Sex differences in the prevalence of metabolic syndrome and associated factors in the general population of Mongolia: A nationwide study.

The prevalence and factors associated with metabolic syndrome (MetS) between men and women in Mongolia were compared using secondary data from the STEPwise approach to non-communicable disease risk factor surveillance conducted in 2019. In total, 5,695 participants (2,577 males and 3,118 females) aged 18-69 years old were enrolled in the study. The prevalence of MetS was 37.4% in total and the prevalence was significantly higher in women (39.2%) than men (35.2%, P = 0.002). The most prevalent MetS components were abdominal obesity in women (74.2%) and high blood glucose levels in men (58.7%). All of the 2,128 participants who were categorized into MetS met the criteria of abdominal obesity. Factors associated with MetS included being 30-69 years old compared to 18-29 years old, low and moderate physical activity levels compared to high levels, history of hypertension and diabetes mellitus, and a high body mass index (overweight and obesity) compared to a normal body mass index in both sexes. Additional factors included Buryat ethnicity compared to Khalkh ethnicity, living in Ulaanbaatar, no education compared to primary education, higher monthly income, and currently drinking in men; and smoking and sufficient fruit and vegetable intake in women. Significant differences were observed between men and women in terms of the prevalence of MetS, components of MetS, and factors associated with MetS. To reduce MetS prevalence in Mongolia, sex-specific programs should be designed to promote health behavior, such as reducing alcohol consumption in men and smoking in women.

Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq.

OBJECTIVE: A complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq. METHODS: We included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells. RESULTS: The gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice. CONCLUSION: RNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.

Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study.

OBJECTIVE: In this study, we collected data over 8 years (2012-2019) from the Japan Society of Obstetrics and Gynecology (JSOG) tumor registry to determine the status of endometrial cancer in Japan, and analyzed detailed clinicopathological factors. METHODS: The JSOG maintains a tumor registry that gathers information on endometrial cancer treated at the JSOG-registered institutions. Data from the patients whose endometrial cancer treatment was initiated from 2012 to 2019 were analyzed retrospectively. RESULTS: A total of 82,969 patients with endometrial cancer underwent treatment from 2012 to 2019. Chemotherapy alone or in combination with hormonal therapy is more common among endometrial cancer patients under 40 years compared with those over 40 years. The number of patients with endometrial cancer, treated with laparoscopic or robot-assisted surgery was observed to have increased yearly. Small cell carcinomas and undifferentiated carcinomas were more likely to be diagnosed at an advanced stage. Lymphadenectomy was most commonly performed for stage IIIC2 disease, whereas positive peritoneal washing cytology was most common for stage IVB and serous carcinoma. CONCLUSION: Multi-year summary reports provided detailed clinicopathological information regarding endometrial cancer that could not be obtained in a single year. These reports were useful in understanding treatment strategies and trends over time based on age, histology, and stage.

Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model.

BACKGROUND: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. METHODS: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. RESULTS: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. CONCLUSIONS: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.

A case of complete remission of intractable gestational choriocarcinoma with subsequent chemotherapy after pembrolizumab.

OBJECTIVE: Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) that originates from abnormal trophoblast proliferation. Although chemotherapy is effective for choriocarcinoma, personalized treatment becomes essential when patients develop chemoresistance. Here, we present the clinical course of a case of intractable choriocarcinoma that achieved complete remission with pembrolizumab following cytotoxic chemotherapy. CASE REPORT: A 38-year-old woman was initially diagnosed with low-risk GTN and treated with single- and multi-agent chemotherapy. She underwent a hysterectomy and was diagnosed with pathological choriocarcinoma with high-risk GTN. She was treated with multiple courses of several chemotherapy regimens. However, she did not achieve remission. Her choriocarcinoma showed high microsatellite instability; therefore, she took ten courses of pembrolizumab, but her hCG value increased. Subsequently, she underwent eight courses of paclitaxel and carboplatin alternating with paclitaxel and etoposide and achieved remission. CONCLUSION: This case suggests that pembrolizumab may improve the efficacy of subsequent chemotherapy.

Factors associated with pentavalent vaccine coverage among 12-23-month-old children in Afghanistan: A cross-sectional study.

