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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.
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Antibacterianos , Levofloxacino , Testes de Sensibilidade Microbiana , Infecções Urinárias , Humanos , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/tratamento farmacológico , Japão/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Farmacorresistência Bacteriana , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Feminino , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Monitoramento Epidemiológico , População do Leste AsiáticoRESUMO
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.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Índice de Massa Corporal , Neoplasias Renais/patologia , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , PrognósticoRESUMO
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.
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Carcinoma de Células Renais , Neoplasias Renais , Tumores Neuroendócrinos , Pancreatectomia , Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/cirurgia , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Pancreatectomia/métodos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Nefrectomia/métodos , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Primárias Múltiplas/patologiaRESUMO
(Introduction) In this study, we investigated the surgical outcomes and cancer control achieved with cytoreductive radical prostatectomy (cRP) in patients with castration-resistant prostate cancer (CRPC). (Patients and Methods) The study included 12 patients who underwent cRP at Kure Medical Center between August 2010 and April 2022 for diagnosis of CRPC. Perioperative outcomes, decline in serum prostate-specific antigen (PSA) levels from baseline, PSA progression-free survival, and postoperative treatment-free survival were recorded. (Results) We observed that 5 of 12 patients showed no metastases at the time of initial diagnosis, 2 had only regional lymph node metastases, and 5 had distant metastases. No patient showed identifiable metastases on imaging studies at the time of surgery. The median PSA value at the time of surgery was 0.47 ng/mL, and 5 patients had PSA values ≥1 ng/mL. All patients underwent laparoscopic cRP. Postoperative adverse events included Clavien-Dindo grade I complications in 4 and grade III complications in 1 patient; however, no patient developed rectal injury. Postoperative serum PSA levels were < 0.2 ng/mL in 8 of 12 patients (66.7%) and undetectable in 5 patients (41.7%). The median postoperative PSA progression-free survival and postoperative treatment-free survival were 12.4 and 14.5 months, respectively. (Conclusion) cRP was associated with a good anti-cancer effect in selected cases of CRPC and may serve as a potentially useful treatment option in this patient population.
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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.
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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.
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Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Ácido gama-Aminobutírico/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pregabalina , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
(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.
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Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Laparoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Resultado do TratamentoRESUMO
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 (Pâ¯=â¯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 (Pâ¯=â¯0.0024, median OS: 21.0 months and 33.7 months, Pâ¯=â¯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 (Pâ¯=â¯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.
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Carcinoma de Células Renais , Neoplasias Renais , Proteína C-Reativa/metabolismo , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Albumina SéricaRESUMO
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.
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Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Masculino , Nefrectomia/métodos , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
[This corrects the article DOI: 10.3892/mco.2020.2020.].
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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 3âmonths 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 3âmonths after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3âmg/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 0.3âmg/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.
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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.
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Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Imidazóis/farmacologia , Neoplasias Renais/tratamento farmacológico , Piperazinas/farmacologia , Sunitinibe/farmacologia , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Sinergismo Farmacológico , Feminino , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
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.
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Antineoplásicos/farmacologia , Carcinoma de Células Renais/mortalidade , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptores de Hialuronatos/metabolismo , Neoplasias Renais/mortalidade , Sunitinibe/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Receptores de Hialuronatos/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
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.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adenocarcinoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anilidas/uso terapêutico , Acetato de Clormadinona/uso terapêutico , Flutamida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Seleção de Pacientes , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Compostos de Tosil/uso terapêuticoRESUMO
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.
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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.
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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.
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Carcinoma de Células Renais/tratamento farmacológico , PTEN Fosfo-Hidrolase/genética , Sorafenibe/farmacologia , Sunitinibe/farmacologia , Biomarcadores Tumorais/genética , Sistemas CRISPR-Cas , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Esferoides Celulares/efeitos dos fármacosRESUMO
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:
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Nefropatias/diagnóstico por imagem , Testes de Função Renal , Neoplasias Renais/cirurgia , Rim/diagnóstico por imagem , Laparoscopia , Nefrectomia/métodos , Compostos Radiofarmacêuticos , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Isquemia Quente/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Rim/fisiopatologia , Rim/cirurgia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cintilografia , Fatores de Tempo , Resultado do TratamentoRESUMO
(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.
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Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Fatores Etários , Idoso , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
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.