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1.
BJU Int ; 134(2): 207-218, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38344879

RESUMO

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Japão/epidemiologia
2.
Int J Urol ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822533

RESUMO

OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.

3.
Eur J Clin Pharmacol ; 79(1): 89-98, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36378297

RESUMO

PURPOSE: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). METHODS: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. RESULTS: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20-23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66-14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. CONCLUSIONS: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Estudos Prospectivos , Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteínas de Membrana/uso terapêutico , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/uso terapêutico
4.
Int J Clin Oncol ; 28(11): 1530-1537, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37552353

RESUMO

BACKGROUND: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years. METHODS: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877). CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Idoso , Carcinoma de Células Renais/patologia , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias Renais/patologia , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
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
6.
World J Urol ; 40(5): 1135-1141, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35218371

RESUMO

PURPOSE: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). METHODS: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). RESULTS: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27-0.56 vs. HR 0.50; 95% CI 0.30-0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50-1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30-0.98 vs. HR 0.49; 95% CI 0.29-0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34-2.06). CONCLUSION: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Castração , Docetaxel/uso terapêutico , Humanos , Masculino , Pontuação de Propensão , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos
7.
Int J Clin Oncol ; 27(9): 1477-1486, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35748967

RESUMO

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Castração , Docetaxel/uso terapêutico , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
8.
World J Surg Oncol ; 20(1): 202, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35701769

RESUMO

INTRODUCTION: Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN. MATERIALS AND METHODS: In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1-38, period 2: 39-76, and period 3: 77-114. The clinical factors associated with longer WIT were analyzed per period. RESULTS: The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004-15.276; p = 0.044), but the tumor diameter and the total RENAL score were not. CONCLUSIONS: A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN.


Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Humanos , Neoplasias Renais/patologia , Nefrectomia/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Isquemia Quente
9.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35216332

RESUMO

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Neoplasias da Próstata/microbiologia , Neoplasias da Próstata/fisiopatologia , Animais , Clostridiales/fisiologia , Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fezes/microbiologia , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/fisiopatologia , Neoplasias da Próstata/metabolismo , Aumento de Peso/fisiologia
10.
Hinyokika Kiyo ; 68(8): 265-269, 2022 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-36071018

RESUMO

A 65-year-old man was found to have a 1.7 cm right renal mass by follow-up abdominal computed tomography for left total nephrectomy after a traffic accident. The renal mass progressed slowly to 2.2 cm in three years and enhanced magnetic resonance imaging revealed marked T2 weighting hyperintensity of the lesion. Although a radiologist (TK) suggested the diagnosis renal anastomosing hemangioma preoperatively, we could not deny the possibility of renal cell carcinoma completely. Therefore, the patient underwent robot-assisted laparoscopic partial nephrectomy. The tumor was successfully removed without any renal arterial clamping or parenchymal excision. Histopathologically, the lesion was composed of capillary-size blood vessels lined by a single layer of endothelial cells, and was diagnosed as a renal anastomosing hemangioma. There were no signs of postoperative recurrence during the 3 month follow-up.


Assuntos
Carcinoma de Células Renais , Hemangioma , Neoplasias Renais , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Células Endoteliais/patologia , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Masculino , Nefrectomia/métodos
11.
Hinyokika Kiyo ; 68(4): 99-105, 2022 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-35613897

RESUMO

Magnetic resonance imaging (MRI) ultrasound fusion biopsy is becoming popular owing to the better detection rate of clinically significant prostate cancer (csPCa). We retrospectively evaluated the accuracy of MRI-targeted biopsy during the period of introduction at a single academic center by comparing findings of its specimen and whole-mount histopathology. Between June 2018 and January 2021, 106 transperineal MRI-ultrasound fusion biopsies using BioJet software were performed. Among the cases, 15 subsequently underwent robotic-assisted laparoscopic radical prostatectomy and were eligible for analysis. This study included all regions of interest (ROIs) with a Prostate Imaging Reporting and Data System v2 category of 3 or greater on pre-biopsy MRI.For each lesion, grade group of MRI-targeted biopsy specimens and prostatectomy specimens were compared. From a total of 25 ROIs identified among 15 males, csPCa was found in 21 (84%) of the concordant locations of prostatectomy specimens. However, MRI-targeted biopsy could diagnose csPCa in only 12 (48%) of them. In the csPCa undetected group, the ROI volume was significantly smaller (median volume 0.23 ml vs 0.40 ml, p=0.03). We also found that in cases where PCa was not detected through MRI-targeted biopsy, the biopsy sample length was significantly shorter (median length 9 mm vs 17 mm, p=0.01). Our data suggest that failure of detecting PCa in MRI-targeted biopsy could be due to technical errors at the introduction period of the technique. A sufficient sampling length of 10 mm or more is desirable, especially for small lesions.