INTRODUCTION: This study aimed to identify the factors associated with the coverage of the third dose of pentavalent vaccine (Penta3) among children aged 12-23 months in Afghanistan. METHODS: The data of 3,040 children aged 12-23 months were taken from the Afghanistan Health Survey 2018, including characteristics of the children and their households, household heads, and mothers/primary care givers. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using a logistic model. Multivariable stepwise logistic regression analysis with forward-selection (Model 1) and backward-selection (Model 2) was performed using variables that showed significant differences by bivariate analysis. RESULTS: The coverage of Penta3 among 12-23-month-old children was 82.3%. Factors associated with Penta3 coverage in the two models of multivariable analysis were 18-23 months old compared to 12-17 months old; having no diarrhea in the last two weeks compared to having diarrhea; no bipedal edema compared to having edema; taking vitamin A supplement; 1-2 children under five years in a household compared to three or more; distance from residence to the nearest health facility ≤2 hours on foot; having a radio; having a TV; educated heads of households; non-smoking of heads of households; and literacy of mothers/primary caregivers. CONCLUSIONS: Penta3 coverage among 12-23-month-old children improved but was still lower than the target. Primary education should be provided to all children throughout the country. TV and radio are useful tools for providing health information. Mobile outreach programs and the establishment of new health facilities should be promoted to improve access to health service for all people in Afghanistan.

Assessment of the underlying causes of adult deaths using a short version of verbal autopsy in Xaiyabouli Province, Lao People's Democratic Republic.

BACKGROUND: In developing countries, it is difficult to collect the data of the underlying cause of death (UCOD), especially when a death does not occur in a health facility. This study aimed to develop a short version of verbal autopsy (VA) and identify the UCOD of adults in Lao People's Democratic Republic (Lao PDR). METHODS: A short version of VA for deaths outside health facilities was developed. This study included all deaths of people aged 15 years old or older in Xaiyabouli Province in 2020. Socio-demographic factors, place of death, and UCOD of the deceased were collected from health facilities or from family members using a questionnaire including the short VA form. UCOD was compared between home deaths and hospital deaths, between the age group of 15-59 years old and the age group ≥ 60 years old, and between males and females. RESULTS: Of all the 1,235 deaths included in this study, 1,012 deaths (81.9%) occured at home and 223 deaths (18.1%) at hospitals. The most common UCOD was senility (13.3%), followed by heart/renal failure (10.5%), pneumonia (9.6%) and traffic accident (7.1%). Compared to hospital deaths, home deaths had more people who were females, 75 years old or older, and Lao-Tai. Home deaths had more deaths than hospital deaths due to accident/injury (16.0% vs. 8.1%), tumor (4.7% vs. 1.8%), and senility (16.2% vs. 0%); fewer deaths due to heart/renal disease (15.1% vs. 32.3%), respiratory disease (12.2% vs. 18.8%), liver/gastro-intestine disease (5.3% vs. 9.0%), and infection (3.1% vs. 14.3%). The age group of 15-59 years had more deaths in the categories of accident/injury (28.1% vs. 4.4%), liver/gastro-intestine disease (8.1% vs. 4.4%), infection (7.2% vs. 3.5%), and tumor (6.0% vs. 2.8%). Males had more deaths due to tumor (5.2% vs. 3.0%) and fewer natural deaths (11.2% vs. 15.9%) than females. CONCLUSIONS: The major UCOD category was heart/renal disease in the adult generation in Xaiyabouli Province. Cost-effective interventions based on the multisectoral noncommunicable disease prevention plan should be appropriately implemented. Mortality surveillance using the short VA tool should be conducted for all home deaths in Lao PDR.

