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1.
Cancer Sci ; 115(2): 529-539, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38083992

RESUMO

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.


Assuntos
Carcinoma de Células de Transição , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/cirurgia , DNA Tumoral Circulante/genética , Estudos Prospectivos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Biomarcadores , Biomarcadores Tumorais/genética
2.
Jpn J Clin Oncol ; 54(4): 489-497, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38157885

RESUMO

OBJECTIVE: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer. METHODS: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed. RESULTS: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149). CONCLUSIONS: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Proteína BRCA1/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteína BRCA2/genética , Receptores Androgênicos/uso terapêutico , Prevalência , Japão/epidemiologia , Antineoplásicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Taxoides/uso terapêutico , Células Germinativas
3.
Int J Urol ; 31(3): 259-264, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38041218

RESUMO

OBJECTIVES: Nocturnal polyuria (NP) is one of the causes of nocturia that impairs quality of life. It is necessary to consider that NP is latent when the initial treatment for nocturia is unsatisfactory. Therefore, it is important to establish a treatment for NP based on the pathophysiology. We have previously reported the relationship between NP and fluctuation in blood pressure. The present study aimed to investigate the association between NP and 24-h blood pressure fluctuations in a multicenter prospective study. METHODS: This study included male patients with lower urinary tract symptoms. We categorized the patients into the nonnocturnal polyuria (non-NP) group (≤0.33) and the NP group (>0.33) based on the nocturnal polyuria index from the frequency volume chart. We measured the 24-h diurnal blood pressure and compared the two groups. RESULTS: Among 90 patients, 46 in the non-NP group and 44 in the NP group were included. There was no significant difference in the systolic and diastolic blood pressure during waking time between the two groups; however, the degree of systolic blood pressure reduction during sleep time in the NP group was significantly less than that in the non-NP group (p = 0.039). In the multivariate analysis, systolic BP during sleep was significantly associated with NP (OR 0.970, p = 0.028). CONCLUSION: NP is associated with inadequate nocturnal blood pressure reduction in males, suggesting that reduction in nocturnal blood pressure may lead to improvement in nocturia.


Assuntos
Sintomas do Trato Urinário Inferior , Noctúria , Humanos , Masculino , Noctúria/epidemiologia , Noctúria/etiologia , Noctúria/diagnóstico , Poliúria/complicações , Estudos Prospectivos , Pressão Sanguínea , Qualidade de Vida
4.
Int J Clin Oncol ; 28(11): 1538-1544, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37740070

RESUMO

BACKGROUND: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). METHODS: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. RESULTS: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. CONCLUSION: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Prognóstico , Neoplasias Renais/patologia , Estudos Retrospectivos , Japão , Nefrectomia
5.
Hinyokika Kiyo ; 69(8): 227-232, 2023 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-37667600

RESUMO

A 73-year-old man with renal cell carcinoma underwent a left-sided open radical nephrectomy at our center. The pathological diagnosis was Fuhrman Grade 2, stage pT3a, clear cell renal cell carcinoma. A follow-up computed tomography (CT) scan revealed lung metastases 9 months after the surgery. The patient was started on ipilimumab with nivolumab combination therapy; however, after two cycles of administration, he developed arthralgia and swelling of the knee. Furthermore, he developed diarrhea almost simultaneously, resulting in the interruption of the ipilimumab plus nivolumab treatment. We diagnosed arthritis and colitis with immune-related adverse events (irAE) and initiated steroid therapy with rehabilitation. His condition improved dramatically, and nivolumab treatment could be resumed after 3 months of treatment interruption.


