RESUMEN
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.
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Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Sulfato de Cobre/farmacología , ATPasas Transportadoras de Cobre/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Leiomiosarcoma/tratamiento farmacológico , Neoplasias Uterinas/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , ATPasas Transportadoras de Cobre/antagonistas & inhibidores , ATPasas Transportadoras de Cobre/genética , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Leiomiosarcoma/genética , Leiomiosarcoma/metabolismo , Ratones , Trasplante de Neoplasias , Trasplante Heterólogo , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismoRESUMEN
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 (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003. 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.
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Brotes de Enfermedades , Infecciones por VIH/epidemiología , Infecciones por VIH/etiología , Inyecciones/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cambodia/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , VIH-1 , Humanos , Enfermedad Iatrogénica/epidemiología , Masculino , Persona de Mediana Edad , Filogenia , Población Rural , Adulto JovenRESUMEN
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.
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Disgerminoma/diagnóstico por imagen , Disgenesia Gonadal 46 XY/complicaciones , Neoplasias Ováricas/diagnóstico por imagen , Adulto , Disgerminoma/complicaciones , Disgerminoma/cirugía , Femenino , Disgenesia Gonadal 46 XY/diagnóstico por imagen , Humanos , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/cirugía , Resultado del TratamientoRESUMEN
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.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Satisfacción del Paciente/estadística & datos numéricos , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico , Administración Oral , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Encuestas y CuestionariosRESUMEN
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.
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Brotes de Enfermedades , Infecciones por VIH/epidemiología , Inyecciones/efectos adversos , Anciano , Cambodia/epidemiología , Niño , Análisis por Conglomerados , Femenino , Humanos , Lactante , Masculino , Persona de Mediana EdadRESUMEN
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.
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Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/estadística & datos numéricos , Promoción de la Salud/métodos , Neoplasias del Cuello Uterino/prevención & control , Adulto , Femenino , Financiación Gubernamental , Humanos , Japón , Gobierno Local , Evaluación de Programas y Proyectos de Salud , Adulto JovenRESUMEN
BACKGROUND: A lymphocyst (lymphocele) is a common complication of lymphadenectomy, which is a widely used surgical method for gynecologic cancers. In cases of infected lymphocysts, therapeutic strategies, including the timing and duration of antibiotics administration and cyst drainage, may vary depending on the physician. The aim of this study was to determine the optimal timing for drainage of lymphocysts infected with bacteria resistant to antibiotic treatment. MATERIALS AND METHODS: Clinical data for 1175 patients who underwent a lymphadenectomy as part of surgery for a gynecologic malignancy between April 2000 and August 2012 at Osaka University Hospital, Osaka, Japan, were analyzed. RESULTS: Of the 282 patients who developed a lymphocyst (24%), 35 with infected lymphocysts (12%) were analyzed. Lymphocyst infection was not associated with tumor origin, type of hysterectomy, or region of lymphadenectomy (P = 0.81, P = 0.59, and P = 0.86, respectively). The total treatment period of cases treated only with antibiotics tended to be shorter than that of cases treated with combined antibiotics and drainage, but the difference was not significant (P = 0.061). However, for severe cases which needed drainage, initiating the drainage by day 5 significantly shortened the total treatment period compared with cases started on or after day 6 (P = 0.042). CONCLUSIONS: The appropriate time point for initiating lymphocyst drainage has been difficult to determine. The present study implies that for severe lymphocyst infections, where drainage is required in addition to antibiotics, the earlier the drainage is performed, the shorter the treatment period is. Further studies may be required to decide other optimal treatment strategies for infected lymphocysts.
