Expression of low-sulfated keratan sulfate in non-mucinous ovarian carcinoma.

Keratan sulfate glycosaminoglycan is composed of repeating N-acetyllactosamine (LacNAc) disaccharide units consisting of galactose (Gal) and N-acetylglucosamine (GlcNAc), both often 6-O-sulfated. Sulfate contents of keratan sulfate are heterogeneous depending upon the origins. In this study, keratan sulfate is classified as either highly sulfated (in which both GlcNAc and Gal residues are 6-O-sulfated) or low-sulfated (in which only GlcNAc residues are 6-O-sulfated). It is reported that highly sulfated keratan sulfate detected by the 5D4 monoclonal antibody is preferentially expressed in normal epithelial cells lining the female genital tract and in their neoplastic counterparts; however, expression of low-sulfated keratan sulfate in either has not been characterized. In the present study, we generated the 294-1B1 monoclonal antibody, which selectively recognizes low-sulfated keratan sulfate, and performed precise glycan analysis of sulfated glycans expressed on human serous ovarian carcinoma OVCAR-3 cells. We found that OVCAR-3 cells do not express highly sulfated keratan sulfate but rather express low-sulfated form, which was heterogeneous in 294-1B1 reactivity. Comparison of mass spectrometry spectra of sulfated glycans in 294-1B1-positive versus -negative OVCAR-3 cells indicated that the 294-1B1 epitope is likely at least 2, and possibly 3 or more, tandem GlcNAc-6-O-sulfated LacNAc units. Then, using the 294-1B1 antibody, we performed quantitative immunohistochemical analysis of 40 specimens from patients with ovarian cancer, consisting of 10 each of serous, endometrioid, clear cell, and mucinous carcinomas, and found that among them low-sulfated keratan sulfate was widely expressed in all but mucinous ovarian carcinoma.

Structural Elucidation and Prognostic Relevance of 297-11A-Sulfated Glycans in Ovarian Carcinoma.

Ovarian carcinoma is usually diagnosed at an advanced stage with peritoneal dissemination and/or lymph node metastasis, and the prognosis for such advanced carcinoma is very poor. Therefore, new biomarkers to predict patient prognosis are needed. Miyamoto et al. previously showed that keratan sulfate (KS) detected by the 5D4 monoclonal antibody was expressed in ovarian carcinoma. However, the detailed structure of such KS was not determined, and the biological significance of this finding remained to be clarified. We previously generated the 297-11A monoclonal antibody, which recognizes galactose (Gal)-6-O-sulfated N-acetyllactosamine (LacNAc) located at the nonreducing terminus. Because the 297-11A epitope overlaps with that of 5D4, here we chose to use the 297-11A antibody as a tool to analyze KS and related structures. We conducted immunohistochemical analysis of 98 ovarian carcinoma cases with 297-11A antibody combined with a series of glycosidases and performed mass spectrometry analysis of the human serous ovarian carcinoma cell line OVCAR-3 to deduce the glycan structure of 297-11A-sulfated glycans. We also performed western blot analysis to assess a potential association of 297-11A-sulfated glycans with the mucin core protein mucin 16 (MUC16; also known as cancer antigen 125 (CA125)). Finally, we examined the relationship between 297-11A expression and patient prognosis. Consequently, 297-11A-sulfated glycans were primarily expressed in serous and endometrioid carcinomas and poorly expressed in mucinous and clear cell carcinomas. We reveal that structurally, 297-11A-sulfated glycans expressed in ovarian carcinoma are O-glycans carrying partially sialylated, Gal-6-O-sulfated LacNAc and that these glycans are likely displayed on MUC16 mucin core proteins. Of clinical importance is that expression of 297-11A-sulfated glycans correlated with shorter progression-free survival in patients. Thus, 297-11A-sulfated glycans may serve as a predictor of ovarian carcinoma recurrence.

Hidden in plain sight - Survival consequences of baseline symptom burden in women with recurrent ovarian cancer.

OBJECTIVE: To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS). METHODS: We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially­platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC≥3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS. RESULTS: The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001). CONCLUSION: Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC≥3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control.

Evaluation of the holding-up uterus technique for placenta accreta spectrum cesarean hysterectomy in shocked patients with a high shock index: a case series study.

BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.

Attitudes toward cancer screening in regional Japan during the COVID-19 pandemic: An anonymous survey.

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.

Impact of visiting restrictions on Edinburgh postnatal depression scale screening scores at one month postpartum during the spread of COVID-19: a single-center case-control study in Japan.

