Barrett E. Cowan

The Prostatic Urethral Lift for the Treatment of Lower Urinary Tract Symptoms Associated with Prostate Enlargement Due to Benign Prostatic Hyperplasia: The L.I.F.T. Study

PURPOSE We report the first multicenter randomized blinded trial of the prostatic urethral lift for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS Men at least 50 years old with AUASI (American Urological Association Symptom Index) 13 or greater, a maximum flow rate 12 ml per second or less and a prostate 30 to 80 cc were randomized 2:1 between prostatic urethral lift and sham. In the prostatic urethral lift group small permanent implants are placed within the prostate to retract encroaching lobes and open the prostatic urethra. Sham entailed rigid cystoscopy with sounds mimicking the prostatic urethral lift. The primary end point was comparison of AUASI reduction at 3 months. The prostatic urethral lift arm subjects were followed to 1 year and assessed for lower urinary tract symptoms, peak urinary flow rate, quality of life and sexual function. RESULTS A total of 206 men were randomized (prostatic urethral lift 140 vs sham 66). The prostatic urethral lift and sham AUASI was reduced by 11.1±7.67 and 5.9±7.66, respectively (p=0.003), thus meeting the primary end point. Prostatic urethral lift subjects experienced AUASI reduction from 22.1 baseline to 18.0, 11.0 and 11.1 at 2 weeks, 3 months and 12 months, respectively, p<0.001. Peak urinary flow rate increased 4.4 ml per second at 3 months and was sustained at 4.0 ml per second at 12 months, p<0.001. Adverse events were typically mild and transient. There was no occurrence of de novo ejaculatory or erectile dysfunction. CONCLUSIONS The prostatic urethral lift, reliably performed with the patient under local anesthesia, provides rapid and sustained improvement in symptoms and flow, while preserving sexual function.

Treatment of LUTS secondary to BPH while preserving sexual function: randomized controlled study of prostatic urethral lift.

INTRODUCTION We analyzed data obtained from a randomized controlled blinded study of the prostatic urethral lift (PUL) to evaluate the sexual side effects of this novel treatment. AIMS We sought to determine whether PUL, when conducted in a randomized study, significantly improved lower urinary tract symptoms (LUTS) and urinary flow rate while preserving sexual function. METHODS Men ≥50 years with prostates 30-80 cc, International Prostate Symptom Score (IPSS) >12, and peak urinary flow rate (Qmax) ≤12 ml/s were randomized 2:1 between PUL and sham. Sexual activity was not an inclusion criterion. In PUL, permanent transprostatic implants are placed to retract encroaching lateral lobes and open the prostatic fossa. Sham entailed rigid cystoscopy with sounds to mimic PUL and a blinding screen. MAIN OUTCOME MEASURES Blinded groups were compared at 3 months and active arm then followed to 12 months for LUTS with IPSS and for sexual function with sexual health inventory for men (SHIM) and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Subjects were censored from primary sexual function analysis if they had baseline SHIM < 5 at enrollment. Secondary stratified analysis by erectile dysfunction (ED) severity was conducted. RESULTS There was no evidence of degradation in erectile or ejaculatory function after PUL. SHIM and MSHQ-EjD scores were not different from control at 3 months but were modestly improved and statistically different from baseline at 1 year. Ejaculatory bother score was most improved with a 40% improvement over baseline. Twelve-month SHIM was significantly improved from baseline for men entering the study with severe ED, P = 0.016. IPSS and Qmax were significantly superior to both control at 3 months and baseline at 1 year. There was no instance of de novo sustained anejaculation or ED over the course of the study. CONCLUSIONS The PUL improves LUTS and urinary flow while preserving erectile and ejaculatory function.

The potential for NX-1207 in benign prostatic hyperplasia: an update for clinicians

Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) affect many older men and can have a significant impact on health-related quality of life. BPH is a progressive condition that may lead to complications including acute urinary retention. There exists an unmet need for a safe and effective, office-based, catheter-free therapy for BPH patients. NX-1207 is a promising first-in-class drug currently in phase III trials for the treatment of BPH. This review provides an overview of the NX-1207 trial program and considers its potential application for patients with symptoms related to BPH. NX-1207 is administered as an office-based procedure by transrectal intraprostatic injection under ultrasound guidance. NX-1207 has selective pro-apoptotic properties, which induce focal cell loss in prostate tissue, leading to prostate volume reduction with both short- and long-term symptomatic improvement. In four US clinical trials to date, NX-1207 has shown evidence of symptomatic improvement substantially better than currently approved BPH medications with no significant safety issues. Larger phase III trials are ongoing to confirm further the efficacy, safety, and tolerability for this minimally invasive, anesthetic-free, clinic-based treatment for BPH.

The effect of diazepam on neonatal seizure: in vivo 31P and 1H NMR study.

ABSTRACT: It is assumed that when anticonvulsants arrest seizure, there is rapid return of brain high energy phosphates and brain lactate to control values. To test this hypothesis, diazepam was administered to neonatal dogs during flurothyl-induced seizure. In vivo 31P nuclear magnetic resonance spectroscopy disclosed that diazepam quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline values. In contrast, in vivo 1H nuclear magnetic resonance spectroscopic measurements showed that arrest of seizure with diazepam did not return brain lactate to control values. The sustained increase in cerebral blood flow and prolonged elevation of brain lactate, acetate, valine, and succinate in the postictal period indicate that metabolic recovery of the brain occurs over an extended period of time after the normalization of EEG, phosphocreatine, and brain pH

Measurement of the sodium membrane potential by NMR

Using nuclear magnetic resonance (NMR), we have developed a method of noninvasively determining the transmembrane sodium potential in erythrocytes by measuring intracellular and extracellular sodium concentrations. The experimental values correlated well with values obtained from standard flame photometric methods.

