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Immune checkpoint inhibitors (ICIs) are effective in treating renal cell carcinoma (RCC) but can also cause immune-related adverse events (irAEs). The relationship between irAEs and the T-cell receptor (TCR) repertoire in RCC patients treated with ICIs remains unclear. We analyzed the relationship between the severity and diversity of irAEs and the TCR repertoire in RCC patients who received dual checkpoint inhibitors (ipilimumab + nivolumab). The TCRß (TRB) repertoires were characterized in peripheral blood samples from six patients with RCC before the initiation of ICI therapy. The diversity and clonality of the TCR repertoire were compared between patients with grade 2 and grade 3 irAEs. The median proportion of top 10 unique reads in the TCR repertoire was significantly higher in grade 3 compared with grade 2 irAEs in RCC patients receiving immune checkpoint inhibitors (grade 2: 0.196%; grade 3: 0.346%; p = 0.0038). We provide insight into the relationship between TCR repertoire and irAEs in RCC patients treated with ICIs. TCR repertoire clonality may be associated with the development of irAEs in RCC patients.
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BACKGROUND: The reality of cisplatin-induced acute kidney injury (CIA) and its effects on long-term renal function remain unclear. The aim of this study was to investigate the incidence and risk factors for CIA development, and if CIA is a useful predictor of long-term renal dysfunction after cisplatin treatment. METHODS: This was a retrospective, single-center, observational, longitudinal follow-up, large cohort study in adult patients with solid tumors treated with cisplatin-based systematic chemotherapy. Electronic medical records were used for all demographic and medical data. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. We assessed long-term renal dysfunction using %ΔeGFR/Y; (the last eGFR value during follow-up)-(the baseline eGFR)/(the baseline eGFR)/year of follow-up × 100. RESULTS: A total of 2191 patients received 8,482 cycles of cisplatin. CIA was observed 359 times (4.2%). Significant risk factors for developing CIA, using multiple linear regression analysis, included: cisplatin administration immediately before the onset of CIA (p < 0.01), liver cancer (p = 0.02), colon cancer (p = 0.04), hypertension (p = 0.03), high estimated glomerular filtration rate (eGFR) (p < 0.01), and high C-reactive protein (CRP) (p = 0.04). Significant risk factors for %ΔeGFR/Y, using multivariate linear regression analysis, included: esophageal cancer (p < 0.01), lung cancer (p < 0.01), pharyngeal cancer (p = 0.02), Head and neck cancer (p < 0.01), liver cancer (p = 0.02), potassium (p < 0.01), and CIA (p < 0.01). CONCLUSIONS: To our knowledge, this is the first study to show that CIA is a significant predictive risk factor for long-term renal dysfunction after cisplatin administration. Effective strategies are needed to prevent CIA in cancer patients.
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Injúria Renal Aguda , Antineoplásicos , Neoplasias Hepáticas , Adulto , Humanos , Cisplatino/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Rim , Taxa de Filtração GlomerularRESUMO
OBJECTIVES: Postoperative urinary incontinence recovery following robot-assisted laparoscopic prostatectomy is an important outcome. We investigated whether factors that affect urinary incontinence can predict the duration of postoperative incontinence recovery. METHODS: A total of 310 patients underwent robot-assisted laparoscopic prostatectomy. Continence recovery was defined as either pad-free or a safety pad only status. Univariate and multivariate analyses were performed on clinical variables to identify those that were associated with continence recovery. A scoring system to predict recovered continence was constructed using statistically significant variables. The validity of this tool was tested in a new cohort of 273 patients. RESULTS: Factors associated with recovery of urinary incontinence were membranous urethral length, preservation of bilateral neurovascular bundles, and a preoperative Prostate Imaging Reporting and Data System score of ≥3 in the apex. Age was related only to incontinence recovery at 1 month. To prepare the score, weighting was performed using the estimated values. Using the developed scoring system, participants in the verification set were divided into three groups. The early recovery group had a median incontinence recovery of 4 (4-12) weeks, the medium recovery group, 12 (4-24) weeks, and the late recovery group, 24 (24-48) weeks, which was a significant difference (p < 0.001). CONCLUSIONS: The applied scoring system based on preoperative factors related to incontinence and derived from patient groups was significantly associated with continence recovery time. In patients undergoing robot-assisted laparoscopic prostatectomy, our unit-weighted regression model of clinical variables can predict the duration of continence recovery.
