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1.
J Med Econ ; 26(1): 1009-1018, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37505931

RESUMO

AIMS: The treatment landscape of renal cell carcinoma has changed with the introduction of targeted therapies. While the clinical benefit of cabozantinib is well-established for Japanese patients who have received prior treatment, the economic benefit remains unclear. The objective of this study was to assess the cost-effectiveness of cabozantinib compared with everolimus, axitinib, and nivolumab in patients with advanced renal cell carcinoma who have failed at least one prior therapy in Japan. METHODS: A cost-effectiveness model was developed using a partitioned survival approach and a public healthcare payer's perspective. Over a lifetime horizon, clinical and economic implications were estimated according to a three-health-state structure: progression-free, post-progression, and death. Key clinical inputs and utilities were derived from the METEOR trial, and a de novo network meta-analysis and cost data were obtained from publicly available Japanese data sources. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were estimated. Costs and health benefits were discounted annually at 2%. RESULTS: Cabozantinib was more costly and effective compared with everolimus and axitinib, with deterministic incremental cost-effectiveness ratios of ¥5,375,559 and ¥2,223,138, respectively. Compared to nivolumab, cabozantinib was predicted to be less costly and more effective. Sensitivity and scenario analyses demonstrated that the key drivers of cost-effectiveness results were the estimation of overall survival and treatment duration, relative efficacy, drug costs, and subsequent treatment costs. LIMITATIONS: METEOR was an international trial but did not enroll any patients from Japan. Efficacy and safety data from METEOR were used as a proxy for the Japanese population following validation by clinical experts, and alternative assumptions specific to clinical practice in Japan were evaluated in scenario analyses. CONCLUSIONS: In Japan, cabozantinib is a cost-effective alternative to everolimus, axitinib, and nivolumab for the treatment of patients with advanced renal cell carcinoma who have received at least one prior line of therapy.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Antineoplásicos/uso terapêutico , Axitinibe/uso terapêutico , Análise Custo-Benefício , Análise de Custo-Efetividade , Everolimo/uso terapêutico , Japão , Nivolumabe/uso terapêutico , Ensaios Clínicos como Assunto , Metanálise como Assunto
2.
Artigo em Inglês | MEDLINE | ID: mdl-37339436

RESUMO

INTRODUCTION: Value-based pricing (VBP) can be a promising tool for optimizing drug prices. However, there is no consensus on the specific value elements and pricing method that should be used for VBP. AREAS COVERED: We performed a systematic review and narrative synthesis to investigate the value elements and pricing method for VBP. The main inclusion criterion was that value elements, VBP method, and estimated prices for actual drugs were reported. We performed a search in MEDLINE and ICHUSHI Web. Eight articles met the selection criteria. Four studies adopted the cost-effectiveness analysis (CEA) approach and the others used different approaches. The CEA approach included the value elements of productivity, value of hope, real option value, disease severity, insurance value in addition to costs and quality-adjusted life years. The other approaches used efficacy, toxicity, novelty, rarity, research and development costs, prognosis, population health burden, unmet needs, and effectiveness. Each study used individual methods to quantify these broader value elements. EXPERT OPINION: Both conventional and broader value elements are used for VBP. To allow VBP to be widely applied to various diseases, a simple, versatile method is preferable. Further research is needed to establish VBP method which enables to incorporate broader values.


Assuntos
Custos de Medicamentos , Humanos , Japão , Custos e Análise de Custo
3.
J Mark Access Health Policy ; 11(1): 2166374, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36684854

RESUMO

Background: Perianal fistula (PF), a complication of Crohn's disease (CD), affects health-related quality of life (QOL). Objective: To elucidate QOL of health states corresponding to different stages of PF associated with CD in Japan. Method: This cross-sectional, observational, web-based questionnaire survey assessed eight different health states in patients with CD and PF and individuals without CD (non-patients) from the Medilead Healthcare Panel (MHP) and determined the utility values (QOL scores) in each health state by the time trade-off method. In patients, we determined also the utility value of the current health state associated with CD and the PF. The analysis excluded respondents with logical inconsistencies. Results: The analysis included 82 patients and 576 non-patients with the same sex and age distribution as the Japanese population. In both groups, mean utility values were higher in remission (patients, 0.78; non-patients, 0.51) than in non-remission states, with lowest values for poor prognosis after proctectomy (patients, 0.13; non-patients, -0.10) and highest values for the state with mild symptoms (patients, 0.60; non-patients, 0.30). In patients, the mean utility value of the current health state was 0.71. Conclusion: QOL decreases with increasing severity of PF and is lower for good prognosis after proctostomy than for remission.