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

BACKGROUND: Choriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy. METHODS: Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses. The growth inhibitory effects of 1,271 FDA-approved compounds were evaluated in vitro screening assays and selected drugs were tested in tumor-bearing mice. Functional analyses of drug effects were performed based on RNA sequencing. RESULTS: Muti-step screening identified vorinostat, camptothecin (S, +), topotecan, proscillaridin A, and digoxin as exhibiting an anti-cancer effect in choriocarcinoma cells. Vorinostat, a histone deacetylase inhibitor, was selected as a promising candidate for validation and the IC50 values for choriocarcinoma cells were approximately 1 µM. RNA sequencing and subsequent pathway analysis revealed that the ferroptosis pathway was likely implicated, and key ferroptosis-related genes (i.e., GPX4, NRF2, and SLC3A2) were downregulated following vorinostat treatment. Furthermore, vorinostat repressed tumor growth and downregulated the expression of GPX4 and NRF2 in JAR cell-bearing mice model. CONCLUSION: Vorinostat, a clinically approved drug for the treatment of advanced primary cutaneous T-cell lymphoma, showed a remarkable anticancer effect both in vitro and in vivo by regulating the expression of ferroptosis-related genes. Therefore, vorinostat may be an effective therapeutic candidate for patients with choriocarcinoma.

Factors associated with positive cancer screening for the uterine cervix and breast in Jakarta Province, Indonesia: a cross-sectional study.

BACKGROUND: In many middle-income countries, cancer incidence and mortality are rapidly increasing, but data for developing a strategy of cancer control are rarely collected or analyzed. This study aimed to identify factors associated with positive cancer screening for the uterine cervix and breast in Jakarta Province, Indonesia. METHODS: The data of 79,660 women who had visual inspection with acetic acid (VIA) and 83,043 women who had clinical breast examination (CBE) in the Jakarta Women Cancer Screening program in 2019 were included in this study. Socio-demographic factors, reproductive factors, lifestyle factors, family history, and the results of VIA and CBE were used for analyses. Binary and multivariate logistic regression analyses were performed to identify factors associated with VIA positive or CBE positive. RESULTS: The positive rate was 0.9% for both VIA and CBE among the screening participants. Factors associated with VIA positive were age < 30 years old, age at menarche ≤ 11 years old, remarriage, lower educational level, having an occupation, partner's occupation other than being an employee, alcohol consumption, smoker, inadequate physical activity, cancer family history, and no Pap smear history. Factors associated with CBE positive were age at menarche ≤ 11 years old, widowed, high education, having an occupation, no breastfeeding history, birth control history, alcohol consumption, smoker, inadequate physical activity, cancer family history, and breast tumor history. CONCLUSION: Factors associated with VIA positive and CBE positive among Indonesian women were revealed. To promote female cancer prevention in Indonesia, the prevalence of screenings should be increased and education about the risk factors should be provided to medical professionals.

Epidemiologic study on gestational trophoblastic diseases in Japan.

OBJECTIVE: This study aims to estimate the population-based incidence of gestational trophoblastic diseases (GTDs) and to identify the characteristics of gestational trophoblastic neoplasia (GTN) in Japan. METHODS: The annual number of GTD and live births from 1974 to 2018 were used to estimate the incidence of GTD. The data of 1,574 GTN cases from 1999 to 2018 were analyzed to identify the characteristics of low-risk GTN, high-risk GTN, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). RESULTS: The incidence of hydatidiform mole was 2.02 per 1,000 live births on average which decreased from 1974 to 2008 and increased from 2009 to 2018. The incidence of low-risk GTN, high-risk GTN, PSTT, and ETT was 15.3, 3.5, 0.3, and 0.07 per 100,000 live births, respectively. The estimated incidence of post-molar GTN was 9.8% of molar patients. High-risk GTN was diagnosed more pathologically, had more various kinds of antecedent pregnancies, and had longer intervals after the antecedent pregnancy compared to low-risk GTN. Furthermore, 8.2% of high-risk GTN occurred after the subsequent non-molar pregnancy of hydatidiform mole. The cumulative percentage of developing high-risk GTN after hydatidiform mole reached 89.3% at the 60th month. CONCLUSION: The incidence of hydatidiform mole, low-risk GTN, high-risk GTN was 2.02 per 1,000 live births, 15.3 per 100,000 live births, and 3.5 per 100,000 live births, respectively. High-risk GTN was diagnosed more pathologically and later after the antecedent pregnancy than low-risk GTN. Following molar patients for five years is needed to improve the mortality of malignant GTN.

