RESUMEN
From the viewpoint of self-medication, it is valuable to develop patient-friendly scored tablets that possess dividing uniformity. In this context, we attempted to optimize the preparation conditions for a tablet with a unique shape, such as a concavely curved scored tablet (CCST). Employing a design of experiment and a response surface method incorporating a thin-plate spline interpolation, and a bootstrap resampling technique, the optimal preparation conditions for CCST were successfully developed. To make it possible to scaleup the optimal solution estimated on a trial-scale, a Bayesian estimation was applied. Credible ranges of critical responses in large-scale manufacturing were estimated as a posterior probability from the trial-scale experiment as a prior probability. In terms of the large-scale manufacturing, the possibility of solving the scaleup problem was suggested using Bayesian estimation. Furthermore, a simulation study using a finite element method revealed that strong tensile stresses generated along the tip of the score line in CCST when an outer force was applied to the back surface of CCST. An advantage in dividing uniformity is indicated by the unique shape of CCST.
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Comprimidos/química , Teorema de Bayes , Química Farmacéutica , Humanos , Modelos Químicos , Solubilidad , Propiedades de Superficie , Comprimidos/farmacología , Resistencia a la TracciónRESUMEN
INTRODUCTION: The Public Health Center (PHC)-known as hokenjo in Japan-assume a crucial role in disease control. Coronavirus disease 2019 (COVID-19) is one of many designated infectious diseases monitored by the agency. During the present pandemic, patients who suspected COVID-19 were instructed to call the Coronavirus Consultation Center in the PHC prior to visiting the hospital. The aim of this study was to elucidate the differences in polymerase chain reaction (PCR) positivity between PHC referrals and direct walk-in patients. METHODS: The present was a single-center, retrospective cohort study conducted at the Tokyo Metropolitan Hospital from March to September, 2020. Patients who received a PCR test for SARS-CoV-2 were included and categorized into the PHC referral or direct walk-in groups. The outcomes included the total number of patients undergoing PCR tests and the percentage of PCR positivity in each group. RESULTS: We identified 1680 patients (781 PHC referred and 899 direct walk-in groups). The percentage of PCR positivity did not significantly differ between the PHC referral and direct walk-in groups during the first wave (30.5% vs. 29.2%; p = 0.78). PCR positivity was significantly higher in the PHC referral group than the direct walk-in group during the second wave (30.1% vs. 23.1%; p = 0.051) and entire study period (30.2% vs. 24.7%; p = 0.011). CONCLUSIONS: Despite health authority recommendations, the number of direct walk-in patients were higher than PHC referral patients. The percentage of PCR positivity was significantly higher in the PHC referral group than in the direct walk-in group.
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Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Derivación y Consulta , Adulto , Anciano , COVID-19/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Pública , Estudios Retrospectivos , SARS-CoV-2 , TokioRESUMEN
Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m2 ), 262 (64.5%); overweight (≥25 to <30 kg/m2 ), 75 (18.5%); and obese (≥30.0 kg/m2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.
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Índice de Masa Corporal , Linfoma de Células B Grandes Difuso/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores SexualesRESUMEN
No standard therapy for peripheral T-cell lymphomas (PTCLs) has been established, and treatment outcomes are poor. Upfront stem cell transplantation has been investigated in several studies, some of which have reported promising outcomes. However, some patients maintain long-term remission after chemotherapy alone. It is thus important to predict sensitivity to first-line chemotherapy to optimize treatment strategies. In the present study, we retrospectively analyzed time to treatment failure (TTF) of first-line chemotherapy in 59 patients with PTCLs. On multivariate analysis for TTF, elevated lactate dehydrogenase level, hypoalbuminemia, and high neutrophil-to-lymphocyte ratio were significant prognostic factors. Using these three factors, we also developed a new model that effectively distinguished patient outcomes. The TTF rate at 1 year from diagnosis was 71.4% in patients with score 0 (0 factor), 31.8% with score 1 (1 factor) and 4.5% with score 2 (2-3 factors) (P < 0.001). The prognostic power was superior to that of the Prognostic Index for PTCL-unspecified score. Patients with scores of 1 and 2 had poor TTF, and may be candidates for upfront stem cell transplantation if they respond to first-line chemotherapy. Further investigation in a larger cohort is warranted to determine the general applicability of this score.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , L-Lactato Deshidrogenasa/sangre , Linfocitos/fisiología , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamiento farmacológico , Neutrófilos/patología , Albúmina Sérica , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos , Humanos , Linfoma de Células T Periférico/sangre , Linfoma de Células T Periférico/patología , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Prednisolona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
Positron emission tomography-computed tomography (PET-CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET-CT. We validated the prognostic value of CR by PET-CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and cell of origin (COO) to patients with CR by PET-CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET-CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET-CT and 71 patients by CT only. Patients with CR by PET-CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN-IPI had a dismal outcome despite achieving CR by PET-CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET-CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET-CT was a better predictor of survival outcomes than CR by CT only. The NCCN-IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET-CT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/metabolismo , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.
