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PURPOSE: To compare the image quality, inter-reader agreement, and diagnostic capability for muscle-invasive bladder cancer (MIBC) of the reconstructed images in sections orthogonal to the bladder tumor obtained by 3D Dynamic contrast-enhanced (DCE)-MRI using the Golden-angle Radial Sparse Parallel (GRASP) technique with the images directly captured using the Cartesian sampling. MATERIALS AND METHODS: This study involved 68 initial cases of bladder cancer examined with DCE-MRI (GRASP: n = 34, Cartesian: n = 34) at 3 Tesla. Four radiologists conducted qualitative evaluations (overall image quality, absence of motion artifact, absence of streak artifact, and tumor conspicuity) using a five-point Likert scale (5 = Excellent/None) and quantitative signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements. The areas under the receiver-operating characteristic curves (AUCs) for the Vesical Imaging-Reporting and Data System (VI-RADS) DCE score for MIBC assessment were calculated. Inter-reader agreement was also assessed. RESULTS: GRASP notably enhanced overall image quality (pooled score: GRASP 4 vs. Cartesian 3, P < 0.0001), tumor conspicuity (5 vs. 3, P < 0.05), SNR (Median 38.2 vs. 19.0, P < 0.0001), and CNR (7.9 vs. 6.0, P = 0.005), with fewer motion artifacts (5 vs. 3, P < 0.0001) and minor streak artifacts (5 vs. 5, P > 0.05). Although no significant differences were observed, the GRASP group tended to have higher AUCs for MIBC (pooled AUCs: 0.92 vs. 0.88) and showed a trend toward higher inter-reader agreement (pooled kappa-value: 0.70 vs. 0.63) compared to the Cartesian group. CONCLUSIONS: Using the GRASP for 3D DCE-MRI, the reconstructed images in sections orthogonal to the bladder tumor achieved higher image quality and improve the clinical work flow, compared to the images directly captured using the Cartesian. GRASP tended to have higher diagnostic ability for MIBC and showed a trend toward higher inter-reader agreement compared to the Cartesian.
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BACKGROUND: Optimal drug selection for metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. We therefore assessed the clinical outcomes of mHSPC treated with new-generation androgen receptor pathway inhibitors (ARSIs) and identified risk factors associated with the prognosis of mHSPC. METHODS: We retrospectively reviewed 324 patients with mHSPC who were treated with ARSIs, including abiraterone acetate, enzalutamide, and apalutamide, between January 2018 and December 2022. In addition to assessing the prostate-specific antigen (PSA) response and overall survival (OS) during ARSI treatment, we investigated several potential risk factors for a poor OS in patients with mHSPC. RESULTS: Patients with a ≥ 90% PSA reduction (hazard ratio [HR]: 0.24, 95% confidence interval [CI], 0.10-0.58; P = .002) and those whose PSA declined to ≤ 0.2 ng/mL (HR: 0.22, 95% CI, 0.08-0.63; P = .005) showed significantly better OS than other patients. Gleason grade group 5 (GG5), presence of liver metastasis, and an LDH ≥ 250 U/L were identified as prognostic factors significantly associated with a poor OS, with HRs of 2.31 (95% CI, 1.02-5.20; P = .044), 7.87 (95% CI, 2.61-23.8; P < .001) and 3.21 (95% CI, 1.43-7.23; P = .005). CONCLUSION: We identified GG5, the presence of liver metastasis, and elevated LDH at the diagnosis as significant factors predicting the OS of mHSPC, but the choice of ARSIs did not affect the prognosis. The potential prognostic impact of these markers requires further investigation.
