RESUMO
This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/terapia , Carcinoma de Células de Transição/patologia , Japão/epidemiologiaRESUMO
Prohibitin-2 (PHB2) is a scaffold protein that has pleiotropic functions, which include interacting with γ-glutamylcyclotransferase (GGCT) in the cytoplasm and repressing the transcriptional activities of the p21Waf1/Cip (p21) gene in the nucleus. The cytotoxic drug fluorizoline binds to PHB1/2 and exerts antiproliferative actions on cancer cells. However, the precise mechanism underlying the antiproliferative effects of fluorizoline is not fully elucidated. In the present study, we first show that fluorizoline induces p21 expression in several human cancer cell lines, including MCF7 breast cancer cells. Treatment of MCF7 cells with fluorizoline suppressed proliferation and prevented cells from entering into the DNA synthesis phase. Knockdown of p21 rescued the suppressed proliferation, indicating that fluorizoline inhibited MCF7 cell growth via the induction of p21. Overexpression of PHB2 in MCF7 cells prevented the induction of p21 expression by fluorizoline and restored the antiproliferative effects and blockade of cell cycle progression. Moreover, treatment of MCF7 cells with fluorizoline inhibited the interaction between endogenous PHB2 and GGCT proteins and reduced the level of nuclear localization of PHB2 proteins. These results indicate that targeting PHB2 with fluorizoline induces the expression of p21 and consequently blocks proliferation of cancer cells. SIGNIFICANCE STATEMENT: This study shows that fluorizoline may be a promising novel anticancer drug candidate that induces p21 expression and blocks cell-cycle progression in human cancer cell lines. In addition, we show that fluorizoline inhibits the interaction between PHB2 and GGCT and reduces the nuclear localization of PHB2 proteins.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Regulação Neoplásica da Expressão Gênica/fisiologia , Proibitinas/metabolismo , gama-Glutamilciclotransferase/metabolismo , Antineoplásicos/síntese química , Neoplasias da Mama/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Proibitinas/antagonistas & inibidores , gama-Glutamilciclotransferase/antagonistas & inibidoresRESUMO
BACKGROUND: In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. METHODS: A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. RESULTS: In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. CONCLUSIONS: Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.
Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Inquéritos Epidemiológicos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To investigate whether robot-assisted partial nephrectomy compared with laparoscopic partial nephrectomy is effective for renal hilar tumor removal. METHODS: This was a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. A total of 22 academic hospitals in Japan participated in the present study. Comparison with historical control values from reported studies of laparoscopic partial nephrectomy was carried out. The warm ischemia time and positive surgical margin rate were set as primary perioperative and oncological outcomes. In the historical control group, these were 27.7 min and 13%, respectively. RESULTS: The analysis population included 105 participants. The mean warm ischemia time was 20.2 (95% confidence interval 16.7-21.8; P < 0.0001 vs 27.7). Two of 103 participants (1.9%) had a positive surgical margin (95% confidence interval 0.5-6.8%). Both results satisfy the prespecified decision criteria for the superiority of robot-assisted partial nephrectomy over the historical control of laparoscopic partial nephrectomy. Resected weight and preoperative estimated glomerular filtration rate were predictive factors of functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSION: Robot-assisted partial nephrectomy for clinical T1 renal hilar tumors results in shorter warm ischemia time than and comparable positive surgical margin rate to those reported for laparoscopic partial nephrectomy.
Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Taxa de Filtração Glomerular , Humanos , Japão , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do TratamentoRESUMO
The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.