WATER: A Double-Blind, Randomized, Controlled Trial of Aquablation® vs Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia

Purpose: We compared the safety and efficacy of Aquablation and transurethral prostate resection for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Materials and Methods: In a double‐blind, multicenter, prospective, randomized, controlled trial 181 patients with moderate to severe lower urinary tract symptoms related to benign prostatic hyperplasia underwent transurethral prostate resection or Aquablation. The primary efficacy end point was the reduction in International Prostate Symptom Score at 6 months. The primary safety end point was the development of Clavien‐Dindo persistent grade 1, or 2 or higher operative complications. Results: Mean total operative time was similar for Aquablation and transurethral prostate resection (33 vs 36 minutes, p = 0.2752) but resection time was lower for Aquablation (4 vs 27 minutes, p <0.0001). At month 6 patients treated with Aquablation and transurethral prostate resection experienced large I‐PSS improvements. The prespecified study noninferiority hypothesis was satisfied (p <0.0001). Of the patients who underwent Aquablation and transurethral prostate resection 26% and 42%, respectively, experienced a primary safety end point, which met the study primary noninferiority safety hypothesis and subsequently demonstrated superiority (p = 0.0149). Among sexually active men the rate of anejaculation was lower in those treated with Aquablation (10% vs 36%, p = 0.0003). Conclusions: Surgical prostate resection using Aquablation showed noninferior symptom relief compared to transurethral prostate resection but with a lower risk of sexual dysfunction. Larger prostates (50 to 80 ml) demonstrated a more pronounced superior safety and efficacy benefit. Longer term followup would help assess the clinical value of Aquablation.

1H nuclear magnetic resonance spectroscopy study of neonatal hypoglycemia.

It has been hypothesized that the mechanism of hypoglycemic brain damage involves energy failure or excessive accumulation of excitatory neurotransmitters. To test these hypotheses, 1H nuclear magnetic resonance spectroscopy was employed to determine brain high-energy phosphates, carbohydrates, neurotransmitters, amino acids, and fatty acids during insulin-induced hypoglycemia in the neonatal dog. Reduction in brain glucose content was associated with an increase in blood/brain lactate ratio, as well as decreases in brain glutamate, aspartate, taurine, and inositol; however, no change was observed in GABA concentration or in brain energy state. In contrast to the adult experimental animal, brain tissue injury due to hypoglycemia is minimal in the neonatal animal. The mechanism of resistance to hypoglycemic brain injury may involve modulation of the rise of excitatory amino acids and decline in inhibitory neurotransmitters and high-energy phosphates.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia

Purpose: We report 2‐year outcomes of a multicenter randomized controlled trial plus 1‐year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods: A total of 197 men at least 50 years old with I‐PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. Results: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8‐point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. Conclusions: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Durability of the Prostatic Urethral Lift: 2-Year Results of the L.I.F.T. Study

Introduction: For a therapy to become an important part of a provider armamentarium it must be safer or better than existing therapies and be durable. The prostatic urethral lift offers rapid improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia with minimal side effects. We report 2‐year results of a multicenter, randomized, blinded trial of the prostatic urethral lift. Methods: A total of 206 men 50 years old or older with an AUA‐SI of 13 or greater, a peak flow rate of 12 ml per second or less and a 30 to 80 cc prostate were randomized 2:1 between the prostatic urethral lift and sham treatment. The prostatic urethral lift is performed by placing permanent transprostatic implants to lift apart the prostate lobes and reduce urethral obstruction. Sham treatment entailed rigid cystoscopy, a blinding screen and sounds that mimicked those of the prostatic urethral lift procedure. Patients were assessed for lower urinary tract symptoms, peak flow rate, quality of life and sexual function. Results: The prostatic urethral lift reduced the AUA‐SI 88% more than sham treatment (−11.1 vs −5.9, p = 0.003). Patients with the prostatic urethral lift experienced an AUA‐SI reduction from 22.1 at baseline to 18.0 (−17%), 11.1 (−50%), 11.4 (−48%) and 12.5 (−42%) at 2 weeks, 3 months, and 1 and 2 years, respectively (p <0.0001). The peak flow rate was increased 4.2 ml per second at 3 months and 2 years (p <0.0001). By 2 years only 7.5% of patients required additional intervention for lower urinary tract symptoms. Adverse events were typically mild and transient. Encrustation did not develop on implants properly placed in the prostate. There was no occurrence of de novo sustained ejaculatory or erectile dysfunction. Conclusions: The prostatic urethral lift preserves sexual function and provides rapid improvement in symptoms, flow and quality of life that are sustained to 2 years.Abbreviations and Acronyms: AUA‐SI: American Urological Association Symptom Index; BPH: benign prostatic hyperplasia; BPHII: BPH Impact Index; FDA: Food and Drug Administration; GEE: general estimating equation; L.I.F.T.: Luminal Improvement Following Prostatic Tissue approximation for the treatment of LUTS secondary to BPH; LUTS: lower urinary tract symptoms; MSHQ‐EjD: Male Sexual Health Questionnaire for Ejaculatory Dysfunction; PUL: prostatic urethral lift; Qmax: peak urinary flow rate; QOL: quality of life; SHIM: Sexual Health Inventory for Men; TURP: transurethral prostate resection.

Two Year Durability after Crossover to the Prostatic Urethral Lift from Randomized, Blinded Sham

To evaluate the 24‐month effectiveness of the prostatic urethral lift (PUL) procedure in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) assessed through a crossover study.