RESUMO
Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.
Assuntos
Carcinoma de Células Renais , Genótipo , Antígenos HLA , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antígenos HLA/genética , Antígenos HLA/imunologia , Nivolumabe/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/genética , Adulto , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.
Assuntos
Antibacterianos , Levofloxacino , Testes de Sensibilidade Microbiana , Infecções Urinárias , Humanos , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/tratamento farmacológico , Japão/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Farmacorresistência Bacteriana , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Feminino , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Monitoramento Epidemiológico , População do Leste AsiáticoRESUMO
BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. METHODS: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. RESULTS: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nivolumabe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Estudo de Associação Genômica Ampla , Intervalo Livre de Progressão , Polimorfismo de Nucleotídeo Único , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genéticaRESUMO
OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Índice de Massa Corporal , Neoplasias Renais/patologia , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , PrognósticoRESUMO
BACKGROUND: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. METHODS: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). RESULTS: We included 222 patients. The median age was 69 years (interquartile range 62-74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. CONCLUSION: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Carcinoma de Células Renais/patologia , Nivolumabe/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/patologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We retrospectivelyevaluated postoperative inguinal hernias (PIHs) after robot-assisted radical prostatectomy(RARP) with a technique for preventing hernias byspermatic cord isolation. Among the RARPs performed from 2016 to 2018, 191 cases were evaluated 12 or more months after surgery. In all the cases, the peritoneum was isolated from the spermatic cord by5 cm or more as a hernia prevention technique during RARP. We compared the background factors between PIH-positive and PIH-negative groups. The PIH-positive group had a significantlylower bodymass index (BMI) than the PIH-negative group (20.6 kg/m2 vs 23.8 kg/m2, pï¼0.0079), but there were no significant differences in other background factors. When patients were classified into three groups byBMI, low (ï¼21.9 kg/m2), intermediate (21.9 to 25.5 kg/m2), and high (ï¼25.5 kg/m2), the rate of PIH was 8.5% for the low group, 2.1% for the intermediate group, and 0% for the high group. Our findings suggest that incidences of inguinal hernias after the preventive technique of spermatic cord isolation in RARP, and the BMIs tended to be low in the hernia cases.
Assuntos
Hérnia Inguinal , Neoplasias da Próstata , Robótica , Cordão Espermático , Hérnia Inguinal/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias/prevenção & controle , Prostatectomia , Neoplasias da Próstata/cirurgia , Cordão Espermático/cirurgiaRESUMO
The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.
Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Testes de Sensibilidade Microbiana/métodos , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Japão/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Levofloxacino/farmacologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Proteus mirabilis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Vancomicina/uso terapêutico , Adulto JovemRESUMO
The clinical outcome of laparoscopic radical prostatectomy (LRP) was retrospectively investigated taking into consideration the surgeon's position during the procedure. The study cohort included 184 consecutive patients who had undergone LRP performed by a single surgeon from February 2013 to July 2018. During the study period,the surgeon stood alternately on either the left or right side of the patient. The D'Amico risk classification was low,intermediate and high in 26 (14.1%),45 (24.5%) and 113 (61.4%) patients,respectively. Mean surgical duration was 203.5 minutes and mean estimated blood loss was 437.6 ml. Nerve sparing (NS) was implemented in 82 (44. 6%) patients. The mean period of having an indwelling urethral catheter was 5. 0 days. Perioperative Clavien-Dindo degree ≥IIIa complications occurred in three (1.6%) patients. Except for cases with presurgical hormonal treatment,surgical margins were positive in 41 (22.3%) patients,among whom 23 (17.4%) had pT2 disease. The 5-year biochemical recurrence-free survival rate was 81.4%,and 84.8% of patients regained urinary continence at 12 months after surgery. Where the surgeon stood during LRP was not associated with significant differences in any parameter. However,the margin positive rate was higher on the side away from where the surgeon stood than the side closer to the surgeon (70.7% vs 29.3%). In conclusion,the position of the surgeon during LRP does not influence the outcome.
