Residual penile curvature correction by modeling during penile prosthesis implantation in Peyronie's disease patients.

With the advent of new surgical techniques to treat Peyronie's disease with concomitant erectile dysfunction, there remains a question of whether manual modeling (MM), an older technique, still has a place in the treatment algorithm within penile prosthesis (PP) surgery. While the implantation of a PP often corrects moderate to severe curvature, penile curvature can remain greater than 30°, even when concurrent MM is performed during prothesis implantation. There are new variations of the MM technique that have been recently utilized in the intraoperative and postoperative setting to achieve penile curvature less than 30° when the implant is fully inflated. The inflatable PP, regardless of the specific model of choice, is preferred over the noninflatable PP when utilizing the MM technique. MM should be the first line of treatment for persisting intraoperative penile curvature after the placement of a PP due to its long-term efficacy, noninvasive approach, and significantly low risk of adverse effects.

Use of phosphodiesterase-5 inhibitors and the incidence of melanoma.

INTRODUCTION: Recent evidence of a causal link between Phosphodiesterase-5-inhibitor (PDE-5i) use and melanoma has caused concern in PDE-5i use and was even addressed in the 2018 American Urological Association guideline on erectile dysfunction (ED). Given that several studies have affirmed this low probability but statistically significant association, one might expect a shift in melanoma diagnoses since PDE-5is were introduced in 1998. We sought to determine if the introduction of PDE-5i drugs for ED treatment increased incidence of melanoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to compare the incidence of melanoma diagnosis in American men between 1973 and 2015, providing over a decade of data before and after PDE-5i introduction in 1998. Interrupted time-series and logistic regression were used to assess this relationship. RESULTS: Over 43 years, the SEER database has reported 292,166 cases of Melanoma, with males accounting for 53.7% of cases (Standard deviation [SD] 3%, Range 47.5-58.3%). After the introduction of PDE-5i, there was no proportional increase in melanoma diagnoses, in fact demonstrating a 2% lower incidence from prediction models (p < 0.05). CONCLUSION: Our analysis of the SEER database demonstrates that the trend in incidence of melanoma has fallen in the era of PDE-5i use for ED. These findings may be of value in counseling patients anxious about the potential association between PDE-5i use and skin cancer; however, continued research analyzing individual-level risk are needed.

Hematospermia Etiology, Diagnosis, Treatment, and Sexual Ramifications: A Narrative Review.

INTRODUCTION: Hematospermia (HS) is the presence of blood in ejaculatory fluid. It is a rare condition that is historically idiopathic or associated with sexual behavior. Technological advances have identified many of the etiologies behind HS, improving treatment. Though often benign, HS remains a source of considerable sexual anxiety for patients. Few papers have outlined a diagnostic and therapeutic approach to HS, and none have explicitly addressed its sexual consequences. OBJECTIVES: To provide a comprehensive overview of HS, emphasizing its sexual ramifications. METHODS: A PubMed literature search was performed through May 2021 to identify all relevant publications related to etiology, diagnosis, treatment, and sexual effects of HS. Original research and reviews were analyzed, and pertinent studies were included in this review. RESULTS: Iatrogenic interventions (eg, transrectal ultrasound-guided prostate biopsies) are the most common cause of HS. Infection and/or nonspecific inflammation is the most common non-iatrogenic etiology. Malignancies, including prostate, testicular, and other genitourinary cancers, are rarely the cause of HS. Diagnostic approaches to HS can be organized according to patient age (less than or greater than 40 years old), persistence of bleeding, and the presence/absence of concerning symptoms. Though HS often spontaneously resolves, treatment may require various medications (eg, antibiotics, anti-inflammatories) or surgical interventions. HS has several sexual ramifications, including libido-affecting anxiety, social repercussions from sexual partners and non-sexual affiliates, increased risk of erectile dysfunction or transmission of sexual infections, and compromised fertility, especially when cryopreservation is utilized. CONCLUSION: HS may significantly affect sexual health through several mechanisms, though there is a paucity of formal data on this subject. Further research is needed to fully understand the severity and extent of HS's effect on sexual well-being, especially in those with refractory bleeding. Drury RH, King B, Herzog B, et al. Hematospermia Etiology, Diagnosis, Treatment, and Sexual Ramifications: A Narrative Review. Sex Med Rev. 2022;10:669-680.