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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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Premature chromatid separation (PCS)/mosaic variegated aneuploidy (MVA) syndrome is a rare chromosome instability syndrome. This syndrome is inherited in an autosomal recessive pattern. Although heterozygous carriers of a monoallelic mutation reportedly have a normal phenotype, PCS-positive cells are found at a higher rate in such carriers than in the general population. We herein report a case in which a PCS carrier was incidentally diagnosed during investigation of male infertility. A diagnosis of nonobstructive azoospermia was made, and chromosome analysis revealed the PCS trait in 81 of 200 cells (40.5%), indicating that the patient was a PCS carrier. PCS carriers are not uncommon, and if both members of a couple are carriers, there would be a 25% likelihood of the child presenting with PCS syndrome. Therefore, a clinical psychological approach that includes genetic counseling should be considered before proceeding to microsurgical testicular sperm extraction.
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BACKGROUND/AIM: Radium-223 therapy has been reported to improve prognosis in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Occasionally, radium-223 and androgen receptor signaling inhibitors (ARSIs) are used in combination for disease control, but the efficacy of this combination is unclear. This study assessed the efficacy of the addition of enzalutamide in patients treated with radium-223. PATIENTS AND METHODS: We included patients with CRPC and bone metastases who were treated with radium-223 at our institution. Patients were assigned to the enzalutamide combination group or non-combination group. We compared progression-free survival (PFS), overall survival (OS), and the completion rate of radium-223 between the two groups. RESULTS: In total, 39 patients with CRPC were included in this retrospective study. The median follow-up duration was 8.8 months. The enzalutamide combination and non-combination groups included 22 (56.4%) and 17 patients (43.6%), respectively. Median PFS was 11.3 months [95% confidence interval (CI)=3.9-19.9] in the combination group, versus 3.0 months (95%CI=1.9-5.5) in the non-combination group (p=0.004). Median OS did not significantly differ between the groups. The radium-223 completion rate was higher in the combination group than in the non-combination group (72.7% vs. 35.3%, p=0.026). CONCLUSION: The combined use of enzalutamide with radium-223 therapy improved PFS and treatment completion rates in patients with CRPC and bone metastases. This combination may be associated with a more favorable prognosis.
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Benzamidas , Neoplasias Óseas , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Humanos , Masculino , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Radio (Elemento)/uso terapéutico , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Anciano de 80 o más Años , Estudios Retrospectivos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
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
Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its therapeutic strategy remains unestablished. Here, we report a case of bladder SCC in which multidisciplinary treatment has resulted in relatively long-term survival. A 68-year-old man presented with gross hematuria. A cystoscopy revealed an invasive bladder tumor. A transurethral resection of bladder tumor (TURBT) was performed, and the pathological diagnosis was SCC. After systemic chemotherapy using etoposide and carboplatin and subsequent TURBT, a radical cystectomy and ileal conduit were performed. Three months postoperatively, the patient had a recurrence in the para-aortic lymph node. Systemic combination chemotherapy with carboplatin plus irinotecan (CBDCA + CPT-11) was administered, followed by amrubicin and an immune checkpoint inhibitor. In addition to this treatment, radiation therapy for the metastatic region led to the reduction of pain and shrinkage of the metastatic lesion. The patient survived for 2 years after the initial diagnosis. Our report indicates that multidisciplinary treatment can be effective for SCC of the bladder, and a therapeutic strategy including the identification of novel biomarkers should be established.
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Anticuerpos Monoclonales , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Japón/epidemiología , Masculino , Anciano , Femenino , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for meta-static non-clear-cell renal cell carcinoma (nccRCC). METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared. RESULTS: The first-line regimen was ICI-ICI in 26 cases and ICI-TKI in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between groups (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535), nor above grade 3 (p=0.3786) between the ICI-ICI and ICI-TKI groups. CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.
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OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.
