Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma.

This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan.

BACKGROUND: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys. METHODS: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019. RESULTS: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization. CONCLUSION: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine.

CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. OBJECTIVE: This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma. STUDY DESIGN: Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). RESULTS: CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001). CONCLUSION: Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

Copper ions are novel therapeutic agents for uterine leiomyosarcoma.

BACKGROUND: Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed. OBJECTIVE: Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo. STUDY DESIGN: Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting beta-expressing cells was investigated both in vitro and in vivo. RESULTS: Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting beta-suppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 µM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 µM, P < .01) and in xenografts compared with that in SK-LMS-1 cells (5.8% vs 62.8%, P < .01). Copper sulfate was identified as a preferential inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta. In SK-LMS-1 cells pretreated with 15 µM copper sulfate for 3 hours, the cisplatin half-maximal inhibitory concentration decreased significantly compared with that in untreated cells and resulted in significantly increased intracellular platinum accumulation (1.9 pg/cell vs 8.6 pg/cell, P < .01). The combination of copper sulfate pretreatment with cisplatin administration was also effective in vivo and caused cisplatin to exhibit significantly increased antitumor effects in mice with SK-LMS-1 xenografts (3.1% vs 62.7%, P < .01). CONCLUSION: Our study demonstrates that adenosine triphosphatase copper transporting beta is overexpressed in uterine leiomyosarcoma cells and that copper sulfate, which acts as an inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta, may be a therapeutic agent in the treatment of uterine leiomyosarcoma.

Histologic correlation between smartphone and coloposcopic findings in patients with abnormal cervical cytology: experiences in a tertiary referral hospital.

BACKGROUND: Smartphones recently have been applied in the medical setting. However, the literature evaluating the utility of smartphones in gynecologic oncology is limited. OBJECTIVE: To evaluate the utility of a smartphone in the detection of uterine cervical lesions in patients with abnormal cervical cytology. STUDY DESIGN: Seventy-five women with abnormal cervical cytology were enrolled. Two doctors independently inspected the uterine cervix by using smartphone or colposcopy. Images were captured using acetic acid, and biopsies were taken as standard-of-care procedures. The diagnostic performance of the smartphone for cervical intraepithelial neoplasm 1 or worse and cervical intraepithelial neoplasm 2 or worse were evaluated, and the kappa value was calculated to determine the chance corrected agreement of the histologic diagnoses based on the smartphone and colposcopic findings. RESULTS: There was a substantial agreement between histologic diagnoses based on the smartphone and colposcopic findings, with a kappa value of 0.67 (95% confidence interval, 0.43-0.90). The sensitivity, specificity, positive predictive value, and negative predictive value of the smartphone in the diagnosis of cervical intraepithelial neoplasm 1 or worse were 0.89 (95% confidence interval, 0.79-0.96), 0.33 (95% confidence interval, 0.08-0.70), 0.91 (95% confidence interval, 0.81-0.97), and 0.30 (95% confidence interval, 0.07-0.65), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of cervical intraepithelial neoplasm 2 or worse were 0.92 (95% confidence interval, 0.81-0.98), 0.24 (95% confidence interval, 0.09-0.45), 0.71 (95% confidence interval, 0.58-0.81), and 0.60 (95% confidence interval, 0.26-0.88), respectively. CONCLUSION: We found that there was a substantial agreement between the histologic diagnoses based on the smartphone and colposcopic findings. The smartphone seems to be useful and may be an alternative to colposcopy.

Trends in incidence and long-term survival of Japanese women with vulvar cancer: a population-based analysis.

OBJECTIVE: The incidence and long-term survival analysis for vulvar cancer, due to its rarity, has not been fully described in Asian population. The objective of the study is to determine the trends in incidence and long-term survival for vulvar cancer in a Japanese population, using a population-based cancer registry data in Osaka, Japan. METHODS: The age-standardized incidence rate of 389 cases of vulvar squamous cell carcinoma (SCC) diagnosed between 1976 and 2010 was calculated, using the 1985 model population of Japan. The annual percentage change (APC) of the age-standardized incidence was estimated by the joinpoint regression models. The 5- and 10-year relative survival of 290 cases with vulvar SCC diagnosed between 1976 and 2008 were analyzed, using a cohort or period approach. Using the 10-year relative survival, the conditional 5-year survival for patients who lived for some years after diagnosis was also calculated. RESULTS: We have found that the age-standardized incidence rate for vulvar cancer trended downward during the period of 1979-1992 (APC - 6.3%; 95% confidence interval (CI) [- 11.3% to - 1.0%]), whereas it trended upward from 1993 to 2010 (APC 1.9%; 95% CI [- 0.7% to 4.6%]). There was no statistically significant difference for the 5- and 10-year relative survival between the two periods of 1976-2000 and 2001-2008. A statistically significant increase in the conditional 5-year survival at 2 years after diagnosis was observed (48.4%; 95% CI [41.1-55.3] versus 75.6%; 95% CI [64.0-83.9]). CONCLUSION: Despite an increasing trend in vulvar cancer incidence among Japanese population, the relative survival rate for vulvar cancer did not change over the 35 years of this study. We found that the conditional 5-year survival for vulvar cancer, as patients survived additional years, approached within reach of 100%. These data can provide valuable information for both patients and clinicians.

