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A wider range of social protection services, including social insurance and social assistance, are gaining global attention as a key driver of improved health service coverage and financial protection among vulnerable populations. However, only a few studies have investigated the associations between social protection and universal health coverage (UHC). Therefore, we conducted a literature review on relevant international organizations with respect to this topic. We found that many international organizations consider the wide range of social protection services, including social insurance and social assistance, essential for achieving UHC in 2030. In specific health programs, social protection is considered an important service to promote health service access and financial protection, especially among vulnerable populations. However, discussions about social protection for achieving UHC are not given high priority in the World Health Organization. Currently, the coverage of social protection services is low among vulnerable populations in low- and middle-income countries. To address this issue, we employed the metrics recommended by the migrant integration policy index (MIPEX). Based on our findings, a conceptual framework was developed. We expect this framework to lead synergy between social protection and health systems around the globe, resulting in healthy ageing.

Background The burden or benefit of anticoagulation treatment affects patient satisfaction, which may in turn affect the adherence to the treatment and subsequent outcomes. Thus, we hypothesized that the patient satisfaction with direct oral anticoagulants (DOACs) may influence the clinical outcome in patients with atrial fibrillation (AF). Methods and Results We investigated the clinical outcomes among 719 DOAC users (age 71.9 ± 9.1 years, 184 females, and 449 persistent AF) enrolled in the SAKURA AF Registry who completed a satisfaction questionnaire with anticoagulation therapy by means of the Anti-Clot Treatment Scale (ACTS), which included 12-item burden and 3-item benefit scales. During a 41.8-month-follow-up, a stroke/systemic embolism (SE) occurred in 27 patients (3.8%) and major bleeding events in 25 (3.5%). A univariate Cox regression analysis revealed that an older age, persistent AF, higher CHA2DS2-VASc score, no history of AF ablation, lower creatinine clearance, and lower ACTS benefit scores were significantly associated with an increased risk of a stroke/SE, but not with major bleeding events. A low benefit score remained an independent predictor of a stroke/SE even after a multivariate adjustment. The ACTS burden scores were not associated with any clinical events. Conclusions We found a strong association between a low benefit satisfaction and increased stroke risk. We should follow patients carefully to educate them on treatment importance for patients unsatisfied with the benefits of DOACs for stroke prevention.

Migrants face several challenges in their daily lives in the host country due to limited knowledge about the language, culture, and social system of the host country. Their vulnerability increases in a time of crisis. During the COVID-19 pandemic, migrant communities were severely affected. Evidence on migrants’ access to COVID-19-related information and services is limited. We conducted a qualitative, descriptive study among migrants from Vietnam, Myanmar, and Nepal living in Japan to explore the barriers and promoting factors for their access to health-related information, health services, and welfare services during the first wave of COVID-19. We used a thematic analysis to identify key themes according to the study’s objectives. Further, these themes were assessed using an adapted version of the ecological model. The migrants mainly relied on the information available on social networking sites and were not aware of formal sources of information. Language was a major barrier, followed by cognitive bottlenecks and time constraints for migrants accessing health-related information and services. Social media, short-form information provided using their native language or plain Japanese and illustrations, and supportive people around could help them to access health-related information and services. The findings from this study demonstrate how migrants can represent a vulnerable group in a host country, even more so in a time of crisis.

Although the “stay-at-home” order is advocated against the coronavirus disease 2019 (COVID-19), the lives of individuals lacking adequate housing are threatened. We developed a framework to assess various populations with unstable housing in terms of socio-economic consequences of COVID-19, risk of COVID-19 infection and progression, existing/urgent measures, and remaining challenges. Within the framework, nine groups vulnerable to homelessness in Japan were classified into (i) “people without accommodation,” (ii) “people living in temporary or crisis accommodation,” and (iii) populations that include “people living in severely inadequate and insecure accommodation.” The assessment revealed that “staying at home” was physically and practically unattainable across groups. The study identified specific institutional, social, and cultural challenges apart from the common economic crisis, whereas the utilization of social welfare was low. Findings suggest that the rapid increase of groups classified as “(i)” and “(ii)” should be addressed by engaging stakeholders to enhance the availability and accessibility of social welfare and rescue measures, and to ensure safe and private accommodations for all groups. It is critical to enhance multi-sectoral collaboration in responding to the common and specific vulnerabilities of these population groups from health, socio-economic, and humanitarian perspectives. Under the pandemic, homelessness should be regarded less as a peculiar problem for specific populations but an extension of daily life. The framework can be a reference when planning the comprehensive yet concise assessment of populations with unstable housing in other countries to inform responses to the pandemic.