Assuntos
Laparoscopia , Neoplasias da Próstata/cirurgia , Cirurgiões , Humanos , Masculino , Prostatectomia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The aim of this study is to clarify the incidences of infected pelvic lymphocele (IPL) after robot-assisted radical prostatectomy (RARP). From 2016 to 2017, we evaluated 173 consecutive patients who underwent RARP. The transperitoneal approach was used for the RARPs. Limited lymph node dissection was performed in the pelvic lymphoceles region surrounding the obturator nerve. Patients with IPL were defined as those with infected pelvic lymphoceles classified as Clavien-Dindo (CD) classification system grade II or greater and a fever over 38 degrees Celsius. All other cases were defined as nonIPL. IPL was observed in 5 cases (2.9%) that were classified as CD grade II in 2 cases, IIIa in 2 cases, and IVa in 1 case. The most severe case (CD grade IVa) required temporary dialysis for acute renal failure during conservative treatment. While the dissected lymph nodes in the IPL group were sificantly greater than those in the nonlPL group (20.8 ± 7.1 vs 10.3 ± 6.0, P = 0.0298) and the preoperative prostate specific antigen in the IPL group was significantly higher than that in the nonIPL group (15.6 ± 21.7 ng/ml vs 9.0 ± 6.1 ng/ml, P = 0.0359), there were no significant differences in the other background factors between the two groups. In the multivariate analysis, the number of dissected lymph nodes was an independent predictive factor for IPL. While the incidences of IPL after RARP were low, the number of dissected lymph nodes was related to IPL.
Assuntos
Linfocele , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Excisão de Linfonodo , Linfocele/microbiologia , Linfocele/cirurgia , Masculino , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgiaRESUMO
We evaluated 52 consecutive cases of patients undergoing second transurethral resections (TUR) for non-muscle invasive bladder cancer (NMIBC) in which the patients were diagnosed with high grade pT1 by the initial TUR under narrow band imaging (NBI). The initial TUR under NBI (NBI-TUR) was performed : Systematic intravesical observation under white light imaging (WLI) and NBI was followed by a multiple site biopsy (MSB), after which lesions detected in positive findings were resected completely under NBI. The tumor detection rates under WLI and NBI were calculated separately and compared with endoscopic findings and MSB samples. The second TUR was performed as a resection that included the surrounding mucosa and muscle layer of the initial NBI-TUR scar under WLI observation, 4-8 weeks after the initial NBI-TUR. The patients were divided into two groups : The residual cancer lesion-positive group (NBIR positive), and the residual cancer lesion-negative group (NBIR negative). The tumor detection rate under NBI was more sensitive compared with that under WLI in the initial NBI-TUR (89.4% vs 59.1% p< 0.0001), and the residual cancer detection rate in the 2nd TUR reached 34.6% (18/52). There was no significant difference in the background factors between the NBIR positive and NBIR negative. While the number of cancer lesions detected under NBI was significantly higher than that under WLI in the NMIBCdiagnosed high grade pT1, the rate of cancer lesions that were difficult to identify in the initial NBI-TUR was still high. These findings demonstrate the limitations of the mono-therapeutic effect of NBI-TUR.
Assuntos
Neoplasias da Bexiga Urinária , Cistoscopia , Humanos , Imagem de Banda Estreita , Neoplasia Residual , Neoplasias da Bexiga Urinária/diagnóstico , Procedimentos Cirúrgicos UrológicosRESUMO
The aim of this study was to reveal the clinical benefits of transurethral resection (TUR) under narrow band imaging (NBI-TUR) for non-muscle-invasive bladder cancer (NMIBC) compared with conventional white light imaging TUR (WLI-TUR). The subjects were 172 patients with NMIBC who were followed for more than 1 year after undergoing TUR with no additional postoperative treatment. In the WLI-TUR group (n=101), lesions that were detected as positive after systematic intravesical observation under WLI were resected completely under WLI. In the NBI-TUR group (n=71), similar observations under WLI were followed by systematic intravesical observation under NBI. After multiple site biopsy under NBI, TUR was performed for all lesions that were detected as positive under NBI. The sensitivity was calculated based on the results of cystoscopy and pathology of multiple site biopsy samples under WLI and NBI in the NBITUR group. The tumor recurrence rate was analyzed in both groups. Background factors did not differ significantly between the two groups, except for the observation period (63.3 months in the WLI-TUR group vs 42.0 months in the NBI-TUR group, p<0.01). The procedure under NBI had significantly higher sensitivity (94.6% vs 75.0%, p<0.01) compared with that under WLI. The recurrence-free rate in the NBITUR group was significantly higher than that in the WLI-TUR group (p=0.013). The tumor recurrencefree rate of NBI-TUR is higher than that of conventional WLI-TUR for patients with NMIBC.
Assuntos
Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Cistoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The aim of this study was to compare the perioperative results of robot-assisted partial nephrectomy (RAPN) with those of laparoscopic partial nephrectomy (LPN) for cT1 renal tumors. From August 2015 to March 2018, 63 consecutive cases undergoing LPN and RAPN (30 cases of LPN and 33 cases of RAPN) for renal tumors ≤7cm in diameter (cTla: 42 cases and cT1b: 21 cases) were evaluated. The trifecta was defined on the basis of the following three criteria: ischemic time less than 25 minutes, no positive surgical margin, and no perioperative complications within four weeks postoperative. The background factors were compared between the two groups. There were no cases requiring changes in the operation methods. There was no significant difference in age, body mass index, gender, or tumor side between the two groups. While the mean tumor diameter and mean RENAL nephrometry score (RNS) were 32.6 mm and 7.3, respectively, there were no differences between the two groups. The warm ischemic time of RAPN was significantly shorter than that of LPN (12.7 min vs 19.9 min, P = 0.0007), and the estimated blood loss of RAPN was less than that of LPN (58.6 ml vs 160.3 ml, P = 0.0005). While there was no apparent tumor damage, tumor exposure on the resection surface was observed in two cases. Perioperative complications were observed in four cases. The trifecta achievement rate of RAPN and that of LPN was 93.9% (31 cases) and 66.7% (20 cases), respectively. The initial perioperative results of RAPN were comparable with those of LPN for cT1 renal tumors.
