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.

Infection prevention and control status at public hospitals and factors associated with COVID-19 infection among healthcare workers in Myanmar: A cross-sectional study.

BACKGROUND: Hospitals should prepare for emerging diseases and protect healthcare workers (HCWs) from work-related infection. This study aims to assess public hospital preparedness for the coronavirus disease 2019 (COVID-19) a year after the Myanmar government began implementing COVID-19 prevention measures, and to identify factors associated with work-related COVID-19 infection among HCWs in Myanmar. METHODS: In January 2021, data were collected from 101 hospitals and 706 HCWs who had COVID-19 in Myanmar in 2020. Data from the hospitals included basic information, the status of infection prevention and control (IPC), the preparedness for COVID-19 (guidelines, checklists, fever screening, patient pathway, and training), handwashing facilities, and availability of personal protective equipment (PPE). Data of COVID-19 infected HCWs included age, occupation, workplace, severity and source of COVID-19 infection, knowledge and practice of handwashing, and working environment. Chi-square test was performed to compare the preparedness for COVID-19 among three hospital levels (primary, secondary and tertiary levels). Logistic regression analysis was performed to identify the associated factors of work-related infection of HCWs. RESULTS: The total number of beds, HCWs, and COVID-19 patients in 2020 at the 101 hospitals was 12,888, 14,421, and 19,835, respectively. The availability of PPE was high in hospitals at all levels. Approximately 80% of hospitals had functional status of IPC, set up fever screening and patient pathway, and provided training on IPC and COVID-19. However, only 39.6% of hospitals had developed COVID-19 guidelines and 55.4% had developed checklists. The percentage of hospitals that prepared each measurement was lowest at the primary level. The factors associated with work-related COVID-19 among HCWs were being 30-39 years old, working as a doctor, working at isolation wards, having disinfection technique training, and having enough PPE at the workplace. CONCLUSION: The preparedness for COVID-19 at public hospitals in Myanmar in January 2021 was insufficient, especially in the availability of the guidelines and checklists and at primary hospitals. A support system for hospital pandemic preparedness and monitoring of IPC implementation is needed. The government should prepare for emerging diseases and provide appropriate and adequate PPE and additional training to all HCWs, especially HCWs who work for isolation wards.

What inhibits "speaking up" for patient safety among healthcare workers? A cross-sectional study in Malaysia.

BACKGROUND: In healthcare, "speaking up" refers to when healthcare workers raise concerns regarding patient safety through questions, sharing information, or expressing their opinion to prevent harmful incidents and ensure patient safety. Conversely, withholding voice is an act of not raising concerns, which could be beneficial in certain situations. Factors associated with speaking up and withholding voices are not fully understood, especially in strong authoritarian societies, such as Malaysia. This study aimed to examine the factors associated with speaking up and withholding the voices of healthcare workers in Malaysia, thus providing suggestions that can be used in other countries facing similar patient safety challenges. METHODS: This cross-sectional study was conducted in a tertiary hospital in Sarawak State, Malaysia. Data were collected from 474 healthcare workers from 43 departments using a self-administered questionnaire for speaking up and withholding voices measures in 4 weeks prior to data analysis as well as socio-demographic factors of healthcare workers (sex, age group, profession, department, weekly work hours for patient care, years of employment in the hospital, and the hierarchical level) and speaking up related climate of the working environment were recorded. Data were analyzed using descriptive statistics. Logistic regression was performed to find out (adjusted) odds ratio of frequent speaking up and withholding voices. RESULTS: Nurse compared to doctors and healthcare workers with short weekly working hours were more likely to speak up. Healthcare workers in emergency and intensive care department, those with short years of employment, and those who worked at low hierarchical levels were less likely to speak up. Healthcare workers in discouraging environment towards speaking up were more likely to withhold their voices. CONCLUSIONS: This study demonstrates the characteristics of healthcare workers who speak up and those who withhold their voices in Malaysia. To ensure patient safety and prevent harm, it is essential to establish an encouraging environment that promotes speaking up and prevents withholding voices among healthcare worker, especially in circumstances where multiple types of healthcare workers with different socio-demographic backgrounds work together.