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Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Incontinência Urinária , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Próstata/cirurgia , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Incontinência Urinária/etiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Recuperação de Função FisiológicaRESUMO
BACKGROUND: The purpose of the study is to evaluate real-world effectiveness and safety of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in Japan. METHODS: This was a retrospective evaluation of medical records from men in Japan who started enzalutamide treatment from November 1, 2014, to March 31, 2018, and received androgen deprivation therapy throughout. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included PSA response rate, time to first use of new antineoplastic therapy, time to first use of cytotoxic chemotherapy, and enzalutamide treatment duration. An exploratory analysis of metastasis-free survival (MFS) was also performed. Adverse events (AEs) were analyzed to assess safety. RESULTS: Based on data from medical records of 205 men in Japan, median time to PSA progression was 27 months (95% confidence interval [CI] 19-not reached [NR]), with 82.5% and 52.0% of men achieving PSA response rates of ≥ 50% and ≥ 90%, respectively. Median time to first use of new antineoplastic therapy was 36 months (95% CI 27-NR) and median enzalutamide treatment duration was 13 months (interquartile range: 7-24). Median time to first use of cytotoxic chemotherapy was NR (95% CI 41-NR). Median MFS was 29 months (95% CI 23-35). In total, 51.7% of men experienced AEs, with malaise (18.5%), decreased appetite (10.7%), and nausea (4.9%) the most frequently reported. CONCLUSIONS: This is the first study to demonstrate the real-world effectiveness and safety of enzalutamide in men with nmCRPC in Japan, further informing healthcare providers about available treatment options for this patient population.
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Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios , Benzamidas , Humanos , Japão , Masculino , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Renal volume change greatly affects renal function after nephrectomy. Although various measuring techniques were reported, no standard measuring method is available. In this study, we examined the computational automated volumetric method, and evaluated the volumetric change to assess the functional outcome in patients undergoing radical nephrectomy. We developed the predictive equation for postoperative renal function from volume alternation and validated the performance. METHODS: Thirty-two patients undergoing radical nephrectomy participated in this study. Renal volume was calculated using three different methods [ellipsoid method, conventional manual voxel count method for renal parenchyma (manual RPV), and automated voxel count method for renal cortex (automated RCV)] through newly developed imaging software. Statistical analysis was performed to evaluate the correlation between renal functional alternation 7 days after the nephrectomy and renal volumetric change. A simple predictive equation for the postoperative renal function by renal volume loss was developed and externally validated through another 12 cases. RESULTS: The automated RCV method had the strongest correlation between renal function alternation and RCV change (R = 0.82), than manual RPV (R = 0.69) and ellipsoid method (R = 0.50). Subsequently, a simple equation for postoperative renal function by renal volume alternation was developed: predicted postoperative estimated glomerular filtration rate (eGFR) from renal volume change = preoperative eGFR × (postoperative renal volume / preoperative renal volume). In the external validation cohort, automated RCV demonstrated the predictive performance of the constructed equations for renal function (R = 0.77). CONCLUSIONS: The computational automated RCV measurements is a simple estimation of renal functional outcome for patients undergoing radical nephrectomy.