4.
J Atheroscler Thromb ; 27(1): 13-24, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31092743

RESUMO

AIM: Although high on-treatment platelet reactivity (HTPR) with dual antiplatelet therapy (DAPT) correlates with long-term adverse outcomes in patients undergoing percutaneous coronary intervention, the correlation in Japanese patients remains unclear. Therefore, we examined the relationship between platelet reactivity during DAPT with aspirin and clopidogrel and 1-year clinical outcomes following successful coronary stent implantation. METHODS: A prospective, multicenter registry study (j-CHIPS) was conducted in patients undergoing coronary stenting and receiving aspirin and clopidogrel at 16 hospitals in Japan. A VerifyNow point-of-care assay was used to assess platelet reactivity, and a cutoff value to define HTPR was established. RESULTS: Between February 2011 and May 2013, 1047 patients were prospectively enrolled, of which 854 patients with platelet function evaluation at 12-24 h after PCI were included in the final analysis. After 1 year of follow-up, the incidence of the primary endpoint (a composite of all-cause mortality, myocardial infarction, stent thrombosis, and ischemic stroke) was significantly higher in patients with HTPR than in those without (5.9% vs. 1.5%, p=0.008), and HTPR showed a modest ability to discriminate between patients who did and did not experience major adverse cardiac and cerebrovascular events (area under the curve, 0.60; 95% confidence interval, 0.511-0.688, p=0.039). HTPR status did not identify patients at risk for major or minor bleeding events. CONCLUSION: HTPR was significantly associated with adverse ischemic outcomes at 1 year after PCI in Japanese patients receiving maintenance DAPT, indicating its potential as a prognostic indicator of clinical outcomes in this high-risk patient population.


Assuntos
Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Stents/efeitos adversos , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Testes de Função Plaquetária , Acidente Vascular Cerebral
5.
Parkinsonism Relat Disord ; 53: 21-27, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29748109

RESUMO

INTRODUCTION: Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. METHODS: Patients aged 30-79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. RESULTS: In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were -0.84 h (rasagiline 1 mg/day) and -0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: -1.27, -1.74, and -2.51 (0.5 mg/day) and -1.27, -2.14, and -3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). CONCLUSIONS: As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised.


Assuntos
Antiparkinsonianos/farmacologia , Indanos/farmacologia , Levodopa/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Japão , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Inibidores da Monoaminoxidase/efeitos adversos
6.
Mol Clin Oncol ; 5(4): 395-401, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27699033

RESUMO

Frequent mutation of the ARID1A gene has been recently identified in ovarian clear-cell adenocarcinoma (CCA); however, the clinical significance of BAF250a expression encoded by the ARID1A gene remains to be determined. The aim of the present study was to assess whether BAF250a expression had an impact on the clinical features of CCA. A total of 97 cases of CCA treated at a single institution were enrolled in the present study. The tissue samples were evaluated by immunohistochemical staining. BAF250a-deficient expression was observed in 30% (29/97) of all CCA cases. Of this, 19% of non-atypical endometriosis, 26% of atypical endometriosis, 39% of endometriosis-related CCA, 5% of benign clear-cell adenofibroma (CCAF), 5% of borderline CCAF and 10% of CCAF-related CCA. BAF250a-deficient expression was significantly more frequent in endometriosis-related CCA compared with that in CCAF-related CCA (P=0.02). No significant difference was observed in the response rate of primary chemotherapy according to BAF250a expression status (P=0.48). Additionally, BAF250a expression status was not significantly correlated with progression-free and overall survival in patients with CCA. Although loss of BAF250a expression was associated with early tumorigenesis in endometriosis-related CCA, this alteration was not significantly correlated with chemosensitivity and prognoses of CCA. Further biomarker analyses, including BAF250a expression, are required to improve the prognoses of CCA.