Assuntos
Artrite , Carcinoma de Células Renais , Colite , Neoplasias Renais , Masculino , Humanos , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Colite/induzido quimicamente
6.
Cancer Sci ; 113(12): 4059-4069, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35848083

RESUMO

Human leukocyte antigen class I (HLA-I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA-I and -II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab. Among the 108 patients, 69 died and 83 showed radiographic progression during follow-up. Homozygous for at least one HLA-I locus, absence of the HLA-A03 supertype, and high HLA-I evolutionary divergence were associated with a radiographic response, but were not associated with survival outcomes. Patients with the HLA-DQB1*03:01 allele had significantly lower disease control rates than patients without the allele (17.4% vs. 53.8%, p = 0.002); its presence was also an independent risk factor for progressive disease (hazard ratio 4.35, 95% confidence interval 1.03-18.46). Furthermore, patients with the HLA-DQB1*03:01 allele had significantly worse progression-free survival than patients without the allele (median progression-free survival 3.1 vs. 4.8 months, p = 0.035). There was no significant relationship between any HLA status and the incidence of severe adverse events. Several germline HLA genotypes, especially HLA-DQB1*03:01, may be associated with radiographic progression. However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.


Assuntos
Carcinoma de Células de Transição , Genes MHC da Classe II , Genes MHC Classe I , Neoplasias da Bexiga Urinária , Humanos , Alelos , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Genótipo , Intervalo Livre de Progressão , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
7.
Br J Cancer ; 126(4): 606-614, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34782748

RESUMO

BACKGROUND: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. METHODS: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (

Assuntos
Linfócitos T CD8-Positivos/metabolismo , Receptores Depuradores Classe A/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Cistectomia , Tratamento Farmacológico , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral , Neoplasias da Bexiga Urinária/imunologia
8.
Jpn J Clin Oncol ; 52(11): 1345-1352, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920793

RESUMO

BACKGROUND: Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis. METHODS: This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients' medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment. RESULTS: Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months. CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Ipilimumab/uso terapêutico , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Japão , Estudos Retrospectivos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
9.
Int J Clin Oncol ; 27(3): 563-573, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34973106

RESUMO

BACKGROUND: This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. METHODS: We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. RESULTS: Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29-0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11-0.59, p < 0.01). CONCLUSIONS: Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Estudos Retrospectivos
10.
Hinyokika Kiyo ; 68(2): 47-51, 2022 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-35259863

RESUMO

A 75-year-old male visited a clinic with the chief complaint of pollakiuria. A computed tomography scan revealed, a left adrenal mass, and the patient was then referred to our hospital. Since a malignant tumor could not be ruled out. We performed laparoscopic left adrenal resection. Postoperative histopathological findings revealed the mass to be a bronchogenic cyst, which had no continuity with the normal adrenal gland. The postoperative course was uneventful, and recurrence has not been observed. Retroperitoneal bronchogenic cysts are rare and often difficult to diagnose preoperatively using imaging studies.


Assuntos
Neoplasias das Glândulas Suprarrenais , Cisto Broncogênico , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais , Idoso , Cisto Broncogênico/diagnóstico por imagem , Cisto Broncogênico/cirurgia , Humanos , Masculino , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/patologia , Tomografia Computadorizada por Raios X
11.
Int J Clin Oncol ; 26(10): 1947-1954, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34191191

RESUMO

BACKGROUND: The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. METHODS: We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. RESULTS: The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9-46.8), not reached (63.5 to not estimable), 46.8 months (37.1-52.9), and 10.4 months (8.9-14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4-56.5), and 11.5 (9.9-16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. CONCLUSION: While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Japão , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular , Prognóstico , Estudos Retrospectivos
12.
Int J Urol ; 28(4): 369-375, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314387

RESUMO

OBJECTIVES: To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. METHODS: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score-based inverse probability of treatment weighting method to adjust for group imbalances. RESULTS: The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. CONCLUSIONS: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
13.
BMC Med Educ ; 21(1): 498, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548032