A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma.

INTRODUCTION: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. METHODS: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. RESULTS: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC=0.961) performed better than CA 125 alone (AUC=0.851; P=0.0150) and HE4 alone (AUC=0.870; P=0.0220), but also performed significantly better than the 2- marker combination of CA125+HE4 (AUC=0.922; P=0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. CONCLUSION: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.

Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study.

BACKGROUND: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. METHODS: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). CONCLUSIONS: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.

Small Cell Carcinomas of the Uterine Cervix and Lung: Proteomics Reveals Similar Protein Expression Profiles.

OBJECTIVE: The phenotypic and pathological features of small cell cervical carcinoma (SMCC) and small small cell lung cancer (SCLC) are very similar; thus, the chemotherapy regimens used for the rare SMCC have been routinely based on regimens used for common SCLC. We set out to explore the protein expression profile similarities between these 2 cancers to prove that linking their therapeutic regimens is justified, with a secondary aim of finding tumor-specific proteins to use as additional biomarkers for more accurate diagnosis of SMCC, and potentially to use as therapeutic targets. METHODS: Protein expression analysis was performed for 3 cases of SMCC and 1 example each of SCLC, mucinous adenocarcinoma of the cervix (MACC), lung mucinous adenocarcinoma (MACL), and squamous cell carcinoma of the cervix (SCC). We used cancer tissue-originated spheroids (CTOS) and isobaric tags for relative and absolute quantitation (iTRAQ)-based comprehensive and quantitative protein expression profile analysis. Expression in corresponding clinical samples was verified by immunohistochemistry. RESULTS: Rather than organ of origin-specific patterns, the SMCC and SCLC samples revealed remarkably similar protein expression profiles-in agreement with their matching tumor pathology phenotypes. Sixteen proteins were expressed at least 2-fold higher in both small cell carcinomas (SMCC and SCLC) than in MACC or SCC. Immunohistochemical analysis confirmed higher expression of creatine kinase B-type in SMCC, compared with MACC and SCC. CONCLUSIONS: We demonstrate a significant overlapping similarity of protein expression profiles of lung and cervical small cell carcinomas despite the significant differences in their organs of origin.

HPV vaccination in Japan: results of a 3-year follow-up survey of obstetricians and gynecologists regarding their opinions toward the vaccine.

BACKGROUND: In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government's recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians. METHODS: We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively. RESULTS: The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine. CONCLUSIONS: Our re-survey of Japan's obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan.

A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage.

BACKGROUND: Sheehan's syndrome occurs because of severe postpartum hemorrhage causing ischemic pituitary necrosis. Sheehan's syndrome is a well-known condition that is generally diagnosed several years postpartum. However, acute Sheehan's syndrome is rare, and clinicians have little exposure to it. It can be life-threatening. There have been no reviews of acute Sheehan's syndrome and no reports of successful pregnancies after acute Sheehan's syndrome. We present such a case, and to understand this rare condition, we have reviewed and discussed the literature pertaining to it. An electronic search for acute Sheehan's syndrome in the literature from January 1990 and May 2014 was performed. CASE PRESENTATION: A 27-year-old woman had massive postpartum hemorrhage (approximately 5000 mL) at her first delivery due to atonic bleeding. She was transfused and treated with uterine embolization, which successfully stopped the bleeding. The postpartum period was uncomplicated through day 7 following the hemorrhage. However, on day 8, the patient had sudden onset of seizures and subsequently became comatose. Laboratory results revealed hypothyroidism, hypoglycemia, hypoprolactinemia, and adrenal insufficiency. Thus, the patient was diagnosed with acute Sheehan's syndrome. Following treatment with thyroxine and hydrocortisone, her condition improved, and she was discharged on day 24. Her next pregnancy was established 2 years after her first delivery. She required induction of ovulation for the next conception. The pregnancy, delivery, and postpartum period were uneventful. An electronic search of the literature yielded 21 cases of acute Sheehan's syndrome. Presenting signs varied, including adrenal insufficiency (12 cases), diabetes insipidus (4 cases), hypothyroidism (2 cases), and panhypopituitarism (3 cases), with a median time of presentation after delivery for each of those conditions being 7.9, 4, 18, and 9 days, respectively. Serial changes in magnetic resonance imaging were reported in some cases of acute Sheehan's syndrome. CONCLUSION: Clinicians should be aware of the risk of acute Sheehan's syndrome after a massive postpartum hemorrhage in order to diagnose it accurately and treat it promptly.