Unmet need for contraception among married women in the Kyrgyz Republic using the datasets from the 2006, 2014 and 2018 Multiple Indicator Cluster Survey: a cross-sectional study.

BACKGROUND: Since the beginning of the family program in 1998, the proportion of married women who used contraception has fluctuated. An unmet need for contraception among women in Kyrgyzstan drastically increased from 2006 (1.1%) to 2014 (19.1%), and remained unchanged until 2018 (19.0%). This study aims to re-investigate the prevalence of an unmet need for contraception from 2006 to 2018 in a comprehensive manner, and examine the factors associated with an unmet need for contraception among married women over the course of 12 years in the Kyrgyz Republic. METHODS: This is a cross-sectional study using secondary data that derived from the Multiple Indicator Cluster Survey (MICS). The study employed three datasets from the MICS 2006, 2014, and 2018. The study included a total of 9,229 women aged 15-49 who were married and fecund, and whose status of the met/unmet need for contraception could be identified. Logistic regression was employed to estimate the relationship of an unmet need for contraception with independent factors. A P value < 0.05 was set as statistically significant. RESULTS: The prevalence of an unmet need for contraception was 19.9% in 2006, 20.4% in 2014, and 22.5% in 2018. Across 12 years, all reversible-contraceptive methods for women constantly declined. Although intrauterine devices were the prominent contraceptive method of usage among Kyrgyz women, the trend of usage drastically decreased over time. Factors associated with unmet need for contraception included women's age, area of residence, mother tongue of household head, age of husband, and number of children ever born. CONCLUSION: The unmet need for contraception among married Kyrgyz women slightly increased, and the trend of modern contraceptive usage declined from 2006 to 2018, particularly the use of pills, injections, and intra-uterine devices. Comprehensive sexual health education for young people and youth-friendly services should be promoted. An effective and reliable supply chain of contraceptive commodities should be prioritized and strengthened. Regular supportive supervision visits are essential to improve the knowledge and skills of healthcare providers to be able to provide intrauterine device service as a contraceptive choice for Kyrgyz women.

Determinants of postpartum depression among women in Kampong Chhnang Province, Cambodia.

OBJECTIVE: This study aimed to identify the prevalence of postpartum depression (PPD) and the factors associated with PPD in Kampong Chhnang Province, Cambodia. STUDY DESIGN: A cross-sectional study. PARTICIPANTS: This study included 440 Cambodian women at 6-8 weeks postpartum who visited health centers between July and September 2021. MATERIALS AND METHODS: Data were collected through face-to-face interviews by midwives and nurses using a structured questionnaire. The Edinburgh Postnatal Depression Scale (EPDS) in the Khmer language was used to screen for PPD, and suspected PPD was defined as a total EPDS score ≥ 10. Logistic regression analyses were performed to identify the factors associated with suspected PPD. FINDINGS: The average age of participants was 28.6 years old. The prevalence of suspected-PPD was 30.2 % (n = 133). Factors associated with suspected PPD were income dissatisfaction (adjusted odds ratio (AOR) = 2.66, 95 % confidence interval (CI) 1.27-5.56, P = 0.010), unintended pregnancy (AOR = 1.99, 95 % CI 1.10-3.61, P = 0.023), and a partner employed as a manual laborer (AOR = 3.85, 95 % CI 1.11-13.33, P = 0.034), farmer (AOR = 3.69, 95 % CI 1.11-12.31, P = 0.034), and factory worker (AOR = 5.43, 95 % CI 1.38-21.41, P = 0.016). In addition, poor relationship with partners (AOR = 2.14, 95 % CI 1.17-3.94, P = 0.014), poor relationship with mother-in-law (AOR = 3.51, 95 % CI 1.70-7.21, P < 0.001), and a history of depression before pregnancy (AOR = 6.34, 95 % CI 1.59-25.34, P = 0.009) were significantly associated with suspected-PPD. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This study highlighted the need for mental health services in primary healthcare settings. Mental health training for healthcare workers, particularly primary-level nurses, should be prioritized and strengthened. Further clinical study on EPDS validation should be carried out to justify the appropriate cut-off EPDS score for Cambodian women. The EPDS should be integrated into routine PNC services to identify women with suspected-PPD. Education on PPD should be provided not only to the nurses and midwives, but also to the women and their families to support the mental health of pregnant and postpartum women.