RESUMO

BACKGROUND: A virtual reality (VR) simulator is utilized as an inexpensive tool for gaining basic technical competence in robotic-assisted surgery (RAS). We evaluated operator 3D motion sickness while using a VR simulator and assessed whether it can be reduced by repeating the training. METHODS: This prospective observational study was conducted at the Department of Urology, Iwate Medical University, a tertiary training hospital in an urban setting. A total of 30 undergraduate medical students participated in the study. We compared whether the VR simulator improved the students' skills in operating the da Vinci robot. Fifteen students underwent training with a VR simulator for 4 h a day for 5 days. Then, motion sickness was determined using the Visual Analog Scale and Simulator Sickness Questionnaire (SSQ) before and after the training. RESULTS: Manipulation time significantly improved after training compared to before training (293.9 ± 72.4 versus 143.6 ± 18.4 s; p < 0.001). Although motion sickness worsened after each training session, it gradually improved with continuous practice with the VR simulator. SSQ subscores showed that the VR simulator induced nausea, disorientation, and oculomotor strain, and oculomotor strain was significantly improved with repeated training. CONCLUSIONS: In undergraduate students, practice with the VR simulator improved RAS skills and operator 3D motion sickness caused by 3D manipulation of the da Vinci robot.


Assuntos
Enjoo devido ao Movimento , Procedimentos Cirúrgicos Robóticos , Estudantes de Medicina , Realidade Virtual , Competência Clínica , Simulação por Computador , Humanos , Estudos Prospectivos , Interface Usuário-Computador
14.
Mol Carcinog ; 59(4): 412-424, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32039517

RESUMO

Somatic copy number alterations (SCNAs) are important biological characteristics that can identify genome-wide alterations in renal cell carcinoma (RCC). Recent studies have shown that SCNAs have potential value for determining the prognosis of RCC. We examined SCNAs using the Affymetrix platform to analyze samples from 59 patients with clear cell RCCs (ccRCCs) including first cohort (30 cases) and second cohort (validation cohort, 29 cases). We stratified SCNAs in the ccRCCs using a hierarchical cluster analysis based on SCNA types, including gain, loss of heterozygosity (LOH), copy neutral LOH, mosaic, and mixed types. In this way, the examined two cohorts were categorized into two subgroups (1 and 2). Although the frequency of mixed type was higher in subgroup 1 than in subgroup 2 in the two cohorts, the association did not reach statistical significance. There was a significant difference in the frequency of metachronous metastasis between subgroups 1 and 2 (subgroup 2 > 1). In addition, subgroup 2 was retained in multivariate analysis of both cohorts. We examined whether there were specific alleles differing between subgroups 1 and 2 in both cohorts. We found that there was indeed a statistically significant difference in the 3p mixed types. Among the 3p mixed type, we found that 3p24.3 mixed type was inversely correlated with the presence of metachronous metastasis in ccRCC. The association was also retained in multivariate analysis in second cohort. We suggest that the 3p24.3 mixed type may be a novel marker to predict a favorable prognosis in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA , Neoplasias Renais/genética , Perda de Heterozigosidade , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Análise por Conglomerados , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Prognóstico
15.
Int J Clin Oncol ; 25(5): 899-905, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31907720

RESUMO

BACKGROUND: Prognostic outcomes and safety following treatment with pembrolizumab in patients with advanced urothelial carcinoma (UC) have not been fully elucidated in clinical practice. The aim of this study was to evaluate the oncological efficacy and safety of pembrolizumab after failure of platinum-based chemotherapy in Japanese patients with advanced UC in a routine clinical setting. METHODS: This retrospective study included 41 consecutive Japanese patients with advanced UC treated with pembrolizumab as second-line or greater therapy at Iwate Medical University Hospital from January 2018 to April 2019. RESULTS: The mean follow-up period was 6.2 months. The objective response rate, median progression-free survival, and median overall survival were 15%, 2.5 months, and 11.9 months, respectively. Univariate analysis identified poor performance status (> 1), liver metastasis, two or more metastatic organs, low hemoglobin levels, two or more prior regimens, high baseline C-reactive protein levels, higher relative C-reactive protein level change after 6 weeks, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks as significant predictors of overall survival. Among these factors, poor performance status (> 1), two or more metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks were identified as independent predictors of overall survival in multivariate analysis. CONCLUSIONS: The introduction of pembrolizumab can result in favorable cancer control outcomes in Japanese patients with advanced UC, and the prognosis of these patients can be stratified according to three potential parameters, including poor performance status, high number of metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Proteína C-Reativa/análise , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
16.
Cancer Sci ; 109(3): 550-559, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29345737

