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BACKGROUND: Surgical resection for pheochromocytoma (PCC) is still challenging. This study assessed the perioperative outcomes of adrenalectomy for PCC and investigated the risk factors for intraoperative hemodynamic instability (HI). METHODS: This retrospective study included 571 patients with adrenal tumors who underwent adrenalectomy at Kobe University Hospital and other related hospitals between April 2008 and October 2023. The perioperative outcomes of laparoscopic adrenalectomy were compared between PCC (n = 92) and non-PCC (n = 464) groups. In addition, we investigated several potential risk factors for intraoperative HI in patients with PCC (n = 107; open, n = 11; laparoscopic, n = 92; robot-assisted, n = 4). RESULTS: While patients with PCC had a significantly larger amount of blood loss in comparison to those with non-PCC (mean, 70 and 30 mL, respectively; p = 0.004), no significant difference was observed in the rate of perioperative grade ≥III complications (1.1% vs. 0.6%; p = 0.516), and no perioperative mortality was observed in either group. A tumor size of ≥40 mm, with preoperative hypertension and urinary metanephrines at a level ≥3 times the upper limit of the normal value, were found to be significant predictors of HI, with odds ratios of 2.74 (p = 0.025), 3.91 (p = 0.005), and 3.83 (p = 0.004), respectively. CONCLUSIONS: Our data suggest that laparoscopic adrenalectomy for PCC may be as safe as that for other types of adrenal tumors and that large tumors and hormonally active disease may be risk factors for intraoperative HI. The optimal perioperative management for PCC with these risk factors should be established.
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Background and Objectives: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. Materials and Methods: The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64-87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus -3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus -0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was -1.7 ± 3.2%. In all cases, there was a clear significant difference (p < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. Conclusions: Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD.
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Antagonistas de Andrógenos , Conservadores de la Densidad Ósea , Densidad Ósea , Denosumab , Osteoporosis , Neoplasias de la Próstata , Humanos , Masculino , Osteoporosis/tratamiento farmacológico , Anciano , Japón/epidemiología , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Anciano de 80 o más Años , Persona de Mediana Edad , Denosumab/uso terapéutico , Denosumab/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Difosfonatos/efectos adversos , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Docetaxel/uso terapéutico , Antígeno Prostático Específico/uso terapéutico , Receptores Androgénicos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Estudios Retrospectivos , Progresión de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.
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Neoplasias Pulmonares , Neoplasias de la Próstata , Carcinoma Pulmonar de Células Pequeñas , Masculino , Humanos , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Carboplatino , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/patología , Resultado del Tratamiento , Neoplasias de la Próstata/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.
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Carcinoma de Células Renales , Fallo Renal Crónico , Neoplasias Renales , Masculino , Humanos , Anciano , Axitinib/uso terapéutico , Axitinib/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Estudios Retrospectivos , Diálisis Renal , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapiaRESUMEN
OBJECTIVES: The objective of this study was to assess the clinical outcomes following combined treatment with pembrolizumab and axitinib as first-line therapy for patients with advanced RCC. METHODS: This study retrospectively included 47 consecutive Japanese patients who were diagnosed with advanced RCC and subsequently received pembrolizumab and axitinib between February 2020 and January 2022. Efficacy and safety of this combined therapy in these patients were comprehensively investigated. RESULTS: The 47 included patients were classified into the following 3 groups by the IMDC system: favorable, 7 (14.9%); intermediate, 24 (51.1%) and poor, 16 (34.0%). Responses to this combined therapy in the 47 patients were as follows: CR, 8 (17.0%); PR, 20 (42.6%); SD, 16 (34.0%) and PD, 3 (6.4%); thus, the ORR was 59.6%. During the observation period, disease progression and death occurred in 19 (40.4%) and 9 (19.1%) patients, respectively, and the median PFS and OS were 18 months and not reached, respectively. Univariate analyses identified the following significant predictors for poor prognostic outcomes: lack of nephrectomy, liver metastasis, bone metastasis, elevated CRP and IMDC poor risk for PFS; and lack of nephrectomy, non-CCC and elevated CRP for OS. AEs and those corresponding to grade ≥ 3 occurred in all (100%) and 30 (63.8%) patients, respectively. CONCLUSIONS: To our knowledge, this is the first study focusing on real-world outcomes following pembrolizumab and axitinib for treatment-naïve advanced Japanese RCC patients, which showed the efficacy and safety of this combined therapy being similar or even superior to those in clinical trial.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Axitinib/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Japón , Estudios RetrospectivosRESUMEN
OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Humanos , Anciano , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/patología , Estudios Retrospectivos , PronósticoRESUMEN