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

BACKGROUND: Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. METHODS: We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. RESULTS: We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). CONCLUSIONS: We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

A novel device for cleaning the camera port during laparoscopic surgery.

AIM: Poor visualization of the operative field due to an obscured camera lens is a problem frequently encountered while performing laparoscopic surgery. Little has been published about the prevention of lens obstruction specifically due to a contaminated camera port used for laparoscopic surgery. The aim of our study is to develop a new device, the Endowiper, for cleaning the laparoscopic port. MATERIALS: The new cleaner for the port's valve is made from rolled gauze. To simulate a surgical environment in the laboratory, we have used pseudo-blood to smudge the port's valve. METHOD: In order to demonstrate the efficacy and safety of the Endowiper, we compared our method using this device with three previously reported port cleaning methods. These methods included use of gauze tightly wrapped around an endoscopic dissecting cramp, a small piece of gauze grasped by an endoscopic dissecting cramp, and a swab. We repeated the performance tests 280 times, 240 using a 12-mm trocar port and 40 with a 5-mm port. RESULTS: With the 12-mm port, the complete port clearance rate achieved was 83.3% by Endowiper, 56.7% by wrapped gauze, 36.7% by small gauze, and 40.0% by swab. Trouble rate encountered during the procedure was 0% by Endowiper, 1.7% by wrapped gauze, 15% by small gauze, and 90% by swab. For the 5-mm port, the complete port clearance rate was 85% by Endowiper and 20% by sterile swab. The trouble rate was 0% by Endowiper and 30% by swab. Endowiper had a significantly superior result related to clearance rate than the other three methods in both the 12- (p < 0.001) and 5-mm (p < 0.001) ports. For trouble rate, Endowiper had a significantly superior result in both the 12- (p < 0.001) and 5-mm (p < 0.01) ports. CONCLUSION: This Endowiper will be an inexpensive device with a benefit to laparoscopic surgeons.

Clinical outcomes of abnormal cervical cytology and human papillomavirus-related lesions in patients with organ transplantation: 11-year experience at a single institution.

OBJECTIVES: The objective of this study is to analyze the clinical outcomes of abnormal cervical cytology and newly diagnosed human papillomavirus (HPV)-related disease after organ transplantation. MATERIALS AND METHODS: Medical records from July 2004 to August 2015 were reviewed, and thirteen patients were identified who had been newly diagnosed with HPV-related disease (cervical intraepithelial neoplasia [CIN] and cervical cancer) after organ transplantation. The median transition time to the aggravation of cervical cytology and the spontaneous regression rate of CIN were evaluated. Clinical outcomes of CIN1 and CIN2 were compared between the general population and patients with organ transplantation. We also reviewed the current literature regarding the incidence of HPV infection, Pap smear abnormality and/or CIN after organ transplantation. RESULTS: The cervical cytology aggravated in nine of the 13 patients (69 %). In seven of the 13 cases (54 %), treatments such as cervical conization, laser vaporization, or radiation therapy, were conducted. HPV-related disease disappeared after treatment in only three of the seven actively treated cases (43 %). In contrast, the lesions persisted in three (43 %) cases after treatment. One patient died from cervical cancer. The spontaneous regression rate of the HPV-related diseases, if left untreated, was 0 %. There was a statistically significant difference in the clinical outcomes of CIN1 and CIN2 between the general population and patients with organ transplantation (p = 0.0026 and 0.0315, respectively; chi-squared test). CONCLUSIONS: HPV-related lesions that are newly diagnosed after organ transplantation do not seem to regress as spontaneously as in the general population. Physicians should recognize the importance of close monitoring and long-term follow-up.

Human papillomavirus vaccination of the daughters of obstetricians and gynecologists in Japan.