Assuntos
Próstata , Neoplasias da Próstata , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
12.
Hinyokika Kiyo ; 67(5): 197-203, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34126663

RESUMO

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Axitinibe , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Duodeno , Humanos , Ipilimumab/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Masculino , Recidiva Local de Neoplasia , Nefrectomia , Nivolumabe/uso terapêutico , Pâncreas , Trombectomia , Veia Cava Inferior
13.
Int J Clin Oncol ; 25(5): 831-841, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31407168

RESUMO

The success of immunotherapy using immune checkpoint inhibitors has changed the practice of cancer treatment tremendously. However, there are still many clinical challenges, such as drug resistance, predictive biomarker development, exploration of combination therapies, and prediction of immune-related adverse events in preclinical settings. To overcome these problems, it is essential to establish faithful preclinical mouse models that recapitulate the clinical features, molecular genetics, biological heterogeneity, and immune microenvironment of human cancers. Here we review the advantages and disadvantages of current preclinical mouse models, including syngeneic murine tumor cell lines, autochthonous tumor models, cancer cell line-derived xenografts, patient-derived-xenografts, and various kinds of immunologically humanized mice. We discuss how these models should be characterized and applied in preclinical settings, and how we should prepare preclinical studies for successful translation from bench to bedside.


Assuntos
Imunoterapia , Neoplasias Experimentais/imunologia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Neoplasias Experimentais/terapia , Pesquisa Translacional Biomédica , Vertebrados/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gan To Kagaku Ryoho ; 47(10): 1415-1420, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33130732

RESUMO

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which T cells are regenerated from induced pluripotent stem cells (iPSCs) that were originally derived from T cells, and succeeded in regenerating cytotoxic T lymphocytes (CTLs) specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. We recently have extended our strategy to solid tumors. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/ß genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of renal cell carcinoma, demonstrating the feasibility of our strategy against solid tumors.


Assuntos
Células-Tronco Pluripotentes Induzidas , Leucemia , Neoplasias , Humanos , Linfócitos T Citotóxicos
15.
Hinyokika Kiyo ; 62(6): 287-94, 2016 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-27452491

RESUMO

Surgical management with radical nephrectomy and thrombectomy has often been performed in renal cell carcinoma (RCC) with tumor thrombus infiltrating the inferior vena cava (IVC). We retrospectively reviewed the outcomes of IVC resection without venous reconstruction in patients with RCC and IVC thrombus at our institution. Eight patients with right RCC underwent radical nephrectomy and IVC resection superior to the level of the renal vein without venous reconstruction from August 2005 to February 2015. Thoracotomy, liver mobilization, and extracorporeal circulation were performed based on the IVC thrombus level. We assessed surgical outcomes, perioperative complications, and survival. At presentation, four patients had level IIIa IVC thrombus, three had level IIIb IVC thrombus, and one had level IV IVC thrombus. Perioperative imaging showed that three of the four patients who underwent neoadjuvant molecular targeting therapy achieved down-staging of the tumor thrombus level. The median operative time was 406 min, and the median estimated blood loss was 3,135 ml. With regard to IVC resectionassociated perioperative complications, one patient needed extracorporeal circulation with IVC ligation and Pringle maneuver owing to low blood pressure. Another patient underwent temporary hemodialysis for 8 days after surgery. There were no perioperative deaths, and none of the patients required permanent hemodialysis. Three patients survived the mean observation period of 25 months, including one patient with no recurrence. Three patients achieved long-term survival of more than 2 years. IVC resection without venous reconstruction may be a feasible option for patients with RCC and IVC tumor thrombus. Further study is needed to determine the most appropriate candidates for this procedure.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Trombose/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/complicações , Feminino , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Estudos Retrospectivos , Trombectomia , Trombose/etiologia , Resultado do Tratamento , Veia Cava Inferior/patologia
16.
Nihon Hinyokika Gakkai Zasshi ; 107(2): 93-99, 2016.
Artigo em Japonês | MEDLINE | ID: mdl-28442676