OBJECTIVES: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. METHODS: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. RESULTS: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. CONCLUSIONS: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Nivolumab/efectos adversos , Ipilimumab/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/métodos , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Nefrectomía/métodosRESUMEN
BACKGROUND: Patients with solitary metastasis of renal cell carcinoma (RCC) have shown to be ideal candidates for surgical metastasectomy (SM). However, whether SM will show more benefit than systemic therapy remains unclear. METHODS: We included 73 patients treated for solitary metastasis after nephrectomy at our institute from April 2008 to December 2018. We compared the clinical outcomes between the SM (n = 29) and no-SM (n = 44) group which were treated with only systemic therapy. RESULTS: Eleven of 29 patients in the SM group received presurgical targeted therapy (PTT). Although 13 of 29 patients in the SM group showed recurrence during the study period, a Cox proportional hazards model showed that SM was significantly associated with a favorable overall survival (hazard ratio: 0.18; p = 0.007). Patients receiving PTT prior to SM showed a longer recurrence-free survival after SM in comparison to those who underwent SM without PTT (median: not reached vs. 27.7 months; p = 0.009). CONCLUSIONS: If resection is feasible, SM may be beneficial for patients with solitary metastasis of RCC, and we showed the possibility that PTT prior to SM may be effective for avoiding recurrence after SM. Further large-scale prospective studies are needed to clarify the ideal treatment strategy for metastatic RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Metastasectomía , Carcinoma de Células Renales/patología , Humanos , Neoplasias Renales/patología , Nefrectomía , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: The purpose of this study was to assess the therapeutic efficacy of molecular targeted therapies following nivolumab in metastatic renal cell carcinoma and to examine the relationship between therapeutic efficacy and the specific molecular targeted therapy used. METHODS: We retrospectively reviewed the medical records of 115 metastatic renal cell carcinoma patients who were treated with nivolumab at our institution and five affiliated hospitals. Among them, 52 patients who received subsequent molecular targeted therapy following nivolumab were selected to survey treatment outcomes. Progression-free survival and overall survival were estimated with Kaplan-Meier curves, and differences were analyzed by the log-rank test. RESULTS: Among the 52 eligible patients, 40 (76.9%) were treated with tyrosine kinase inhibitors and 12 (23.1%) were treated with mammalian target of rapamycin inhibitor. The median time to treatment failure and progression-free survival of subsequent molecular targeted therapy were 5.6 and 8.0 months, respectively. The median overall survival from the initiation of first-line therapy was not reached. The disease control rate of subsequent molecular targeted therapy was 69.2% (partial response: 25.0%, stable disease: 44.2%). The median progression-free survival of subsequent tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor were 9.2 and 8.0 months, respectively (P = 0.37). The progression-free survival of patients whose best response to prior nivolumab was either progressive disease or stable disease/partial response were 6.3 and 11.3 months, respectively (P = 0.36). CONCLUSIONS: Molecular targeted therapies following nivolumab had comparatively better therapeutic efficacy, which was confirmed regardless of the type of molecular targeted agent used.
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Carcinoma de Células Renales , Neoplasias Renales , Nivolumab , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/tratamiento farmacológico , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Nivolumab/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Although bone metastasis beyond the vertebrae and pelvis has been a key factor in prognostic models of metastatic hormone-sensitive prostate cancer (mHSPC), the clinical significance of it is still unclear. The present study evaluated the prognostic impact of the volume of bone metastasis beyond the vertebrae and pelvis on the outcomes of mHSPC and created an ideal risk classification based on it. METHODS: We retrospectively reviewed 197 patients with mHSPC who were treated with combined androgen blockade as the initial treatment between June 2003 and October 2019. We calculated the bone scan index (BSI), including the BSI beyond the vertebrae and pelvis (bBSI), using BONENAVI, and investigated the association between the BSI and the overall survival (OS) of mHSPC. RESULTS: According to the CHAARTED criteria, 91 and 106 patients were classified into the low- and high-volume groups, respectively. Of the 79 patients who did not have visceral metastasis in the high-volume group, those with a bBSI ≤ 0.27 (n = 16) showed a favorable OS, as did those in the low-volume group. The modified CHAARTED high-volume group (presence of visceral metastases or 4 bone lesions with a bBSI > 0.27) showed a significantly shorter OS than others, with a hazard ratio (HR) of 4.69 (p < 0.001), which was higher than that observed with the original CHAARTED criteria (HR = 4.33). CONCLUSIONS: Our data suggested that considering the volume of bone metastasis beyond the vertebrae and pelvis may help to improve the accuracy of risk classification. Further large-scale prospective studies are needed to validate our findings.
