Pharmacotherapy in Stress Urinary Incontinence; A Literature Review.

PURPOSE OF REVIEW: Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field. RECENT FINDINGS: One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine's risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT2C agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.

The role of transcorporal cuff placement in high-risk and ultra-high-risk patients: are they actually helpful?

PURPOSE: To assess the incidence of artificial urinary sphincter (AUS) explant in high-risk patients and to evaluate the relationship between transcorporal cuff (TCC) placement and explant risk in this population. METHODS: We retrospectively reviewed all AUS insertions performed on high-risk patients by a single surgeon from 2010 to 2020. "High-risk" was defined as having ≥ 1 urethral risk factor: pelvic radiation, urethroplasty, recalcitrant urethral/bladder neck stenosis, urethral stenting, or previous AUS erosion/infection. Patients with ≥ 2 factors were "ultra-high-risk." Time-to-event analyses were used to assess all-cause-, infection/erosion-related-, and mechanical failure-related explant-free survival. Subgroup analyses were performed for patients with a history of radiation and urethral dissection. RESULTS: The final cohort included 68 men, mean age of 67 years (SD 11), and 77 AUS cuffs. Mean follow-up was 32 months (IQR 6-50). 29% of cuffs (n = 22) were transcorporal. 32 cuffs (42%) were explanted. All-cause explant-free survival was 64% at 1 year and 52% at 2 years. Classification as "ultra-high-risk" was not associated with explant risk (all p-values > 0.05). TCC placement was associated with an increased risk of explant for infection/erosion across all patients (HR 2.74, p = 0.03) and in radiated patients (n = 50; HR 4.1, p = 0.04), but not in patients with prior urethral dissection (n = 52; HR 1.98, p = 0.21). CONCLUSION: High-risk patients have a high rate of AUS explant and TCC placement may not be protective in this population. TCC placement was associated with an increased risk of infection/erosion in radiated patients, but not in those with a history of open urethral surgery.

Bilateral hydronephrosis and acute kidney injury secondary to pelvis lipomatosis.

A 57-year-old African American male presented with vague abdominal pain and bilateral flank pain. The patient was found to have bilateral hydronephrosis and significant renal function impairment secondary to pelvic lipomatosis. Pelvic lipomatosis represents a clinically-diagnosed unique cause of ureteral obstruction and subsequent renal impairment. We present a case report of newly diagnosed pelvic lipomatosis, the clinical and imaging characteristics for diagnosis, and its conservative management with serial ureteral stent exchanges.

Testosterone Replacement Therapy and BPH/LUTS. What is the Evidence?

Contrary to the previous dogma that prostatic growth is directly proportional to testosterone levels, emerging research has suggested a lack of testosterone may be a risk factor for lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Within this review article, we have demonstrated the current understanding of the physiology of hypogonadism and its interplay with prostatic and lower urinary tract physiology. The current evidence suggests that not only does testosterone replacement therapy (TRT) not worsen LUTS, but that hypogonadism itself is an important risk factor for LUTS/BPH.

Penetrating Posterior Urethral Injuries: Case Report and Management Strategies.

Penetrating posterior urethral trauma from gunshot wounds (GSW) is rare and requires prompt treatment to minimize complications. Data regarding the management of such cases is scarce in the literature and poorly addressed in the guidelines. Different management approaches exist, including urinary diversion with immediate versus delayed urethroplasty/fistula repair. We present our case series to add to our experience to the literature. Three patients aged 18-44 presented with ballistic posterior urethra injuries from GSW. Initial management involved urethral catheter placement, with one patient requiring operative placement of urethral and suprapubic catheters (SPTs). Complications included recurrent membranous stricture, urinary retention, rectourethral fistula, and erectile dysfunction (ED). Posterior urethral injuries from GSW are complex as they can be either isolated or affect adjacent organs. Bladder, ureteral, and urethral injuries must be ruled out. Unlike bladder neck injuries, immediate urethroplasty/fistula repair would be very challenging and not advised for standard prostatic or membranous injuries. Urethral catheter or suprapubic tube is recommended and can result in fistula closure and urethral patency. It is critical to maintain close follow-up with the patient due to the possibility of stricture recurrence. Urethroplasty in a delayed fashion can be very successful.

Treatment of obstructive sleep apnea relieves stuttering priapism in patient with sickle cell disease: a case report.

