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1.
Biochem Biophys Res Commun ; 734: 150730, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39366177

RESUMO

A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.

2.
Int J Clin Oncol ; 29(1): 64-71, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37864612

RESUMO

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/efeitos adversos , Estudos Retrospectivos , Pontuação de Propensão , Japão , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Derivação Urinária/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fístula Anastomótica , Resultado do Tratamento
3.
Int J Urol ; 31(6): 678-684, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38402449

RESUMO

OBJECTIVE: In December 2021, enfortumab vedotin (EV), an antibody-drug conjugate directed against nectin-4, was approved in Japan as a new treatment after platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This study evaluated, using real-world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). MATERIALS AND METHODS: Fifty-five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non-EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. RESULTS: The median (range) follow-up period after pembrolizumab discontinuation was 6.3 (0.7-31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non-EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non-EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non-EV group; hazard ratio 0.26; 95% confidence interval 0.16-0.41; p < 0.001) was an independent prognostic factor for OS. CONCLUSION: EV prolonged OS in mUC following pembrolizumab therapy in real-world data.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma de Células de Transição , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Japão/epidemiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Progressão da Doença , Taxa de Sobrevida , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversos
4.
Int J Urol ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253898

RESUMO

OBJECTIVE: Artery and vein (AV) clamps can control venous bleeding in the surgical field and prevent carbon dioxide embolism, especially when large veins are expected to open. However, whether AV clamps cause more renal damage than artery-only (AO) clamps remains unclear. This study aimed to compare renal function and blood loss in surgeries using AO and AV clamps based on high RENAL nephrometry scores (RNS) in robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed the medical records of 500 patients who underwent RAPN between March 2016 and December 2021. We performed 1:1 propensity matching for these patients. RESULTS: A total of 340 patients with pathological malignancies who were followed up for at least 12 months were included in this analysis. A total of 291 patients with AO clamping and 49 patients with AV clamping were included. Overall, the AV clamp group had higher total RNSs and larger diameters than the AO clamp group. Propensity score-matched analysis included 37 patients in each clamp group. The median warm ischemia times of the AV and AO clamps were 25 and 22 min, respectively, with no significant difference. There were no statistically significant differences between the groups in the amount of blood loss, rate of acute kidney injury (AKI), or renal function at 1, 3, or 12 months post-RAPN. CONCLUSION: Compared with the AO clamp, the AV clamp did not have a detrimental impact on blood loss or renal dysfunction. Consequently, AV clamps may be considered for patients presenting with moderate-to-high-complexity RNSs.

5.
Int J Urol ; 30(12): 1096-1102, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37592739

RESUMO

OBJECTIVES: To investigate the predictive factors for pentafecta achievement of robot-assisted partial nephrectomy (RAPN) for intermediate highly complex renal tumors (RENAL score ≥ 7). METHODS: We retrospectively analyzed the data of 247 patients with renal tumors with a RENAL score ≥ 7 who underwent RAPN. Baseline characteristics and perioperative outcomes were compared between the pentafecta achieved group and the unachieved group. A multivariable logistic regression model was used to identify the predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. RESULTS: Of the 247 patients, 75 (30.3%) patients were in the achieved group and 172 (69.7%) patients were in the unachieved group. The median warm ischemia time and total operation time were 18 min versus 23 min (p < 0.001) and 179 min versus 201 min (p < 0.001) in the achieved and unachieved groups, respectively. In the unachieved group, six patients (3.4%) had major perioperative complications (Clavien-Dindo classification system ≥3). The median preservation rates of estimated GFR at the 1-year postoperative period were 96.5% versus 83.0% (p < 0.001) in the achieved and unachieved groups. Multivariable logistic regression models revealed that age and tumor size were independent predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. There were no significant differences in cancer-free survival between the two groups (p = 0.456). CONCLUSION: Age and tumor size were independent predictive factors for pentafecta achievement, although there was no difference in oncological outcomes between the pentafecta achieved group and the unachieved group in RAPN for cT1 renal tumors with a RENAL score ≥ 7.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos
6.
Int J Urol ; 28(4): 440-443, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508874

