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1.
Mol Clin Oncol ; 21(4): 74, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39170625

RESUMO

The treatment paradigm for non-metastatic castration-resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first-line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first-line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow-up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression-free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate-specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first-line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first-line treatment.

2.
Food Funct ; 15(16): 8562-8571, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39072556

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is fatty liver mainly related to metabolic syndrome. NAFLD with inflammation and hepatocellular damage is defined as nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. We have previously reported that a hexane insoluble fraction from an anthocyanin-rich purple rice ethanolic extract (PRE-HIF) can suppress prostate carcinogenesis. However, the extract's effect on NASH has not yet been established. In the present study, we investigated the chemopreventive effect of a PRE-HIF on NASH and liver fibrosis using a connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rat NASH model. Seven-week-old male Cx32ΔTg rats were fed a control diet, a high-fat diet (HFD), or an HFD with 1% PRE-HIF and intraperitoneal administration of dimethylnitrosamine for 17 weeks. Histological findings of NASH such as fat deposition, lobular inflammation, hepatocyte ballooning injury, and bridging fibrosis were observed in the HFD group but not in the control group, and all histological parameters were significantly improved by PRE-HIF treatment. Corresponding to the histological changes, increased expression of inflammatory cytokine mRNAs (TNF-α, IL-6, IL-18, IFN-γ, IL-1ß, TGF-ß1, TIMP1, TIMP2, COL1A1), along with and activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling were observed in the HFD group, which was significantly decreased by PRE-HIF. The number and area of hepatic precancerous glutathione S-transferase placental form-positive foci tended to be decreased by PRE-HIF. These results indicate that intake of purple rice as a dietary supplement may reduce steatohepatitis, liver injury, and fibrosis in NASH by inactivation of NF-κB or JNK.


Assuntos
Cirrose Hepática , NF-kappa B , Hepatopatia Gordurosa não Alcoólica , Oryza , Extratos Vegetais , Animais , Masculino , NF-kappa B/metabolismo , NF-kappa B/genética , Extratos Vegetais/farmacologia , Ratos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Oryza/química , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Citocinas/metabolismo , Citocinas/genética
3.
Oncology ; : 1-11, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38952143

RESUMO

INTRODUCTION: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients. METHODS: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated. RESULTS: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.

4.
Cureus ; 16(6): e62098, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38989329

RESUMO

INTRODUCTION: The training box is an effective tool used by surgical trainees. Suturing training is the common method of practicing laparoscopic surgery; however, the cost of needles and threads for long-term practice remains a problem. In this study, we incorporated the original Japanese training for laparoscopic surgery by making an origami paper crane (laparoscopic origami training (LOT)) and evaluated its effect on the clinical results as a long-term practice. METHODS: LOT was performed using a single 7.5 × 7.5 cm origami paper in the training box of laparoscopic surgery. In the bench-top study, the total time required to make one paper crane was measured and evaluated, and a self-efficacy questionnaire was designed to analyze the efficacy of LOT. In clinical practice, we retrospectively compared two resident groups, one that had previously trained on LOT (trained group) and the other that did not (less-trained group), by analyzing the pneumoperitoneum time (PT) for 10 cases. RESULTS: After making paper cranes in approximately 100 cases, the making time was reduced to approximately 10 min. Long-term results analyzing up to 1500 cases revealed that in addition to shortening the time required to make a paper crane, the shape of the crane also improved. Consequently, the median PT was significantly shorter in the trained group than in the less-trained group (129.0 (62-287) versus 208.5 (127-343) min; p<0.001). CONCLUSION: LOT contributed to introducing safe laparoscopic surgery to residents and improved their laparoscopic outcomes. We believe that this is a useful practice methodology that can be recommended to general physicians who wish to practice laparoscopic surgeries.

5.
BMC Urol ; 24(1): 145, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997692

RESUMO

BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.