BACKGROUND: Most adolescents in Japan have recently been refraining from receiving the human papillomavirus (HPV) vaccine, following media reports of adverse medical events surrounding the vaccination and suspension of the Japanese governmental recommendation. We have previously reported that HPV vaccination of young girls is heavily influenced by guidance from their physicians concerning the vaccine and by the knowledge and attitude of the girls' mothers towards cervical cancer. However, it has been unclear as to how the obstetricians and gynecologists were themselves affected by the negative media reports. METHODS: A questionnaire, including questions about their working status, attitudes toward HPV vaccination and about cervical cancer, and the HPV vaccination status of their daughters, was posted to obstetricians and gynecologists. RESULTS: None of the daughters of the responding obstetrician and gynecologists received the HPV vaccination after the announced suspension of the governmental recommendation for the vaccine. The number who received the HPV vaccine in the 6th to 9th grade in 2014 was significantly lower than those in 2012 (p = 0.012). However, 64.7 % of the responders whose daughters were eligible and in the 6th to 12th grade still intended to vaccinate their daughters in the future. Of the responders, 65 % also intended to recommend vaccination to their teenage patients. CONCLUSIONS: Our study revealed that obstetricians and gynecologists, like the general population, were negatively influenced by media reports of the adverse effect of the HPV vaccine and the suspension of the governmental recommendation. However, their intention to vaccinate their daughters was much higher than that of the general population. Restart of the governmental recommendation for HPV vaccines and better education about the HPV vaccine, including its adverse effects, and about cervical cancer and cervical cancer screening, are strongly recommended, for both the general public and for doctors, for improved prevention of cervical cancer.

Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.

BACKGROUND: Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening. METHODS: The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening. RESULTS: We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p < 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p < 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p < 0.0001). CONCLUSIONS: In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.

Development of an efficient strategy to improve HPV immunization coverage in Japan.

BACKGROUND: In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan. METHODS: We conducted an internet survey in Japan of mothers of 12-16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage. RESULTS: Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter. CONCLUSIONS: Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities.

Utility of an Internal Retractor (EndoGrab) for the Management of the Vesicouterine Ligament during Laparoscopic Radical Hysterectomy.

BACKGROUND/AIMS: The study aims to prevent serious urologic injury during a radical hysterectomy; we propose that one of the most important procedural steps is the careful management of the vesicouterine ligament (VUL). PATIENTS AND METHODS: Between January 2013 and October 2014, we used a novel internal retractor in 17 patients undergoing a laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer to obtain and secure a better surgical view. For management of the VUL during the laparoscopic procedure, we routinely used an internal retractor (EndoGrab; Virtual Ports, Misgav, Israel) and vessel tape to reposition the ureter in a safe lateral-caudal direction. RESULTS: Using an EndoGrab, we were easily able to reproduce a suitable surgical view that simulated the one obtained by an abdominal route for radical hysterectomy. Using this improved laparoscopic procedure, we completed radical hysterectomies in all 17 cases without a ureteral injury complication. CONCLUSION: Our modified method using an EndoGrab is effective for the prevention of ureteral injury during a LRH, and its ease of use makes it suitable even for those surgeons early in their laparoscopic learning curve.

Project conducted in Hirakata to improve cervical cancer screening rates in 20-year-old Japanese: Influencing parents to recommend that their daughters undergo cervical cancer screening.

AIM: In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. METHODS: We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). CONCLUSION: For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.

Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives.

Advances in surgical and medical treatments for ovarian cancer have improved prognoses. Platinum drugs in particular are pivotal for the medical treatment of ovarian cancer. However, previous studies have revealed that some histological subtypes, such as clear cell carcinoma, are resistant to medical treatment, including that with platinum drugs. Consequently, the clinical prognosis of advanced clear cell carcinoma is remarkably inferior, primarily because of its chemoresistant behavior. The prevalence of clear cell carcinoma is approximately 5 % in the West, but in Japan, its prevalence is particularly high, at approximately 25 %. Current medical treatments for advanced clear cell carcinoma are difficult to administer, and they have poor efficacy, warranting the development of novel target-based therapies. In this review, we describe medical treatments for clear cell carcinoma and discuss future prospects for therapy. In particular, we focus on the mechanism of platinum resistance in clear cell carcinoma, including the role of annexin A4, one of the most investigated factors of platinum resistance, as well as the mutant genes and overexpressed proteins such as VEGF, PI3K/AKT/mTOR signaling pathway, ARID1A, hepatocyte nuclear factor-1ß, ZNF217. We also review targeted molecular therapeutics for epithelial ovarian cancer and discuss their role in clear cell carcinoma treatment. We review the drugs targeting angiogenesis (bevacizumab, sorafenib, and pazopanib), growth factors (gefitinib, erlotinib, lapatinib, trastuzumab, and AMG479), and signaling pathways (temsirolimus, dasatinib, and imatinib), and other drugs (oregovomab, volociximab, and iniparib). This current review summarizes and discusses the clinical significance of these factors in ovarian clear cell carcinoma as well as their potential mechanisms of action. It may provide new integrative understanding for future studies on their exact role in ovarian clear cell carcinoma.