RESUMO

OBJECTIVES: To assess the correlation of urine loss rate after catheter removal with long-term continence after robot-assisted radical prostatectomy. METHODS: We enrolled 163 patients on whom robot-assisted radical prostatectomy was carried out and whose urine loss rate we were able to evaluate after catheter removal. Urinary incontinence was evaluated from immediately after removal of the catheter to the date of discharge, and at 1, 3, 6 and 12 months after surgery. Urine loss rate was defined as the urine loss volume divided by the total urine volume. RESULTS: The continence rates of patients with ≤1% urine loss rate on the day of catheter removal were 100% at 6 and 12 months after surgery. A multivariate analysis proved that ≤10% urine loss rate on the day of catheter removal was a significant predictor of continence at 3 months after surgery. Furthermore, the continence rate at 12 months of patients who did not achieve ≤10% urine loss rate on the day of catheter removal was 79.5%. Among them, the continence rate at 12 months of patients who achieved ≥15% urine loss rate improvement from the day of catheter removal to the next day was 95.2%; the factor differed significantly between the continence and incontinence groups at 12 months after surgery. CONCLUSIONS: The urine loss rate on the day of catheter removal is significantly related to the acquisition of urinary continence. Furthermore, our findings suggest that long-term urinary continence can be expected, even in the event of poor urine loss rate on the day of catheter removal, if it improves on the next day.


Assuntos
Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Catéteres , Humanos , Laparoscopia/efeitos adversos , Masculino , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Recuperação de Função Fisiológica , Procedimentos Cirúrgicos Robóticos/efeitos adversos
7.
Hinyokika Kiyo ; 67(5): 205-209, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34126664

RESUMO

Lymphoepithelioma-like carcinoma (LELC) of the ureter is very rare and only 14 previous cases have been reported. Here, we report a case of LELC of the ureter. A 76-year-old woman was admitted to our hospital complaining of gross hematuria. Left ureteral cancer was suspected by the imaging examination, and laparoscopic left total nephroureterectomy was performed. Histopathological examination showed pure type of LELC in the ureter. She is alive without disease recurrence at fifteen months after surgery.


Assuntos
Carcinoma de Células Escamosas , Ureter , Neoplasias Ureterais , Idoso , Feminino , Humanos , Recidiva Local de Neoplasia , Nefroureterectomia , Ureter/diagnóstico por imagem , Ureter/cirurgia , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/cirurgia
8.
Hum Mol Genet ; 27(15): 2712-2724, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767721

RESUMO

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.


Assuntos
Síndrome de Birt-Hogg-Dubé/patologia , Montagem e Desmontagem da Cromatina/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Supressoras de Tumor/genética , Síndrome de Birt-Hogg-Dubé/genética , Variações do Número de Cópias de DNA , Mutação em Linhagem Germinativa , Humanos , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Sequenciamento do Exoma
9.
Biochem Biophys Res Commun ; 522(4): 931-938, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31806376

RESUMO

FLCN is a tumor suppressor gene which controls energy homeostasis through regulation of a variety of metabolic pathways including mitochondrial oxidative metabolism and autophagy. Birt-Hogg-Dubé (BHD) syndrome which is driven by germline alteration of the FLCN gene, predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas, pulmonary cysts and less frequently, salivary gland tumors. Here, we report metabolic roles for FLCN in the salivary gland as well as their clinical relevance. Screening of salivary glands of BHD patients using ultrasonography demonstrated increased cyst formation in the salivary gland. Salivary gland tumors that developed in BHD patients exhibited an upregulated mTOR-S6R pathway as well as increased GPNMB expression, which are characteristics of FLCN-deficient cells. Salivary gland-targeted Flcn knockout mice developed cytoplasmic clear cell formation in ductal cells with increased mitochondrial biogenesis, upregulated mTOR-S6K pathway, upregulated TFE3-GPNMB axis and upregulated lipid metabolism. Proteomic and metabolite analysis using LC/MS and GC/MS revealed that Flcn inactivation in salivary gland triggers metabolic reprogramming towards the pentose phosphate pathway which consequently upregulates nucleotide synthesis and redox regulation, further supporting that Flcn controls metabolic homeostasis in salivary gland. These data uncover important roles for FLCN in salivary gland; metabolic reprogramming under FLCN deficiency might increase nucleotide production which may feed FLCN-deficient salivary gland cells to trigger tumor initiation and progression, providing mechanistic insight into salivary gland tumorigenesis as well as a foundation for development of novel therapeutics for salivary gland tumors.