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OBJECTIVES: To compare functional and surgical outcomes of robot-assisted partial nephrectomy for complex tumors with RENAL scores ≥10 and non-complex tumors at a single academic institution. METHODS: We retrospectively analyzed the data of all patients who underwent robot-assisted partial nephrectomy at Kobe University Hospital (Kobe, Hyogo, Japan) from 2011 to 2020. Functional and surgical outcomes for complex tumors (RENAL score ≥10) were compared with those of patients with non-complex tumors (RENAL <10). Outcomes analyzed included blood loss, warm ischemia time, console time, perioperative complications, and preoperative and postoperative renal function. RESULTS: A total of 348 patients were included in our present study, with a median follow-up time of 35.1 months. Of these, 299 patients (85.9%) had non-complex tumors and 49 patients (14.1%) had complex tumors. Warm ischemia time and console time were significantly longer in the complex tumors group. Major perioperative complications (Clavien-Dindo classification system ≥3) were significantly more frequent in the complex tumors group than the non-complex tumor group (16.3% vs 5.7%, P = 0.018). Postoperative preservation of estimated glomerular filtration rate and percentage of chronic kidney disease upstage by 1 year were significantly inferior in the complex tumors group. The positive surgical margin rate was 0% and 0.3% in the complex and non-complex tumor groups, respectively. There were no significant differences in recurrence-free survival between the two groups (P = 0.11). CONCLUSIONS: Robot-assisted partial nephrectomy for complex renal tumors is safe, with no difference in oncological outcomes, although more postoperative complications and decreased renal function can be observed than non-complex tumors.
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Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Tasa de Filtración Glomerular , Humanos , Riñón/fisiología , Riñón/cirugía , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high-risk prostate cancer. METHODS: Fifty-two patients with clinically localized high-risk prostate cancer underwent pelvic lymph node dissection accompanied by robot-assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription-polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. RESULTS: In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P < .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien-Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. CONCLUSIONS: No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.
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Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Calicreínas/sangre , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Pelvis/patología , Pelvis/cirugía , Antígeno Prostático Específico/sangre , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Procedimientos Quirúrgicos Robotizados/métodosRESUMEN
BACKGROUND: Association between systemic inflammation and clinical outcome of immune checkpoint inhibitors (ICIs) has received focus. Our objective was to evaluate the utility of the neutrophil-to-lymphocyte ratio (NLR) in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab as well as the prognostic impact of the C-reactive protein (CRP) level. MATERIALS AND METHODS: Sixty-five mRCC patients treated with nivolumab were enrolled. We retrospectively investigated several factors, including the NLR and the CRP level, for their association with progression-free survival (PFS) and overall survival (OS). In addition, we evaluated their impact on the objective response. RESULTS: The CRP level was confirmed to be positively correlated with the NLR in a correlation analysis. An NLR ≥ 5 was significantly associated with a worse PFS (hazard ratio [HR]: 4.54, 95% confidence interval [CI] 1.93-10.7; p < 0.001), and an NLR ≥ 5 and a CRP ≥ 2.1 mg/dL were identified as a significant factors predicting worse OS with HRs of 4.88 (95% CI 1.35-17.7; p < 0.016) and 3.89 (95% CI 1.01-15.0; p = 0.049), respectively. In addition, patients with a ≥ 25% decrease in the NLR and CRP level showed a significantly better response to nivolumab than those without a ≥ 25% decrease in the NLR and CRP level, with odds ratios of 9.54 (95% CI 2.09-49.8, p = 0.001) and 4.36 (95% CI 1.03-18.9, p = 0.032), respectively. CONCLUSION: Both the NLR and CRP levels were significantly associated with the clinical outcome of nivolumab in mRCC patients. The potential prognostic impact of those markers needs to be further prospectively investigated.
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Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Nivolumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/sangre , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Linfocitos/patología , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Sequential treatment starting with target therapy is still the standard care for metastatic renal cell carcinoma (mRCC), even in the era of immune checkpoint inhibitors. Our objective was to compare the clinical outcomes between axitinib and nivolumab as second-line therapy following prior targeted therapy in mRCC patients. METHODS: We identified 41 patients treated with axitinib and 39 patients treated with nivolumab as a second-line regimen after targeted therapy, and retrospectively compared the treatment efficacy and safety in these patients. RESULTS: The clinical benefit rate of axitinib was significantly higher than that of nivolumab (82.9% versus 56.4%; p = 0.014) and patients who received axitinib tended to show longer progression-free survival (PFS) than those who received nivolumab (10.3 months versus 7.3 months; p = 0.067). There was no difference in the overall survival (OS) of the two groups (both not reached; p = 0.581). The incidence of grade ≥ 3 adverse events (AEs) was similar between the two groups, but one patient in the nivolumab group died due to an immune-related AE. In addition, a Cox proportional hazards model showed that the pre-treatment KPS, the baseline neutrophil-to-lymphocyte ratio (NLR), and an objective response in second-line therapy were significantly associated with PFS, while the pre-treatment KPS, the number of metastatic organs, and an objective response in second-line therapy significantly contributed to the predicted OS. CONCLUSIONS: Although the prognosis did not differ markedly between the two groups, axitinib resulted in a better tumor response rate. Further randomized prospective studies are needed for the ideal order of this sequential treatment.