Assuntos
Técnicas de Cultura de Células , Metabolismo Energético , Neoplasias da Próstata/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Masculino , Células PC-3RESUMO
Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and is resistant to most of the current therapies. Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor, JQ1, has been found to suppress the malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remain largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA não Traduzido/metabolismo , Fatores de Transcrição/metabolismo , Azepinas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Elementos Facilitadores Genéticos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Invasividade Neoplásica , Neoplasias da Próstata/genética , RNA não Traduzido/genética , Triazóis/farmacologiaRESUMO
BACKGROUND: Nivolumab, which has a promising anti-tumor efficacy and a manageable safety profile, has being rapidly introduced in metastatic renal cell cancer therapy in Japan. We evaluated the efficacy and adverse events of nivolumab in real world clinical practice in Japan. METHODS: The medical records of 45 consecutive patients who started treatment with nivolumab, up to September 2018, were reviewed and statistically analyzed. RESULTS: The median follow-up period was 22.3 months. The best responses were a complete response in three patients (8%), a partial response in 14 patients (36%), stable disease in 14 patients (36%), and progressive disease in eight patients (20%). The median progression-free survival period and 1 year progression-free survival rate were 14.9 months and 54.5%, respectively. The estimated overall survival period and 1-year and 2-year overall survival rates from initiation of nivolumab were not reached, and 91.1%, and 86.2%, respectively. Twenty-seven patients (60%) experienced adverse events including four (10%) severe adverse events (Grade 3 or 4). The most common adverse event was rash (n = 9, 20%). Five patients discontinued nivolumab therapy, because of an adverse event (Grade 3 diarrhea, one patient; Grade 2 fatigue, one patient; Grade 3 uveitis, two patients; and Grade 3 adrenal insufficiency, one patient). CONCLUSIONS: Nivolumab has a relatively favorable efficacy and safety profile for Japanese metastatic renal cell cancer patients in clinical practice.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/patologia , Diarreia/induzido quimicamente , Exantema/induzido quimicamente , Humanos , Japão , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines. METHODS: To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated. RESULTS: Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents. CONCLUSIONS: Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Fatores de Ribosilação do ADP , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Proteínas de Ciclo Celular , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia , Oxirredutases , Prognóstico , Proteínas Proto-Oncogênicas , Medição de Risco , Superóxido DismutaseRESUMO
Inhibition of gamma-glutamylcyclotransferase (GGCT), which is highly expressed in various cancer tissues, exerts anticancer effects both in vitro and in vivo. Previous studies have shown that depletion of GGCT blocks the growth of MCF7 breast cancer cells via upregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21); in addition, induction of autophagy plays a role in the upregulation of p21 upon GGCT knockdown. However, the mechanisms underlying induction of p21 in cancer cells are not fully understood. Here, we show that GGCT knockdown in PC3 human prostate cancer and A172 glioblastoma cells upregulates the mRNA and nuclear protein levels of Forkhead box O transcription factor 3a (FOXO3a), a transcriptional factor involved in tumor suppression. Simultaneous knockdown of FOXO3a and GGCT in PC3 and A172â¯cells attenuated upregulation of p21, followed by growth inhibition and cell death. Furthermore, simultaneous knockdown of GGCT and AMP-activated protein kinase (AMPK) α, a metabolic stress sensor, in PC3 and A172â¯cells led to marked attenuation of cellular responses induced by GGCT knockdown, including an increase in FOXO3a phosphorylation at Ser413, upregulation of p21, growth inhibition, and cell death. These results indicate that the AMPK-FOXO3a-p21 axis plays an important role in inhibition of cancer cell growth by depletion of GGCT.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Transdução de Sinais , gama-Glutamilciclotransferase/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Proteína Forkhead Box O3/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação , gama-Glutamilciclotransferase/metabolismo , Quinases Ativadas por p21/metabolismoRESUMO
Nonhuman primates (NHPs) are considered to be the most valuable models for human transgenic (Tg) research into disease because human pathology is more closely recapitulated in NHPs than rodents. Previous studies have reported the generation of Tg NHPs that ubiquitously overexpress a transgene using various promoters, but it is not yet clear which promoter is most suitable for the generation of NHPs overexpressing a transgene ubiquitously and persistently in various tissues. To clarify this issue, we evaluated four putative ubiquitous promoters, cytomegalovirus (CMV) immediate-early enhancer and chicken beta-actin (CAG), elongation factor 1α (EF1α), ubiquitin C (UbC), and CMV, using an in vitro differentiation system of cynomolgus monkey embryonic stem cells (ESCs). While the EF1α promoter drove Tg expression more strongly than the other promoters in undifferentiated pluripotent ESCs, the CAG promoter was more effective in differentiated cells such as embryoid bodies and ESC-derived neurons. When the CAG and EF1α promoters were used to generate green fluorescent protein (GFP)-expressing Tg monkeys, the CAG promoter drove GFP expression in skin and hematopoietic tissues more strongly than in ΕF1α-GFP Tg monkeys. Notably, the EF1α promoter underwent more silencing in both ESCs and Tg monkeys. Thus, the CAG promoter appears to be the most suitable for ubiquitous and stable expression of transgenes in the differentiated tissues of Tg cynomolgus monkeys and appropriate for the establishment of human disease models.