BACKGROUND: This study aimed to evaluate whether "visiting restrictions" implemented due to the coronavirus disease 2019 (COVID-19) pandemic are a risk factor for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS). METHODS: This case-control study participants who gave birth during the spread of COVID-19 (COVID-19 study group) and before the spread of COVID-19 (control group). Participants completed the EPDS at 2 weeks and 1 month after childbirth. RESULTS: A total of 400 cases (200 in each group) were included in this study. The EPDS positivity rate was significantly lower with visiting restrictions than without (8.5% vs.18.5%, p = 0.002). Multivariate analysis of positive EPDS screening at the 1st month checkup as the objective variable revealed that visiting restrictions (odds ratio (OR): 0.35, 95% confidence interval (CI): 0.18-0.68), neonatal hospitalization (OR: 2.17, 95% CI: 1.08-4.35), and prolonged delivery (OR: 2.87, 95% CI: 1.20-6.85) were factors associated with an increased risk of positive EPDS screening. CONCLUSION: Visiting restrictions on family during the hospitalization period for delivery during the spread of COVID-19 pandemic did not worsen EPDS screening scores 1 month postpartum, but stabilized the mental state of some mothers.

Impact of maternal late hospital arrival on adverse outcome of offspring affected by placental abruption: A regional multicenter nested case-control study in Japan.

AIMS: To elucidate the influence of the time-intervals between the onset and arrival (TIME 1), onset and delivery (TIME 2), and the decision to deliver and delivery (TIME 3) on severe adverse outcomes of offspring born to mothers complicated by placental abruption outside the hospital. METHODS: This is a multicenter nested case-control study about placental abruption at Fukui Prefecture, a regional area in Japan, through 2013 to 2017. Multiple pregnancy, fetal or neonatal congenital abnormality, and unknown detailed information at onset of placental abruption were excluded. A composite of perinatal death and cerebral palsy or death at 18-36 months of corrected age was defined as the adverse outcome. The relationship between time-intervals and the adverse outcome was analyzed. RESULTS: The 45 subjects for analysis were divided into two groups, including a group with and without adverse outcome (poor, n = 8; and good, n = 37). TIME 1 was longer in the poor group (150 vs. 45 min, p < 0.001). A subgroup analysis targeted to 29 cases with preterm birth at the third trimester indicates that TIME 1 and TIME 2 were longer in the poor group (185 vs. 55 min, p = 0.02; and 211 vs. 125 min, p = 0.03), while TIME 3 was shorter in the poor group (21 vs. 53 min, p = 0.01). CONCLUSIONS: Long time-intervals between onset and arrival or onset and delivery may be correlated with perinatal death or cerebral palsy in surviving infants affected by placental abruption.

Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016-A3) of the treatment strength and prognostic outcomes of conventional or dose-dense chemotherapy.

AIM: To evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer. METHODS: We compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy-seven older patients of 301 who received dose-dense-paclitaxel-carboplatin (dTC) and 93 older patients of 304 who received conventional-paclitaxel-carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed. RESULTS: The RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25-2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15-2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen. CONCLUSIONS: The RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast.

During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD) activity. YAP/TAZ-TEAD activity is controlled by multiple factors and signaling, such as cAMP signaling. cAMP signaling is believed to be involved in the regulation of trophoblast function but is not yet fully understood. Here we showed that YAP/TAZ-TEAD expressions and their activities were altered by cAMP stimulation in BeWo cells, a human choriocarcinoma cell line. The repression of YAP/TAZ-TEAD activity induced the expression of ST-specific genes without cAMP stimulation, and transduction of constitutively active YAP, i.e. YAP-5SA, resulted in the repression of 8Br-cAMP-induced expressions of ST-specific genes in a TEAD-dependent manner. We also investigated the role of YAP/TAZ-TEAD in maintaining CT cells and their differentiation into ST and EVT cells using human trophoblast stem (TS) cells. YAP/TAZ-TEAD activity was involved in maintaining the stemness of TS cells. Induction or repression of YAP/TAZ-TEAD activity resulted in marked changes in the expression of ST-specific genes. Using primary CT cells, which spontaneously differentiate into ST-like cells, the effects of YAP-5SA transduction were investigated, and the expression of ST-specific genes was found to be repressed. These results indicate that the inhibition of YAP/TAZ-TEAD activity, with or without cAMP stimulation, is essential for the differentiation of CT cells into ST cells.

Cancer among children, adolescents and young adults in the Hokushin region, Japan, between 2010 and 2015.