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Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Microglobulina beta-2/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Prednisona/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Rituximab , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p=0.010) of MDA-MB-231 cells and an equivalent detection rate (p=0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p=0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC+ and CTC- was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p=0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p=0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Estudios de Casos y Controles , Recuento de Células , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Resultado del TratamientoRESUMEN
Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level <3.2 mg/L, number of extranodal sites >1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted.
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Encéfalo/patología , Linfoma de Células B Grandes Difuso/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos Biológicos , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Recurrencia , Espacio Retroperitoneal , Estudios Retrospectivos , Factores de Riesgo , Rituximab/administración & dosificación , Albúmina Sérica/análisis , Resultado del Tratamiento , Vincristina/administración & dosificaciónAsunto(s)
Lactato Deshidrogenasas/sangre , Linfoma de Células B Grandes Difuso/diagnóstico , Evaluación del Resultado de la Atención al Paciente , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/análisis , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica , Proteína C-Reactiva/análisis , Ciclofosfamida , Doxorrubicina , Femenino , Humanos , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prednisona , Pronóstico , Proyectos de Investigación , Rituximab , Análisis de Supervivencia , VincristinaRESUMEN
Methods for the enumeration and molecular characterization of circulating tumor cells (CTC) have been actively investigated. However, such methods are still technically challenging. We have developed a novel epithelial cell adhesion molecule independent CTC enumeration system integrated with a sorting system using a microfluidics chip. We compared the number of CTC detected using our system with those detected using the CellSearch system in 46 patients with various cancers. We also evaluated epidermal growth factor receptor (EGFR) and PIK3CA mutations of captured CTC in a study of 4 lung cancer and 4 breast cancer patients. The percentage of samples with detected CTC was significantly higher with our system (65.2%) than with CellSearch (28.3%). The number of detected CTC per patient using our system was statistically higher than that using CellSearch (median 5, 0; P = 0.000172, Wilcoxon test). In the mutation analysis study, the number of detected CTC per patient was low (median for lung, 4.5; median for breast, 5.5); however, it was easy to detect EGFR and PIK3CA mutations in the CTC of 2 lung and 1 breast cancer patient, respectively, using a commercially available kit. Our system is more sensitive than CellSearch in CTC enumeration of various cancers and is also capable of detecting EGFR and PIK3CA mutations in the CTC of lung and breast cancer patients, respectively.
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Células Neoplásicas Circulantes , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Estudios de Casos y Controles , Recuento de Células , Línea Celular Tumoral , Separación Celular , Fosfatidilinositol 3-Quinasa Clase I , Análisis Mutacional de ADN , Receptores ErbB/genética , Femenino , Citometría de Flujo , Humanos , Dispositivos Laboratorio en un Chip , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/genética , Eliminación de SecuenciaRESUMEN
Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases and is a highly lethal disease. For the last several decades, the standard treatment for SCLC has been deadlocked, and new therapeutic strategies are urgently needed. HER2 is a member of the HER family and has been reported to be overexpressed in 30% of SCLC cases with poor prognosis. However, the clinical relevance of HER2-targeted therapy for SCLC remains unclear. Here, we first identify that cytotoxic drugs induce significant HER2 overexpression through microRNA-125a (miR-125a) and miR-125b downregulation, which in turn act as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in SCLC. In this study, we showed that treatment of the HER2-positive SCLC cells, SBC-3 and SBC-5, with cytotoxic drugs induced a significant upregulation of HER2. Cisplatin (CDDP) treatment of SCLC cells resulted in a significant downregulation of miR-125a and miR-125b. We confirmed that miR-125a and miR-125b bound to the 3'-untranslated regions of HER2 mRNA, and that downregulation of miR-125a and miR-125b resulted in upregulation of HER2 in SCLC cells, suggesting a relationship between cytotoxic drug exposure and miR-125/HER2 dysregulation. Furthermore, using a calcein assay, we demonstrated a significantly enhanced cytotoxic effect of CDDP and trastuzumab that was mediated via antibody-dependent cellular cytotoxicity. Finally, we clearly demonstrated the enhanced antitumor effect of these agents in an orthotopic lung cancer model in vivo. Our results offer a novel therapeutic strategy for HER2-positive SCLCs by using trastuzumab combined with cytotoxic drugs.