WHO Regional Office for the Western Pacific (WPRO) organized an online meeting connecting WHO Collaborating Centres (WHO CCs) in the region on 25 August 2020, to share experiences and promote networking on COVID-19 response. The meeting shared regional update on situation and responses, and COVID-19 related experiences of selected WHO CCs, followed by discussions on opportunities for enhancing collaboration between WPRO and WHO CCs. Priorities of WPROs support to countries included a health systems approach rather than single intervention. On behalf of WHO CCs in Japan, the National Center for Global Health and Medicine (NCGM) delivered a presentation on the results of a survey about COVID-19 related activities of these WHO CCs. These activities were categorized into collaboration with WHO, research and development, public health responses, and clinical services. Collaboration with WHO included sending consultants through the scheme of GOARN, strengthening of COVID-19 testing, and contribution to development of WPRO guidelines. Research and development involved establishment of a nationwide registry of COVID-19 clinical data. Following the meeting, NCGM further enhanced its activities as WHO CC. Since WHO CCs in the country have a wide range of expertise that could contribute to health system strengthening, it is worthwhile for the WHO CCs to consider amending existing work plans for supporting countries in the region to incorporate a health systems approach as part of COVID-19 response strategies.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy.Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/mA total of 35 patients were enrolled. The recommended dose was defined as 100 mg/mCombination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

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.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.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.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).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.

Critical building blocks for the response to HIV were made until 2012 despite a series of political, social and financial challenges. A rapid increase of HIV service coverage was observed from 2012 to 2015 through collaborative efforts of government and non-governmental organisations (NGOs). Government facilities, in particular, demonstrated their capacity to expand services for antiretroviral therapy (ART), prevention of mother-to-child transmission (PMTCT) of HIV, tuberculosis and HIV co-infection and methadone-maintenance therapy (MMT). After nearly three decades into the response to HIV, Myanmar has adopted strategies to provide the right interventions to the right people in the right places to maximise impact and cost efficiency. In particular, the country is now using strategic information to classify areas into high-, medium- and low-HIV burden and risk of new infections for geographical prioritisation – as HIV remains concentrated among key population (KP) groups in specific geographical areas. Ways forward include: • Addressing structural barriers for KP to access services, and identifying and targeting KPs at higher risk; • Strengthening the network of public facilities, NGOs and general practitioners and introducing a case management approach to assist KPs and other clients with unknown HIV status, HIV-negative clients and newly diagnosed clients to access the health services across the continuum to increase the number of people testing for HIV and to reduce loss to follow-up in both prevention and treatment; • Increasing the availability of HIV testing and counselling services for KPs, clients of female sex workers (FSW), and other populations at risk, and raising the demand for timely testing including expansion of outreach and client-initiated voluntary counselling and testing (VCT) services; • Monitoring and maximising retention from HIV diagnosis to ART initiation and expanding quality HIV laboratory services, especially viral load; • Prioritising integration of HIV and related services in high-burden areas; • Increasing the proportion of PLHIV receiving testing and treatment at public facilities by improving human resources and increasing public facilities providing these services to ensure sustainability; • Obtaining intelligence and tailoring services in hard-to-reach/under-served areas; • Strengthening planning, monitoring, and coordination capacity especially at regional levels.

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

INTRODUCTION: In Cambodia the Linked Response (LR) approach for strengthening linkages between HIV and reproductive health services especially for the prevention of mother-to-child transmission of HIV (PMTCT) was scaled up in 2009. This article describes the LR scale-up and the concomitant evolution of key PMTCT indicators at the national level. METHODS: A descriptive analysis of routine LR PMTCT programme data and national laboratory data from 2008 to 2012 was conducted. RESULTS: LR data show that between 2008 and 2012 the number of LR/PMTCT sites increased from 67 to 956 (of 1004) public health facilities to cover 74 (of 77) operational districts. In LR operational districts the number of pregnant women (PW) tested for HIV increased from 41800 in 2009 to 269935 [of whom 375 (0.14%) were newly tested positive for HIV] in 2012; the number of PW living with HIV and exposed infants receiving antiretrovirals increased from 49 and 44 in 2009 to 720 and 551 in 2012 respectively. Concomitantly national PMTCT programme data showed that the percent of PW tested for HIV increased from 34.4% (117832 of 342929 estimated PW) in 2008 to 86.1% (324996 of 377340) in 2012. In 2012 65.3% (862 of 1321) of estimated HIV-positive PW and 72.7% (960 of 1321) of exposed infants received antiretrovirals. By 6-8 weeks postpartum 7.4% (8 of 108) and 1.5% (6 of 409) of DNA-polymerase chain reaction tested positive in 2008 and in 2012 respectively. CONCLUSIONS: The LR approach provided a model which catalyzed increased access of PW to HIV testing and treatment thereby contributing to the scale-up of PMTCT service provision and improved coverage in Cambodia.