Assuntos
Cistos/metabolismo , Cistos/patologia , Nucleotídeos/biossíntese , Proteínas Proto-Oncogênicas/metabolismo , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Proteínas Supressoras de Tumor/metabolismo , Adulto , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cistos/diagnóstico por imagem , Feminino , Ontologia Genética , Glicólise , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Biogênese de Organelas , Via de Pentose Fosfato , Proteínas Proto-Oncogênicas/deficiência , Glândulas Salivares/diagnóstico por imagem , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/deficiência , Regulação para Cima
10.
Cancer Immunol Immunother ; 69(10): 2041-2051, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32424467

RESUMO

Recently, the effectiveness of anti-programmed death 1 (PD-1) antibody therapy in the treatment of renal cell carcinoma (RCC) has been established. Nevertheless, efficacy has been reported to be limited to only 10-30% of patients. To develop more effective immunotherapy for RCC, we analyzed the immunological characteristics in RCC tissues by immunohistochemistry (IHC). We prepared a tissue microarray that consisted of tumor tissue sections (1 mm in diameter) from 83 RCC patients in Kanagawa Cancer Center between 2006 and 2015. IHC analysis was performed with antibodies specific to immune-related (CD8 and Foxp3) and immune checkpoint (programmed death ligand 1 (PD-L1) and 2 (PD-L2), B7-H4 and galectin-9) molecules. The numbers and proportions of positively stained tumor cells or immune cells were determined in each section. From multivariate analysis of all 83 patients, higher galectin-9 expression was detected as a factor associated with worse overall survival (OS) (P = 0.029) and that higher stage and higher B7-H4 expression were associated with worse progression-free survival (PFS) (P < 0.001 and P = 0.021, respectively). Similarly, in multivariate analysis of 69 patients with clear cell RCC, though not statistically significant, there was a trend for association between higher galectin-9 expression and worse OS (P = 0.067), while higher stage was associated with worse PFS (P < 0.001). This study suggests that higher galectin-9 expression is an independent adverse prognostic factor of OS in RCC patients. Therefore, to develop more effective personalized immunotherapy to treat RCC, it may be important to target not only PD-1/PD-L1, but also other immune checkpoint molecules such as galectin-9.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Galectinas/metabolismo , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
World J Urol ; 38(10): 2477-2484, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31875247

RESUMO

OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.


Assuntos
Braquiterapia , Pontuação de Propensão , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia de Intensidade Modulada , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
BMC Cancer ; 19(1): 298, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940117

RESUMO

BACKGROUND: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). RESULTS: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/imunologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico
13.
BMC Urol ; 18(1): 97, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400941

RESUMO

BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/biossíntese , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Receptor de Morte Celular Programada 1/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/tendências , Receptor de Morte Celular Programada 1/genética , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/genética
14.
Hinyokika Kiyo ; 64(7): 303-306, 2018 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-30089339