Adolescents and young adults with cancer encounter age-related challenges. Cancer treatment and support are not always tailored to the needs of each patient due to difficulty in the collection of accurate data. The present study aimed to investigate cancer among children and adolescents and young adults in the four adjacent prefectures of Japan (Toyama, Ishikawa, Fukui and Nagano) by analyzing data from a unique regional cancer database. We retrieved and analyzed the data of pediatric and adolescent and young adult patients aged between 0 and 39 years at cancer diagnosis (including carcinoma in situ), which was registered in the Hokushin Ganpro database between 2010 and 2015. A total of 5718 cases (1571 males and 4147 females) were identified during this period. The overall male-to-female ratio was 1:2.6. There was no distinct difference in the number of cancer cases per 100 000 population between males and females until 19 years of age. The difference became more pronounced after 20 years of age. The number of cancer cases (per 100 000 population) in the 0-14-, 15-19-, 20-29- and 30-39-year age groups was estimated to be 13.4, 14.5, 44.0 and 101.5, respectively. Carcinomas were the most common type of cancer in the adolescents and young adults (15-39 years) population (74%), whereas they were not the predominant cancer type in the pediatric (0-14 years) population. Although further research is needed to understand the needs of adolescents and young adults with cancer, we believe that our findings will help guide efforts to improve the management strategy for adolescents and young adults with cancer.

A fatal case of hemophagocytic lymphohistiocytosis associated with gestational psittacosis without symptoms of pneumonia.

Psittacosis is a zoonotic infection caused by Chlamydia psittaci. Most patients present with acute respiratory symptoms and systemic illness. When C. psittaci infects pregnant women, it causes severe clinical manifestations called gestational psittacosis. Here we report a case of gestational psittacosis. Our patient lacked respiratory symptoms, and pathological postmortem examinations revealed severe placentitis. Both DNA and immunohistochemical analyses were positive for C. psittaci from formalin-fixed paraffin-embedded tissues. The chlamydial DNA in the placenta was about 100 times more abundant than that in the lungs; therefore, the placenta rather than the lungs was the probable target of the C. psittaci infection during this pregnancy. We could not identify the source of infection. Gestational psittacosis should be considered in the differential diagnosis for fever of unknown origin during pregnancy, even in cases lacking respiratory symptoms.

Multi-institutional survey of cancer disparities in disabled patients in the region of northwestern Japan.

BACKGROUND: Potential disparities between cancer patients with and without disabilities remained to be validate in Japan. METHODS: We surveyed retrospective data on hospital cancer registration as well as information on disability certificates obtained through the Hokushin Ganpro database. In total, 93,545 cancer patients in 10 principal hospitals covering the region of northwestern Japan were registered with the Hokushin Ganpro database between 2010 and 2015. The database included the following data: diagnosis date, cancer type, staging, treatment, cancer detection process, and possession of a disability certificate. RESULTS: We found that 2983 patients, which accounted for 3.2% of the total patients, had disabilities. No significant differences in gender, age at diagnosis, cancer stage distribution, and cancer incidence rates were observed between the disabled and non-disabled patients. Even though the proportion of early-stage cancer among disabled patients differed only slightly from that in non-disabled patients, early-stage cancer was more frequently diagnosed in patients with disabilities during their regular hospital visits than in those without disabilities, who had more opportunity for early cancer detection during cancer screening. According to in-house data reflecting treatment period and process from a single hospital, all 16 disabled patients treated with chemotherapy completed the treatment until disease progression or end of predetermined cycles. CONCLUSION: These results indicate that deep disparities between cancer patients with and without disabilities are not apparent and that the disabled patients in the region of northwestern Japan receive appropriate hospital follow-up.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Clinical management of chemotherapy for elderly gynecological cancer patients.

AIM: Since there are no established guidelines for the treatment of gynecological cancer in the elderly, medical treatment policy is currently decided by discussion with patients and their families based on doctors' experiences, referring to data from nonelderly patients and healthy elderly patients. The aim of this review was to clarify the current position of chemotherapy for elderly gynecological cancer patients and discuss the problems to be addressed in the future. METHODS: Little evidence has been accumulated for anticancer drug treatment in elderly individuals with gynecological cancer. This review presents outlines and representative papers on general cancer chemotherapy for the elderly, and problems that need to be solved in gynecological cancer fields in the future are identified. RESULTS: In 2018, the American Society of Clinical Oncology (ASCO) published guidelines for "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary". This guideline emphasizes that, when administering chemotherapy to patients over 65 years of age, vulnerabilities should be identified using geriatric assessment (GA). However, there have been no reports of clinical studies using GA in patients with cervical or uterine cancers, and only a few clinical studies using GA have been reported in patients with ovarian cancer. CONCLUSIONS: Scoring systems suitable for elderly Japanese patients remain lacking. A Japanese gynecological GA needs to be developed in cooperation with other disciplines.

Mentality of pregnant women and obstetric healthcare workers about prenatal SARS-CoV-2 testing: A regional survey over the first wave of the COVID-19 pandemic in Japan.