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Drenaje , Neoplasias de los Genitales Femeninos/cirugía , Escisión del Ganglio Linfático/efectos adversos , Linfocele/terapia , Infección de la Herida Quirúrgica/terapia , Tiempo de Tratamiento/normas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Drenaje/métodos , Drenaje/normas , Esquema de Medicación , Farmacorresistencia Bacteriana , Femenino , Neoplasias de los Genitales Femeninos/epidemiología , Humanos , Linfocele/epidemiología , Linfocele/etiología , Persona de Mediana Edad , Infección de la Herida Quirúrgica/complicaciones , Infección de la Herida Quirúrgica/epidemiología , Adulto JovenRESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Medios de Comunicación de Masas , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Aceptación de la Atención de Salud , Neoplasias del Cuello Uterino/prevención & control , Vacunación/estadística & datos numéricos , Adolescente , Niño , Femenino , Conocimientos, Actitudes y Práctica en Salud , Directrices para la Planificación en Salud , Humanos , Japón , Infecciones por Papillomavirus/complicaciones , Vacunas contra Papillomavirus/uso terapéutico , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/etiología , Adulto JovenRESUMEN
BACKGROUND: In the Asia-Pacific region, limited systematic assessment has been conducted on HIV service delivery models. Applying an analytical framework of the continuum of prevention and care, this study aimed to assess HIV service deliveries in six Asia and Pacific countries from the perspective of service availability, linking approaches and performance monitoring for maximizing HIV case detection and retention. METHODS: Each country formed a review team that provided published and unpublished information from the national HIV program. Four types of continuum were examined: (i) service linkages between key population outreach and HIV diagnosis (vertical-community continuum); (ii) chronic care provision across HIV diagnosis and treatment (chronological continuum); (iii) linkages between HIV and other health services (horizontal continuum); and (iv) comprehensive care sites coordinating care provision (hub and heart of continuum). RESULTS: Regarding the vertical-community continuum, all districts had voluntary counselling and testing (VCT) in all countries except for Myanmar and Vietnam. In these two countries, limited VCT availability was a constraint for referring key populations reached. All countries monitored HIV testing coverage among key populations. Concerning the chronological continuum, the proportion of districts/townships having antiretroviral treatment (ART) was less than 70% except in Thailand, posing a barrier for accessing pre-ART/ART care. Mechanisms for providing chronic care and monitoring retention were less developed for VCT/pre-ART process compared to ART process in all countries. On the horizontal continuum, the availability of HIV testing for tuberculosis patients and pregnant women was limited and there were sub-optimal linkages between tuberculosis, antenatal care and HIV services except for Cambodia and Thailand. These two countries indicated higher HIV testing coverage than other countries. Regarding hub and heart of continuum, all countries had comprehensive care sites with different degrees of community involvement. CONCLUSIONS: The analytical framework was useful to identify similarities and considerable variations in service availability and linking approaches across the countries. The study findings would help each country critically adapt and adopt global recommendations on HIV service decentralization, linkages and integration. Especially, the findings would inform cross-fertilization among the countries and national HIV program reviews to determine county-specific measures for maximizing HIV case detection and retention.
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Síndrome de Inmunodeficiencia Adquirida/mortalidad , Conducta Cooperativa , Servicios de Salud/normas , Modelos Organizacionales , Calidad de la Atención de Salud , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adolescente , Adulto , Asia , Asia Sudoriental/epidemiología , Consejo , Femenino , Investigación sobre Servicios de Salud/métodos , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Nepal/epidemiología , Papúa Nueva Guinea/epidemiología , Embarazo , Tuberculosis , Adulto JovenRESUMEN
PURPOSE: We retrospectively analyzed oncologic and reproductive outcomes of fertility-seeking premenopausal women with complex atypical hyperplasia (CAH) or Grade 1 endometrial adenocarcinoma (G1EA) who underwent medical management with high-dose medroxyprogesterone acetate (MPA) therapy. METHODS: Patients were given a dose of 400-600 mg of MPA orally on a daily basis. They had histologically confirmed CAH or G1EA at presumed stage IA and wished to preserve fertility. Endometrial tissue sampling was carried out by dilation and curettage before and after the treatment and the pathologic response to MPA treatment was assessed. RESULTS: A total of 27 premenopausal patients received MPA therapy. The median follow-up time was 39.2 months (3.4-153.8 months). Complete response was achieved in 81.8 % (9/11) of CAH cases and 68.8 % (11/16) of G1EA. Although no recurrences were found in CAH patients, nine G1EA patients (81.8 %) eventually recurred and underwent total hysterectomy. Neither therapeutic death nor irreversible toxicities were observed during the follow-up periods. Five patients (4 CAH and 1 G1EA) became pregnant and had nine live births. CONCLUSION: The high efficacy of fertility-sparing treatment with MPA was shown demonstrated. MPA therapy can be considered acceptable for the purpose of enabling patients to preserve their fertility. However, the rate of recurrence was high in patients with G1EA. Even in responders, close follow-up is required and a total hysterectomy needs to be considered without delay. Patients should be aware of the risks and limitations of this conservative treatment.