RESUMO

A 62-year-old woman underwent laparoscopic radial nephrectomy for the left renal cell carcinoma in September 2008. In July2016, the patient developed asymptomatic gross hematuria. Computed tomography (CT) revealed the enlargement of the left ureteral stump and an 11mm nodule in the superior lobe of the right lung. Since [F-18] fluoro-D-glucose-positron emission tomography-CT FDG PET-CT demonstrated a lung tumor, we decided to perform right upper lobectomybyvideo-assisted thoracoscopic surgeryin September. The patient was diagnosed with metastatic renal cell carcinoma. We then removed the left ureteral stump and performed partial cystectomy in November. A pathological examination revealed that the tumor was metastatic clear cell renal cell carcinoma invading the muscle layer. Two months later, the patient developed gross hematuria again. Cystoscopy revealed a 1cm tumor around the scar of partial cystectomy. Transurethral resection was performed, and a pathological examination revealed metastatic renal cell carcinoma. We herein report this case of renal cell carcinoma in which recurrence occurred in the ureteral stump, 8 years after radical nephrectomy.


Assuntos
Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Ureterais/secundário , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Nefrectomia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/cirurgia
15.
Hinyokika Kiyo ; 63(3): 119-124, 2017 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-28331170

RESUMO

We describe a case of testicular tumor with multiple metastasis to the lung,retoroperitoneal lymph node, and brain. After chemotherapy the retroperitoneal lymph node and brain metastasis disappeared,but the multiple pulmonary metastases but not disappear,although they were reduced in size. Since the human chorionic gonadotoropin (HCG) was persistently dected at a low level,we performed a testosterone tolerance test. The HCG level became undetectable for a while,but was detected at a low level again. Then the patient underwent residual tumor removal of some of the residual pulmonary disease,which was diagnosed as tumor necrosis. The patient has been followed on an ambulatory basis after surgery for 12 months without recurrence. In this case a definitive diagnosis was difficult,because of the low positive level of HCG.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Gonadotropina Coriônica/sangue , Neoplasias Pulmonares/tratamento farmacológico , Espaço Retroperitoneal/patologia , Neoplasias Testiculares/tratamento farmacológico , Adulto , Neoplasias Encefálicas/secundário , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Neoplasias Testiculares/química , Neoplasias Testiculares/patologia
16.
Hinyokika Kiyo ; 63(6): 245-249, 2017 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-28694418

RESUMO

A 74-year-old man underwent transurethral resection for a bladder tumor (TURBT). The pathological diagnosis was urothelial carcinoma, grade 3 pT2 at least. He desired preservation of the bladder. Thus, MEC (methotrexate 100-150 mg/body (day 1), etoposide 100 mg/m2 (day 2-4), cisplatin 20 mg/m2 (day 2-6)) chemotherapy was administered for 2 courses. The next year, he had a relapse in the bladder, and the pathological diagnosiswasurothelial carcinoma, grade 2 pTa and pTis. He underwent Calmette-Guerin Bacillus (BCG) immunotherapy for 6 courses that resulted in a complete response without recurrence for 6 years. Six months after the latest examination, he complained of difficulty in voiding. An 8 cm tumor in the bladder and enlargement of obturator lymph node were detected. The pathological diagnosis by TURBT was small cell carcinoma. He rejected cystectomy, so we applied MEC therapy again. After 2 courses of MEC therapy, the bladder tumor and lymphadenopathy markedly shrunk in image and almost disappeared subsequently. The patient refused further therapy, but he had been followed without recurrence for 48 monthsafter the chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Metotrexato/administração & dosagem , Fatores de Tempo , Neoplasias da Bexiga Urinária/patologia
18.
Asian J Endosc Surg ; 17(2): e13289, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355303