Assuntos
Animais Geneticamente Modificados , Vetores Genéticos , Macaca fascicularis/genética , Regiões Promotoras Genéticas , Transgenes , Actinas/genética , Animais , Antígenos Virais/genética , Células Cultivadas , Galinhas/genética , Clonagem de Organismos/métodos , Clonagem de Organismos/normas , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Elementos Facilitadores Genéticos/genética , Feminino , Técnicas de Transferência de Genes/normas , Vetores Genéticos/genética , Proteínas Imediatamente Precoces/genética , Masculino , Camundongos , Fator 1 de Elongação de Peptídeos/genéticaRESUMO
Voiding cystourethrography is the most important fluoroscopic examination in pediatric urology for the investigation of lower urogenital tract diseases, such as vesicoureteral reflux or urethral stricture. However, this invasive procedure imposes a significant burden on children and their parents, and recently there has been a paradigm shift in the diagnosis and treatment of vesicoureteral reflux. In the 2011 revision, the American Academy of Pediatrics guidelines on urinary tract infection recommended abandoning routine voiding cystourethrography after the first febrile urinary tract infection. In 2014, the randomized intervention for children with vesicoureteral reflux study recommended discontinuation of routine continuous antibiotic prophylaxis for vesicoureteral reflux. The time is now ripe to radically reconsider indications for voiding cystourethrography and the procedure itself.
Assuntos
Cistografia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Infecções Urinárias/diagnóstico por imagem , Refluxo Vesicoureteral/diagnóstico por imagem , Ansiedade/etiologia , Ansiedade/psicologia , Pré-Escolar , Cistografia/métodos , Cistografia/psicologia , Fluoroscopia/efeitos adversos , Fluoroscopia/métodos , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/psicologia , Guias de Prática Clínica como Assunto , Sociedades Médicas/normas , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Uretra/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/fisiopatologia , Infecções Urinárias/etiologia , Micção , Urologia/métodos , Urologia/normas , Refluxo Vesicoureteral/complicaçõesRESUMO
Previous studies show that gamma-glutamylcyclotransferase (GGCT) is expressed at high levels in various cancer tissues and that its knockdown inhibits MCF7 cancer cell growth via upregulation of p21WAF1/CIP1 (p21). However, the detailed underlying mechanism is unclear. Here, we used yeast two-hybrid screening and co-immunoprecipitation to identify Prohibitin-2 (PHB2) as a novel protein that interacts with GGCT. We also show that nuclear expression of PHB2 in MCF7 cells falls upon GGCT knockdown, and that overexpression of PHB2 inhibits p21 upregulation. A chromatin immunoprecipitation assay revealed that nuclear PHB2 proteins bind to the p21 promoter, and that this interaction is abrogated by GGCT knockdown. Moreover, knockdown of PHB2 alone led to significant upregulation of p21 and mimicked the cellular events induced by GGCT depletion, including G0/G1 arrest, cellular senescence, and growth inhibition, in a p21 induction-dependent manner. Taken together, the results indicate that PHB2 plays a central role in p21 upregulation following GGCT knockdown and as such may promote deregulated proliferation of cancer cells by suppressing p21.
Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Repressoras/metabolismo , gama-Glutamilciclotransferase/metabolismo , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Proibitinas , Ligação Proteica , gama-Glutamilciclotransferase/genéticaRESUMO
BACKGROUND: This study was conducted to determine whether the location of the bladder neck in postoperative cystography predicts recovery of continence after radical prostatectomy. METHODS: Between 2008 and 2015, 203 patients who underwent laparoscopic radical prostatectomy (LRP, n = 99) and robot assisted radical prostatectomy (RARP, n = 104) were analyzed. The location of the bladder neck was visualized by postoperative routine cystography, and quantitative evaluation of the bladder neck position was performed according to the bladder neck to pubic symphysis (BNPS) ratio proposed by Olgin et al. (J Endourol, 2014). Recovery of continence was defined as no pad use or one security pad per day. To determine the predictive factors for recovery of continence at 1, 3, 6 and 12 months, several parameters were analyzed using logistic regression analysis, including age (≤68 vs. > 68, BMI (≤23.4 vs. > 23.4 kg/m2), surgical procedure (LRP vs. RARP), prostate volume (≤38 vs. > 38 mL), nerve-sparing technique, vesico-urethral anastomosis leakage, and BNPS ratio (≤0.59 vs. > 0.59). RESULTS: The mean postoperative follow-up was 1131 days (79-2880). At 1, 3, 6 and 12 months after surgery, continence recovery rates were 25, 53, 68 and 81%, respectively. Although older age (> 68) and RARP were significant risk factors for incontinence within 3 months, neither was significant after 6 months. A high BNPS ratio (> 0.59) was the only significant risk factor for the persistence of incontinence at all observation points, up to 12 months. CONCLUSIONS: A lower bladder neck position after prostatectomy predicts prolonged incontinence.
Assuntos
Convalescença , Cistografia/tendências , Complicações Pós-Operatórias/diagnóstico por imagem , Prostatectomia/tendências , Bexiga Urinária/diagnóstico por imagem , Incontinência Urinária/diagnóstico por imagem , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Prostatectomia/efeitos adversos , Estudos Retrospectivos , Incontinência Urinária/etiologiaRESUMO
BACKGROUND: To evaluate the effect of intravesical bacillus Calmette-Guerin (BCG) instillation therapy after second transurethral resection (TUR) on primary T1 bladder cancer. METHODS: The subjects were 180 patients diagnosed with T1 bladder cancer at our university and at affiliated hospitals between January 1990 and December 2015. Tumor residual rate, intravesical recurrence rate, and risk factors for intravesical recurrence were investigated. RESULTS: The median follow-up period was 26 (1-175) months. Of the 180 patients, 78 (43%) underwent a second TUR. Residual tumors were detected in 42 patients (53.8%), and no up-staging cases were observed. Within the whole group, 42 patients were treated with intravesical BCG therapy following a second TUR (group 1), 36 were treated with second TUR alone (group 2), 28 were treated with intravesical BCG therapy alone (group 3), and 74 were treated without second TUR or intravesical BCG therapy (group 4). The 1- and 5-year recurrence-free survival rates of the four groups were 80.7 and 59.7% (group 1), 69.0 and 26.3% (group 2), 76.3 and 56.6% (group 3), 64.6 and 48.6% (group 4), respectively. There was no significant difference between group 1 and group 3 (p = 0.401). Intravesical BCG therapy was the only factor preventing intravesical recurrence (p = 0.013). CONCLUSIONS: Intravesical BCG therapy alone showed a significant preventive effect with regard to intravesical recurrence. In our cohort, however, second TUR did not improve recurrence-free survival in those individuals who underwent BCG instillation.