Assuntos
Antibacterianos , Cefalosporinas , Fosfomicina , Ureteroscopia , Humanos , Estudos Retrospectivos , Feminino , Masculino , Fosfomicina/uso terapêutico , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Idoso , Cefalosporinas/uso terapêutico , Antibioticoprofilaxia/métodos , Adulto , Infecção da Ferida Cirúrgica/prevenção & controle
6.
Cancer Diagn Progn ; 4(4): 475-481, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962546

RESUMO

Background/Aim: Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy. Patients and Methods: The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan-Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS). Results: At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05]. Conclusion: CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.

7.
J Clin Med ; 13(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929893

RESUMO

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

8.
Cancers (Basel) ; 16(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38730675

RESUMO

BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

9.
Int J Urol ; 31(9): 986-993, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38764245

RESUMO

OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.


Assuntos
Antagonistas de Androgênios , Antagonistas de Receptores de Andrógenos , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Acetato de Abiraterona/uso terapêutico , Acetato de Abiraterona/administração & dosagem , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/administração & dosagem , Antagonistas de Receptores de Andrógenos/uso terapêutico , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , População do Leste Asiático , Japão/epidemiologia , Metástase Neoplásica , Nitrilas/administração & dosagem , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Feniltioidantoína/análogos & derivados , Prognóstico , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/sangue , Estudos Retrospectivos , Tioidantoínas/uso terapêutico , Tioidantoínas/administração & dosagem , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem
10.
J Surg Oncol ; 129(7): 1311-1324, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38470556

RESUMO

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.


Assuntos
Imageamento Tridimensional , Neoplasias Renais , Nefrectomia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Tomografia Computadorizada por Raios X , Humanos , Nefrectomia/métodos , Estudos Retrospectivos , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Neoplasias Renais/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Seguimentos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia
11.
IJU Case Rep ; 7(2): 110-114, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440703

RESUMO

Introduction: As an aggressive adenocarcinoma phenotype, primary signet ring cell carcinoma of the urinary bladder is an extremely rare variant. The prognosis of metastatic signet ring cell carcinoma of the urinary bladder is extremely poor and the clinical course for its specific pathogenesis remains unelucidated. Case presentation: A 64-year-old Japanese male patient was diagnosed with invasive urothelial carcinoma with glandular differentiation of a signet ring cell-type with pT4aN0M0, and he was eventually diagnosed with metastatic signet ring cell carcinoma of the urinary bladder. He was initially responsive to systemic combination induction chemotherapy of S-1 and cisplatin followed by avelumab switch maintenance therapy; however, signet ring cell carcinoma of the urinary bladder relapse occurred in the pathological findings of a biopsy from the right thigh. Immunohistochemical analysis of this specimen identified strong positive staining for nectin-4 and, following enfortumab-vedotin treatment, the patient showed a good response. Conclusion: We thus describe a rare case of metastatic signet ring cell carcinoma of the urinary bladder with nectin-4 expression diagnosed by a biopsy of a metastatic site.

12.
IJU Case Rep ; 7(2): 101-104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440712

RESUMO

Introduction: The bladder exstrophy-epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation: We report the case of a 44-year-old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy-epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion: This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy-epispadias complex.

14.
Sci Rep ; 14(1): 2520, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291115

RESUMO

We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Metformina , Neoplasias da Bexiga Urinária , Humanos , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Esteroides/uso terapêutico , Metformina/uso terapêutico
15.
J Clin Med ; 12(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38137795