RESUMO

INTRODUCTION: The number of facilities adopting intracorporeal urinary diversion (ICUD) using robots instead of extracorporeal urinary diversion (ECUD) is increasing. However, guidance on how to introduce robot-assisted radical cystectomy (RARC) + ICUD in each urological institute remains unclear. This study aimed to verify the feasibility of the transition from laparoscopic radical cystectomy (LRC) + ECUD to RARC + ICUD. METHODS: We retrospectively analyzed 26 consecutive patients who underwent ICUD with an ileal conduit after RARC between 2018 and 2020 (RARC + ICUD early group). We then compared these patients with 26 consecutive patients who underwent ECUD with an ileal conduit after LRC between 2012 and 2019 (LRC + ECUD late group) at Yokohama City University Hospital. RESULTS: In the RARC + ICUD early group compared with the LRC + ECUD late group, the median total operation time was 516 versus 532.5 min (P = .217); time to cystectomy, 191 versus 206.5 min (P = .234); time of urinary diversion with an ileal conduit, 198 versus 220 min (P = .016); postoperative maximum C-reactive protein levels, 6.98 versus 12.46 mg/L (P = .001); number of days to oral intake, 3 versus 5 days (P = .003); length of hospital stay, 17 versus 32 days (P < .001). The postoperative complication rates (within 90 days) were 23.1% and 42.3% in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .237). Clavien-Dindo classification ≥3 was noted in 1 and 4 patients in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .350). CONCLUSION: Regarding perioperative outcomes, the RARC + ICUD early group was not inferior to the LRC + ECUD late group. This study suggests the feasibility of a transition from LRC + ECUD to RARC + ICUD.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Derivação Urinária/efeitos adversos , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Resultado do Tratamento
19.
J Robot Surg ; 18(1): 109, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441829

RESUMO

The influence of chronic kidney disease stage on robot-assisted partial nephrectomy outcomes remains underexplored. This study aimed to assess the impact of chronic kidney disease stage on functional and surgical outcomes of robot-assisted partial nephrectomy and identify preoperative predictors of significant postoperative 1-year renal-function loss (RFL). Clinical data of 408 patients who underwent robot-assisted partial nephrectomy at Yokohama City University Hospital between 2016 and 2023 were retrospectively reviewed. The da Vinci Surgical System was applied in all patients, and outcomes assessed included surgical parameters, postoperative estimated glomerular filtration rate, trifecta and pentafecta achievements, and complications. Significant RFL was defined as estimated glomerular filtration rate reduction ≥ 25% from baseline. Higher chronic kidney disease stages correlated with older age, hypertension, diabetes, and solitary kidneys. Postoperative estimated glomerular filtration rate decline was most pronounced in patients with chronic kidney disease stages 4-5. Although the chronic kidney disease stage did not significantly affect most surgical parameters, pentafecta achievement was higher in patients with chronic kidney disease stage 3 than in those with stages 4-5. Two patients required hemodialysis after robot-assisted partial nephrectomy. Multivariable logistic regression analysis showed that preoperative hemoglobin level and maximum tumor diameter were significant predictive factors for significant RFL. In conclusion, preoperative CKD stage did not influence on surgical outcome except for pentafecta achievement. RAPN may be feasible for patients with CKD stages 4-5 because of no rapid progression to hemodialysis induction and no procedure-related mortality. Preoperative hemoglobin levels and tumor diameter emerged as predictors of significant RFL.


Assuntos
Neoplasias Renais , Insuficiência Renal Crônica , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Insuficiência Renal Crônica/complicações , Nefrectomia , Hemoglobinas
20.
J Endourol ; 38(4): 347-352, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38243789

RESUMO

Objective: Complete endophytic renal tumors (CERTs) are the most challenging for robot-assisted partial nephrectomy (RAPN). This study aimed to determine the impact of CERT on outcomes of RAPN. Methods: All RAPN cases for localized renal tumor undertaken at Yokohama City University Hospital between 2016 and 2023 were enrolled. Tumor characteristics and surgical, functional, and oncologic outcomes of RAPN were compared between CERT and non-CERT groups. Results: Consecutive 666 patients were enrolled, and 76 (11.4%) were identified as CERT (3 points of "E" score). CERT showed smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher "N" scores (p < 0.001) and "L" scores (p = 0.006) than non-CERT. The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and relatively lower trifecta achievement rates (p = 0.101) than the non-CERT group. In multivariable analysis, the CERT was an independent predictor for trifecta achievement but not for pentafecta achievement. Conclusions: CERT was associated with longer warm ischemia time, positive surgical margin, and lower trifecta achievement, but not with surgical complication and pentafecta achievement in RAPN. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia , Margens de Excisão
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