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1.
J Infect Chemother ; 30(7): 579-589, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38588797

RESUMEN

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.


Asunto(s)
Antibacterianos , Levofloxacino , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/epidemiología , Infecciones Urinarias/tratamiento farmacológico , Japón/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Levofloxacino/farmacología , Levofloxacino/uso terapéutico , Farmacorresistencia Bacteriana , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Femenino , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/aislamiento & purificación , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Monitoreo Epidemiológico , Pueblos del Este de Asia
2.
Int J Urol ; 30(3): 319-327, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36448526

RESUMEN

OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Índice de Masa Corporal , Neoplasias Renales/patología , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pronóstico
3.
Clin J Gastroenterol ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693425

RESUMEN

Von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder caused by a germline mutation, is associated with non-functional and slow-growing pancreatic neuroendocrine tumor (PNET) and kidney cancer. We describe the case of a 46 year-old man with a 35 mm mass in the pancreatic head causing stricture of the bile duct and main pancreatic duct, a 55 mm mass in the pancreatic tail causing obstruction of the splenic vein (SV), and multiple masses of > 36 mm on both kidneys. We performed a two-stage resection. First, a total pancreatectomy with superior mesenteric vein (SMV) resection and reconstruction and retroperitoneoscopic right partial nephrectomy (NP) for five lesions was performed, followed by retroperitoneoscopic left partial NP of the five lesions 6 months later. Postoperative histopathological examination revealed NET G2 in the pancreatic head with SMV invasion and somatostatin receptor type 2A (SSTR2A) positivity, NET G2 in the pancreatic tail showed SV invasion and negative SSTR2A, and multiple clear cell renal cell carcinomas (RCC) were also noted. Multiple liver recurrences occurred 22 months after primary surgery. The patient remains alive 41 months after primary surgery. Kidney cancer generally determines VHL prognosis; however, we experienced dual-advanced PNETs with a more defined prognosis than multiple RCC associated with VHL.

4.
Curr Urol ; 17(1): 52-57, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37692134

RESUMEN

Objectives: This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma. Marterials and methods: Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied. Patients who were treated with nivolumab as second-line therapy were included in the second-line group, while the others were included in the later-line group. The clinicopathological characteristics, effects of nivolumab, and prognoses of these groups were compared. Results: Twenty and thirty-eight patients were included in the second-line and later-line groups, respectively. There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups. The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group (15% vs. 50%, p = 0.0090). The 50% progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group (not reached and 5 months, p = 0.0018). Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival (p = 0.0028, hazard ratio = 0.108). The 50% overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months, respectively (p = 0.2652). Conclusions: The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

5.
Gan To Kagaku Ryoho ; 39(9): 1443-5, 2012 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-22996788

RESUMEN

Were port a 51-year-old male left renal pelvic cancer patient with paclitaxel (PTX)-induced peripheral neuropathy, which was successfully treated with pregabalin. From June 2010, a gemcitabine/PTX (GP) regimen was used as third-line treatment. In order to relieve the PTX-induced peripheral neuropathy, pregabalin (75mg/day, at night) was administered from day 6 of the 16th course. Moreover, pregabalin was increased to 150mg/day from day 12 of the course. Sensory neurotoxicity after the administration of pregabalin was decreased from CTCAE (version 4. 0) grade 3 to 1 at day 19 of the course. Therefore, there is a possibility that the PTX -induced peripheral neuropathy may be improved by pregabalin administration. Further trials may be needed to confirm the value of pregabalin.


Asunto(s)
Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ácido gamma-Aminobutírico/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Pregabalina , Ácido gamma-Aminobutírico/uso terapéutico
6.
Nihon Hinyokika Gakkai Zasshi ; 113(2): 56-62, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-37081653

RESUMEN

(Objectives)The usefulness of partial nephrectomy for renal tumors has been highlighted in various guidelines. Since 2006, we have been actively performing laparoscopic partial nephrectomy for renal tumors. We investigated the postoperative recurrence of renal tumors diagnosed as renal cell carcinoma after laparoscopic partial nephrectomy. (Patients and methods)From August 2006 to March 2020, 320 patients who underwent laparoscopic partial nephrectomy at our hospital and were pathologically diagnosed with renal cancer were included. A retrospective statistical study was conducted to analyze the postoperative recurrence. (Results)Postoperative recurrence was observed in 11 patients (3.4%). The median time to recurrence was 12 months (3-26 months), non-distant metastasis was observed in four cases (1.3%), and distant metastasis was observed in seven cases (2.2%). No statistically significant difference was found in the factors related to recurrence, in this study. (Conclusions)In this study, no statistically significant factors were found, but the higher the clinical stage, the higher the recurrence rate.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Nefrectomía/métodos , Laparoscopía/métodos , Recurrencia Local de Neoplasia/cirugía , Resultado del Tratamiento
7.
Int Urol Nephrol ; 54(6): 1225-1232, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35314918