RESUMO

BACKGROUND: Ureteral stricture (US) postureteroscopic lithotripsy (URSL) has emerged as a severe complication with the widespread use of laser technology. Furthermore, managing a complex US is challenging. Therefore, this study evaluated the efficacy of robot-assisted ureteroureterostomy (RAUU) in addressing US post-URSL and analyzed the pathology of transected ureteral tissues to identify the risk factors for US. METHODS: we conducted a prospective cohort study on patients who underwent RAUU for URSL-induced US from April 2021 to May 2023. RESULTS: A total of 14 patients with a mean age of 49.8 years were included in this study. The mean stricture length on radiography was 22.66 ± 7.38 mm. Nine (64.2%) patients had experienced failure with previous interventions. The overall success rate was 92.9%, both clinically and radiographically, without major complications, at a mean follow-up of 12.8 months. The pathological findings revealed microcalcifications and a loss of ureteral mucosa in 57.1% and 28.6% of patients, respectively. CONCLUSIONS: The RAUU technique shows promise as a viable option for US post-URSL in appropriately selected patients despite severe pathological changes in the ureter. Therefore, the migration of microcalcifications to the site of ureteral perforation may be a significant factor contributing to US development.

16.
Cancer Med ; 12(24): 21666-21679, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986680

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.


Assuntos
Melanoma , Humanos , Melanoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Eosinófilos , Estudos Retrospectivos , Biomarcadores
17.
Cancers (Basel) ; 15(22)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38001593

RESUMO

Malnutrition is associated with prognosis in cancer. The geriatric nutritional risk index (GNRI), based on the ratio of actual to ideal body weight and also serum albumin level, is a simple screening tool for assessing nutrition. We investigated the GNRI as a prognostic factor for oncological outcomes in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) using a Japanese multicenter cohort. This study included a total of 175 patients with LATITUDE high-risk mHSPC, of whom 102 had received androgen deprivation therapy (ADT) plus upfront abiraterone acetate, and 73 had received ADT plus bicalutamide (Bica), from 14 institutions associated with the Tokai Urologic Oncology Research Seminar. Patients were classified into GNRI-low (<98) or GNRI-high (≥98) groups. The GNRI was based on the body mass index and serum albumin level. Kaplan-Meier analysis revealed that the median overall survival (OS) of a GNRI-low group (median 33.7 months; 95% confidence interval [CI]: 26.2-not reached [NR]) was significantly worse than that of a GNRI-high group (median: NR; 95% CI: NR-NR; p < 0.001). Multivariate analysis identified Bica and low GNRI (<98) as independent prognostic factors for reduced times to both castration-resistant prostate cancer and OS, and, therefore, a poor prognosis. Our findings indicate the GNRI may be a practical prognostic indicator in the evaluation of survival outcomes in patients with LATITUDE high-risk mHSPC.

18.
Diagnostics (Basel) ; 13(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37891994

RESUMO

BACKGROUND: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution. METHODS: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio. RESULTS: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group (p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio (p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1). CONCLUSION: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

19.
Transl Androl Urol ; 12(5): 790-801, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37305626

RESUMO

Background and Objective: The prognosis of advanced urothelial carcinoma (aUC) is poor. To date, the gold standard of treatment for patients with aUC has been cisplatin-based chemotherapy. More recently, immune checkpoint inhibitors (ICIs) have been widely used for such patients, which has led to an improvement in their prognosis. In clinical practice, predicting the effectiveness of antitumor drugs or the prognosis of patients is important for making decisions on treatment strategies. Various parameters obtained from blood tests in the pre-ICI era have been adopted for patients in the ICI era. In this review, we summarize the parameters reflecting the status of aUC patients treated with ICIs based on current evidence. Methods: We conducted a literature search using PubMed and Google Scholar. The publications chosen were all peer-reviewed journals published over an unlimited time period. Key Content and Findings: Numerous inflammatory or nutritional parameters can be obtained from routine blood tests. These reflect malnutrition or systemic inflammation in patients with cancer. As in the pre-ICI era, these parameters are useful for predicting the effectiveness of ICIs and the prognosis of patients treated with ICIs. Conclusions: Various parameters are related to systemic inflammation and malnutrition, and are easily obtained from a routine blood test. Using these parameters from various studies as reference points is useful in making decisions on treatment for aUC.

20.
Int J Urol ; 30(10): 866-874, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37278575

RESUMO

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Melanoma , Humanos , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Eosinófilos/patologia , Melanoma/tratamento farmacológico , Melanoma/induzido quimicamente , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Biomarcadores
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