Background: Stuttering priapism is recurrent, self-limited episodes of sustained penile erection and is common in patients with sickle cell disease (SCD). Prevention of stuttering priapism is important to avoid progression to episodes of ischemic priapism which can cause erectile dysfunction. Priapism has been shown to be associated with increased nocturnal hypoxemia in patients with SCD. Case Description: A 43-year-old male with nocturnal episodes of stuttering priapism that was refractory to treatment with multiple medications was found to have obstructive sleep apnea (OSA). Following treatment of this condition with a continuous positive airway pressure (CPAP), the patient had immediate symptom relief and has had three months without an episode of priapism. Conclusions: OSA should be considered as an underlying cause of nocturnal stuttering priapism in patients with SCD, particularly in patients who present with stuttering priapism later in life or patients who present strictly with nocturnal episodes. Appropriate management of OSA can significantly decrease the incidence of stuttering priapism in patients with SCD.

Manual Dexterity Predictors of Artificial Urinary Sphincter Success.

OBJECTIVE: To determine better in-office measures for artificial urinary sphincter outcomes, we investigated the ability of preoperative timed peg-transfer, pinch strength, grip strength, and Disabilities of the Arm Shoulder and Hand Outcome questionnaire in predicting postoperative satisfaction, confidence, and ease of use of artificial urinary sphincter placement for stress urinary incontinence. MATERIALS AND METHODS: A timed 9-hole peg test, pinch and grip strength assessment, and upper extremity questionnaire were administered during the preoperative visit before sphincter placement. In addition to standard preoperative workup, short-form International Consultation of Incontinence Questionnaire and physician handshake were recorded. Activation occurred 6 weeks after surgery along with assessment of adequacy of pump placement. Three months from surgery a repeat incontinence questionnaire and a survey measuring satisfaction, difficulty of use, and confidence were given. Correlation between preoperative assessment variables and the postoperative questionnaire was assessed. RESULTS: Thirty-nine patients were included. Average age and body mass index were 68.8 years and 28.8 kg/m2, respectively. Prior prostatectomy accounted for 92.3% of patients, and 46.2% had prior pelvic radiation. Postoperatively, 59.0% of patients were very satisfied; 64.1% of patients reported no difficulty of use; 53.8% felt confidence within 1 day; and 66.7% had much better bladder control. Average pad improvement count was 5.3. Pinch test was associated with satisfaction (P = .011) while peg test was associated with confidence (P = .049). Handshake and upper extremity questionnaire were not significant. CONCLUSION: The pinch and 9-hole peg transfer tests are cost-effective and easily performed adjuncts that could be used during artificial urinary sphincter evaluation for patients with unclear manual functional status.

Malignant priapism: case report and update on management protocols.

Background: Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm. While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. Herein, we describe three cases of malignant priapism and suggest a step-by-step approach for clinical management. Case Description: This study reports three cases of malignant priapism resulting from advanced genitourinary cancers. All patients experienced a sub-acute progression of penile pain and ultimately underwent palliative penectomy, resulting in sustained symptom relief. Conclusions: Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes and emphasis should be put on palliative care. Similar to previous cases, our cases died shortly after the diagnosis of malignant priapism. Conventional procedures such as shunting may not necessarily provide symptom relief in these patients. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts.

Antibiotic Duration After Urethroplasty: An Attempt at Improving Antibiotic Stewardship.

OBJECTIVE: To evaluate if decreasing postop abx prophylaxis affects UTI and wound infection rates in patients following urethroplasty. METHODS: A retrospective review of patients who underwent urethroplasty from 9/2017 - 3/2020 by a single surgeon was performed. All patients received urine culture specific perioperative IV abx prior to urethroplasty and kept a urethral catheter for 3 weeks postop. Patients undergoing a urethroplasty from 9/2017 to 12/2018 received extended postop abx prophylaxis for 3 weeks until catheter removal (Group 1). Patients from 12/2018 to 3/2020 received abx for 3 days around catheter removal (Group 2). UTIs, abx complications, and wound infections between groups were evaluated. UTIs were defined as a positive urine culture or reported lower urinary tract symptoms/fevers treated with empiric abx. RESULTS: 120 patients underwent urethroplasty. Group 1 consisted of 60 patients with mean age of 51.9 years and mean stricture length of 3.6 cm. Group 2 had 60 patients with mean age of 53.1 years and mean stricture length of 3.8 cm. 10 patients had UTIs after urethroplasty. There was no significant difference in UTI (6.7% vs 11.7%; P = 0.529) or wound infection rates (3.3% vs 1.7%;' P = 1.000) between the two groups. CONCLUSION: Extended postoperative antibiotic prophylaxis does not appear to significantly affect UTI or wound infection rates following urethroplasty. The retrospective nature of the study has limitations, however, this is the first comparison of two different antibiotic administration protocols to our knowledge.

Worldwide trends in penile implantation surgery: data from over 63,000 implants.