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Testes de Função Renal , Rim/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia , Tamanho do Órgão , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of the combination of docetaxel, ifosfamide and cisplatin as salvage chemotherapy after failure of standard cisplatin-based regimens for metastatic urothelial carcinoma. METHODS: We prospectively administered docetaxel, ifosfamide and cisplatin chemotherapy to patients with metastatic urothelial carcinoma refractory to standard cisplatin-based regimens from 2003 to 2013. Patients who had received only adjuvant and/or neoadjuvant chemotherapy were excluded. Eligible patients received every 28 days docetaxel 60 mg/m(2) on Day 1, ifosfamide 1.0 g/m(2) on Days 2-6 and cisplatin 20 mg/m(2) on Days 2-6. The primary endpoints were progression-free survival and overall survival, calculated from the start of docetaxel, ifosfamide and cisplatin chemotherapy. Secondary endpoints included objective response and related toxicity. RESULTS: Twenty-six cases received a median of 3.0 cycles of docetaxel, ifosfamide and cisplatin chemotherapy (interquartile range: 2-5), resulting in a median progression-free survival of 3 months (interquartile range: 2-9.5 months) and median overall survival of 8.5 months (interquartile range: 6.5-18.75 months), respectively. Of 26 patients, seven (27%) achieved major treatment responses, with one complete response (4%) and six partial responses (23%). Most of Grade 3/4 toxicities were hematologic events, including leukopenia (77%), anemia (54%) and thrombocytopenia (46%). No death from toxicity was observed. CONCLUSIONS: Our results indicate that docetaxel, ifosfamide and cisplatin chemotherapy is a tolerable and moderately active regimen for metastatic urothelial carcinoma after failure of standard cisplatin-based regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia de Salvação/métodos , Neoplasias Urológicas/tratamento farmacológico , Idoso , Anemia/induzido quimicamente , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Avaliação de Estado de Karnofsky , Leucopenia/induzido quimicamente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
Idiopathic thrombocytopenic purpura associated with renal cell carcinoma is relatively rare. We report the case of a 48-year-old woman with massive renal cell carcinoma, measuring approximately 20 × 14 × 14 cm, who presented with severe thrombocytopenia: platelet count, 2000 cells/µL. After confirming normal bone marrow, she received high-dose dexamethasone and intravenous gamma globulin, which raised the platelet count to normal levels. She then underwent left radical nephrectomy. The pathological examination showed chromophobe renal cell carcinoma. After the resection, the platelet count was maintained within the normal range without any treatment. The current case is the first report of chromophobe renal cell carcinoma causative of severe idiopathic thrombocytopenic purpura.
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Carcinoma de Células Renais/complicações , Neoplasias Renais/complicações , Púrpura Trombocitopênica Idiopática/etiologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Carga TumoralRESUMO
OBJECTIVE: This study evaluated the efficacy of combined therapy with probucol and cilostazol on endothelial function in silent lacunar cerebral infarcts (SLCI) and mild hypercholesterolemia. SUBJECTS AND METHODS: Flow-mediated vasodilatation (FMD) and nitroglycerin-induced vasodilatation (NMD) were measured before and after 4 weeks of combined therapy with probucol (500 mg/day) and cilostazol (200 mg/day) in 34 patients with a mean age of 72 ± 7 years (range 57-80 years) with SLCI, mild hypercholesterolemia (low-density lipoprotein cholesterol >100 mg/dl) and impaired endothelial function (FMD <6%). Patients were randomly allocated to one of the following two treatment groups: (1) aspirin (100 mg/day) with behavioral modifications, such as diet and/or exercise therapy (A group or control group, n = 17), and (2) probucol and cilostazol treatment (PC group, n = 17), also with behavioral modifications. RESULTS: Although the baseline FMD was not different between the two treatment arms (2.7 ± 1.5 vs. 2.6 ± 1.5%, n.s.), the posttreatment FMD was significantly improved in the PC group (from 2.7 ± 1.5 to 3.5 ± 1.7%, p < 0.05) but not in the A group (from 2.6 ± 1.5 to 2.9 ± 1.4%, n.s.). No differences were observed between baseline and posttreatment NMD in either group. The effects of treatments on lipid profiles were more profound in the PC group. CONCLUSION: Combined treatment with probucol and cilostazol resulted in subacute improvement in FMD/endothelial function in patients with SLCI with mild hypercholesterolemia. This combination therapy has the potential to reduce the risk of cardiovascular events via improvements in endothelial function and lipid profiles.
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Antagonistas Colinérgicos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Probucol/uso terapêutico , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Tetrazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Antagonistas Colinérgicos/administração & dosagem , Cilostazol , Quimioterapia Combinada , Endotélio Vascular/efeitos dos fármacos , Feminino , Comportamentos Relacionados com a Saúde , Hemodinâmica , Humanos , Estilo de Vida , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Probucol/administração & dosagem , Estudos Prospectivos , Tetrazóis/administração & dosagem , Vasodilatação/efeitos dos fármacosRESUMO
Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases treated in Juntendo University-affiliated hospitals from 2015 to 2022. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months after treatment. The relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with detectable CTCs at baseline. Furthermore, patients demonstrating negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positivity. Two biomarkers-higher hemoglobin at baseline and achieving negative reversion of CTCs-were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC.
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Introduction: Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators. Methods: We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival. Results: The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10-5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042). Discussion: PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.
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Células Supressoras Mieloides , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/sangue , Idoso , Prognóstico , Pessoa de Meia-Idade , Neutrófilos/imunologia , Progressão da Doença , Idoso de 80 Anos ou mais , Metástase NeoplásicaRESUMO
PURPOSE: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes. METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients. CONCLUSION: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.