7.
Oncology ; 90(4): 179-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26986224

RESUMO

OBJECTIVE: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. METHODS: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. RESULTS: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. CONCLUSION: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas.


Assuntos
Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Estudo Historicamente Controlado , Humanos , Histerectomia/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
8.
Cardiovasc Interv Ther ; 30(1): 72-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24566833

RESUMO

Although percutaneous transluminal septal myocardial ablation (PTSMA) has been the established treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), the efficacy for specific HOCM is not elucidated. We report a successful case of PTSMA for heart failure with severe left ventricular outflow tract (LVOT) obstruction due to sigmoid-shaped interventricular septum and diffuse left ventricular hypertrophy with Mönckeberg's arteriosclerosis and aortic valvular stenosis. While the PTSMA relieved LVOT obstruction and symptoms in the acute phase, the modest recurrence was confirmed 6 months later, which is rare in the case of idiopathic HOCM. The possible mechanisms of LVOT obstruction and recurrence are discussed.


Assuntos
Técnicas de Ablação/métodos , Estenose da Valva Aórtica/cirurgia , Cardiomiopatia Hipertrófica/complicações , Insuficiência Cardíaca/cirurgia , Esclerose Calcificante da Média de Monckeberg/complicações , Obstrução do Fluxo Ventricular Externo/complicações , Cardiomiopatia Hipertrófica/cirurgia , Angiografia Coronária , Ecocardiografia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Obstrução do Fluxo Ventricular Externo/cirurgia
9.
J Gynecol Oncol ; 26(1): 40-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25310854

RESUMO

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.


Assuntos
Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias do Endométrio/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina Trifosfatases/deficiência , Adenosina Trifosfatases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Enzimas Reparadoras do DNA/deficiência , Proteínas de Ligação a DNA/deficiência , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/deficiência , Proteína 2 Homóloga a MutS/metabolismo , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/deficiência , Proteínas Nucleares/metabolismo , Prognóstico , Estudos Retrospectivos
10.
Can Urol Assoc J ; 8(9-10): E644-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25295138

RESUMO

A 72-year-old man diagnosed with hydronephrosis and perinephric abscess because of an impacted urinary stone in the left uretero-pelvic junction was admitted to hospital with high-grade fever. The insertion of a percutaneous drain improved his general condition. Then, imaging from the percutaneous drainage tube revealed a fistula formation between the cavity of the perinephric retroperitoneal abscess, the descending colon, and the left renal pelvis. The patient received conservative management, including insertion of a percutaneous drain, discontinuation of oral intake and antimicrobial chemotherapy. Three days after the percutaneous drainage and discontinuation of oral intake, imaging revealed no apparent fistula. Fistula formation between a perinephric abscess and the descending colon is very rare; this is the first case of a long-term favourable outcome by conservative management.

11.
J Gynecol Oncol ; 24(1): 37-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23346312

RESUMO

OBJECTIVE: Compared with serous adenocarcinoma (SAC), clear cell carcinoma (CCC) often shows chemo-resistance, which would potentially lead to a poor prognosis. On the other hand, there have been arguments over prognoses of CCC and SAC disease. In the present study, multivariate analysis to compare prognosis of CCC patients with that of SAC was aimed for the patients selected from central pathologic review. METHODS: Between 1984 and 2009, a total of 500 ovarian cancer patients were treated at our university hospital. Among them, 111 patients with CCC and 199 patients with SAC were identified through central pathological review. Overall survival and progression-free survival were compared using Kaplan-Meier method, and prognostic factors were investigated by multiple regression analyses. RESULTS: Median age was 52 years for CCC and 55 years for SAC (p=0.03). The ratio of stage I patients were significantly higher in CCC compared with SAC (55% vs. 13%, p<0.01). Among evaluable cases, response rate was significantly lower in CCC than that in SAC (32% vs. 78%, p<0.01). No significant differences of progression-free survival and overall survival were observed in stage I patients; however, prognoses of CCC were significantly poorer than those of SAC in advanced-stage disease. In stage II-IV patients, not only residual tumors and clinical stages, but also clear cell histology were identified as predictors for poor prognosis. CONCLUSION: Clear cell histology was identified as a prognostic factor for advanced-stage ovarian cancers. Histologic subtypes should be considered in further clinical studies, especially for advanced epithelial ovarian cancers.