BACKGROUND: Penile prosthesis implantation represents the gold standard of treatment for severe or medically refractory erectile dysfunction (ED). We sought to address the paucity of currently available literature about global penile prosthesis usage in regard to geography, patient age, surgical approach, implanter volume, and etiology of ED. METHODS: From device manufacturer information, we compiled data on over 63,000 implants performed worldwide. Data was grouped and then analyzed to examine trends in penile implantation between the years of 2005-2012. RESULTS: The number of implants was seen to steadily increase over the study period. Of the 63,013 total procedures recorded, 85.9% were performed within the United States. 60-78% of procedures were done using the penoscrotal (PS) approach, with only Belgium/Netherlands as an outlier with an infrapubic (INF) majority. The US was notable for having an increasing number of implanters doing 16-30, 31-50, or >100 implants yearly. Etiology of ED worldwide was variable, but "organic," post-prostatectomy, and diabetes accounted for the vast majority of cases worldwide. CONCLUSIONS: Penile prosthesis implantation is an increasing practice, as evidenced by a steady increase in the number of implants performed over a 7-year study period. Acceptance of this treatment option for ED is variable by region with the US leading the annual number of implantations by a wide margin. Worldwide, there appears to be a predominance of surgeons placing implants via the PS approach.

A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome.

OBJECTIVE: To quantify reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS), create a demographic of patient reports, and examine the cluster of symptoms to correlate consistency of postfinasteride syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster of sexual, physical, and psychological and/or neurologic symptoms associated with 5-alpha reductase inhibitor use that emerge or continue after discontinuation of medication. MATERIALS AND METHODS: FAERS dataset of 5-alpha reductase inhibitors from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories for completion, but not every report was fully completed. Statistical analysis compared variables of interest between the 2 doses of finasteride (1 mg vs 5 mg). RESULTS: From FAERS, 2048 monotherapy cases were identified: 1581 of finasteride 1 mg, 240 of finasteride 5 mg, and 226 of unreported doses. Possibly related to labeling changes, from 2011 to 2014, there was a significant increase in adverse events (AEs) reported involving 1 mg dosing. Finasteride use was reported with many sexual AEs including diminished libido, erectile dysfunction, and ejaculatory complaints. Other common AEs included dermatologic, metabolic, and psychological and/or neurologic complaints. There were more AE reports with the 1 mg dose than the 5 mg dose. One case of dutasteride reported back pain, not generally attributed to PFS. CONCLUSION: FAERS data suggests that finasteride exposure is reported with a diverse collection of symptoms, particularly in younger men on 1 mg dosage compared to older men on 5 mg. Many of these complaints fall well out of the realm of previously established AEs from long-term controlled studies.

Immune Characterization of the Programmed Death Receptor Pathway in High Risk Prostate Cancer.

BACKGROUND: Programmed cell death-1 (PD-1), a T-cell inhibitory receptor, and its ligand, PD-L1, have been reported to be expressed in many tumor types, and this expression has led to the development of many drugs targeting the PD-1 pathway. The objective of this study was to determine the expression of PD-1 and PD-L1 in high-grade prostate cancer tissues, and correlate the expression with disease and patient characteristics. MATERIALS AND METHODS: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed and scored from 0 to 5 on prostatectomy/biopsy tissue samples taken from 25 men with high-grade prostate cancer. Charts were then retrospectively reviewed for numerous patient and disease characteristics. Statistical analyses were done to investigate the association of these patient and disease characteristics with PD-1, PD-L1, and CD3 expression. RESULTS: A score of 3 to 5 on the semiquantitative 0 to 5 score was deemed "high" expression whereas a score of 0 to 2 was deemed "low" expression. Of the 25 samples, 2 (8%) scored high for PD-1 expression, 2 (8%) scored high for PD-L1 expression, and 18 (72%) scored high for CD3 expression. There was no statistically significant difference between high and low expression groups of PD-1, PD-L1, or CD3 for any of the variables we collected. CONCLUSION: An overall low expression of PD-1 and PD-L1, and a concurrent high expression of CD3+ T cells was found in high-risk prostate cancer tissue. No significant association was found between expression of PD-1, PD-L1, or CD3, and patient or disease characteristics. Because of this, one might be able to question the role of PD-L1 in local immune suppression in prostate cancer.

Testosterone replacement therapy and voiding dysfunction.

Testosterone replacement therapy (TRT) represents an increasing popular treatment option for men with late-onset hypogonadism (LOH). Because of unsubstantiated beliefs of testosterone's effect on the prostate, the FDA has recently placed a warning on testosterone products, stating that TRT may worsen benign prostatic hyperplasia (BPH). Within this review article we have demonstrated the current understanding of the physiology of testosterone and its relationship with prostatic and lower urinary tract physiology. The current evidence suggests that not only does TRT not worsen lower urinary tract symptoms (LUTS), but that hypogonadism itself is an important risk factor for LUTS/BPH.