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Carcinoma de Células Transicionales , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/mortalidad , Progresión de la Enfermedad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Japón/epidemiología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Neoplasias Urológicas/mortalidad , Estudios de CohortesRESUMEN
Introduction: Leiomyosarcoma of the inferior vena cava is associated with poor prognosis. Complete resection is the only curative treatment. We present a patient with this disease in whom cine magnetic resonance imaging was valuable in selecting the surgical strategy and mitigating invasiveness. Case presentation: A 68-year-old woman presented with right-sided abdominal pain. Computed tomography revealed an 86 mm tumor in the right retroperitoneal space that extended into the inferior vena cava and reached superiorly to the right atrium. Percutaneous needle biopsy confirmed leiomyosarcoma. Cine magnetic resonance imaging demonstrated no adhesions between the tumor and the upper segment of inferior vena cava wall, nor with the right atrial wall, indicating resectability. Radical tumor resection was successfully performed without requiring thoracotomy. Conclusion: Cine magnetic resonance imaging appears to be useful in inferior vena cava leiomyosarcoma for evaluating adhesions between the tumor and vessel wall.
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Introduction: Renal cell carcinoma with an inferior vena cava tumor thrombus is a challenging disease that requires a multimodal treatment approach. Pembrolizumab plus lenvatinib has displayed promising efficacy in metastatic renal cell carcinoma. Case presentation: A 61-year-old man was diagnosed with metastatic renal cell carcinoma and a tumor thrombus adhering to the inferior vena cava wall by cine magnetic resonance imaging. After 6 months of pembrolizumab and lenvatinib therapy, tumor shrinkage was detected, excluding the advanced portion of the inferior vena cava thrombus, and nephrectomy and thrombectomy were performed. Adhesion of the tumor thrombus to the inferior vena cava wall was observed during surgery. Resection produced a remarkable pathological complete response with no viable cells in the resected specimens, including the thrombus site. Conclusion: This case highlights the potential of pembrolizumab plus lenvatinib for treating advanced renal cell carcinoma with an inferior vena cava thrombus and the utility of cine magnetic resonance imaging for evaluating thrombus adhesion to the inferior vena cava.
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Introduction: The performance of robot-assisted laparoscopic pyeloplasty has recently been increasing in frequency. However, patients with duplicated renal pelvises and ureters can present challenges. Case presentation: A 71-year-old woman presented with flank pain and was diagnosed with ureteropelvic junction obstruction with an incomplete duplicated collecting system. Preoperative imaging did not reveal the details of the stenosis. Therefore, three reconstructive procedures were prepared: The Anderson-Hynes procedure, end-to-side pyeloureterostomy, and upper pole ureter to lower pole pyeloplasty with the Anderson-Hynes procedure for the lower pole. These procedures were determined by the length of the intact ureter and the presence of crossed vessels. During the surgery, the crossing vein was severed, allowing successful reconstruction with Anderson-Hynes anastomosis. Conclusion: Preoperative evaluation and preparation of multiple surgical techniques are crucial in robot-assisted laparoscopic pyeloplasty for incomplete duplicated collecting systems.
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Key Clinical Message: Renal cell carcinoma as a secondary malignant neoplasm is relatively rare; however, the possibility of secondary renal cell carcinoma following chemoradiotherapy for childhood nephroblastoma should be considered. Abstract: The occurrence of secondary renal cell carcinoma (RCC) following chemoradiotherapy for nephroblastoma is relatively rare, especially in microphthalmia transcription factor family translocation renal cell carcinoma. A 13-year-old Japanese male was referred to our department for treatment of a right kidney mass. The patient had undergone open left nephrectomy and adjuvant chemotherapy for nephroblastoma, 12 years before. Diagnostic imaging revealed a tumor in the right kidney and a lesion suspected to be metastasis in the left eighth rib. Chromophobe RCC or translocation RCC was suspected from the imaging pattern. TNM classification was cT1aN0M1, and the clinical stage was IV. Partial nephrectomy by robot-assisted surgery for the right renal tumor and resection of the left eighth rib were performed. Pathologically, the renal tumor was diagnosed as translocation RCC, and the rib lesion demonstrated no evidence of malignancy. We are currently undergoing imaging follow-up and the patient has been recurrence-free for 15 months. In this study, we present a rare case of secondary translocation RCC after successful treatment of nephroblastoma.
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The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.
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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
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
Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60-70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.