RESUMO

(Purpose) It has recently been suggested that a slow delivery rate of shockwaves by extracorporeal shock wave lithotripsy (SWL) improved treatment outcomes for urinary stones. We retrospectively analyzed the treatment outcomes of different shockwave delivery rates at 120 and 60 shockwaves per minute. (Patients and method) A total of 88 patients were treated at a fast delivery rate of 120 shockwaves per minute between July 2010 and April 2012, and 139 patients were treated at a slow delivery rate of 60 shockwaves per minute between May 2012 and May 2014 (n=227) using a Sonolith® Praktis lithotripter. The treatment outcome of stone-free rate (SFR) after one SWL session was assessed at four weeks. (Result) SWL at 60 shockwaves per minute resulted in a significantly higher SFR compared with SWL at 120 shockwaves per minute (39.8% and 59.0%, respectively, p=0.0047), particularly for upper ureter (U1) stones (53.1% and 72.0%, respectively, p=0.028). Multivariate analysis showed that younger age, stone sizes of 10 mm or less, U1 stones, and slow delivery rate were significant predictors of a stone-free outcome. There were fewer adverse events after the delivery rate of 60 shockwaves per minute (p=0.058). (Conclusion) Our study suggests that SWL at 60 shockwaves per minute should be recommended to successfully treat urinary stones using the Sonolith® Praktis lithotripter.


Assuntos
Ondas de Choque de Alta Energia , Litotripsia/métodos , Cálculos Urinários/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Nihon Hinyokika Gakkai Zasshi ; 106(3): 178-84, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26419075

RESUMO

Neurofibromatosis type 1 (NF1) is a distinct genetic disorder due to the NF1 gene mutation which induces the aberrant activation of the RAS-signaling. Because RAS-related proteins function as oncogenic factors, NF1 patients frequently develop malignant tumors, especially of neural crest origin, such as peripheral nerve sheath. In addition, malignant tumors of the pancreas, colorectum, and lung have been reported to frequently arise in NF1 patients. However, the association between germ cell tumor and NF1 has not been clarified yet. A 29-year-old male with dyspnea was referred to our hospital because of the large mass in the anterior mediastinum and cervical lymph node swelling. The diagnosis was extragonadal germ cell tumor with cervical lymph node metastasis, and complete remission was obtained by multidisciplinary treatment consisted of combination chemotherapy and surgical resection. To our acknowledgement, this is the first case of extragonadal germ cell tumor in NF1 patients. We discuss the relevance between activation of the RAS-signaling and the development of germ cell tumor.


Assuntos
Neoplasias do Mediastino/etiologia , Neoplasias Embrionárias de Células Germinativas/etiologia , Neurofibromatose 1/complicações , Adulto , Humanos , Metástase Linfática , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Gradação de Tumores , Neoplasias Embrionárias de Células Germinativas/cirurgia , Tomografia Computadorizada por Raios X
18.
Hinyokika Kiyo ; 60(2): 83-6, 2014 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-24755819

RESUMO

A 35-year-old female, who had undergone Caesarean sections in 2000 and 2001, presented with repeated candida vaginitis and cystitis. She reported that a piece of gauze was excreted through the urethra in 2005. The patient visited an outpatient clinic, but no foreign body was identified by cystoscopy. She again visited the clinic in 2012 complaining of miction pain, and a calcified mass was identified in the bladder. The patient was then referred to our hospital. During a transurethral operation, crushed stones, which included the gauze, were removed from the bladder. We concluded that remnant gauze left in the abdominal cavity during the previous pelvic surgery, had migrated into the bladder and formed a calcified mass.


Assuntos
Migração de Corpo Estranho , Tampões de Gaze Cirúrgicos , Bexiga Urinária , Adulto , Feminino , Humanos , Cavidade Peritoneal
19.
Am Soc Clin Oncol Educ Book ; 44(2): e430734, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38207251

RESUMO

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.


Assuntos
Pesquisa Biomédica , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/terapia , Biomarcadores , Perfilação da Expressão Gênica
20.
Asian J Endosc Surg ; 17(3): e13348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965686

RESUMO

Arterio-ureteral fistulas (AUFs), which are relatively rare but potentially life-threatening, require prompt diagnosis and treatment. We reported a case of AUFs following robot-assisted laparoscopic radical cystectomy (RARC) with extended pelvic lymph node dissection and ileal conduit urinary diversion for muscle-invasive bladder cancer, which resulted in massive hemorrhage. Urine leaked from the anastomosis between the ureter, and the end of the ileal conduit was infected, which resulted in an AUF between the pseudoaneurysm of the right common iliac artery and the ureter. The AUF was managed successfully by vascular intervention with an arterial stent graft.


Assuntos
Falso Aneurisma , Cistectomia , Artéria Ilíaca , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Doenças Ureterais , Fístula Urinária , Fístula Vascular , Humanos , Cistectomia/efeitos adversos , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Fístula Urinária/etiologia , Fístula Urinária/cirurgia , Doenças Ureterais/etiologia , Doenças Ureterais/cirurgia , Artéria Ilíaca/cirurgia , Fístula Vascular/etiologia , Fístula Vascular/cirurgia , Masculino , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Pessoa de Meia-Idade
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