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BACKGROUND: A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment. METHODS: Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9 weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated. RESULTS: Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4 mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002). CONCLUSIONS: Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 are helpful in reconsidering treatment continuation.
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OBJECTIVES: To evaluate the clinical characteristics of oligometastatic disease (OMD) in metastatic urothelial carcinoma (mUC) with visceral metastases when classified into synchronous and metachronous metastases. METHODS: Of 957 cases of de novo mUC treated between 2008 and 2023, 374 with visceral metastases were analyzed. Cases were classified into OMD with up to three metastatic lesions and polymetastatic disease (PMD), and into synchronous and metachronous metastases. The clinical characteristics and overall survival (OS) for each group were analyzed. RESULTS: Overall, 196 (52.4%) had synchronous metastasis and 178 (47.6%) had metachronous metastasis. Median OS for synchronous metastases was significantly shorter than for metachronous metastases (12.1 months vs. 15.3 months, p = 0.011). Among the synchronous metastases, 48 (24.5%) were OMD and 148 (75.6%) were PMD. There was no significant difference in OS between the OMDs and PMDs (median 14.9 months vs. 11.7 months, p = 0.32), and only decreased albumin level was identified as a significant predictor of poor OS. Among the metachronous metastases, 64 (36.0%) were OMD and 114 (64.0%) were PMD. There was no significant difference in OS between the OMD and PMD (median 21.2 months vs. 15.0 months, p = 0.35), and no significant predictors of poor OS were identified. CONCLUSIONS: For mUC with visceral metastases, the timing of metastasis appearance was associated with prognosis, with synchronous metastases being a poorer prognostic factor compared to metachronous metastases. There was no prognostic difference between OMD and PMD with visceral metastases when classified into synchronous or metachronous metastases.
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BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.
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Anticorpos Monoclonais Humanizados , Humanos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Resistencia a Medicamentos Antineoplásicos , Adulto , Biomarcadores Tumorais , Antineoplásicos Imunológicos/uso terapêutico , Intervalo Livre de Progressão , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/mortalidade , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , NeutrófilosRESUMO
The measurement of cellular forces, which reflect crucial biological attributes, has the potential to replace conventional cell assessment methods, such as morphology, proliferation, and molecular expression analysis, in medical cell diagnosis and cell culture studies. In medical cell evaluations, force inference techniques have gained prominence due to their non-invasiveness and lack of requirement for specialized equipment. Among those techniques, the method proposed by Ishihara et al., which estimates forces in densely packed cells based only on cell geometry, is a promising method. However, its applicability range of this method has not been fully established. In this study, we employed a two-dimensional vertex model to numerically assess the applicability of this method on homogeneous and heterogeneous cells. Our comparisons between the true values from numerical simulations and the estimated values from the inference method revealed a significant correlation between estimation accuracy and cell roundness in systems of homogeneous cell. Moreover, the method demonstrated efficient force estimations in heterogeneous-cell systems. These findings may be useful when the force inference method is employed to evaluate medical cells.
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Fenômenos Mecânicos , Fenômenos BiomecânicosRESUMO
Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.
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BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.
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Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nivolumabe/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Renais/patologiaRESUMO
OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , População do Leste Asiático , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Estudos RetrospectivosRESUMO
The kidney is a relatively rare site for solitary fibrous tumors (SFTs). Previously, rare cases of SFT with dedifferentiation that showed an abrupt transition between low- and high-grade areas, similar to other dedifferentiated sarcomas, have been described. Herein, we report the case of a 75-year-old man who presented with gross hematuria. Computed tomography revealed a left renal tumor; a laparoscopic left nephrectomy was performed. The tumor was pathologically diagnosed as dedifferentiated SFT of the kidney. Dedifferentiated SFT may have worse prognosis than conventional SFT. Although this patient has been disease-free for 7 months, careful long-term follow-up is still required.