Background Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government. Methods The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program. Results The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test. Conclusions These results suggest that, for a generation of young women 20–25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.

Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

Background In 2014–2015, 242 individuals aged 2–89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent ( Conclusions Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.

// Akiko Morimoto 1,2 , Satoshi Serada 2 , Takayuki Enomoto 3 , Ayako Kim 2 , Shinya Matsuzaki 1 ,Tsuyoshi Takahashi 2,4 ,Yutaka Ueda 1 , Kiyoshi Yoshino 1 , Masami Fujita 1 , Minoru Fujimoto 2 , Tadashi Kimura 1 and Tetsuji Naka 2 1 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Japan 2 Laboratory for Immune Signals, National Institute of Biomedical Innovation, Japan 3 Department of Obstetrics and Gynecology, Niigata University Medical School, Japan 4 Department of Surgery, Osaka University Graduate School of Medicine, Japan Correspondence: Tetsuji Naka , email: // Keywords : Annexin A4; platinum resistance; annexin repeat; chloride ion Received : April 04, 2014 Accepted : August 03, 2014 Published : August 04, 2014 Abstract Platinum resistance has long been a major issue in the treatment of various cancers. We previously reported that enhanced annexin A4 (ANXA4) expression, a Ca 2+ -regulated phospholipid-binding protein, induces chemoresistance to platinum-based drugs. In this study, we investigated the role of annexin repeats, a conserved structure of all the annexin family, responsible for platinum-resistance as well as the effect of knockdown of ANXA4. ANXA4 knockdown increased sensitivity to platinum-based drugs both in vitro and in vivo . To identify the domain responsible for chemoresistance, ANXA4 deletion mutants were constructed by deleting annexin repeats one by one from the C terminus. Platinum resistance was induced both in vitro and in vivo in cells expressing either full-length ANXA4 or the deletion mutants, containing at least one intact annexin repeat. However, cells expressing the mutant without any calcium-binding sites in the annexin repeated sequence, which is essential for ANXA4 translocation from the cytosol to plasma membrane, failed to acquire platinum resistance. After cisplatin treatment, the intracellular chloride ion concentration, whose channel is partly regulated by ANXA4, significantly increased in the platinum-resistant cells. These findings indicate that the calcium-binding site in the annexin repeat induces chemoresistance to the platinum-based drug by elevating the intracellular chloride concentration.

Administration of the human papillomavirus (HPV) vaccine decreased dramatically in Japan after extensive news of adverse vaccine events and suspension of the governmental recommendation for the vaccine. In this study, we investigated the knowledge and acceptance of vaccinated adolescents concerning cervical cancer, cancer screening and the HPV vaccine. Furthermore, we analyzed whether and by how much the news affected acceptance of the vaccination. This study was conducted as a part of Osaka Clinical resEArch of HPV vacciNe (OCEAN) study. A questionnaire was distributed to 2,777 study registrants. The response rate was 38 %. The recognition rate of the news of the vaccine’s adverse events was 80 %; it was 68 % for awareness of the government’s announcement of the suspension of its recommendation for the vaccine. Among those who had a chance to hear or see the negative news during their vaccination period, 46 (60 %) continued vaccination while knowing of the news, 22 (29 %) discontinued vaccination, and 9 (11 %) continued vaccination without an awareness of the news. Reports of the vaccine’s adverse events were the main reason for not continuing the vaccination series. Those who consulted doctors after hearing the adverse news were significantly more likely to continue their vaccinations than those who did not. Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

Objective To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas. Study design Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study. Results A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable. Conclusion Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.