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Carcinoma Endometrioide/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Preservación de la Fertilidad , Acetato de Medroxiprogesterona/uso terapéutico , Adulto , Antineoplásicos Hormonales/uso terapéutico , Carcinoma Endometrioide/patología , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía , Recurrencia Local de Neoplasia/tratamiento farmacológico , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Although platinum drugs are often used for the chemotherapy of human cancers, platinum resistance is a major issue and may preclude their use in some cases. We recently reported that enhanced expression of Annexin A4 (Anx A4) increases chemoresistance to carboplatin through increased extracellular efflux of the drug. However, the precise mechanisms underlying that chemoresistance and the relationship of Anx A4 to platinum resistance in vivo remain unclear. In this report, the in vitro mechanism of platinum resistance induced by Anx A4 was investigated in endometrial carcinoma cells (HEC1 cells) with low expression of Anx A4. Forced expression of Anx A4 in HEC1 cells resulted in chemoresistance to platinum drugs. In addition, HEC1 control cells were compared with Anx A4-overexpressing HEC1 cells in xenografted mice. Significantly greater chemoresistance to cisplatin was observed in vivo in Anx A4-overexpressing xenografted mice. Immunofluorescence analysis revealed that exposure to platinum drugs induced relocation of Anx A4 from the cytoplasm to the cellular membrane, where it became colocalized with ATP7A, a copper transporter also well known as a mechanism of platinum efflux. ATP7A expression suppressed by small interfering RNA had no effect on HEC1 control cells in terms of chemosensitivity to platinum drugs. However, suppression of ATP7A in Anx A4-overexpressing platinum-resistant cells improved chemosensitivity to platinum drugs (but not to 5-fluorouracil) to a level comparable to that of control cells. These results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.
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Adenosina Trifosfatasas/metabolismo , Anexina A4/metabolismo , Antineoplásicos/farmacología , Carboplatino/farmacología , Proteínas de Transporte de Catión/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos , Adenosina Trifosfatasas/genética , Animales , Transporte Biológico , Proteínas de Transporte de Catión/genética , Línea Celular Tumoral , ATPasas Transportadoras de Cobre , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/metabolismo , Femenino , Fluorouracilo/farmacología , Humanos , Ratones , Ratones Endogámicos ICR , Interferencia de ARN , ARN Interferente Pequeño , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Uterine adenomyoma is often overlooked, and cervical adenomyoma is extremely rare. Previous reports suggest that a uterine adenomyoma usually occurs in the uterine corpus but rarely in the uterine cervix. Approximately 20 reports of cervical adenomyoma have been published to date. However, cervical adenomyoma has been rarely investigated using magnetic resonance imaging. We encountered a large multicystic tumor in the uterine cervix of a 26-year-old woman that was difficult to diagnose preoperatively. On the basis of cytology, biopsy, and imaging findings, the cervical multicystic tumor measured approximately 13.0 cm. The patient underwent vaginal adenomyomectomy, and the tumor was completely resected. A histologic diagnosis of cervical adenomyoma was made because of proliferation of endocervical glands and the presence of rounded smooth muscle stroma. Awareness of this tumor in the uterine cervix is important for accurate diagnosis and treatment. Herein we present a rare case of a large cervical adenomyoma, with imaging studies, an image of the operation, histologic findings, and a literature review.
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Adenomioma/cirugía , Cuello del Útero/patología , Neoplasias del Cuello Uterino/cirugía , Adenomioma/diagnóstico , Adulto , Biopsia , Cuello del Útero/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Ultrasonografía , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
BACKGROUND: Migrants are individuals who move to a different country from their usual place of residence. Japan's migrant population, particularly technical interns and students, has been growing. Even before the pandemic, previous studies have highlighted difficulties faced by migrants in utilizing healthcare services. This study examined the uptake of COVID-19 vaccination, testing, and medical care among Myanmar migrants in Japan; identified the factors associated with this uptake; and described the difficulties encountered when utilizing these services. METHODS: A cross-sectional study was conducted between March and April 2023 targeting Myanmar migrants over 18 years residing in Japan for more than 6 months. An online self-administered questionnaire in Myanmar language covered socioeconomic characteristics; history of COVID-19 vaccination, testing, and medical care; and difficulties encountered while utilizing these services with multiple-choice questions. Multivariate logistic regression analysis was performed separately to identify the factors associated with the uptake of COVID-19 vaccination, testing, and medical care. RESULTS: Among the 207 participants, 52% (n = 108) were under 30 years, 30% (n = 62) were male, and 31% (n = 65) were low-skilled workers (technical interns and students). Overall, 91% (n = 189) had received the COVID-19 vaccination, 76% (n = 157) had been tested for COVID-19, and 43% (n = 68) tested positive. However, only 77% (n = 52) of COVID-19 patients sought medical care. Participants under 30 years of age were less likely to receive the COVID-19 vaccine compared to those aged 30 and older (adjusted odds ratio [aOR] 0.10, 95% confidence interval [CI] 0.01-0.88, p = 0.038). Low-skilled workers were less likely to seek medical care compared to those holding other categories of residential status (aOR 0.12, 95% CI 0.02-0.79, p = 0.027). Among service users, 5% faced difficulties with COVID-19 vaccination, 10% with testing, and 17% with receiving medical care. Long waiting times and complex reservation processes were the main difficulties encountered. CONCLUSIONS: The uptake of COVID-19 vaccination, testing, and medical care in this sample was reasonably good. However, individuals under 30 years of age showed lower uptake of vaccination, while low-skilled workers had lower uptake of medical care. Strengthening education and support for young migrants and low-skilled workers regarding COVID-19 and other infectious diseases is essential, especially in workplaces and educational institutions.