Assuntos
Neoplasias Renais , Laparoscopia , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the relationship between chronic kidney disease and primary non-muscle-invasive bladder cancer. METHODS: Disease outcomes were analyzed in 418 patients treated with transurethral resection for primary non-muscle-invasive bladder cancer, and were correlated to traditional risk factors as well as chronic kidney disease stage according to estimated glomerular filtration rate: ≥60 (G1-2), 45-59 (G3a) or <45 (G3b-5). RESULTS: The median follow-up time was 40.0 months. There were 287 (68.7%), 98 (23.4%), and 33 (7.9%) patients with G1-2, G3a and G3b-5 chronic kidney disease, respectively. T1 tumor was present in 29.6% of G1-2, 43.9% of G3a and 51.4% of G3b-5 chronic kidney disease (P = 0.004). The proportion of histological grade 3 non-muscle-invasive bladder cancer was higher in G3a and G3b-5 than G1-2 (P < 0.001). Higher chronic kidney disease stage was associated with worse recurrence-free (P < 0.001) and progression-free survival (P = 0.017). In multivariable analysis, G3b-5 was found to be an independent predictor for recurrence (hazard ratio 1.87; P = 0.004) and progression (hazard ratio 2.96; P = 0.019). Chronic kidney disease stage was also strongly associated with the European Association of Urology bladder cancer risk groups (P < 0.001), and with shorter time to recurrence and progression in each group. CONCLUSIONS: Chronic kidney disease predicts the clinical outcome of primary non-muscle-invasive bladder cancer. Adding chronic kidney disease to the conventional risk factors might increase the accuracy of risk stratification.
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Taxa de Filtração Glomerular/fisiologia , Rim/fisiopatologia , Recidiva Local de Neoplasia/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Neoplasias da Bexiga Urinária/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/fisiopatologia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Neoplasias da Bexiga Urinária/fisiopatologiaRESUMO
OBJECTIVES: To investigate the impact of pretreatment serum C-reactive protein (CRP) level and its change after targeted therapy on the anti-tumour effect of targeted agents in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: The serum CRP level in 190 cases of molecular targeted therapy for mRCC was measured before starting the prescription of molecular targeted agents and when computed tomography showed the maximum effect. Patients in which the pretreatment CRP level was ≥0.5 mg/dL were classified into a 'higher-CRP' group and others into a 'lower-CRP' group. The higher-CRP group was further classified into two subgroups, i.e. those whose serum CRP level decreased after molecular targeted therapy ('decreased-CRP' subgroup), and those whose level did not decrease after therapy ('non-decreased-CRP' subgroup). All patients were also classified according to their other clinical details and progression-free survival (PFS) rates of each subgroup were compared. RESULTS: Of the 190 patients, 97 were categorised as lower CRP and 93 as higher CRP, with 50 and 43 patients in the higher-CRP group further categorised as decreased- and non-decreased-CRP subgroups, respectively. For the maximum effects of the targeted therapy, determined based on the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in the lower-CRP group, significantly more patients had a complete response (CR) and partial response (PR) (P = 0.002) and significantly fewer had progressive disease (PD) (P < 0.001) vs the higher-CRP group. In the higher-CRP group, significantly fewer patients had PD in the decreased-CRP subgroup (P < 0.001) than those in the non-decreased-CRP subgroup. The 2-year PFS rate for the lower-CRP group (39.1%) was significantly better vs the decreased-CRP subgroup (21.2%; P = 0.013) and significantly better vs the non-decreased CRP subgroup (0%; P < 0.001). Multivariate analyses in the higher-CRP group revealed that decreased CRP was an independent predictive factor for PFS (P = 0.002, hazard ratio 2.454, 95% confidence interval 1.404-4.290). CONCLUSION: A decrease of CRP and pretreatment CRP levels show promise as a novel predictive factor for anti-tumour effects in patients treated with molecular targeted therapy.