Assuntos
Vacina BCG/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVES: To evaluate the current status of urological laparoendoscopic single-site and reduced port surgery in Japan. METHODS: Of the 152 institutions to which councilors of the Japanese Society of Endourology belong, 42 (28%) have carried out laparoendoscopic single-site and reduced port surgery. A total of 32 of these institutions agreed to participate in this survey. Patients who had undergone surgery between January 2008 and March 2014 were included in the present study. RESULTS: Overall, 1145 cases of laparoendoscopic single-site and reduced port surgery were recorded during the study period. The most frequent procedures were adrenalectomy and radical nephrectomy. Laparoendoscopic single-site and reduced port surgery represented 12% (872/7311) of all laparoscopic procedures carried out at participating institutions. The number of patients who underwent pyeloplasty, donor nephrectomy and simple nephrectomy tended to increase, whereas those who underwent adrenalectomy, radical nephrectomy and nephroureterectomy peaked in 2012, and then tended to decrease in 2013. The rates of conversion, perioperative and postoperative complications, were 2.7%, 2.2% and 4.5%, respectively. CONCLUSIONS: The number of laparoendoscopic single-site and reduced port urological surgeries in Japan has increased for benign indications, such as pyeloplasty, donor nephrectomy and simple nephrectomy. In contrast, procedures such as adrenalectomy and radical nephrectomy are trending down after reaching a peak in 2012. Overall, laparoendoscopic single-site and reduced port urological surgery in Japan is being safely carried out when compared with other reported series of laparoendoscopic single-site surgery and conventional laparoscopic surgery.
Assuntos
Adrenalectomia/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Adolescente , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Adrenalectomia/tendências , Adulto , Idoso , Conversão para Cirurgia Aberta/estatística & dados numéricos , Feminino , Humanos , Japão/epidemiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Utilização de Procedimentos e Técnicas/tendências , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/tendências , Adulto JovemRESUMO
γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers-glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma-and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.
Assuntos
Alanina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , gama-Glutamilciclotransferase/antagonistas & inibidores , Alanina/análogos & derivados , Inibidores Enzimáticos/química , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias/enzimologia , Neoplasias/genética , Interferência de RNA , gama-Glutamilciclotransferase/genética , gama-Glutamilciclotransferase/metabolismoRESUMO
A 65-year-old man was referred to our hospital with a chief complaint of hyperglycemia. Computed tomography showed left clear-bordered adrenal mass. The serum aldosterone/renin ratio was elevated, and the low-dose dexamethasone suppression test revealed no suppression of serum cortisol. Adrenal venous samplingdemonstrated excess secretion of cortisol from the left adrenal gland, and excess secretion of aldosterone from bilateral adrenal glands. Laparoscopic left partial adrenalectomy for primary aldosteronism combined with Cushing's syndrome was performed. The result was insulin withdrawal and the reduction of antihypertensive drugs.
Assuntos
Adrenalectomia , Síndrome de Cushing/cirurgia , Hiperaldosteronismo/cirurgia , Idoso , Síndrome de Cushing/complicações , Humanos , Hiperaldosteronismo/complicações , Laparoscopia , MasculinoRESUMO
PURPOSE: This article is a standardization document of the International Children's Continence Society (ICCS); it represent a consensus of ICCS on the management of pediatric daytime urine incontinence (DUI). MATERIALS AND METHODS: This document was designed and written by a multi-disciplinary core group of authors appointed by the ICCS' board. RESULTS: Based on evidence of studies and the experience of experts, the treatment guideline of DUI is assembled in this standardization document. Guidelines and the algorithm of management include non-pharmacological treatment (urotherapy), as well as the pharmacological therapy and other modalities that are presented for DUI in general, as along with recommendations for individual conditions. CONCLUSION: The final document is not a systematic literature review. It includes relevant research when available as well as experts' opinion on the current understanding of daytime incontinence in children. This document illustrates that specific treatment of DUI based on an exact diagnosis is effective. The mainstay of treatment is urotherapy, but a combination of treatment modalities is often necessary. Neurourol. Urodynam. 36:43-50, 2017. © 2015 Wiley Periodicals, Inc.