RESUMO

Use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and lack significant side-effects when given in vivo. Peptide-based vaccine therapy against several cancers including urological cancers has made progress for several decades, but there is no worldwide approved peptide vaccine. Peptide vaccines were also shown to induce a high frequency of immune response in patients accompanied by clinical efficacy. These data are discussed in light of the recent progression of immunotherapy caused by the addition of immune checkpoint inhibitors thus providing a general picture of the potential therapeutic efficacy of peptide-based vaccines and their combination with other biological agents. In this review, we discuss the mechanism of the antitumor effect of peptide-based vaccine therapy, development of our peptide vaccine, recent clinical trials using peptide vaccines for urological cancers, and perspectives of peptide-based vaccine therapy.


Assuntos
Imunoterapia Ativa/métodos , Neoplasias Urológicas/tratamento farmacológico , Vacinas de Subunidades Antigênicas/uso terapêutico , Antígenos de Neoplasias/imunologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/imunologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/imunologia , Vacinas de Subunidades Antigênicas/síntese química
17.
Cancer Immunol Immunother ; 67(9): 1371-1380, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29971464

RESUMO

PURPOSE: A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups. RESULTS: A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019). CONCLUSIONS: Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.


Assuntos
Vacina BCG/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Proteínas Ativadoras de GTPase/imunologia , Imunoterapia Ativa/métodos , Cinesinas/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias da Bexiga Urinária/terapia , Vacinas de Subunidades Antigênicas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas Anticâncer/imunologia , Intervalo Livre de Doença , Feminino , Antígeno HLA-A24/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Linfócitos T Citotóxicos/imunologia , Neoplasias da Bexiga Urinária/imunologia , Vacinas de Subunidades Antigênicas/imunologia
18.
BMC Urol ; 18(1): 28, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29716558

RESUMO

BACKGROUND: Reduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision. CASE PRESENTATION: Case 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (-)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1. CONCLUSIONS: Although more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Neoplasias Esplênicas/cirurgia , Ferida Cirúrgica , Umbigo/cirurgia , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Esplênicas/diagnóstico por imagem
20.
World J Surg Oncol ; 16(1): 224, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445961

RESUMO

PURPOSE: We investigated that preoperative membranous urethral length (MUL) would be associated with the recovery of urinary continence after robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: We studied 204 patients who underwent RALP between May 2013 and March 2016. All patients underwent pelvic magnetic resonance imaging (MRI) preoperatively to measure MUL. Urinary continence was defined as the use of one pad or less (safety pad). The 204 patients were divided into two groups: continence group, those who achieved recovery of continence at 3, 6, and 12 months after RALP, and incontinence group, those who did not. We retrospectively analyzed the patients in terms of preoperative clinical factors including age, body mass index (BMI), estimated prostate volume, neurovascular bundle salvage, history of preoperative hormonal therapy, and MUL. RESULTS: The safety pad use rate was 69.6%, 86.9%, and 91.1% at 3, 6, and 12 months, respectively. On univariate and multivariate analyses, MUL were significant factors in every term of recovery of urinary continence in both groups. According to the receiver operating characteristic (ROC) curve analysis, the preoperative MUL that could best predict early recovery of urinary continence at 3 months after RALP was 12 mm. CONCLUSIONS: We suggest that preoperative MUL > 12 mm would be a predictor of early recovery of urinary continence after RALP.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Uretra/fisiopatologia , Incontinência Urinária/epidemiologia , Adulto , Idoso , Humanos , Japão/epidemiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Período Pré-Operatório , Prognóstico , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Fatores de Tempo , Uretra/anatomia & histologia , Uretra/diagnóstico por imagem , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia
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