Clinical Parameters Outperform Molecular Subtypes for Predicting Outcome in Bladder Cancer: Results from Multiple Cohorts, Including TCGA.

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.

Renal Cell Carcinoma Presenting as an Isolated Eyelid Metastasis.

Background: Renal cell carcinoma (RCC) has a propensity to metastasize with the most common sites of metastasis being the lungs and bones. Cutaneous metastasis of RCC to the eyelid is exceedingly rare, with only six cases reported in the past decade. We are reporting a case of metastatic renal cell carcinoma (mRCC) that presented with a painless eyelid mass. Case Presentation: We describe a case of a 66-year-old man with a history of chronic kidney disease stage III presenting with a rapidly growing left lower eyelid lesion thought to be a capillary hemangioma. Biopsy revealed polygonal clear cells with small central nuclei with thin-walled vasculature and strong immunostaining with PAX8 consistent with mRCC, clear cell type. Subsequent abdominal CT scan revealed a 5.1 × 4.7 × 4.3 cm heterogeneously enhancing mass with central necrosis in the upper pole of the left kidney. The patient was treated with excision of the eyelid lesion followed by robotic partial nephrectomy of the primary tumor. Follow-up CT scan at 3 and 6 months showed no evidence of recurrence. Conclusion: Isolated eyelid metastasis is an extremely rare form of presentation of mRCC. Interestingly, that patient did not have any other site of metastasis. Cytoreductive partial nephrectomy has been previously reported to be oncologically safe in selected patients.

Racial/ethnic differences in the association of childhood adversities with depression and the role of resilience.

BACKGROUND: Adverse childhood experiences (ACE) including childhood abuse and trauma increase depressive symptoms. The role of resilience and how it interacts with both ACEs and the potential development of depressive symptoms, including how race and ethnicity moderate these effects, are much less studied. The aims of this study were to examine: 1) whether there is a dose-response relationship between trauma and depressive symptoms; 2) whether early trauma affected European Americans (EA) and African Americans (AA) in a similar fashion; and 3) whether resilience mitigates the effect of trauma. METHODS: The present study comprised a cross-sectional study of subjects from a longitudinal cohort. All subjects were 19 years or older with traumatic experiences prior to age 18. Subjects were assessed for depressive symptoms as well as resilience. RESULTS: In 413 subjects enrolled, ACEs were significantly associated with depression severity in a dose-response fashion (p<0.001). Notably, AAs had lower depression scores at low to moderate levels of ACEs than EAs, but reported comparable levels of depression with severe exposure to ACEs (pInteraction=0.05). In both EAs and AAs, young adults with high and medium levels of resilience showed less depressive symptoms compared to those with low resilience (p<0.05). LIMITATIONS: to consider are the cross-sectional design, possibility of other confounders, and potential for recall bias of this study. CONCLUSION: While ACEs were significantly associated with severity of depression in a dose-response fashion, higher resilience mitigated the impact of childhood adversities on depressive symptoms in young adults. The results are encouraging, and guides research for therapeutics to boost resilience.

Intracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review.

INTRODUCTION: Intracavernosal injection (ICI) of a vasoactive agent has been an important part of the diagnosis, evaluation, and treatment of erectile dysfunction (ED) since its initial description by Virag in 1982. AIM: To review the literature and summarize the use of ICI and its role in the diagnosis, evaluation, and treatment of ED. METHODS: Literature review. MAIN OUTCOME MEASURE: To define the role of ICI's utility in the diagnosis, evaluation, and treatment of ED. RESULTS: When used in conjunction with color penile Doppler ultrasound for ED evaluation and diagnosis, ICI helps to detect penile vascular abnormalities and allows for differentiation between the multiple vasculogenic causes of impotence, thus helping clinicians to select the optimal treatment modality for each patient. Patients utilizing ICI continue to report high efficacy and satisfaction rates relative to other treatment options despite ICI's designation as a second-line therapy since the introduction of oral phosphodiesterase type 5 inhibitors in 1998. In recent years, ICI has also become an important part of penile rehabilitation programs following radical prostatectomy, as regular use of ICI is thought to increase the rate at which patients experience return of spontaneous erection through preservation of penile tissue integrity and prevention of corporeal smooth muscle atrophy. CONCLUSIONS: ICI of vasoactive agents remains an important tool in treating and diagnosing ED, with high patient satisfaction and efficacy rates. However, the dropout rate for ICI therapy remains relatively high, and it may be associated with priapism, ecchymoses, hematoma formation, and penile fibrosis. Patients should be educated on the benefits and limitations of ICI therapy prior to beginning treatment in order to minimize dropout rates. Additional studies are necessary to better understand the possible long-term benefits of ICI therapy and how to most effectively structure the penile rehabilitation program after radical prostatectomy. Belew D, Klaassen Z, and Lewis RW. Intracavernosal injection for the diagnosis, evaluation, and treatment of erectile dysfunction: A review. Sex Med Rev 2015;3:11-23.