RESUMEN

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate prognostic factors and to establish a prognostic model using them for upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). MATERIALS AND METHODS: Two hundred eleven patients who were diagnosed as mRCC at initial diagnosis and were treated with TKI and/or ICI were classified into 2 groups: those undergoing CN (upfront CN group, 117 cases) and those who initially underwent systemic therapy (non-upfront CN group, 94 cases). In the upfront CN group, the patients' background and overall survival (OS) were compared with those in the other two groups, and prognostic factors were analyzed. A prognostic model of the upfront CN group was established. RESULTS: The median of the observation period for the upfront CN group was 25 months. The rates of patients with clear cell histology, with a Karnofsky performance status (KPS) of ≥ 80%, with a single metastatic organ, with a normal pretreated C-reactive protein level, and with an intermediate risk according to the International mRCC Database Consortium (IMDC) model were significantly higher than those in the non-upfront CN group (87.2% and 30.9%, p < 0.0001; 92.3% and 77.7%, p = 0.0025; 41.9% and 24.5%, p = 0.0080; 47.9% and 13.8%, p < 0.0001; 66.7% and 45.7%, p = 0.0023, respectively). The 50% OS in the upfront CN group was 33.1 months, significantly better than that in the non-upfront CN group (11.1 months, p < 0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and a KPS of < 80% were independent predictive factors for OS (hazard ratio: 1.653 and 2.995, p = 0.0339 and 0.0054, respectively). Using these two parameters to stratify the upfront CN group, the 50% OSs in cases with no risk factors, in those with one factor, and in those with two factors were 43.4 months, 29.1 months, and 7.7 months, respectively (p < 0.0001). CONCLUSION: The upfront CN group was able to be stratified by our prognostic model into three subgroups with different prognoses. This model can provide useful information for making decisions in consideration of upfront CN in patients with mRCC.


Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Masculino , Nefrectomía/métodos , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
8.
Urol Oncol ; 40(10): 455.e11-455.e18, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35851184

RESUMEN

INTRODUCTION AND OBJECTIVES: Intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria is thought to consist of patients with different prognoses. This study investigated the impact of a pretreated modified Glasgow prognostic score (mGPS), which is defined on the basis of the pretreated serum albumin and C-reactive protein level, on predicting the prognosis of patients with metastatic renal cell carcinoma (mRCC) and its usefulness for the re-stratification of patients into a more improved risk model. MATERIALS AND METHODS: One hundred ninety-six mRCC patients treated with first-line tyrosine kinase inhibitor (TKI) were retrospectively investigated. All patients were classified into either a high-mGPS or a low-mGPS group on the basis of mGPS score upon starting systemic therapy, the overall survival (OS) and cancer specific survival (CSS) rates in each group were compared. We use decision curve analysis and calculate C-index based on OS and CSS to compare IMDC+mGPS model and IMDC model. RESULTS: The categories of favorable, intermediate, and poor risk groups in the IMDC model were assessed in 32, 113, and 51 cases, respectively. The low- and high-mGPS groups consisted of 149 and 47 cases. The median OS in the high- and low-mGPS groups were 38.4 months and 5.6 months, and their median CSSs were 41.0 months and 5.6 months, respectively (P < 0.0001). Multivariate analysis showed that a high mGPS, multiple metastatic organs, and hypercalcemia were independent predictive factors for a worse OS (P = 0.0260). Next, we divided the intermediate risk group into two subgroups using the mGPS score. The OS and CSS for the high-mGPS subgroup were significantly worse than those for the low-mGPS one (P = 0.0024, median OS: 21.0 months and 33.7 months, P = 0.0007, median CSS: 21.0 months and 39.8 months), and there was no significant difference in OS between the high-mGPS subgroup in the intermediate risk group and poor risk group (P = 0.2250). The value of C-index based on OS at IMDC and IMDC+mGPS model were 0.6771 and 0.6967, and those based on CSS were 0.6850 and 0.7080, respectively. In decision curve analysis to evaluate the clinical net benefit using the IMDC+mGPS model compared to the IMDC model, there was no significant difference between the two groups. CONCLUSION: mGPS is useful for establishing a more improved prognostic model that is able to stratify mRCC patients treated with first-line TKI.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Proteína C-Reactiva/metabolismo , Carcinoma de Células Renales/patología , Humanos , Neoplasias Renales/patología , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Albúmina Sérica
10.
Curr Urol ; 15(4): 187-192, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35069080