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Neoplasias Pulmonares/tratamiento farmacológico , MicroARNs/genética , Receptor ErbB-2/genética , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Trastuzumab/farmacología , Regiones no Traducidas 3'/genética , Animales , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Immunoblotting , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Masculino , Ratones SCID , MicroARNs/metabolismo , Receptor ErbB-2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Trastuzumab/administración & dosificación , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Antineoplásicos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/prevención & control , Factores de RiesgoRESUMEN
BACKGROUND: Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. PATIENTS AND METHODS: We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS: The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. CONCLUSION: Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.
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Antineoplásicos/uso terapéutico , Citotoxinas/uso terapéutico , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Timoma/mortalidad , Neoplasias del Timo/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
This report describes a patient with intravascular large B-cell lymphoma (IVLBCL) with central nervous system involvement at the time of diagnosis who achieved complete remission for over 5 years in response to therapy. The patient, a 71 year-old woman, was previously healthy with the exception of taking verapamil for paroxysmal supraventricular tachycardia. She had presented with pyrexia and gradually progressive anemia. Brain magnetic resonance imaging revealed an infarct-like lesion in the pons, although no paralysis was observed. She was diagnosed with IVLBCL on the basis of random skin biopsy. After eight cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, abnormal laboratory data had normalized, and no pontine lesion was evident on magnetic resonance imaging without receiving any intrathecal chemotherapy. IVLBCL is associated with poor prognosis, particularly in patients with central nervous system involvement. Early initiation of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy and drug interactions between anticancer agents and verapamil as a p-glycoprotein inhibitor were considered the possible reasons for favorable outcome in the present case.
RESUMEN
BACKGROUND: Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features. Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation. METHODS: The study is a retrospective review of 187 Japanese patients with TETs who attended our institution from 1976 to 2012. Relevant clinical features of patients with TETs and their tumors, including histology, staging, treatment strategies, and overall survival, were investigated. Differences in survival were assessed by the Kaplan-Meier method and uni- and multi-variate Cox proportional hazards regression analyses. RESULTS: The 187 patients included 52 patients with stage I, 37 with stage II, 22 with stage III, and 76 with stage IVa/IVb tumors according to the Masaoka-Koga Staging System. As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification. Either insufficient data were available to classify the tumors of the remaining eight patients or they had rare types. Immunological abnormalities were present in 26 patients, most of whom had thymomas (21.8% of the thymoma group). Most of the patients who presented with symptoms had myasthenia gravis or extensive thymic carcinoma. Secondary cancers were present in 25 patients (13.3%). The overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%, respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively. OS differed significantly between stage IVa thymomas and thymic carcinomas. The stage and whether the tumors were thymomas or thymic carcinomas were significant determinants of survival according to multivariate analysis. CONCLUSION: The efficacy of treatments for thymoma and thymic carcinoma should be investigated separately because these tumors differ in their clinical features and prognosis.
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Carcinoma/patología , Neoplasias Glandulares y Epiteliales/patología , Timoma/patología , Neoplasias del Timo/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/terapia , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Timoma/mortalidad , Timoma/terapia , Neoplasias del Timo/mortalidad , Neoplasias del Timo/terapia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The clinical significance of proteinuria has not been fully understood among patients who are affected with non-Hodgkin lymphoma (NHL). METHODS: A 1-year prospective cohort study was conducted to ascertain the association between proteinuria and mortality in 46 hospitalized NHL patients. Proteinuria was defined as persistent dipstick test >= 1+, and the urinary protein creatinine ratio (UPCR),as a quantitative index of protein excretion, was measured simultaneously. A multivariable linear regression model was constructed to determine factors associated with UPCR. Statistical associations between proteinuria and time to mortality were analyzed using the Kaplan-Meier method and multivariable proportional hazards regression analysis, adjusted for covariates including disease severity, renal function, and serum interleukin-6(IL-6) concentration. RESULTS: The prevalence of proteinuria was 15.2% in the NHL patients. UPCR was significantly associated with the serum IL-6 level (standardized beta = 0.360, p = 0.0440). The cumulative mortality was significantly higher in proteinuric patients than in non-proteinuric patients, with a graded relationship between the severity of UPCR and mortality. The mortality risk increased with increasing UPCR grade: the hazard ratio (95% confidence interval) was 4.90 (1.29 - 32.3) for UPCR 30 - 300 mg/gand 17.8 (2.84 - 150) for UPCR > 300 mg/g, respectively, when UPCR < 30 mg/g was set as the reference. CONCLUSIONS: Proteinuria is a simple sign of coexisting systemic inflammation due to NHL and a harbinger of a poor prognosis.