RESUMEN
This report utilizes a novel proteomic method for discovering potential therapeutic targets in endometrial cancer. We used a biotinylation-based approach for cell-surface protein enrichment combined with isobaric tags for relative and absolute quantitation (iTRAQ) technology using nano liquid chromatography-tandem mass spectrometry analysis to identify specifically overexpressed proteins in endometrial cancer cells compared with normal endometrial cells. We identified a total of 272 proteins, including 11 plasma membrane proteins, whose expression increased more than twofold in at least four of seven endometrial cancer cell lines compared with a normal endometrial cell line. Overexpression of bone marrow stromal antigen 2 (BST2) was detected and the observation was supported by immunohistochemical analysis using clinical samples. The expression of BST2 was more characteristic of 118 endometrial cancer tissues compared with 59 normal endometrial tissues (p < 0.0001). The therapeutic effect of an anti-BST2 antibody was studied both in vitro and in vivo. An anti-BST2 monoclonal antibody showed in vitro cytotoxicity in BST2-positive endometrial cancer cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. In an in vivo xenograft model, anti-BST2 antibody treatment significantly inhibited tumor growth of BST2-positive endometrial cancer cells in an NK cell-dependent manner. The anti-BST2 antibody had a potent antitumor effect against endometrial cancer both in vitro and in vivo, indicating a strong potential for clinical use of anti-BST2 antibody for endometrial cancer treatment. The combination of biotinylation-based enrichment of cell-surface proteins and iTRAQ analysis should be a useful screening method for future discovery of potential therapeutic targets.
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Antígenos CD/metabolismo , Membrana Celular/metabolismo , Neoplasias Endometriales/tratamiento farmacológico , Terapia Molecular Dirigida , Proteoma/metabolismo , Animales , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/farmacología , Antígenos CD/genética , Antígenos CD/inmunología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Citotoxicidad Inmunológica , Neoplasias Endometriales/metabolismo , Endometrio/metabolismo , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Inyecciones Intraperitoneales , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteómica , Interferencia de ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: The criterion standard of practice for gynecologists is to measure the endometrial thickness with ultrasonography in women presenting with postmenopausal bleeding. A recent study reported that a thin endometrial stripe upon ultrasonography did not reliably exclude type II endometrial carcinoma. The aim of the present study was to reevaluate the reliability of ultrasonographic measurement of the endometrium for prediction of endometrial carcinomas of both types I and II in postmenopausal women. METHODS: We collected clinical data from patients with endometrial carcinoma who underwent surgical treatment at the Department of Obstetrics and Gynecology of the Osaka University Hospital, Osaka, Japan, during our study period from 2010 to 2012. Only the postmenopausal cases were included in our study. We excluded cases with insufficient clinical data. RESULTS: Preoperative measurement of the endometrium by transvaginal ultrasonography revealed that the endometrium was greater than 4 mm in 80 (89%) of the 90 type I cases and in 41 (93%) of the 44 type II cases. The median of the endometrial thickness measured with transvaginal ultrasonography preoperatively in type I cases, including both patients with myometrial invasion less than 1/2 and those with myometrial invasion greater than 1/2, was 13 mm (range, 1-78 mm). That of type II cases was 15 mm (range, 1-54 mm). This difference was not statistically significant (P = 0.46 by Mann-Whitney U test). These results implied that endometrial thickness was not significantly associated with the type of tumors. CONCLUSIONS: Ultrasonographic measurements of the endometrium for prediction of endometrial carcinomas in postmenopausal women are reliable for both type I and type II tumors. These results encourage us to continue to use the "4-mm (5-mm) rule" to evaluate endometrial thickness in postmenopausal women, in opposition to a previous report.