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Biomarcadores Tumorais/metabolismo , Proteína C-Reativa/metabolismo , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Terapia de Alvo Molecular , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/sangue , Feminino , Humanos , Neoplasias Renais/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan. METHODS: In this multicenter, prospective study, provisionally registered patients with histologically confirmed metastatic clear cell RCC received natural IFN-α (3 dosages of 3 million U per week) for 2 weeks. Only IFN-α-tolerant patients were registered to this trial, and treated additionally with oral sorafenib (400 mg, bid). The primary end point of the study was rate of response (CR + PR) to sorafenib plus IFN-α treatment assessed using RECIST v1.0. The secondary end points were disease control rate (CR + PR + SD), progression free survival (PFS), overall survival (OS), and safety of the combined treatment. PFS and OS curves were plotted using the Kaplan-Meier method. RESULTS: From July 2009 to July 2012, a total of 53 untreated patients were provisionally registered, and 51 patients were finally registered. Rate of Response to the combined therapy of sorafenib plus IFN-α was 26.2 % (11/42) (CR 1, PR 10). The median PFS was 10.1 months (95 % CI, 6.4 to 18.5 months), and the median OS has not been reached yet. The combined therapy increased neither the incidence of adverse effects (AE) nor the incidence of unexpected AE. A limitation was that a relatively high number of patients (9 patients) were excluded for eligibility criteria violations. CONCLUSION: Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients. TRIAL REGISTRATION: UMIN000002466 , 9(th) September, 2009.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Interferon-alfa/administração & dosagem , Japão , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Sorafenibe , Resultado do TratamentoRESUMO
OBJECTIVES: To examine the usefulness of an absorbable hemostatic gelatin sponge for hemostasis after transrectal prostate needle biopsy. SUBJECTS AND METHODS: The subjects comprised 278 participants who underwent transrectal prostate needle biopsy. They were randomly allocated to the gelatin sponge insertion group (group A: 148 participants) and to the non-insertion group (group B: 130 participants). In group A, the gelatin sponge was inserted into the rectum immediately after biopsy. A biopsy-induced hemorrhage was defined as a case in which a subject complained of bleeding from the rectum, and excretion of blood clots was confirmed. A blood test was performed before and after biopsy, and a questionnaire survey was given after the biopsy. RESULTS: Significantly fewer participants in group A required hemostasis after biopsy compared to group B (3 (2.0%) vs. 11 (8.5%), P=0.029). The results of the blood tests and the responses from the questionnaire did not differ significantly between the two groups. In multivariate analysis, only "insertion of a gelatin sponge into the rectum" emerged as a significant predictor of hemostasis. CONCLUSION: Insertion of a gelatin sponge into the rectum after transrectal prostate needle biopsy significantly increases hemostasis without increasing patient symptoms, such as pain and a sense of discomfort.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Hemorragia Gastrointestinal/prevenção & controle , Esponja de Gelatina Absorvível/uso terapêutico , Hemostasia/fisiologia , Hemostáticos/uso terapêutico , Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Métodos Epidemiológicos , Hemorragia Gastrointestinal/etiologia , Técnicas Hemostáticas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Neoplasias da Próstata/patologia , Reto/cirurgia , Valores de Referência , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
PURPOSE: We evaluated the safety and efficiency of using the mesh plug method (MP) to repair inguinal hernias in patients with a history of radical retropubic prostatectomy (RRP). We also investigated how RRP influences the development of inguinal hernias and impacts their repair. METHODS: Among 488 adult male patients who underwent inguinal hernia repair during a recent 5-year period, 37 had a history of RRP. We compared the characteristics and surgical outcomes of the patients who had undergone RRP (post-RRP group) with those who had not (non-RRP group). RESULTS: All post-RRP hernias were treated by MP. The 37 post-RRP patients had a collective 41 hernias, 40 of which were of the indirect type. The side affected by the hernia did not differ significantly between the groups. We compared the short-term surgical outcomes of the indirect post-RRP hernias vs. the indirect non-RPP hernias without recurrence and incarceration. The operation times, postoperative hospital stay, and mobility rates did not differ significantly between the two groups. The blood loss was almost equal in both groups. CONCLUSION: Inguinal hernia repair after RRP may be difficult because of inflammatory changes in the preperitoneal cavity, but the surgical outcomes of MP were equivalent in patients with or without a history of RPP in this study. MP is a safe and effective method for post-RPP hernia repair.
Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Complicações Pós-Operatórias/cirurgia , Prostatectomia , Telas Cirúrgicas , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Polipropilenos , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Antineoplásicos Imunológicos/uso terapêutico , Proteína C-Reativa/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Renais/sangue , Humanos , Neoplasias Renais/sangueRESUMO
AIM: This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method. RESULTS: The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length > 5.0 mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p = 0.985), while the high-risk group had significantly worse BRFS than the other groups (p < 0.001). CONCLUSION: Maximum PSM length > 5.0 mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.
RESUMO
Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.