and astrophysical probes such as gravitational wave productions, which have extensively been explored. This interdisciplinary physics is built based on a widely-accepted conjecture that the thermal chiral phase transition in QCD-like theories with massless (light) three flavors is of first order. We find that such a first order feature may not hold, when ordinary or dark quarks are externally coupled to a weak enough background field of photon or dark photon (which we collectively call a ``magnetic" field). We assume that a weak ``magnetic" background field could be originated from some ``magnetogenesis" in the early Universe. We work on a Nambu-Jona-Lasinio model which can describe the chiral phase transition in a wide class of QCD-like theories. We show that in the case with massless (light) three flavors, the first-order feature goes away when $2 f_\pi^2 \lesssim eB ( \ll (4 \pi f_\pi)^2)$, where $eB$ is the ``magnetic" field strength and $f_\pi$ the pion decay constant at the vacuum. This disappearance is the generic consequence of the presence of the ``magnetically" induced scale anomaly and the ``magnetic" catalysis for the chiral symmetry breaking, and would impact or constrain modeling dark QCD coupled to an external ``magnetic" field., Comment: 23 pages, 6 figures; references added; version published in Phys.Rev.D

ObjectiveSurgery for placenta accreta spectrum is associated with significant maternal morbidity and mortality. The role of gynecologic oncologists in the surgical management of placenta accreta spectrum is currently under investigation. This study examined the practices, experiences, and interests of gynecologic oncologists in placenta accreta spectrum surgeries.MethodsThe intervention was an anonymous, cross-sectional, 20-question survey sent to 1084 members of the Society of Gynecologic Oncology in the USA.ResultsA total of 184 gynecologic oncologists responded to the survey (response rate 17.0%). Most participating gynecologic oncologists have been practicing for >10 years after fellowship (53.2%), practice in urban-teaching hospitals (84.8%) with delivery volumes ≥3000/year (54.3%), and have a multidisciplinary approach (82.5%). Three-quarters (78.7%) feel that the rate of placenta accreta spectrum is increasing over time. One-third (35.5%) perform ≥6 hysterectomies for placenta accreta spectrum yearly. Less than half (45.5%) practice conservative management. Approximately half are involved from the beginning of the case (49.7%) and perform the surgery in the main operating room (59.4%). Almost three-quarters (71.6%) have experienced surgical blood loss >5 L and one-third (36.6%) have experienced cases with blood loss >10 L. About half (50.3%) of participants are interested in placenta accreta spectrum surgery for future practice. Gynecologic oncologists engaging in a multidisciplinary approach are more likely to practice in an urban-teaching hospital, have higher surgical volume, be involved from the beginning of the case, and be interested in placenta accreta spectrum surgery. Those >10 years post-training and in the Southern US region are more likely to practice conservative management or delayed hysterectomy.ConclusionThis society-based cross-sectional survey suggests that gynecologic oncologists are actively involved in the surgical management of placenta accreta spectrum in the USA. Nearly half of gynecologic oncologists who responded to the survey expressed interest in surgery for placenta accreta spectrum.

To investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy.Locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival.This study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false-negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false-positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3-year postoperative survival rate in this group was 39.7%.Including LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.

Introduction: In laparoscopic surgery, the cooperation of the first assistant surgeon is essential for the creation and maintenance of an appropriate and safe surgical field. The aim of this study is a validation of the impact of our educational system for first assistant laparoscopic surgeon residency in a single university-affiliated teaching hospital.Methods: Five residents were recruited for this study. We created a slide-set as an educational tool using Microsoft’s PowerPoint that was in line with our surgical procedure to master the assistant skills of laparoscopic gynecologic surgery. Immediately after surgery, the attending doctor and residents reviewed videos of the first assistant’s operative procedures. This study evaluated the effect of our educational check-list against the transition of evaluation scores before and after training in two groups of residents, those with minimal experience (Group 1) or with high experience (Group 2).Results: Before receiving our training tool, there was an expected significant difference in the review scores of the two experience groups (29.1±3.1 vs 48.7±3.9, p=0.01). After our modified training, the inexperienced residents of Group 1 received review scores comparable to or higher than those of the experienced residents of Group 2 (81.9±5.9 vs 70.4 ±7.5, p=0.23). As they assisted with more surgeries, the concordance between the resident’s self-assessment and the attending doctor’s assessment scores increased significantly (pConclusions: Our educational system for first assistant surgeons is effective for new residents, as it proved capable of imparting them with many of the same skill sets as much more experienced attending doctors.