Hematospermia Etiology, Diagnosis, Treatment, and Sexual Ramifications: A Narrative Review.

INTRODUCTION: Hematospermia (HS) is the presence of blood in ejaculatory fluid. It is a rare condition that is historically idiopathic or associated with sexual behavior. Technological advances have identified many of the etiologies behind HS, improving treatment. Though often benign, HS remains a source of considerable sexual anxiety for patients. Few papers have outlined a diagnostic and therapeutic approach to HS, and none have explicitly addressed its sexual consequences. OBJECTIVES: To provide a comprehensive overview of HS, emphasizing its sexual ramifications. METHODS: A PubMed literature search was performed through May 2021 to identify all relevant publications related to etiology, diagnosis, treatment, and sexual effects of HS. Original research and reviews were analyzed, and pertinent studies were included in this review. RESULTS: Iatrogenic interventions (eg, transrectal ultrasound-guided prostate biopsies) are the most common cause of HS. Infection and/or nonspecific inflammation is the most common non-iatrogenic etiology. Malignancies, including prostate, testicular, and other genitourinary cancers, are rarely the cause of HS. Diagnostic approaches to HS can be organized according to patient age (less than or greater than 40 years old), persistence of bleeding, and the presence/absence of concerning symptoms. Though HS often spontaneously resolves, treatment may require various medications (eg, antibiotics, anti-inflammatories) or surgical interventions. HS has several sexual ramifications, including libido-affecting anxiety, social repercussions from sexual partners and non-sexual affiliates, increased risk of erectile dysfunction or transmission of sexual infections, and compromised fertility, especially when cryopreservation is utilized. CONCLUSION: HS may significantly affect sexual health through several mechanisms, though there is a paucity of formal data on this subject. Further research is needed to fully understand the severity and extent of HS's effect on sexual well-being, especially in those with refractory bleeding.

Predictive value of pseudouridine in prostate cancer.

BACKGROUND: Recent studies have shown that certain small nucleolar RNAs (H/ACA snoRNAs) and the protein dyskerin (DKC1) are upregulated in prostate cancer and are thought to contribute to progression of disease. These components convert uridine to pseudouridine (abbreviated ψ), a type of post-transcriptional modification of RNA. Given the increased abundance of H/ACA snoRNAs and expression of DKC1 in prostate carcinomas, and because whole-body turnover of RNA increases in support of rapidly-growing cancer cells, we examined the value of pseudouridine as a biomarker for prostate cancer. METHODS: Using a monoclonal antibody against pseudouridine, we tested its ability to distinguish between two 25-base RNA oligonucleotide sequences that differed by only one ψ-substitution, and subsequently measured ψ in RNA isolated from several prostate cancer cell lines representing different stages of disease using dot blot assays and pseudouridinylated RNA linked immunosorbent assay (PURLISA). We also performed immunohistochemistry on a tissue micro array (12 cases/24 cores) containing prostate adenocarcinomas and normal adjacent tissue (NAT). RESULTS: High levels of pseudouridine were detected in androgen-independent cell lines (PC3 and Du145) compared to androgen-sensitive (LNCaP) and immortalized human prostate (RWPE) cells. Immunohistochemistry of a tissue micro array (TMA) containing normal adjacent and cancerous prostate tissue revealed a significant difference in immunoreactivity between normal and malignant tissue (P ≤ 0.0001). CONCLUSION: Our results provide new information on the relationship between pseudouridine expression and clinical progression of prostate cancer.

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications.

Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC. This, along with previous observations of an increase in the number of such NE cells in aggressive tumors, has been suggested as a mechanism of resistance development during prostate cancer progression. Dovitinib (TKI-258/CHIR-258) is a pan receptor tyrosine kinase (RTK) inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It has shown efficacy in mouse-model of PCa bone metastasis, and is presently in clinical trials for several cancers. We observed that both androgen receptor (AR) positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. The NE differentiation was also observed when mice harboring PC3-xenografted tumors were systemically treated with Dovitinib. The mechanistic underpinnings of this differentiation are unclear, but seem to be supported through MAPK-, PI3K-, and Wnt-signaling pathways. Further elucidation of the differentiation process will enable the identification of alternative salvage or combination therapies to overcome the potential resistance development.

Combination effect of therapies targeting the PI3K- and AR-signaling pathways in prostate cancer.

Several promising targeted-therapeutics for prostate cancer (PCa), primarily affecting the androgen receptor (AR) and the PI3K/AKT/mTOR-pathway, are in various phases of development. However, despite promise, single-agent inhibitors targeting the two pathways have not shown long-term benefits, perhaps due to a complex compensatory cross talk that exists between the two pathways. Combination therapy has thus been proposed to maximize benefit. We have carried out a systematic study of two-drug combination effect of MDV3100 (AR antagonist), BKM120 (PI3K inhibitor), TKI258 (pan RTK inhibitor) and RAD001 (mTOR inhibitor) using various PCa cell lines. We observed strong synergy when AR-positive cells are treated with MDV3100 in combination with any one of the PI3K-pathway inhibitors: TKI258, BKM120, or RAD001. Growth curve based synergy determination combined with Western blot analysis suggested MDV3100+BKM120 to be the most effective in inducing cell death in such conditions. In the case of dual targeting of the PI3K-pathway BKM120+TKI258 combination displayed exquisite sensitivity in all the 5 cell lines tested irrespective of androgen sensitivity, (LNCaP, VCaP, 22Rv1, PC3 and Du145). The effect of blockade with BKM120+TKI258 in PC3 cells was similar to a combination of BKM120 with chemotherapy drug cabazitaxel.Taken together, our observation supports earlier observations that a combination of AR-inhibitor and PI3K-inhibitor is highly synergistic. Furthermore, combining BKM120 with TKI258 has better synergy than BKM120+RAD001 or RAD001+TKI258 in all the lines, irrespective of androgen sensitivity. Finally, BKM120 also displayed synergy when combined with chemotherapy drug cabazitaxel. No antagonism however was observed with any of the drug combinations.

Correlation of clinical findings and results of percutaneous balloon compression for patients with trigeminal neuralgia.

OBJECTIVE: To investigate pain relief and recurrence after percutaneous balloon compression (PBC) and its association with type of pain, prior surgery, or other clinical factors. METHODS: Fifty-nine patients with medically refractory trigeminal pain were enrolled into this study. Patients were divided into those with typical trigeminal neuralgia (TN), and those with other types of trigeminal pain or "atypical pain." The post-surgical rate of recurrence was estimated by the Kaplan-Meier method. Cox-proportional hazards models were used to investigate associations between patient characteristics and recurrence of pain. RESULTS: Forty-two patients had TN, 17 patients had atypical pain. At last follow-up, 40 patients had excellent, 9 good, 7 fair and 3 poor pain relief. Recurrence was observed in 35 patients, and was associated with pain type (relative risk (RR)=2.38, 95% confidence interval (CI): 1.22-4.63, P=0.011) and pain duration before PBC (RR=1.33, 95% CI: 1.02-1.72, P=0.033). Other clinical factors were not significant. Two patients had transient paresis of the sixth cranial nerve, however, there were no permanent post-surgical complications. CONCLUSIONS: Our study demonstrates the safety and efficacy of PBC with 83% of patients being pain free at last follow-up. Patients with atypical pain and longer pre-surgical symptom duration appear to have a higher risk of recurrence. Repeat surgery is just as effective as initial surgery, justification for being conservative in parameter selection at the initial procedure to minimize complications.