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Neoplasias Endometriales/patología , Posmenopausia , Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Anciano , Anciano de 80 o más Años , Animales , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Japón , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , UltrasonografíaRESUMEN
BACKGROUND: Recurrent or persistent clear cell carcinoma (CCC) of the ovary is particularly chemotherapy resistant. The purpose of this study was to review our extensive institutional experiences with recurrent or persistent CCC with the aim of finding a more effective chemotherapy regimen. METHODS: The medical records of 67 patients treated for CCC of the ovary were retrospectively reviewed to select patients subsequently treated for recurrence or persistence of the disease. RESULTS: The review identified 20 patients treated for recurrent or persistent CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were administered. Gemcitabine monotherapy showed the best response rate [1 partial response (20%) and 2 stable diseases out of 5 patients so treated]. A partial response was observed with a combination of docetaxel plus irinotecan in 1 of 11 patients (9%). Stable disease was observed in 1 of 9 cases on a paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet. The median overall survival time was 8 months (range, 2-52). One group of patients who received gemcitabine therapy showed significantly better survival (n = 5, median 18 months) compared with a group who did not (n = 15, median 7 months) (P = 0.0108, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that gemcitabine administration was a significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727-115.2255, P = 0.02). CONCLUSION: Although most chemotherapeutic regimens for recurrent or persistent CCC have little or no effect, gemcitabine showed modest activity and is the most effective agent we have tested to date.
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Adenocarcinoma de Células Claras/tratamiento farmacológico , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Carcinoma Epitelial de Ovario , Desoxicitidina/administración & dosificación , Docetaxel , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Estudios Retrospectivos , Terapia Recuperativa/métodos , Tasa de Supervivencia , GemcitabinaRESUMEN
Global migration has been increasing since before the COVID-19 pandemic. The pandemic has clearly shown a lack of preparedness for the next public health emergency when it comes to vulnerable populations including migrants. To include the issues of migration and health in the current global health agenda, it is important to establish/strengthen a network for collaboration among various stakeholders from both the migrant-sending and host countries of migrants especially in the Asian-Pacific region. As the initial step for networking in Asia, in March 2023, a hybrid style international symposium was held in Japan and agreed on a goal and five pillars: surveillance and monitoring, risk communications, community engagement, access to health and social protection services, and supportive environments. Considering the transition of context from the COVID-19 crisis to 'Build Forward Better', through the Asian network, we will envisage the better world, where vulnerable populations including migrants will not be left behind from health security.
RESUMEN
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.
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Promoción de la Salud , Cobertura Universal del Seguro de Salud , Humanos , Accesibilidad a los Servicios de Salud , Política Pública , Asistencia MédicaRESUMEN
Objectives: This study aimed to review the progress and challenges of COVID-19 vaccine roll-out for migrants in Japan and discuss the approaches to address the challenges and better prepare for future waves of COVID-19 and other pandemics. Methods: We conducted a literature review using an assessment framework which we developed building upon existing frameworks and tools on access to health services and COVID-19 vaccination among migrants. Results: COVID-19 vaccination coverage among foreigners might be lower than that of nationals although the data on foreigners were not widely available. A gap appeared to exist between the government's efforts to disseminate vaccine-related information through multi-lingual websites and migrant communities as recipients. A series of barriers for migrants were identified at different stages of the vaccination process. While efforts were made by different units of local governments, NGOs, migrant communities, and international exchange associations, linkages across sectors and scaling-up appeared to be an issue. No foreigners were explicitly excluded from the entitlements of COVID-19 vaccination. The national level guidance, however, allowed sub-national levels to make a decision on whether or not undocumented foreigners should be reported to the immigration office or law enforcement when providing the services. In consequence, units in charge of public health and vaccination of some municipalities did not offer vaccination to those in need. Conclusion: Migrants, especially those unregistered face various barriers in accessing COVID-19 vaccination. It is critical to assess and address challenges concerning channels of information dissemination, pathways to access services, obstacles for vulnerable migrants, and data for evidence-based actions.
RESUMEN
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.