Selecting the best treatment for individual patients with cancer has attracted attention for improving clinical outcomes. Recent progress in organoid culture may lead to the development of personalized medicine. Unlike molecular-targeting drugs, there are no predictive methods for patient response to standard chemotherapies for ovarian cancer. We prepared organoids using the cancer tissue-originated spheroid (CTOS) method from 61 patients with ovarian cancer with 100% success rate. Chemosensitivity assays for paclitaxel and carboplatin were performed with 84% success rate using the primary organoids from 50 patients who received the chemotherapy. A wide range of sensitivities was observed among organoids for both drugs. All four clinically resistant organoids were resistant to both drugs in 18 cases in which clinical response information was available. Five out of 18 cases (28%) were double-resistant, the response rate of which was compatible with the clinical remission rate. Carboplatin was significantly more sensitive in serous than in clear cell subtypes (P = 0.025). We generated two lines of organoids, screened 1135 drugs, and found several drugs with better combinatory effects with carboplatin than with paclitaxel. Some drugs, including afatinib, have shown an additive effect with carboplatin. The organoid sensitivity assay did not predict the clinical outcomes, both progression free and overall survival.

Although an infrequent occurrence, the placenta can adhere abnormally to the gravid uterus leading to significantly high maternal morbidity and mortality during cesarean delivery. Contemporary national statistics related to a morbidly adherent placenta, referred to as placenta accreta spectrum, are needed.This study aimed to examine national trends, characteristics, and perioperative outcomes of women who underwent cesarean delivery for placenta accreta spectrum in the United States.This is a population-based retrospective, observational study querying the National Inpatient Sample. The study cohort included women who underwent cesarean delivery from October 2015 to December 2017 and had a diagnosis of placenta accreta spectrum. The main outcome measures were patient characteristics and surgical outcomes related to placenta accreta spectrum assessed by the generalized estimating equation on multivariable analysis. The temporal trend of placenta accreta spectrum was also assessed by linear segmented regression with log transformation.Of 2,727,477 cases who underwent cesarean delivery during the study period, 8030 (0.29%) had the diagnosis of placenta accreta spectrum. Placenta accreta was the most common diagnosis (n=6205, 0.23%), followed by percreta (n=1060, 0.04%) and increta (n=765, 0.03%). The number of placenta accreta spectrum cases increased by 2.1% every quarter year from 0.27% to 0.32% (P=.004). On multivariable analysis, (1) patient demographics (older age, tobacco use, recent diagnosis, higher comorbidity, and use of assisted reproductive technology), (2) pregnancy characteristics (placenta previa, previous cesarean delivery, breech presentation, and grand multiparity), and (3) hospital factors (urban teaching center and large bed capacity hospital) represented the independent characteristics related to placenta accreta spectrum (all, P.05). The median gestational age at cesarean delivery was 36 weeks for placenta accreta and 34 weeks for both placenta increta and percreta vs 39 weeks for non-placenta accreta spectrum cases (P.001). On multivariable analysis, cesarean delivery complicated by placenta accreta spectrum was associated with increased risk of any surgical morbidities (78.3% vs 10.6%), Centers for Disease Control and Prevention-defined severe maternal morbidity (60.3% vs 3.1%), hemorrhage (54.1% vs 3.9%), coagulopathy (5.3% vs 0.3%), shock (5.0% vs 0.1%), urinary tract injury (8.3% vs 0.2%), and death (0.25% vs 0.01%) compared with cesarean delivery without placenta accreta spectrum. When further analyzed by subtype, cesarean delivery for placenta increta and percreta was associated with higher likelihood of hysterectomy (0.4% for non-placenta accreta spectrum, 45.8% for accreta, 82.4% for increta, 78.3% for percreta; P.001) and urinary tract injury (0.2% for non-placenta accreta spectrum, 5.2% for accreta, 11.8% for increta, 24.5% for percreta; P.001). Moreover, women in the placenta increta and percreta groups had markedly increased risks of surgical mortality compared with those without placenta accreta spectrum (increta, odds ratio, 19.9; and percreta, odds ratio, 32.1).Patient characteristics and outcomes differ across the placenta accreta spectrum subtypes, and women with placenta increta and percreta have considerably high surgical morbidity and mortality risks. Notably, 1 in 313 women undergoing cesarean delivery had a diagnosis of placenta accreta spectrum by the end of 2017, and the incidence seems to be higher than reported in previous studies.