Objective The Shimodaira-Taniguchi conization procedure addresses the disadvantages of the loop electrosurgical excision procedure (LEEP) by using a high frequency current and a triangular probe with a linear excision electrode to extract the tissue as a single informative specimen, without incurring accompanying thermal trauma. The aim of the present study was to analyze the surgical efficacy of the Shimodaira-Taniguchi conization procedure for adenocarcinoma in situ (AIS) of the uterine cervix. Study design At the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has long been routinely performed for AIS. Medical records of patients during the period from 2005 to 2011, whose post-conization diagnosis was AIS, were retrospectively analyzed. A literature review was conducted of the PubMed database to clarify the surgical outcome efficacy of the Shimodaira-Taniguchi procedure compared to other procedures. Results During the study period, a post-conization diagnosis of AIS was made in 10 patients. A positive resection margin was detected in 4 of the 10 cases (40%), and residual disease was observed in 3 cases (30%). A review of the relevant literature indicates that the rate of positive margin and residual disease by the Shimodaira-Taniguchi procedure, including our cases, was not significantly different from the cold knife, LEEP or laser procedures ( p =0.32, 0.99, and 0.40, respectively, for positive margin, and p =0.76, 0.94, and 0.063, respectively, for residual disease). Conclusion AIS was demonstrated to be efficaciously treated, with a low risk of residual disease, by the Shimodaira-Taniguchi conization procedure. Further study is still needed to establish a standard of conservative treatment for AIS.

This report describes a case of aggressive angiomyxoma (AAM), arising in the vulvovaginal region, which was initially misdiagnosed as lymphedema due to a vaginal ulcer caused by Behcet’s disease. AAM is a very rare disease, usually found only in women of reproductive age, occurring predominantly in the pelviperineal region. AAM is basically a benign tumor usually treated by surgical resection. However, even after apparently complete resection, local recurrence of the tumor often occurs, thus its characterization as “aggressive” angiomyxoma. In contrast, vulvar edema is a condition with a very similar appearance that is observed relatively commonly, and which has many causes, e.g., obesity, inflammation, and benign or malignant tumors. Here we report a case of AAM which was initially mistaken for vulvovaginal edema, and initially believed to arise as a result of an ulcerative vaginal lesion associated with the patient’s underlying Behcet’s disease. We have reviewed the literature concerning vulvovaginal edema. We present herein this work to others as a precautionary tale, to prevent similar misdiagnosis and delay of treatment.

INTRODUCTION To achieve the global goal of eliminating mother-to-child transmission of HIV, retention of HIV-positive women and their babies throughout the cascade of prevention of mother-to-child transmission of HIV (PMTCT) services is necessary. Little evidence has been published on coverage of the cascade in resource-limited settings. Along with PMTCT service expansion in Cambodia, a national routine reporting system was developed. This study examines coverage of six PMTCT interventions to improve our understanding of retention throughout the cascade. METHOD WE DEVELOPED INDICATORS TO MONITOR COVERAGE OF THE SIX KEY INTERVENTIONS: (1) maternal antiretroviral treatment or prophylaxis; (2) delivery in a health facility; (3) infant ARV prophylaxis at birth; (4) infant co-trimoxazole prophylaxis at six weeks; (5) first infant DNA-PCR test at six weeks; and (6) second infant DNA-PCR test at 30 weeks. Programme data from April 2008 to December 2011 in 11 operational districts were used to identify those eligible for each intervention. RESULTS Women eligible for maternal antiretroviral treatment or prophylaxis in the study were aged 18 to 48 with a median age of 30 years. Coverage of the six interventions were: (1) 79.9% (258/323); (2) 92.2% (236/256); (3) 69.9% (179/256); (4) 73.3% (184/251); (5) 85.7% (215/251); and (6) 61.6% (135/219). Among those eligible, 29.7% (65/219) received all six interventions. DISCUSSION This study revealed critical gaps in PMTCT service delivery under routine conditions in Cambodia. Service optimization by reducing gaps will help eliminate HIV infection among infants and improve maternal survival. Further operational studies are needed to identify determinants of service uptake.

Antiretroviral therapy (ART) retention and 5 early-warning indicators (EWIs) of HIV drug resistance (HIVDR) were abstracted at 27 adult and 4 pediatric clinics in Vietnam in 2009. Of 4531 adults and 313 children, 81.2% and 84.4% respectively were still on ART at 12 months. More than 90% of the clinics monitored achieved the World Health Organization (WHO) targets for lost-to-follow-up (LTFU), ART prescribing practices, and ARV supply continuity. Only 83.9% of the clinics met the target for first-line ART retention and 79.3% met the target for clinic appointment-keeping. Clinic factors (i.e. number of patients, administrative level, and geographical region) were associated with ART retention and LFTU. Data were useful in guiding public health action to optimize ART services.

