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Background: Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors.Methods: Between 1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were retrospectively registered for this study. The prognostic impacts of various clinicopathologic and surgical treatment factors including levels of venous thrombus, venous wall invasion status and likelihood of aggressive cytoreductive operation, were investigated using Kaplan-Meier method and following multivariate Cox proportional hazards model for all patients and those still alive at 1, 2, and 3 years of follow-up. To investigate the impact of follow-up duration on the statistical analyses, multivariate logistic regression analyses were used to explore prognostic factors using restricted data until 1, 2, and 3 years of follow-up.Results: The median follow-up duration was 40.4 months. The 5-year OS was 47.6%. Several independent predictive factors were identified in each subgroup analysis in terms of yearly-based survival and restricted follow-up duration. The presence of tumor thrombus invading to venous wall was independently related to OS in the full-range follow-up data and in survivors at 2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3 years of follow-up, many independent predictive factors changed with follow-up duration, but surgical category could be universal and independent predictive factors.Conclusion: The most universal factors affecting improvement both in short-term and long-term survivals could be cytoreductive surgery and absence of venous wall invasion. It may mean that feasible aggressive cytoreductive operation following more reliable preoperative imaging for predicting venous wall invasion status would improve OS for patients with RCC extending into venous systems. [ABSTRACT FROM AUTHOR]

Unlabelled: Introduction: Disseminated intravascular coagulation causes thrombotic tendency leading to multiple organ failure and occurs in a wide variety of diseases including malignancy. Disseminated intravascular coagulation is a latent complication in people with prostate cancer.Case Presentation: A 51-year-old Japanese man with advanced castration-resistant prostate cancer was admitted to our hospital because of extensive purpura and severe anemia. Prolonged plasma coagulation time, hypofibrinogenemia and normal platelet count suggested that a decrease in fibrinogen induced a bleeding tendency causing purpura. However, elevated plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers, with positive fibrin monomer test, manifested disseminated intravascular coagulation and subsequent fibrinolysis. Plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers decreased after administration of low-molecular-weight heparin. However, low fibrinogen and α2-antiplasmin levels were not improved and plasmin-antiplasmin complex did not decrease, which revealed excessive fibrinolysis complicated with disseminated intravascular coagulation. We suspected that prostate cancer cell-derived urokinase-type plasminogen activator caused excessive fibrinolysis. Administration of tranexamic acid for fibrinogenolysis was added together with high-dose anti-androgen therapy (fosfestrol) for prostate cancer. Thereafter, prostate-specific antigen and plasmin-antiplasmin complex decreased, followed by normalized fibrinogen and α2-antiplasmin levels, and the patient eventually recovered from the bleeding tendency. Immunohistochemical staining of the biopsied prostate tissue exhibited that the prostate cancer cells produced tissue factor, the coagulation initiator, and urokinase-type plasminogen activator.Conclusion: This patient with rare complications of disseminated intravascular coagulation and excessive fibrinolysis is a warning case of potential coagulation disorder onset in patients with prostate cancer. We propose that combined administration of tranexamic acid and low-molecular-weight heparin together with high-dose anti-androgen therapy is a useful therapeutic option for patients with this complicated coagulation disorder. [ABSTRACT FROM AUTHOR]

Interferon-α (IFN-α) has extremely broad effects on the immune system, and the influence of IFN-α on regulatory T (Treg) cells is not fully known. In this report, Treg cells were analyzed in patients with metastatic renal cell carcinoma (RCC) following IFN-α monotherapy or treatment with IFN-α and interleukin (IL)-2. CD4and FoxP3Treg cells were significantly decreased for 2 weeks after the initiation of IFN-α monotherapy, but recovered later as treatment proceeded. Patients treated with both IFN-α and IL-2 increased their Treg cell levels during the first 2 weeks after initiation of treatment. Patients who derived complete response (CR), partial response (PR), or stable disease (SD) from IFN-α monotherapy had lower Treg cell levels before treatment than did patients whose disease progressed. Low Treg cell levels before treatment may therefore be advantageous to subsequent immunotherapy with IFN-α, and predictive for treatment results in RCC patients. [ABSTRACT FROM AUTHOR]