Cell surface membrane lysosome-associated membrane glycoprotein 2 promotes cell adhesion via abundant N-glycans in choriocarcinoma.

INTRODUCTION: Lysosome-associated membrane glycoprotein 2 (LAMP-2) is a target protein for glycosylation by N-acetylglucosaminyltransferase IV (GnT-IV), which catalyzes the formation of ß1,4GlcNAc branches on the mannose core of N-glycans in choriocarcinoma cells. However, the role of LAMP-2, especially when it is expressed in the cell surface membrane of choriocarcinoma cells, has not been well investigated in the progression of choriocarcinoma. This study aimed to elucidate the function of the cell surface membrane LAMP-2 in the malignancy of choriocarcinoma. METHODS: We evaluated the localization of LAMP-2 in some choriocarcinoma cell lines and clinical samples of choriocarcinoma, normal placenta, hydatidiform mole, and invasive mole by flow cytometry, immunocytochemistry, and immunohistochemistry. We performed functional experiments using the knockout or overexpression model of LAMP-2 in the presence or absence of galectins. RESULTS: LAMP-2 was observed in the cell surface membrane of some choriocarcinoma cell lines and tumor cells of choriocarcinoma tissue and trophoblasts of the placenta, hydatidiform mole, and invasive mole. Cell surface membrane LAMP-2 knockout decreased cell adhesion and invasion in choriocarcinoma cells. Conversely, cell surface membrane LAMP-2A overexpression increased cell adhesion and invasion. Experiments in the presence of galectins revealed that abundant N-glycans bound to the peptide core of the luminal side of the cell surface membrane LAMP-2 mediated cell adhesion of choriocarcinoma cells by interacting with galectins in the extracellular matrix (ECM). DISCUSSION: Cell surface membrane LAMP-2, which is glycosylated by GnT-IV, contributes to the malignancy of choriocarcinoma by promoting cell adhesion with the ECM via abundant N-glycans.

The current situation of health services for hydatidiform mole in Cambodia.

AIM: Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. METHODS: A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. RESULTS: A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n = 29), provincial hospitals (n = 42), district hospitals (n = 20), health centers (n = 6), and others (n = 29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. CONCLUSIONS: The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

Short tandem repeat analysis to identify the causative pregnancy of high-risk gestational trophoblastic neoplasia: Molar versus nonmolar pregnancy and its relation to the outcome.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. METHODS: We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. RESULTS: In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. DISCUSSION: STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.

Next-generation genome sequencing of a matched normal-tumor pair from a patient with intractable gestational choriocarcinoma: A case report.

Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) originating from trophoblastic cells with abnormal proliferation. Although chemotherapy is effective for treating this cancer, when patients develop chemoresistance, personalized treatment, such as the use of drugs matching their genomes, is required. The present report describes a case of intractable gestational choriocarcinoma identified using a next-generation sequencing (NGS)-based tumor panel. A 51-year-old woman was diagnosed with gestational choriocarcinoma via pathological and short tandem repeat analyses. The patient did not achieve remission despite many regimens of chemotherapy, including high-dose therapy with autologous peripheral blood stem cell transplantation. To identify drugs tailored to this particular choriocarcinoma, NGS was performed on the tumor of the patient, and the tumor genome was compared with that of the patient's blood sample using the NCC Oncopanel System. Consequently, 245 single nucleotide variants (SNVs) with a mean SNV allele frequency of 63.1% were identified. This high frequency was because the genome of the gestational choriocarcinoma contained part of the genome of the partner. Therefore, our experience of the present intractable case of choriocarcinoma suggested that matched normal-tumor pair analysis is not appropriate for treatment decisions in GTN cases. When using an NGS-based tumor panel to assess choriocarcinoma, researchers must consider whether the genomic DNA of the patient and their partner are involved in the GTN.

A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review.

BACKGROUND: Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. CASE PRESENTATION: A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. CONCLUSION: Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

Core 2 ß1,6-N-acetylglucosaminyltransferases accelerate the escape of choriocarcinoma from natural killer cell immunity.

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 O-glycan formed by core2 ß1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 O-glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly-N-acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.