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Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Nivolumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Axitinib/efectos adversos , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Nomograms have been developed for the prediction of progression-free survival (PFS) and liver toxicity in patients with advanced renal cell carcinoma (RCC) who are treated with pazopanib. The objectives of this study were to review clinical outcomes, to perform an external validation of these nomograms and to develop a new nomogram in Japanese patients. METHODS: A retrospective chart review of 150 Japanese patients with advanced RCC who received pazopanib at Kobe University Hospital and affiliated hospitals from March 2014 to June 2017 was performed. We evaluated the clinical efficacy and safety of pazopanib using logistic regression analysis to analyze the prognostic factors for overall survival (OS) and PFS. For nomogram validation, concordance index (C-index) and calibration were used. RESULTS: The median PFS and OS in this study was 13.1 and 37.4 months, respectively. Multivariate analyses identified prognostic factors for OS (number of metastasis, white blood cell (WBC) count and lactate dehydrogenase) and PFS (number of metastasis, WBC count). The C-index of nomograms for 12-month PFS was 0.598. The C-index of nomograms for liver toxicity was 0.558. A new Nomogram for predicting 12-month PFS for patients who received pazopanib was developed and performed internal validation. The C-index of the nomogram was 0.768. CONCLUSION: The clinical effect and safety of pazopanib reported in this study was similar to previous studies. This study suggests careful application of nomograms to Japanese patients treated with pazopanib. We have developed a new nomogram for predicting 12-month PFS with pazopanib therapy from Japanese patients.
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Inhibidores de la Angiogénesis/efectos adversos , Carcinoma de Células Renales/mortalidad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/mortalidad , Neoplasias Renales/mortalidad , Nomogramas , Pirimidinas/efectos adversos , Sulfonamidas/efectos adversos , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Femenino , Humanos , Indazoles , Neoplasias Renales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3-4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI. The tumor thrombus level before the induction of pazopanib was 3 in one patient and 4 in the remaining six patients. After pazopanib, shrinkage of the primary site and thrombus diameter and length were observed in all patients except one (with a rhabdoid tumor). The mean decreases of primary tumor diameter, tumor thrombus diameter, and length were 14, 9, and 31 mm, respectively. The tumor thrombus level decreased in three (43%) patients and remained stable in the remaining patient. Our findings suggest that presurgical treatment with pazopanib may shrink the tumor thrombus and decrease the surgical invasiveness in RCC patients with a high-level tumor thrombus.
Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Trombosis de la Vena/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Indazoles , Neoplasias Renales/sangre , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Pirimidinas , Estudios Retrospectivos , Sulfonamidas , Vena Cava Inferior/efectos de los fármacos , Vena Cava Inferior/patología , Trombosis de la Vena/patologíaAsunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Antineoplásicos/uso terapéutico , Axitinib/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Indazoles/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective was to investigate the efficacy and tolerability of combined therapy with paclitaxel and carboplatin (TC) in patients with advanced urothelial carcinoma after the failure of first-line chemotherapy with gemcitabine and cisplatin (GC). PATIENTS AND METHODS: This was a retrospective study including a total of 16 patients with advanced urothelial carcinoma who showed evidence of progressive and/or recurrent disease after first-line therapy with GC and subsequently received second-line chemotherapy consisting of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve 5). TC therapy was repeated every 3 weeks and was continued until disease progression or intolerable toxicity was observed. RESULTS: The baseline patient characteristics were rather favorable; only 3 of 16 patients had liver metastases and 7 patients had an Eastern Cooperative Oncology Group performance status of 0. Of these, response to TC therapy was achieved in 5 (31.3%), including 2 with complete and 3 with partial response. The median progression-free and overall survival times in the 16 patients were 7.9 and 17.3 months, respectively. CONCLUSIONS: TC therapy appeared to show modest activity with acceptable tolerability in patients refractory to GC therapy; therefore, TC chemotherapy might be considered as an alternative option as a second-line regimen for advanced urothelial carcinoma following GC therapy.