PurposeTo investigate the factors that affect the operative data and to evaluate the validity of a laparoscopic adrenalectomy (LA) for pheochromocytoma.Patients and MethodsBetween July 1993 and January 2008, 172 LAs were performed in this department, and 34 of them were for pheochromocytoma. The characteristics and operative data of LAs for pheochromocytoma were examined with respect to the intraoperative systolic blood pressure (SBP) and the side of tumor.ResultsThe intraoperative SBP rose to 180 mm Hg or more in 17 (50) cases of LAs for pheochromocytomas. The analysis of SBP (<180 versus >180 mm Hg), however, showed that there were no differences in the operative data between the two groups. The tumor size was significantly associated with operative time (P< 0.05) or the blood loss (P< 0.05) in an LA for pheochromocytoma. The blood loss in LAs for right adrenal tumors was greater (150 versus 79 mL) than for left tumors (P< 0.01). In particular, some procedures for right large tumors had considerable blood loss and long procedural time. In a comparison of the operative data between pheochromocytoma and other adrenal tumors, the tumor was larger (4.3 versus 2.5 cm) and the blood loss was greater (100 versus 30 mL) than for other adrenal tumors.ConclusionsThe operative data showed no correlation with the intraoperative high SBP, but they were associated with the tumor state. Although the procedure seems to be influenced by the size and state of tumor, LA is not contraindicated for pheochromocytoma, and it can therefore be performed safely. [ABSTRACT FROM AUTHOR]

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer. [ABSTRACT FROM AUTHOR]

This study aims to highlight the differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) versus ipilimumab (IPI) plus NIVO. We used the FAERS database. Drugs presented a disproportionate distribution of toxicities. Serious AEs were higher in patients receiving IPI + NIVO. These findings may help clinicians select therapy and improve the safety profile. Introduction: Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset. Material and Methods: We downloaded AE datasets of IPI + NIVO and CAB + NIVO from the Food and Drug Administration Adverse Event Reporting System database. We used the Medical Dictionary for Regulatory Activities to treat each AE as a preferred term and grouped it into the System Organ Class (SOC). We performed logistic regression analyses to compare IPI + NIVO and CAB + NIVO. Results: The incidence rates of 7 types of toxicities were higher for CAB + NIVO than for IPI + NIVO. On the other hand, the incidence rates of 3 types of toxicities were higher for IPI + NIVO than for CAB + NIVO. Serious AEs were higher in patients receiving IPI + NIVO. Conclusion: Our findings suggest that both combination therapies presented a disproportionate distribution of toxicities in several SOC. These findings may help clinicians select suitable therapy for the individual and improve the safety profile in patients with advanced renal cell carcinoma receiving NIVO + IPI and NIVO + CAB in a real-world setting. [ABSTRACT FROM AUTHOR]

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADTbased combination therapies would make a valuable contribution to the development of personalized medicine. [ABSTRACT FROM AUTHOR]

Hormonal therapies including androgen deprivation therapy and androgen receptor (AR) pathway inhibitors such as abiraterone and enzalutamide have been widely used to treat advanced prostate cancer. However, treatment resistance emerges after hormonal manipulation in most prostate cancers, and it is attributable to a number of mechanisms, including AR amplification and overexpression, AR mutations, the expression of constitutively active AR variants, intra-tumor androgen synthesis, and promiscuous AR activation by other factors. Although various AR mutations have been reported in prostate cancer, specific AR mutations (L702H, W742L/C, H875Y, F877L, and T878A/S) were frequently identified after treatment resistance emerged. Intriguingly, these hot spot mutations were also revealed to change the binding affinity of ligands including steroids and antiandrogens and potentially result in altered responses to AR pathway inhibitors. Currently, precision medicine utilizing genetic and genomic data to choose suitable treatment for the patient is becoming to play an increasingly important role in clinical practice for prostate cancer management. Since clinical data between AR mutations and the efficacy of AR pathway inhibitors are accumulating, monitoring the AR mutation status is a promising approach for providing precision medicine in prostate cancer, which would be implemented through the development of clinically available testing modalities for AR mutations using liquid biopsy. However, there are few reviews on clinical significance of AR hot spot mutations in prostate cancer. Then, this review summarized the clinical landscape of AR mutations and discussed their potential implication for clinical utilization. [ABSTRACT FROM AUTHOR]

A correction to the article "Enhanced Antitumor Effects of an Engineered Measles Virus Edmonston Strain Expressing the Wild-type N, P, L Genes on Human Renal Cell Carcinoma," by Xin Meng and colleagues is presented.