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Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Receptores Androgênicos/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso de 80 Anos ou mais , Povo Asiático/genética , Metástase Neoplásica , Isoformas de ProteínasRESUMO
OBJECTIVE: Japanese weekly magazines, which have a circulation of over 2 700 000, play important roles in communicating with the public. They offer a wide range of information, entertainment, gossip, politics and economics, and often include articles on cancer. However, cancer articles in magazines have not been systematically analyzed. METHODS: We investigated cancer-related articles and advertisements in six major Japanese weekly magazines to demonstrate trends in public interest regarding cancer. RESULTS: The total number of articles assessed from July 2009 to December 2010 was 36 914, of which 696 (1.9%) were cancer articles. The total number of advertisements was 21 718, of which 340 (1.6%) were related to cancer. The number of cancer articles demonstrated an upward trend during the study period. Articles focused on lung (n = 145) and urogenital cancer (n = 122). The most common content comprised therapies and diagnosis (n = 340) and case reports on individual patients (n = 160). After a famous Japanese comedian revealed his prostate cancer diagnosis, the number of articles on prostate cancer increased from 2.0 to 6.6 per month. Immunotherapy including some dubious folk therapies was the most frequently reported cancer therapy in articles and advertisements (30.4%). A small group of oncologists were repeatedly referred to in comment sources; 35.6% of comments were presented by only five doctors. CONCLUSIONS: Cancer articles in weekly magazines are common paper media for providing cancer information to the public. However, the information provided might place emphasis on unestablished treatments or biased opinions.
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Disseminação de Informação/métodos , Neoplasias , Publicações Periódicas como Assunto , Publicidade , Humanos , Japão , MasculinoRESUMO
OBJECTIVE: To assess the clinicopathologic factors influencing survival in patients with metastatic urothelial carcinoma undergoing salvage chemotherapy. METHODS: A retrospective review was conducted on cases of metastatic urothelial carcinoma who underwent cisplatin-based salvage chemotherapy at our institution between April 2003 and July 2011. The association of various clinicopathologic factors with survival was assessed. Survival curves were constructed by the Kaplan-Meier method. A log-rank test for univariate analysis and a Cox proportional hazards model for multivariate analysis were used. RESULTS: Eighty-three cases were identified in the study. Among them, 64 patients were dead during the follow-up. The median survival was 14.6 months. Multivariate analysis evaluating variables at the start of chemotherapy demonstrated that liver metastasis, performance status score ≥ 2 and leukocyte counts ≥ 8000/µl were significant predictive factors for poor outcome. Based on these three pre-induction variables, a risk model predicting the overall survival from the initiation of chemotherapy was constructed, which classified patients into three groups with significantly different overall survival (P < 0.0001). Additionally, factors after induction of chemotherapy were studied, and poor response for chemotherapy and absence of focal treatment for metastatic lesions were also significantly associated with poorer survival. CONCLUSIONS: Liver metastasis, poor performance status and higher leukocyte counts were independent poor prognostic indicators for metastatic urothelial carcinoma. Our risk classification enables an accurate prediction of survival that can be useful in deciding which patients are likely to benefit from salvage chemotherapy.
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Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação/métodosRESUMO
Introduction: Complications of cystectomy and neobladder reconstruction such as anastomotic leakage have been reported. It is a common complication; however, most cases improve conservatively. The use of fibrin glue for fistulas has been reported, but no reports have shown its effectiveness for urinary tract anastomotic leakage. We experienced a case of intractable neobladder-urethral anastomosis leakage after radical cystectomy and neobladder reconstruction, which was effectively managed using fibrin glue. Case presentation: A 70-year-old man underwent radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer with urothelial carcinoma. After surgery, the urethral catheter fell off and the anastomotic leakage did not improve by adjusting the position of the urethral catheter and percutaneous nephrostomy. We closed the intractable neobladder-urethral anastomotic leakage by injecting fibrin glue and the leakage completely disappeared. Conclusion: Injecting fibrin glue into anastomotic site can be effective in severe neobladder-urethral anastomosis leakage.