Health care workers (HCWs) in high TB burden countries bear significant risks of being infected with Mycobacterium tuberculosis and developing TB disease through their work. In recent years, an increasing number of people living with HIV (PLHIV) are taking part in delivering HIV and other health services in resource-limited settings with high TB burden. The greater involvement of PLHIV in health service delivery has many beneficial consequences on individuals and health systems, however, the involvement creates considerable opportunities for them to be exposed to patients with infectious TB disease. Due to their immunodeficiency, PLHIV are far more likely to develop active TB following the infection. Available evidence and recently revised WHO policy guidance on TB infection control suggest simple, predominantly administrative control measures are feasible and effective in reducing the infection. Nevertheless, many countries are still at the early stage of developing infection control policies. We call for evidence-based infection control measures in order to ensure a safe working environment for PLHIV in support of their greater involvement in health care. More research is needed to strengthen knowledge on TB infection risks amongst PLHIV through involvement in service delivery, and optimal interventions to reduce it.

Purpose Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC. Methods A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150 mg/m2), epirubicin (50 mg/m2) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175 mg/m2) and carboplatin (AUC 5). Results TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p = 0.017 for progression-free survival and p = 0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p = 0.55 for progression-free survival and p = 0.63 for overall survival). Conclusions TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.

The aim of the present study was to analyze the long-term outcome of cervical intraepithelial neoplasia 3 (CIN 3) after treatment with the Shimodaira-Taniguchi conization procedure, based on the status of the resection margins.In the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has been routinely performed for CIN 3. Medical records of patients during the period from 2001 to 2008, whose post-conization diagnosis was CIN 3, were retrospectively analyzed for outcome versus margin status.During the median follow-up period of 565 days (range 34-3,013), CIN disease was again detected in 14 of 243 patients; it was found in 7 patients among 198 margin-negative cases, and in 7 patients among 45 margin-positive cases. There was a significant difference in the reappearance rate demonstrated between the cases with positive and negative margins (p = 0.0018). Among the patients whose first follow-up post-conization cytology was normal, recurrence-free probability was significantly higher in margin-negative cases than in margin-positive ones (hazard ratio, 5.19; 95% CI, 1.175-22.994; p = 0.0041).For the first time, we demonstrate that after treatment of CIN 3 lesions by Shimodaira-Taniguchi conization the status of the resection margin was a significant predictor for long-term outcome.

A primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare lesion. To date, only 49 cases have been reported. The presence of mural nodules in a PRMC may indicate a worse prognosis. We report the case of a 40-year-old Japanese woman with a PRMC with mural nodules. Microscopic examination revealed that the stromal cells of the nodules were spindle-shaped and varied in size. The nodules were immunoreactive for vimentin but negative for cytokeratin and EMA, and the nuclei of the stromal cells were pleomorphic and strongly Ki-67 immunoreactive. The nodules were diagnosed as true sarcoma. To the best of our knowledge, this is 11th published case report of a PRMC with mural nodules.

Katsuya Suzuki1, Shigekazu Tsubaki2, Masami Fujita3, Naoto Koyama1, Michio Takahashi1, Kenji Takazawa41Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Kawasaki; 2Samoncho Clinic, Tokyo; 3Shinanozaka Clinic, Tokyo; 4Tokyo Medical University Hachioji Medical Center, Tokyo, JapanAbstract: Safflower seed extract (SSE) contains characteristic polyphenols and serotonin derivatives (N-(p-coumaroyl) serotonin and N-feruloylserotonin), which are reported to inhibit oxidation of low-density lipoprotein (LDL), formation of atherosclerotic plaques, and improve arterial stiffness as assessed by pulse wave analysis in animal models. The effects of long-term supplementation with SSE on arterial stiffness in human subjects were evaluated. This double-blind, placebo-controlled study was conducted in 77 males (35–65 years) and 15 postmenopausal females (55–65 years) with high-normal blood pressure or mild hypertension who were not undergoing treatment. Subjects received SSE (70 mg/day as serotonin derivatives) or placebo for 12 weeks, and pulse wave measurements, ie, second derivative of photoplethysmogram (SDPTG), augmentation index, and brachial-ankle pulse wave velocity (baPWV) were conducted at baseline, and at weeks 4, 8, and 12. Vascular age estimated by SDPTG aging index improved in the SSE-supplemented group when compared with the placebo group at four (P = 0.0368) and 12 weeks (P = 0.0927). The trend of augmentation index reduction (P = 0.072 versus baseline) was observed in the SSE-supplemented group, but reduction of baPWV by SSE supplementation was not observed. The SSE-supplemented group also showed a trend towards a lower malondialdehyde-modified-LDL autoantibody titer at 12 weeks from baseline. These results suggest long-term ingestion of SSE in humans could help to improve arterial stiffness.Keywords: safflower, serotonin derivatives, antioxidants, augmentation index, pulse wave velocity

Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the sensitivity of cancers differs in individual cases. Because cisplatin is reported to suppress glucose uptake, we investigated the correlation between glucose uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both cell lines had a decreased number of cells accompanied by cell death 24 h after cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3 h after high-dose cisplatin treatment, which correlated with the sensitivity to the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not change with cisplatin treatment. In contrast, the membrane localization of GLUT1 disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did not show an early decrease in glucose uptake after cisplatin treatment. The early decrease in glucose uptake and later cell death also correlated in cultured cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake at an early time point after high dose cisplatin treatment reflected cisplatin chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer patients. (Cancer Sci 2010)

Purpose A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline. Methods During the 2000–2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed. Results Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of ≥ or

Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, has been unreliable; SCC is elevated in cervical squamous cell carcinomas ranging from 28–85% of the time. Recent proteomics-based analyses show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently utilized serum tumor markers for gynecologic cancers and the novel biomarkers that are now under investigation.

Objective To clarify the frequency of pregnancy complicated by ovarian endometriosis and to investigate the size change and outcome of ovarian endometriosis during pregnancy. Design Retrospective study. Setting Departments of obstetrics and gynecology of the Osaka University and Izumiotsu Municipal Hospitals of Osaka, Japan. Patient(s) Women who delivered between 1996 and 2007. Intervention(s) None. Main Outcome Measure(s) The frequency of pregnancies complicated by ovarian endometriosis and the size change of the lesions during pregnancy. Result(s) The frequency of ovarian endometriosis-complicated pregnancy has almost quadrupled over the last 12 years, to become the most common adnexal mass detected during pregnancy; it was 0.14% (five cases among 3558 deliveries) during the 6-year period from 1996 to 2001, but has increased to 0.52% (19 cases among 3599 deliveries) during the 6-year period from 2002 to 2007, a statistically significant increase of 3.8-fold. Among 25 ovarian endometriotic lesions observed during pregnancy in 24 women (one case had two lesions), the size of the cyst decreased in 13 lesions (52%), went unchanged in 7 (28%), and increased in 5 (20%), that demonstrated decidualization, abscess and rupture. Conclusion(s) Ovarian endometriosis during pregnancy can be safely observed conservatively; however, further investigation is required to predict the occurrence of abscess formation or rupture of ovarian endometriosis, and to distinguish the enlargements due to malignant transformation from those related to decidualization.

The aim of this study was to determine if there is a prognostic value for the presence of symptoms at the time of recurrence detection in surgically resected endometrial carcinoma patients.During the study period of 2000-2006, complete surgical removal of endometrial carcinoma was achieved in 271 stage I-IV endometrial cancer cases at the Department of Obstetrics and Gynecology of Osaka University Hospital, Osaka, Japan. A subsequent recurrence was detected in 29 (11%) of these cases. Patient characteristics and clinicopathological features were retrospectively reviewed utilizing their clinical records.Among the 29 cases with a recurrence, 13 (45%) had symptoms, whereas in the other 16 cases (55%) the recurrent disease was found only during routine follow-up procedures. Although the time to detection of recurrence was similar for both asymptomatic and symptomatic cases, progression-free survival after detection in the 16 asymptomatic patients was significantly longer than for the 13 symptomatic patients (P = 0.017); this was found to be especially true in those who underwent chemotherapy as their adjuvant therapy (P = 0.023).A better prognosis after recurrence was demonstrated in cases that were asymptomatic at the time of recurrence detection than in those in which the tumor was symptomatic. This finding implies that, after the initial surgical resection, intensive follow-up intervention looking for asymptomatic recurrences may significantly improve the prognosis of endometrial carcinoma patients. A further in-depth prospective study is required to establish a standard strategy of follow-up care for endometrial cancer patients.