RESUMEN

BACKGROUND: There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI. MATERIALS AND METHODS: A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed. RESULTS: Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively. CONCLUSIONS: Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

11.
Anticancer Res ; 41(10): 4875-4883, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34593435

RESUMEN

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study aimed to examine the role of CD44 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analyzed the effect of CD44 knockdown on sunitinib resistance in RCC cell lines using WST-1 assays. CD44 expression in mRCC patients treated with first-line sunitinib was determined by immunohistochemistry. We validated the findings of this study by in silico analysis. RESULTS: CD44 knockdown increased sensitivity to sunitinib. Immunohistochemical analysis revealed that 19 (34.5%) of 55 mRCC cases were positive for CD44. CD44-positive cases were associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, high CD44 expression was significantly associated with poor PFS after sunitinib but not after avelumab + axitinib therapy. CONCLUSION: CD44 is involved in sunitinib resistance and may be a promising marker for sunitinib treatment in mRCC.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Renales/mortalidad , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Neoplasias Renales/mortalidad , Sunitinib/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Estudios de Seguimiento , Humanos , Receptores de Hialuranos/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas
12.
Anticancer Res ; 41(9): 4287-4294, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475048

RESUMEN

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study examined the potential role of p53 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analysed the effects of p53 knockout on sunitinib resistance. p53 expression in 53 mRCC patients receiving first-line sunitinib was determined immunohistochemically. We performed in silico analysis to examine the predictive value of p53 in mRCC. RESULTS: WST-1 assays showed that p53 knockout decreased sensitivity to sunitinib. Sunitinib and nutlin-3 together suppressed cell growth. Immunohistochemistry revealed 11 p53-positive cases among 53 patients with mRCC. Kaplan-Meier analysis showed that p53-positive cases tended to be associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, TP53 mutation was significantly associated with poor PFS after sunitinib treatment. CONCLUSION: p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Resistencia a Antineoplásicos , Imidazoles/farmacología , Neoplasias Renales/tratamiento farmacológico , Piperazinas/farmacología , Sunitinib/farmacología , Proteína p53 Supresora de Tumor/genética , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Proliferación Celular/efectos de los fármacos , Simulación por Computador , Sinergismo Farmacológico , Femenino , Técnicas de Inactivación de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/efectos de los fármacos
13.
Mol Clin Oncol ; 12(6): 557-564, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32337038

RESUMEN

The present study investigated the outcomes of targeted therapy for elderly patients with metastatic renal cell carcinoma (mRCC). A total of 277 patients with mRCC who were treated with tyrosine kinase inhibitor as a first-line therapy from January 2008 to May 2018 were retrospectively investigated by reviewing clinicopathological data. Patients 75 years or older were classified into the older-aged group (n=55) while all others were classified into the younger-aged group (n=222). The preoperative clinicopathological characteristics and the overall survival (OS) rate for these two groups were subsequently compared. The median age in the older- and younger-aged groups was 78 and 63 years (P<0.0001), respectively. A total of 7, 42 and 6 cases in the older-aged group and 46, 118 and 58 cases in the younger-aged group were classified into favorable, intermediate, and poor risk groups, respectively. The rate of patients with cardiovascular diseases (29.1%) and malignant diseases other than RCC (20.0%) was significantly higher in the older-aged group compared with the younger-aged group (6.8%; P<0.0001 and 7.2%; P=0.0042, respectively). There was a significant improvement in the OS rate for patients beginning targeted therapy after 2011 compared with those starting therapy prior to 2010. The 50% OS rate in patients starting targeted therapy before 2010 and after 2011 was, respectively, 17.1 and 38.6 months for the older-aged group (P=0.0066), while there was no significant difference for the younger-aged group (P=0.1441; 50% OS; 35.9 vs. 30.5 months). The results of the present study indicated that the prognosis for older patients has improved since the introduction of targeted therapy.

