Increased Cytokine Gene Expression and Cognition Risk Associated with Androgen Deprivation Therapy

Background: Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. Methods: Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge database. Results: A total of 1952 DEGs in the Alzheimer patient cohort and 101 DEGs were identified in ADT treated prostate cancer patients. Comparing both data sets provided a subset of 33 commonly expressed genes involving cytokine-cytokine signaling with an over representation of cytokine-cytokine receptor interaction, inflammatory cytokines, signaling by interleukins together with alterations in the circulating lymphocyte repertoire, adaptive immune responses, regulation of cytokine production, and changes in T-cell subsets. Additionally, lipopolysaccharide, tumor necrosis factor, and toll-like receptors were identified as upstream transcriptional regulators of these pathways. The most commonly expressed genes viz. IL-17A, CCL2, IL-10, IL-6, IL-1RN, LIF/LIFR were further validated by quantitative RT-PCR exhibited higher expression in antiandrogen treated neuronal, glial, and androgen-responsive prostate cancer cells, compared to no-androgen antagonist treatment. Conclusions: Our findings suggest that changes in cytokine signaling under the influence of ADT in prostate cancer patients may be linked with cognitive impairment presenting new avenues for diagnostic and therapeutic development in combating brain deficits

Penile Fracture with Associated Urethral Rupture

Penile fracture of the erect penis is an uncommon but emergent urological trauma. Potential outcomes include erectile dysfunction, penile curvature, and urethral injury. Treatment is emergent surgical repair. We present the case of a 42-year-old man with a penile fracture complicated by a urethral rupture and subsequent repair. A discussion of the key aspects of this condition is presented

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass

Background and Aims The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. Methods This is retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all of the following were achieved: reaching the papilla, cannulating the desired duct and providing endoscopic therapy as clinically indicated. Results A total of 579 patients (median age 51, 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (IQR 109-210) with median ERCP time 40 minutes (IQR 28-56). Median hospital stay was 2 days (IQR 1-3). Adverse events were 18% (laparoscopy-related 10%, ERCP-related 7%, both 1%) with the clear majority (92%) classified as mild/moderate whereas 8% were severe and 1 death occurred. Conclusion Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher due to the added laparoscopy-related events

Identification of Key Genes Associated with Progression and Prognosis of Bladder Cancer through Integrated Bioinformatics Analysis

Bladder cancer prognosis remains dismal due to lack of appropriate biomarkers that can predict its progression. The study aims to identify novel prognostic biomarkers associated with the progression of bladder cancer by utilizing three Gene Expression Omnibus (GEO) datasets to screen differentially expressed genes (DEGs). A total of 1516 DEGs were identified between non-muscle invasive and muscle invasive bladder cancer specimens. To identify genes of prognostic value, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A total of seven genes, including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9 were confirmed with strong prognostic values in bladder cancer and validated by qRT-PCR conducted in various human bladder cancer cells representing stage-specific disease progression. ULCAN, human protein atlas and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression. Moreover, Kaplan–Meier analysis and Cox hazard ratio analysis were performed to determine the prognostic role of these genes. Univariate analysis performed on a validation set identified a 3-panel gene set viz. CDKN2A, CTSV and FOXM1 with 95.5% sensitivity and 100% specificity in predicting bladder cancer progression. In summary, our study screened and confirmed a 3-panel biomarker that could accurately predict the progression and prognosis of bladder cancer