Asunto(s)
Inflamación/etiología , Linfoma no Hodgkin/complicaciones , Proteinuria/etiología , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biomarcadores/orina , Distribución de Chi-Cuadrado , Creatinina/orina , Femenino , Hospitalización , Humanos , Inflamación/diagnóstico , Inflamación/mortalidad , Mediadores de Inflamación/sangre , Interleucina-6/sangre , Japón , Estimación de Kaplan-Meier , Modelos Lineales , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteinuria/diagnóstico , Proteinuria/mortalidad , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Heterogenous clinical or biological features are characteristic of thymic carcinoma. Well-defined clinical entities remain unclear because of rarity. The aim of this study was to clarify disease profiles, outcomes, and prognostic factors for survival among patients diagnosed with thymic carcinoma. PATIENTS AND METHODS: A retrospective review was conducted of the medical records of 68 thymic carcinoma patients among 187 patients diagnosed with thymic epithelial tumors between 1980 and 2013 in our institution. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and uni- and multivariate Cox proportional hazards regression analyses. RESULTS: The study included 38 males (55.9%) and 30 females (44.1%). The median age at diagnosis was 63.5 years. The most common subtypes of thymic carcinoma were squamous cell carcinoma (69.1%), neuroendocrine carcinoma (16.2%), and mucoepidermoid carcinoma (5.9%). Masaoka-Koga staging of the 68 patients demonstrated no patients (0%) in Stage I, 3 (4.3%) in Stage II, 14 (20.6%) in Stage III, 12 (17.6%) in Stage IVa, and 39 (57.4%) in Stage IVb. The median survival time for all stages was 36.4 months (95% confidence interval 23.7-56.4); those for stages II, III, IVa, and IVb were: not reached, 65.8, 24.6, and 27.3 months, respectively. The difference by Masaoka-Koga staging was significant (p = 0.04). Overall survival rates at 1-, 5-, and 10-year were 76.3%, 36.0%, and 6.2%, respectively. By univariate analyses, the only favorable prognostic factor for overall survival was surgical intervention (p = 0.03), and, for Stage IVb, lymphatic metastasis without distant metastasis. However, clinically interesting variants did not differ significantly for predicting survival. CONCLUSION: Surgical intervention results in better survival of thymic carcinoma, even in Stage IVb. The survival value of administration of curative-intent radiotherapy, or of identification of "resectability" in Stage IVb patients must continue to be discussed.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias del Timo/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias del Timo/mortalidad , Neoplasias del Timo/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Cisplatino/administración & dosificación , Combinación de Medicamentos , Neoplasias Esofágicas/secundario , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Recurrencia , Neoplasias Gástricas/patología , Tegafur/administración & dosificaciónRESUMEN
BACKGROUND: The clinical characteristics and prognostic factors of thymic carcinoma have not been investigated in detail because of its rarity. The aim of this study was to elucidate the disease profile, outcomes, and prognostic factors for survival among patients with advanced thymic carcinoma treated with palliative-intent chemotherapy. PATIENTS AND METHODS: A retrospective review was conducted of the medical records of 40 patients treated with palliative-intent chemotherapy for advanced thymic carcinoma between 1991 and 2011 in our institution. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS: The study included 22 males (55.0%) and 18 females (45.0%). The median age at diagnosis was 58.5 years. The most common metastatic sites at diagnosis were lung (45.0%), lymph nodes (20.0%), liver (15.0%), bone (15.0%), and brain (5.0%). The most common histological subtypes were squamous cell carcinoma (70.0%), followed by neuroendocrine carcinoma (17.5%), and mucoepidermoid carcinoma (7.5%). The response rate for first-line chemotherapy was 47.5%. The median survival time was 24.5 months (95% confidence interval 20.9-43.5 months). Overall survival rates at 1-, 2-, and 5-years were 72.5%, 52.5%, and 17.5%, respectively. In uni- and multivariate analyses, the only favorable prognostic factor for overall survival was response to first-line chemotherapy (p=0.01). CONCLUSION: Response to first-line chemotherapy may be implicated as a potential surrogate for survival in advanced thymic carcinoma.