13.
Oncol Lett ; 4(5): 883-888, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23162616

RESUMO

The aim of this study was to evaluate the outcomes of patients with a gynecological malignancy who received palliative care with and without surgical procedures for malignant bowel obstruction (MBO) and to explore prognostic factors to aid the selection of patients who would benefit from palliative surgery. Medical records of patients with MBO due to a gynecological malignancy treated at our institute between 2005 and 2010 were reviewed. Successful palliation following surgery was defined as the ability to tolerate solid food for at least 60 days. Clinical variables were analyzed using Chi-square or Fisher's exact tests. Survival was evaluated using the Kaplan-Meier method and log-rank test. A total of 53 cases were identified; 20 had bowel surgery for MBO as a palliative procedure and 33 did not. Colostomy was performed in 11 (55%) of 20 patients and ileostomy was performed in 7 (35%). The postoperative morbidity was 35% and mortality within 30 days was 5%. Successful palliation following surgery was achieved in 14 (70%) of 20 cases with a median period of 146 days (range, 61-294). Survival following the diagnosis of MBO was longer in cases with surgery than those without (median survival time, 146 versus 69 days; P<0.0001). Although age, presence of ascites, laboratory values and types of prior anticancer therapy were not significantly different, a longer interval from last anticancer therapy to diagnosis of MBO was observed in patients who underwent surgery compared with those who did not (median, 57 versus 30 days; P<0.05), as well as superior performance status. Among the patients with surgery, the interval was also longer in patients with successful palliation compared with those without (median, 83 versus 32 days; P<0.05). The palliative benefit of surgery for MBO in selected patients with gynecological malignancy was observed. The interval from last anticancer therapy to diagnosis of MBO may serve as a prognostic factor when considering surgical intervention.

14.
Am J Cardiol ; 110(9): 1282-9, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22835413

RESUMO

The aim of this study was to evaluate the 5-year clinical outcomes of patients who underwent sirolimus-eluting stent implantation for chronic total occlusion (CTO). Among 10,759 patients treated exclusively with sirolimus-eluting stent in the j-Cypher registry, clinical outcomes were compared between 1,210 patients with revascularization for CTO and 9,549 patients with revascularization for non-CTO only. The cumulative 5-year incidence of all-cause death (13.2% vs 14.3%, p = 0.56) and definite stent thrombosis (1.9% vs 1.6%, p = 0.76) was similar between the 2 groups. The adjusted risk for CTO relative to non-CTO for all-cause death and definite stent thrombosis was insignificant (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.81 to 1.16, and HR 0.99, 95% CI 0.6 to 1.65, respectively). The cumulative incidence of target lesion revascularization was significantly higher in the CTO group (20.7% vs 14.8%, p <0.001). The adjusted risk for target lesion revascularization was significant (HR 1.31, 95% CI 1.13 to 1.52, p <0.001). In the subgroup analysis, the risk for CTO for all-cause death tended to be lower in the subgroup of patients with left ventricular ejection fractions ≤40% (HR 0.68, 95% CI 0.45 to 1.01, p = 0.053), while the risk was significantly higher in the subgroup of patients with end-stage renal disease without hemodialysis (HR 1.66, 95% CI 1.02 to 2.70, p = 0.04). In conclusion, sirolimus-eluting stent implantation for CTO appears to be as safe as that for non-CTO for up to 5 years, except for the modestly elevated risk for target lesion revascularization and the higher risk for all-cause death in patients with end-stage renal disease without hemodialysis.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Oclusão Coronária/mortalidade , Oclusão Coronária/terapia , Reestenose Coronária/terapia , Stents Farmacológicos/estatística & dados numéricos , Sirolimo/administração & dosagem , Idoso , Angioplastia Coronária com Balão/métodos , Angioplastia Coronária com Balão/mortalidade , Causas de Morte , Doença Crônica , Estudos de Coortes , Intervalos de Confiança , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/mortalidade , Stents Farmacológicos/efeitos adversos , Feminino , Mortalidade Hospitalar/tendências , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Prognóstico , Sistema de Registros , Retratamento/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
15.
Int J Gynecol Pathol ; 31(3): 254-63, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22498943