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.

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.

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.

Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis.

OBJECTIVE: In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients' survival. METHODS: Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts. RESULTS: During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234-1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330-2.669), P = 0.905}. CONCLUSIONS: Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. METHODS: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch's t-test was used for comparisons between two independent groups. RESULTS: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). CONCLUSIONS: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.

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.

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.

The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia.

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN). METHODS: Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated. RESULTS: The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies. CONCLUSION: The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.

The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer.

BACKGROUND: The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. METHODS: Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. RESULTS: Median follow-up was 64.8 (range 4.8-143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan-Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). CONCLUSIONS: Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age.

BACKGROUND: Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. METHODS: The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31-40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. RESULTS: A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1-270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p < 0.001); stage I disease (85.9% vs. 70.4%, p < 0.001); mucinous type (69.2% vs. 35.6%, p < 0.001); conservative surgery (83.8% vs. 41.6%, p < 0.001); no adjuvant chemotherapy (67.2% vs. 44.7%, p < 0.001); and CA125 ≤ 35 U/mL (39.4% vs. 28.8%, p < 0.05). There was a significant difference in the overall survival (p = 0.0051) and the disease-free survival (p = 0.0039) between the two groups. Multivariate analysis revealed that the independent prognostic factors for the overall survival were age, stage, histology, and ascitic fluid cytology. CONCLUSION: In epithelial ovarian neoplasms, younger patients had a survival advantage over older patients.

Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background.

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes?

BACKGROUND: In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy. METHODS: A retrospective cohort study was conducted during 2001-2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes. RESULTS: In the 68-month median follow-up period (range 6-178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320-1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187-2.322); P = 0.558]. Moreover, Kaplan-Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141). CONCLUSIONS: Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence.

Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma.

BACKGROUND: Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. MATERIALS AND METHODS: The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III-IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. RESULTS: The median age of patients with PmOC and MmOC was 55 (18-81) and 51 years (30-82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303-3.654), P = 0.0036]. CONCLUSION: The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study.

AIM: Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. METHODS: Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. RESULTS: A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. CONCLUSION: Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.

Reproductive outcomes of 105 malignant ovarian germ cell tumor survivors: a multicenter study.

BACKGROUND: Malignant ovarian germ cell tumors usually occur in young women. Until the 1970s, before establishment of systemic chemotherapy, malignant ovarian germ cell tumors had a very poor prognosis. Recently, prognosis has improved, and fertility-sparing treatment is being adopted in patients who desire to become pregnant. However, the number of malignant ovarian germ cell tumor survivors who actually became pregnant remains unknown. OBJECTIVE: The present study aimed to clarify the reproductive outcomes in malignant ovarian germ cell tumor survivors by using data from a multicenter database and an additional survey on reproductive outcomes. STUDY DESIGN: The study used the Tokai Ovarian Tumor Study Group database on ovarian cancer patients. We assessed the database from 1986 through 2016 and selected malignant ovarian germ cell tumor patients <40 years of age who received fertility-sparing treatment. Questionnaires on reproductive outcomes were sent to the registered facilities. The following data were collected and used in this study: age, date of onset, surgical procedure, chemotherapy regimen, tumor type, International Federation of Gynecology and Obstetrics stage, survival outcome and period, number of pregnancies and childbirths, marital status, childbearing desire, method of pregnancy, gestational weeks at delivery, birthweight of the baby, obstetric complications, and menstrual status after fertility-sparing treatment. RESULTS: A total of 110 malignant ovarian germ cell tumor patients who received fertility-sparing treatment were identified. The median follow-up period was 10.4 years. Five patients were excluded because of death or loss of fertility after treatment for recurrence. Thus, 105 patients were finally included. The additional survey revealed that 42 of 45 patients who desired childbirth became pregnant. The total number of pregnancies was 65, and 56 babies were born to 40 malignant ovarian germ cell tumor survivors. CONCLUSION: The reproductive outcomes of malignant ovarian germ cell tumor survivor are promising with fertility-sparing treatment. Malignant ovarian germ cell tumor survivors can become pregnant and give birth if they desire.