14.
Anticancer Res ; 40(4): 1943-1951, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234883

RESUMEN

BACKGROUND/AIM: Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC. MATERIALS AND METHODS: We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib. RESULTS: PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009). CONCLUSION: PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Fosfohidrolasa PTEN/genética , Sorafenib/farmacología , Sunitinib/farmacología , Biomarcadores de Tumor/genética , Sistemas CRISPR-Cas , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Inactivación de Genes , Humanos , Estimación de Kaplan-Meier , Masculino , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Esferoides Celulares/efectos de los fármacos
15.
Can Urol Assoc J ; 14(11): E582-E587, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32520703

RESUMEN

INTRODUCTION: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because many of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC, and its usefulness for re-classification of patients with a more sophisticated risk model. METHODS: From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared. RESULTS: The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively. CONCLUSIONS: The SII is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.

16.
Int Urol Nephrol ; 52(1): 77-85, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31552574

RESUMEN

PURPOSE: There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. METHODS: Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. RESULTS: Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. CONCLUSIONS: Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Adenocarcinoma/diagnóstico , Anciano , Anciano de 80 o más Años , Anilidas/uso terapéutico , Acetato de Clormadinona/uso terapéutico , Flutamida/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Nitrilos/uso terapéutico , Selección de Paciente , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Compuestos de Tosilo/uso terapéutico
17.
Urol Int ; 82(2): 162-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19322002

RESUMEN

INTRODUCTION: The purpose of this study is, using technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA), to evaluate the decrease of renal function caused by warm ischemia. PATIENTS AND METHODS: The (99m)Tc-DMSA scan was performed before and 1, 3 and 6 months after the operation for 19 consecutive patients. The patients were divided into three groups by warm ischemic time (group A: 40 min intersection 60 min). Renal function of the unresected part was defined as the uptake to unresected part relative to the uptake to the contralateral kidney. The reduction of renal function was expressed as a ratio of the function after the surgery divided by function before the surgery and was compared between the three groups. RESULTS: The reduction in group C after 1 and 3 months tended to be greater than that in group A or B, although not reaching statistical significance (one-way ANOVA test, 1 month: p = 0.15 and 3 months: p = 0.13). There was a significant difference in reduction of renal function between the three groups after 6 months (one-way ANOVA test, p = 0.02). The Scheffé test showed a statistical significance between groups A and C (p < 0.05). CONCLUSION: Renal function calculated by (99m)Tc-DMSA shows that prolonged ischemic time causes significant damage to the kidney.


Asunto(s)
Enfermedades Renales/diagnóstico por imagen , Pruebas de Función Renal , Neoplasias Renales/cirugía , Riñón/diagnóstico por imagen , Laparoscopía , Nefrectomía/métodos , Radiofármacos , Ácido Dimercaptosuccínico de Tecnecio Tc 99m , Isquemia Tibia/efectos adversos , Adulto , Anciano , Femenino , Humanos , Riñón/fisiopatología , Riñón/cirugía , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Cintigrafía , Factores de Tiempo , Resultado del Tratamiento
18.
Nihon Hinyokika Gakkai Zasshi ; 110(1): 1-11, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31956211

RESUMEN

(Objective) The aim of this study is to investigate the treatment outcome of laparoscopic radical prostatectomy (LRP). (Patients and methods) The study cohort consisted of 926 hormone-naïve patients with localized prostate cancer who underwent LRP at the Hiroshima Endourological Association from January 2007 to December 2016. (Results) The mean age was 69.4 years, the mean initial PSA was 9.1 ng/ml, and the mean follow-up period was 40.3 months. The D'Amico Risk Classification was Low: 232 cases, Intermediate: 344 cases, and High: 350 cases. Nerve preservation was performed bilaterally for 138 patients and unilaterally for 181 patients. The mean operative time was 181.0 minutes and the mean estimated blood loss was 360.7 ml. As the number of experienced cases increased, the operative time was significantly shorter and the estimated blood loss was significantly decreased. According to Clavien-Dindo classification, the ratio of perioperative complication degree IIIa or above was 4.0% (37 cases). The pathological results were Gleason score (GS) ≤6: 174 cases, GS7: 514 cases, GS ≥8: 232 cases, pT2≥: 704 cases, pT3a: 172 cases, pT3b: 47 cases, pT4: 3 cases, pN0: 917 cases, and pN1: 9 cases. Positive surgical margins were found in 278 cases (30.0%). The biochemical recurrence-free survival rate at 5 years was 78.1%. In multivariate analysis, age (≥70 yrs), initial PSA (≥10 ng/ml), biopsy GS (GS ≥8), cancer positive core ratio at biopsy (≥30%), pT (pT≥3), pathological GS (GS≥8), positive surgical margin and total number of patients in the facility were predictive factors of postoperative biochemical PSA recurrence. Younger age and nerve preservation were found to be predictive factors for the early recovery of urinary continence after surgery, with 88% regaining urinary continence at 12 months after surgery. (Conclusion) This study revealed the clinical outcome and appropriate candidates for LRP in Japanese patients.