The management of hydatidiform mole using prophylactic chemotherapy and hysterectomy for high-risk patients decreased the incidence of gestational trophoblastic neoplasia in Vietnam: a retrospective observational study.

The management of hydatidiform mole (HM) and the incidence of post-molar gestational trophoblastic neoplasia (GTN) in Vietnam has not been reported to date. This study aimed to study the incidence of HM and post-molar GTN and identify factors associated with post-molar GTN at a tertiary hospital in Vietnam. Five hundred and eighty-four patients who were treated for HM at Tu Du Hospital between January and December 2010 were included in this study. The mean age and gestational age at the first evacuation were 28.8 years old and 11.0 weeks, respectively. After the initial evacuation and pathological examination, 87 patients who were older than 40 or did not wish to have children underwent a hysterectomy, while the others underwent second curettage. All 472 patients who had human chorionic gonadotropin (hCG) ≥ 100,000 IU/L before treatment received one cycle of methotrexate with folinic acid as prophylactic chemotherapy. The incidence of HM was 11.1 per 1,000 deliveries; 47 patients (8.0%) developed post-molar GTN. Gestational week, hCG level at one week after the first evacuation, and pathological remnants were significantly associated with the development of post-molar GTN. The results of this study suggest that prophylactic chemotherapy and hysterectomy may be useful for high-risk HM patients to reduce post-molar GTN in settings in which the risk of post-molar GTN and loss to follow-up after HM are greater and hCG measurements and appropriate GTN treatments are unavailable. However, future studies on the long-term outcomes and side effects of prophylactic therapies on HM are required.

Outcome of cesarean scar pregnancy treated with local methotrexate injection.

Local injection of methotrexate (MTX) has been widely used for caesarean scar pregnancy (CSP), but the optimal candidate remains undetermined. The aim of this study is to determine the risk factors associated with treatment failure among patients who received a single dose of local MTX. This is a retrospective cohort study. Clinical information was compared between treatment success vs. failure groups. Risk factors related to treatment failure were also investigated with multivariate analysis. Of 47 patients diagnosed with CSP, 30 received local MTX injection. The initial serum ß- human chorionic gonadotropin (hCG) level in the failure group was significantly higher than in the success group (p = 0.048), and the cut-off value was 47,000 mIU/ml. The rate of type 2 position of the gestational sac in the failure group was significantly higher than in the treatment success group (p = 0.031). A high initial serum ß-hCG level (≥ 47,000 mIU/ml) was identified as the independent risk factor for treatment failure (adjusted odds ratio = 21.9; 95% confidence interval = 1.3-383.1). Type 2 gestational sac position and a higher level of ß-hCG at diagnosis appear to be associated with poor outcomes after local injection of a single dose of MTX.

Evaluation of a routine second curettage for hydatidiform mole: a cohort study.

OBJECTIVE: The aim of this study was to evaluate routine second curettage for hydatidiform mole (HM) by comparing the characteristics and outcomes of developing gestational trophoblastic neoplasia (GTN). STUDY DESIGN: This was a cohort study including 173 patients diagnosed with HM between January 2002 and August 2019 who were followed up at Nagoya University Hospital, Japan. After an evacuation, 105 and 68 patients were managed with the routine method (routine group) and elective method (elective group) for a second curettage, respectively. The routine second curettage was performed around 7 days after the first evacuation. Patients in the elective group underwent a second curettage if there was ultrasonographic evidence of molar remnants in the uterine cavity. Socio-clinical factors were retrospectively compared between the routine and elective groups, and between patients showing regression and those who developed GTN. RESULTS: The incidence of GTN was 15.2% in the routine group and 20.6% in the elective group, and the difference was not significant (P = 0.364). The median GTN risk score was significantly higher in the routine group than in the elective group (P = 0.033). Presence of a complete HM, gestational age, and a pre-treatment human chorionic gonadotropin level of ≥ 200,000 mIU/mL were independent risk factors for GTN in molar patients. CONCLUSION: The incidence of GTN was unchanged but the risk score of GTN was higher in the routine group than in the elective group. Routine second curettage may not be necessary, but further study will be needed to confirm this.