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PURPOSE: We developed a new technique to fold a neobladder (NB) simply by using a modified Vesica Ileale Padovana (VIP) with a hybrid approach. We provide a step-by-step description of our technique as it was used in this initial experience. METHODS: A total of 10 male patients with a median age of 66 years underwent robot-assisted radical cystectomy (RARC) with an orthotopic NB via a hybrid approach from March 2022 to February 2023. After the isolation of the bladder and bilateral pelvic lymphadenectomy, Wallace plate creation was performed, and the robot was undocked. We extracorporeally performed the removal of the specimen and a side-to-side ileoileal anastomosis, and then the VIP NB posterior plate was rotated 90 degrees counterclockwise using a 45 cm detubularized ileum. The robot was redocked; then, circumferential urethra-ileal anastomosis, side-to-middle anterior wall closure, and ureteric afferent limb anastomosis were performed. RESULTS: The median estimated blood loss was 524 mL, and the mean operative time was 496 min. Patients had a high continence rate, and no high-grade complications were observed. CONCLUSION: The NB configuration using the modified VIP method for a hybrid approach is a feasible surgical technique to minimize the movement of robotic forceps. In particular, it may be more useful in Asian individuals with narrow pelvises.
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BACKGROUND: It is estimated that by 2040 there will be 1,017,712 new cases of prostate cancer worldwide. Androgen deprivation therapy (ADT) is widely used as a treatment option for all disease stages. ADT, and the resulting decline in androgen levels, may indirectly affect gut microbiota. Factors affecting gut microbiota are wide-ranging; however, literature is scarce on the effects of ADT on gut microbiota and metabolome profiles in patients with prostate cancer. METHODS: To study the changes of gut microbiome by ADT, this 24-week observational study investigated the relationship between testosterone levels and changes in gut microbiota in Japanese patients with prostate cancer undergoing ADT. Sequential faecal samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, and 24 weeks after ADT. Blood samples were collected at almost the same times. Bacterial 16 S rRNA gene-based microbiome analyses and capillary electrophoresis-time-of-flight mass spectrometry-based metabolome analyses were performed. RESULTS: In total, 23 patients completed the study. The α- and ß-diversity of gut microbiota decreased significantly at 24 weeks after ADT (p = 0.017, p < 0.001, respectively). Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine changed significantly after ADT (p < 0.05). There was a significant positive correlation between the abundance of Proteobacteria, a known indicator of dysbiosis, and the concentration of lactate (R = 0.49, p < 0.01). CONCLUSIONS: The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer.
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Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Androgênios , Disbiose/induzido quimicamente , Testosterona , LactatosRESUMO
Objectives: To investigate the role of urine spermine and spermine risk score in predicting prostate cancer (PCa) diagnoses in combination with multiparametric magnetic resonance imaging (mpMRI). Methods: Three hundred forty seven consecutive men with elevated prostate-specific antigen (PSA) with mpMRI examination were prospectively enrolled in this study. In 265 patients with PSA levels between 4 and20 ng/ml, pre-biopsy urine samples were analyzed for spermine levels with ultra-high performance liquid chromatography (UPLC-MS/MS). Transperineal image-guided prostate biopsies with 16-18 cores were performed. Logistic regressions were used to form different models for the prediction of the PCa, and the performances were compared using the area under the curve (AUC). Results: The median serum PSA level and prostate volume were 7.4 ng/mL and 33.9 mL, respectively. PCa and high-grade PCa (ISUP group ≥2, HGPCa) were diagnosed in 66.0% (175/265) and 132/265 (49.8%) cases, respectively. The urine spermine levels were significantly lower in men with PCa (0.87 vs. 2.20, P < 0.001). Multivariate analyses showed that age, PSA, PV, urine spermine level, and Prostate Imaging Reporting and Data System (PI-RADS) findings were independent predictors for PCa. The Spermine Risk Score is a multivariable model including PSA, age, prostate volume, and urine spermine. Adding the Spermine Risk Score to PI-RADS improved the AUC from 0.73 to 0.86 in PCa and from 0.72 to 0.83 in high grade PCa (HGPCa) prediction (both P < 0.001). At 90% sensitivity for HGPCa prediction using Spermine Risk Score, 31.1% of unnecessary biopsies could be avoided. In men with equivocal MRI PI-RADS score 3, the AUC for HGPCa prediction was 0.58, 0.79, and 0.87 for PSA, PSA density, and Spermine Risk Score, respectively. Conclusion: Urine Spermine Risk Score, including mpMRI could accurately identify men at high risk of HGPCa and reduce unnecessary prostate biopsies. Spermine Risk Score could more accurately predict HGPCa than PSA density in men with MRI showing equivocal PI-RADS 3 lesions.