RESUMO

Ovarian clear-cell adenocarcinoma (CCA) is known to be a type of cancer in humans with a high frequency of expression of the mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 (HIF-1), and glucose transporter 1 (Glut1). In this study, we aimed to determine how these alterations contribute to tumor development of CCAs. Immunohistochemical expressions of phosphorylated-mTOR (p-mTOR), HIF-1α, and Glut1 were analyzed in 36 CCAs and 60 coexistent putative precursor lesions: 19 nonatypical and 16 atypical endometriotic lesions, and 11 benign and 14 borderline clear-cell adenofibroma (CCAF) components. Twenty-one cases with solitary endometriosis were also examined. The frequencies of immunopositivity for p-mTOR (in cytoplasm or nucleus), HIF-1α (in nucleus), and Glut1 increased in accordance with higher cytological atypia in the putative precursors: 58%, 5%, and 16% in the nonatypical endometriosis; 63%, 37%, and 50% in the atypical endometriosis; 77%, 95%, and 95% in the endometriosis-associated CCAs; 27%, 0%, and 0% in the benign-CCAF components; 64%, 79%, and 43% in the borderline CCAF components; and 71%, 100%, and 93% in the CCAF-associated CCAs, respectively. p-mTOR, HIF-1α (in the nucleus), and Glut1 were positive in 10%, 5%, and 19% of the solitary endometriosis, respectively. In the putative precursor lesions coexisting with CCA, a strong correlation in the expression between p-mTOR and HIF-1α and between HIF-1α and Glut1 was identified. Expressions of p-mTOR, HIF-1α, and Glut1 have already been evident in the putative precursor lesions of CCA, and these alterations cumulatively occur in the development of ovarian CCA.


Assuntos
Adenocarcinoma de Células Claras/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Ovarianas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenofibroma/metabolismo , Adenofibroma/patologia , Biomarcadores Tumorais/metabolismo , Endometriose/metabolismo , Endometriose/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
16.
Gan To Kagaku Ryoho ; 38(11): 1837-40, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22083192

RESUMO

Among the 161 cases of pT1 ovarian cancer treated at our hospital during the last 25 years, the impact of systematic lymphadenectomy was evaluated in 93 cases of the pT1N0M0 group(N0 group), 59 cases of the pT1NxM0(Nx group), and 9 cases of the pT1N1M0(N1 group). Significantly greater relapse-free survival(RFS)and overall survival(OS)were observed in 108 cases of the N0+N1 group compared to the Nx group(p=0. 006, p=0. 02). Multivariate analysis showed that systematic lymphadenectomy was a significant prognostic factor(hazard ratio 0. 473(95%CI, 0. 235-0. 951; p=0. 036). The present study suggested the systematic lymphadenectomy had a significant therapeutic effect on pT1 stage ovarian cancers.


Assuntos
Excisão de Linfonodo , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
Gynecol Oncol ; 122(2): 233-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21601912