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, The immunohistochemical analysis of ovarian cancer specimens revealed that cluster of differentiation 70 (CD70) is expressed in approximately 70% of patients who received platinum‐based neoadjuvant chemotherapy. CD70 is induced in cisplatin‐treated ovarian cancer cells and is strongly expressed in platinum‐resistant cells. The CD70 antibody‐drug conjugate is effective against CD70‐expressing ovarian cancer both in vitro and in vivo. Our translational research indicates that the effectiveness of CD70 antibody‐drug conjugate merits further investigation as a novel therapeutic strategy for women with ovarian cancer.

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.

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 3versus 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.

ObjectiveTo examine trends and outcomes related to adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer.MethodsThis retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000 to 2016. Surgically treated women with American Joint Commission on Cancer stages T1–2 cervical cancer who had high risk factors (nodal metastasis and/or parametrial invasion) and received additional therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for systemic chemotherapy versus external beam radiotherapy with chemotherapy.ResultsAmong 2462 patients with high risk factors, 185 (7.5%) received systemic chemotherapy without external beam radiotherapy, of which the utilization significantly increased over time in multivariable analysis (adjusted odds ratio per 1 year increment 1.06, 95% confidence interval (CI) 1.02 to 1.09). In weighted models, adjuvant chemotherapy and combination therapy (external beam radiotherapy and chemotherapy) had comparable overall survival among patients aged ConclusionUtilization of adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer is increasing in the United States in the recent years. Our study suggests that survival effects of adjuvant systemic chemotherapy may vary based on patient and tumor factors. External beam radiotherapy with chemotherapy remains the standard for high risk, early stage cervical cancer, and use of adjuvant systemic chemotherapy without external beam radiotherapy should be considered with caution.

To examine characteristics and short-term perioperative outcomes related to minimally invasive pelvic exenteration for gynecologic malignancy.This comparative effectiveness study is a retrospective population-based analysis of the National Inpatient Sample from 10/2008-9/2015. Women with cervical, uterine, vaginal, and vulvar malignancies who underwent pelvic exenteration were evaluated based on the use of laparoscopic or robotic-assisted surgery. Patient demographics and intraoperative/postoperative complications related to a minimally invasive surgical approach were assessed.Among 1376 women who underwent pelvic exenteration, 49 (3.6%) had the procedure performed via a minimally invasive approach. The majority of minimally invasive cases were robotic-assisted (51.0%). Women in the minimally invasive group were more likely to be old, white, have cervical/uterine cancers, and receive urinary diversion, but less frequently received vaginal reconstruction or colostomy when compared to those in the open surgery group (P0.05). Overall perioperative complication rates were similar between the minimally invasive and open surgery groups (79.6% versus 77.7%, P = 0.862), but the minimally invasive group had a decreased risk of high-risk complications compared to the open surgery group (adjusted-odds ratio 0.19, 95% confidence interval 0.07-0.51). Specifically, a minimally invasive approach was associated with decreased incidence of sepsis and thromboembolism compared to an open approach (P0.05). The minimally invasive group had a shorter length of stay (median, 9 versus 14 days) and lower total charge (median, $127,875 versus $208,591) compared to the open surgery group (P0.05).Laparotomy remains the main surgical approach for pelvic exenteration for gynecologic malignancy and minimally invasive surgery was infrequently utilized during the study period in the United States. Before widely adopting this surgical approach, the utility and role of minimally invasive pelvic exenteration requires further investigation.

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.

The aim of this study was to examine the survival effect of adjuvant therapy in stage II–III endometrial cancer based on peritoneal cytology results. The National Cancer Institute’s Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II–III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p

To examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget's disease.This is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget's disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status.The median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83).Positive surgical margin appears to be common in invasive vulvar Paget's disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.