Asunto(s)
Laparoscopía/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Factores de Edad , Anciano , Estudios de Seguimiento , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tasa de Supervivencia , Resultado del Tratamiento
19.
J Sex Med ; 5(12): 2808-15, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18823317

RESUMEN

INTRODUCTION: Some Japanese women are known to have negative attitudes toward erectile dysfunction (ED) drugs, but the environment underlying these perceptions is unclear. AIM: To reveal the underlying environment that shapes women's perceptions of ED drugs in Japan. METHODS: A web-based questionnaire was conducted through an Internet-based market research company. A total of 2,593 women in five age groups (20s, 30s, 40s, 50s, and 60s or older) were randomly invited to participate in this study, with an almost equal number in each age group. The questionnaire contained 30 items related to individual background and sexual information, concerns about the image of ED drugs, ED drug-related perceptions, and attitude toward sexual information media. MAIN OUTCOME MEASURES: The women's attitude and the independent predictors that affect their partner's use of ED drugs were clarified. RESULTS: Answers were obtained from 1,077 women, of whom 35.4% (n=381) had a negative image of ED drugs. Although 69.5% (n=749) agreed that a sexual relationship with a male partner was important, only 26.7% (n=288) agreed that this remained important if ED drugs were used. However, 56.7% (n=611) and 57.7% (n=621) of respondents, respectively, answered that they would allow their partner's use of ED drugs if they imagined that they understood the safety and effectiveness of ED drugs and that their quality of life was improved by their partner's use of the drugs. Lack of information about ED drugs was a significant predictor for acceptance of a partner's use of ED drugs among women with a negative image of ED drugs, since they were more likely to accept the use of these drugs if they were convinced about their safety and effectiveness or positive effect on quality of life. CONCLUSION: Lack of information about ED drugs may influence the perception of women in Japan regarding these drugs.


Asunto(s)
Actitud Frente a la Salud , Comparación Transcultural , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/psicología , Conocimientos, Actitudes y Práctica en Salud , Inhibidores de Fosfodiesterasa/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Cultura , Femenino , Encuestas Epidemiológicas , Humanos , Japón , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Educación Sexual , Encuestas y Cuestionarios , Adulto Joven
20.
Urol Oncol ; 36(7): 339.e9-339.e15, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29773493

RESUMEN

INTRODUCTION AND OBJECTIVES: Pretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 60 patients undergoing molecular targeted therapy for mRCC was measured before and after CN. The cutoff value of CRP was determined to be 0.5mg/dl.; thus, all patients were classified into lower CRP groups and higher ones according to their CRP before CN. The higher CRP group was further classified into 2 groups based on the kinetics after CN, "normalized CRP group" and "nonnormalized CRP group," respectively. The overall survival (OS) of these groups was compared. RESULTS: The median of the observation period was 21.6 months. The OS of patients in the lower CRP, normalized CRP, and nonnormalized CRP groups were 28.6, 23.1, and 12.3 months, respectively (nonnormalized CRP group vs. others, P<0.0001). Multivariate analysis revealed that the postoperative CRP level (≥0.5mg/dl) (hazard ratio = 0.218; 95% CI: 0.091-0.522; P = 0.0006) was an independent predictive factor of OS. CONCLUSION: The CRP level after CN can be a predictive factor for OS in patients with mRCC treated with tyrosine kinase inhibitor.


Asunto(s)
Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Carcinoma de Células Renales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Neoplasias Renales/mortalidad , Nefrectomía/mortalidad , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/sangre , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
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