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BACKGROUND/AIM: This study aimed to determine useful predictive factors for selecting patients with advanced urothelial carcinoma (UC) who might benefit clinically from treatment with pembrolizumab. PATIENTS AND METHODS: We retrospectively analyzed 54 patients who underwent pembrolizumab treatment for UC. The hemoglobin, albumin, lymphocyte and platelet (HALP) score, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated as indices of systemic inflammatory response, and the relationships between these scores and the initial tumor response or overall survival, as well as other clinicopathological factors, were assessed. RESULTS: High NLR and PLR were associated with a poor initial tumor response to pembrolizumab. A HALP score <30.05 and a PLR ≥173.73 were associated with worse overall survival. In the multivariate Cox regression analysis, a high PLR was a significant independent prognostic factor for unfavorable outcomes. CONCLUSION: A high pretreatment PLR may be a valuable indicator for choosing therapy other than pembrolizumab in patients with advanced UC.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Plaquetas/patologia , Carcinoma de Células de Transição , Linfócitos/patologia , Neoplasias da Bexiga Urinária , Idoso , Idoso de 80 Anos ou mais , Plaquetas/efeitos dos fármacos , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/tratamento farmacológico , Feminino , Humanos , Japão , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/patologiaRESUMO
OBJECTIVE: To investigate the incidence of colorectal cancer and chronic radiation proctitis after prostate radiotherapy using periodic total colonoscopy screening. METHODS: From February 2013 to January 2018, 270 patients who underwent external beam radiation therapy for prostate cancer were advised to receive periodic total colonoscopy screening annually. We evaluated the incidence and characteristics of colorectal cancer and chronic radiation proctitis. RESULTS: First, second, third, fourth and fifth total colonoscopy were performed in 256 (95%), 151 (56%), 60 (22%), 23 (8.5%) and 7 (2.6%) patients at a median of 14, 31, 42, 54 and 72 months after radiotherapy, respectively. The prevalence proportion of colorectal cancer in the first colonoscopy since radiotherapy was 3.9%. Twelve (4.4%) patients were diagnosed with colorectal cancer, including four invasive cancers, during a follow-up period. Eight of these 12 patients had not experienced rectal bleeding. The median time to diagnosis of colorectal cancer was 21 months. Chronic radiation proctitis was observed in 136 (50%) patients, including 67 (25%) patients with symptomatic bleeding. CONCLUSIONS: The high detection rate of asymptomatic radiation proctitis suggests the utility of total colonoscopy to screen for early-stage colorectal cancer prior to or following radiotherapy for prostate cancer. Considering the longevity after localized prostate cancer treatment, the awareness of chronic radiation-induced proctitis and the risk of colorectal cancer masked by bleeding is needed in treatment decision -making.
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Neoplasias Colorretais , Neoplasias Induzidas por Radiação , Proctite , Neoplasias da Próstata , Lesões por Radiação , Colonoscopia , Detecção Precoce de Câncer , Humanos , Masculino , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/etiologia , Proctite/diagnóstico , Proctite/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologiaRESUMO
OBJECTIVE: To investigate the prognostic significance of contact with the renal sinus in patients with clear cell renal cell carcinoma. METHODS: A total of 787 pT1N0M0 clear cell renal cell carcinoma patients who had undergone radical or partial nephrectomy were reviewed retrospectively. A tumor in contact with the renal sinus was defined as a tumor radiologically attached to the renal sinus. Metastatic-free survival rates were analyzed in the total and propensity score-matched cohorts. A risk score model for metastasis after surgery was developed. RESULTS: Of the 787 patients, 411 (52.2%) had tumors in contact with renal sinus. The contact with renal sinus group showed poorer metastatic-free survival in both total and matched cohorts. In multivariate analysis, contact with renal sinus was an independent prognostic factor of metastasis, as well as Fuhrman grade, microvascular invasion and age. The scoring model likewise consisted of Fuhrman grade, microvascular invasion, age and contact with renal sinus. Metastasis-free survival curves were clearly stratified according to risk, with 5-year metastasis-free survival rates of 95.7% and 65.2% in the low- and high-risk groups, respectively (P < 0.001). CONCLUSIONS: Contact with the renal sinus is a significant risk factor for metastasis in T1 clear cell renal cell carcinoma after surgery. More intensive follow up should be recommended for patients with renal cell carcinoma that is in contact with the renal sinus.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Sodium glucose co-transporter 2 inhibitors constitute a new class of antidiabetic medication. Sodium glucose co-transporter 2 inhibitors have been shown to exert anticancer effects. However, the clinical value of these drugs as anticancer agents is yet to be evaluated. CASE PRESENTATION: A 72-year-old man presented to our hospital with frequent cough and dyspnea. Contrast-enhanced computed tomography revealed renal cell carcinoma cT3bN0M1. Ipragliflozin, a sodium glucose co-transporter 2 inhibitor, treatment was initiated to control blood glucose levels. Two years after diagnosis, computed tomography revealed remarkable tumor regression without any systemic therapy other than ipragliflozin. CONCLUSION: Sodium glucose co-transporter 2 inhibitors are potentially applicable as anticancer agents among patients with metastatic renal cell carcinoma.