AIM: To clarify the mentality of pregnant women and obstetric healthcare workers about prenatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing. METHODS: A multicenter questionnaire survey about prenatal SARS-CoV-2 screening testing was conducted among pregnant women, midwives and nurses (M&Ns), and obstetricians at all delivery facilities in Fukui Prefecture between June 30, 2020 and July 22, 2020. RESULTS: Of 297 pregnant women, 150 (50.5%) underwent prenatal polymerase chain reaction (PCR) testing, and 107 of them (71.3%) answered that because of prenatal PCR tests, they could give birth with relief. One hundred forty-five (48.8%) were concerned about the disadvantages of receiving positive prenatal PCR results. Of 287 M&Ns, 151 (52.6%) answered that prenatal PCR screening testing could reduce anxiety about infection to themselves; this belief was more common among M&Ns working at the nonreception facility than among those at COVID-19 reception facilities (60.7% vs. 47.1%, P = 0.02). Of 57 obstetricians, 31 (54.4%) agreed to prenatal SARS-CoV-2 PCR screening testing, the rate of which was significantly higher among obstetricians at nonreception facilities than those at reception facilities (70.3% vs. 25.0%, P < 0.01). Fourteen obstetricians (24.6%) were concerned about excessive medical treatment for asymptomatic pregnant women with false-positive PCR results. CONCLUSIONS: Pregnant women experience anxieties during the COVID-19 pandemic, and prenatal SARS-CoV-2 screening may reduce their anxiety to some extent. However, obstetrics staff at COVID-19 reception facilities are aware of the limits of prenatal screening and are concerned about excessive medical intervention due to false-positive results.

Periodontal disease in preoperative patients with digestive cancer: a retrospective, single-institution experience in Fukui, Japan.

BACKGROUND: The careful preoperative oral assessment may be useful for safe surgery under general anesthesia. The purpose of this study was to investigate the presence of periodontitis in patients with malignant digestive disease before surgery under general anesthesia. METHODS: Patients with digestive malignant disease who underwent periodontal examination and orthopantomograph examination for preoperative oral health assessment were participated. The authors investigated the patients' general characteristics and clinical oral information, including the presence of periodontitis. RESULTS: One hundred twenty patients participated in this study. The mean and standard deviation of the number of teeth was 20.8 ± 8.2, and there was a statistically significant correlation between age and number of teeth. The periodontal pocket depth was 3.0 ± 1.0, and mobile teeth were observed in 62 patients. There was a statistically significant correlation between number of teeth and number of mobile teeth. However, there was no significant difference between the age of patients without mobile teeth and the age of patients with mobile teeth. CONCLUSIONS: This retrospective study performed in single-institution clarified the presence of periodontitis in patients with malignant digestive disease before surgery. Regardless of age, it is important to assess the oral health, including periodontitis, for safe surgery under general anesthesia.

The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review.

BACKGROUND: The process of follicle development is tightly regulated by pituitary gonadotropins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and intraovarian regulators (eg, steroids, growth factors, and cytokines). METHODS: This review outlines recent findings on the mechanisms of human follicle development, based on the research on animal models such as mice, rats, cows, and sheep. MAIN FINDINGS: Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and anti-Müllerian hormone are involved in primordial follicle activation during the gonadotropin-independent phase. The intraovarian regulators, such as androgen, insulin-like growth factor system, activin, oocyte-derived factors (growth differentiation factor-9 and bone morphogenetic protein 15), and gap junction membrane channel protein (connexin), play a central role in the acquisition of FSH dependence in preantral follicles during the gonadotropin-responsive phase. Antral follicle development can be divided into FSH-dependent growth and LH-dependent maturation. The indispensable tetralogy for follicle selection and final maturation of antral follicles involves (a) acquisition of LH dependence, (b) greater capacity for E2 production, (c) activation of the IGF system, and (d) an antiapoptotic follicular microenvironment. CONCLUSION: We reproductive endocrinologists should accumulate further knowledge from animal model studies to develop methods that promote early folliculogenesis and connect to subsequent gonadotropin therapy in infertile women.

The study protocol of the evaluation for the preventive efficacy of the HPV vaccine for persistent HPV16/18 infection in Japanese adult women: the HAKUOH study.

BACKGROUND: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years. METHODS: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm). DISCUSSION: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects. TRIAL REGISTRATION: Trial registration number: NCT04022148 . Registration began on December 1, 2019.

Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer.

BACKGROUND: The mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin-dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients. METHODS: Expression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0-12. The expression scores calculated were correlated with clinicopathological parameters and patient survival. RESULTS: High immunoreactivity of phospho-Drp1Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (p = 0.006), and non-responders to adjuvant chemotherapy (p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p = 0.011) and platinum-resistant recurrence (p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1Ser637 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039-9.561]. CONCLUSIONS: Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.