RESUMO

OBJECTIVES: Currently, pegylated liposomal doxorubicin (PLD) is regarded as one of the standard treatment options in recurrent ovarian cancers (ROC). Bevacizumab has shown significant antitumor activity for ROC in single-agent or in combination with cytotoxic agents. We have conducted a preliminary study to investigate effects of combination of bevacizumab and PLD for heavily pretreated patients with ROC. METHODS: Thirty patients with ROC were treated with combination therapy with weekly bevacizumab and PLD, 2 mg/kg of continuous weekly bevacizumab and 10 mg/m(2) of PLD (3 weeks on, 1 week off). The treatment was continued until development of disease progression, or unmanageable adverse effects. Response evaluation was based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and Gynecologic Cancer Intergroup (GCIG) CA125 response criteria. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. RESULTS: Overall response rate was 33%, and clinical benefit rate (CR+PD+SD) was 73%. Median progression-free survival was 6 months (range: 2-20 months), and a 6-months progression-free survival was 47%. Any hematological toxicities more than grade 3 were not observed. Two cases developed non-hematologic toxicities more than grade 2; a case with grade 3 hand-foot syndrome, another with grade 3 gastrointestinal perforation (GIP). The case with GIP was conservatively treated and recovered after 2 months, and there was no case with treatment-related death. CONCLUSION: The present investigation suggested that combination therapy with bevacizumab and PLD was active and well tolerated for patients with ROC. We recommend the regimen be evaluated in further clinical studies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos
18.
Masui ; 60(4): 465-9, 2011 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-21520597

RESUMO

We report a late thrombosis of sirolimus-eluting stent 6 months after implantation of a drug-eluting stent. A 70-year-old man (52 kg, 148 cm) was diagnosed as acute cauda equina syndrome, and spinal surgery was scheduled. One week before the operation, the patient's aspirin and clopidogrel regimen was replaced with heparin injection, which was then discontinued 8 hours before the operation. The operation was completed uneventfully. The patient complained of severe chest pain 1 hour after the end of operation. Coronary angiography demonstrated stent thrombosis. PCI (removal of the thrombosis and plain old balloon angioplasty) was performed, and incomplete stent apposition was diagnosed with coronary angiography.


Assuntos
Stents Farmacológicos/efeitos adversos , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Trombose/etiologia , Idoso , Doença das Coronárias/terapia , Humanos , Masculino , Período Perioperatório , Polirradiculopatia/cirurgia , Fatores de Tempo
19.
Int J Gynecol Cancer ; 21(2): 263-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21270609

RESUMO

OBJECTIVE: Although treatment for recurrent epithelial ovarian, tubal, and peritoneal cancers is usually not curative and intends to be palliative, a certain significance of secondary cytoreductive surgery (SCS) for recurrent tumor has been reported; still, there are limitations in this strategy including difficulty in predicting successful complete resection and selecting good candidates. The purpose of this study was to explore the potential survival benefit of SCS in patients with recurrent epithelial ovarian, tubal, and peritoneal cancers. METHODS: Among all patients who underwent primary therapy for epithelial ovarian, tubal, and peritoneal cancers between 1994 and 2006 at our institute, medical records of patients who were submitted to SCS for recurrence following complete remission after primary therapy were retrospectively investigated. Kaplan-Meier method and log-rank test were used for survival analysis, and Cox proportional hazard regression model was used for quantifying the relations between survival and covariates. RESULTS: Thirty-four patients met the inclusion criteria. Complete resection of all visible tumors at SCS was achieved in 24 of patients (75%). Median postrecurrence survival was 60 months. On univariate analysis, solitary recurrence, disease-free interval, CA125 value at recurrence, and complete resection were significant prognostic factors on postrecurrence survival; whereas on multivariate analysis, CA125 value at recurrence and complete resection were independent prognostic factors. In addition, a comparison according to the initial method that detected recurrence revealed that patients whose recurrence was detected with CA125 elevations had significantly worse postrecurrence survival than those detected with routine examinations including image scans (P = 0.021). CONCLUSIONS: In the present study, the impact of SCS on the significant survival benefit was identified for patients with low CA125 value at recurrence as well as with complete resection. Although further analyses are needed, patients whose recurrence was diagnosed by routine examinations without CA125 elevation might be better candidates for SCS.


Assuntos
Neoplasias das Tubas Uterinas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Idoso , Antígeno Ca-125/sangue , Neoplasias das Tubas Uterinas/sangue , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Ovarianas/sangue , Neoplasias Peritoneais/sangue , Estudos Retrospectivos , Análise de Sobrevida
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