Assuntos
Incontinência Urinária/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Algoritmos , Toxinas Botulínicas/uso terapêutico , Criança , Consenso , Tratamento Conservador , Humanos , Antagonistas Muscarínicos/uso terapêutico , Padrões de Referência , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária/etiologia , Incontinência Urinária de Urgência/tratamento farmacológico , Incontinência Urinária de Urgência/terapiaRESUMO
The present article is the abbreviated English translation of the Japanese guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia updated as of the end of 2016. The target patients are men aged >50 years complaining of lower urinary tract symptoms, with or without benign prostatic hyperplasia, and the target readers are non-urological general physicians and urologists. Mandatory assessment for general physicians is medical history, physical examination, urinalysis and measurement of serum prostate-specific antigen. Additional mandatory assessment for urologists is symptoms and quality of life assessment by questionnaires, uroflowmetry, residual urine measurement, and prostate ultrasonography. Nocturia requires special attention, as it can result from nocturnal polyuria and/or sleep disturbance rather than lower urinary tract disorders. Functional lower urinary tract disorders with or without benign prostatic hyperplasia are primarily managed by conservative therapy and medications, such as α1 -blockers and phosphodiesterase-type 5 inhibitors. Use of other medications or combination pharmacotherapy is to be reserved for urologists. 5α-Reductase inhibitors and anticholinergics or ß3 agonists are indicated for men with enlarged prostates and overactive bladder symptoms, respectively. Surgical intervention for bladder outlet obstruction is considered for persistent symptoms or benign prostatic hyperplasia-related comorbidities. Surgical modalities should be optimized by the patient's characteristics, performance of equipment and the surgeon's experience.
Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/complicações , Obstrução do Colo da Bexiga Urinária/cirurgia , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Quimioterapia Combinada , Humanos , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/uso terapêutico , Qualidade de Vida , Ultrassonografia , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/etiologiaRESUMO
OBJECTIVE: To report on a multi-institutional series of non-robotic urological laparoendoscopic single-site surgery in Japan. METHODS: Consecutive cases of laparoendoscopic single-site surgery carried out between February 2009 and December 2012 at nine academic institutions were included. We examined the surgical outcomes, including conversion and complications rates. RESULTS: Four hundred and sixty-nine cases were included in the analysis. The most common procedure was adrenalectomy (n = 177) and the second most common procedure was radical nephrectomy (n = 143). The procedures also included nephroureterectomy (n = 40), living donor nephrectomy (n = 40), pyeloplasty (n = 30), urachal remnant excision (n = 9), simple nephrectomy (n = 7), radical prostatectomy (n = 6) and others (n = 17). The access sites included umbilicus (n = 248, 53%) and other sites (n = 221, 47%). A transperitoneal approach was used in 385 cases (82%), and retroperitoneal approach in 84 cases (18%). The median operation time of all procedures was 198 min. Conversion to reduced port surgery, conventional laparoscopy, or open surgery was noted in 27 cases (5.8%), 12 cases (2.6%), and two cases (0.4%), respectively, with an overall conversion rate of 8.7%. Intraoperative complications occurred in 10 cases (2.1%). Post-operative complications were noted in 29 cases (6.2%), including five major complications (1.1%). No mortality was recorded in this series. CONCLUSIONS: Non-robotic laparoendoscopic single-site surgery is technically feasible and safe for various urologic diseases in Japan. Furthermore, urological laparoendoscopic single-site surgery is a promising minimally invasive surgical option that is feasible for experienced urological surgeons in intermediate-volume centers as well as high-volume centers.