Use of the Schelin Catheter for transurethral intraprostatic anesthesia prior to Rezum treatment.

Minimally invasive surgery techniques (MIST) have become newly adopted in urological care.  Given this, new analgesic techniques are important in optimizing patient outcomes and resource management. Rezum treatment (RT) for BPH has emerged as a new MIST with excellent patient outcomes, including improving quality of life (QoL) and International Prostate Symptom Scores (IPSSs), while also preserving sexual function.  Currently, the standard analgesic approach for RT involves a peri-prostatic nerve block (PNB) using a transrectal ultrasound (TRUS) or systemic sedation anesthesia.  The TRUS approach is invasive, uncomfortable, and holds a risk of infection.  Additionally, alternative methods such as, inhaled methoxyflurane (Penthrox), nitric oxide, general anesthesia, as well as intravenous (IV) sedation pose safety risks or mandate the presence of an anesthesiology team.  Transurethral intraprostatic anesthesia (TUIA) using the Schelin Catheter (ProstaLund, Lund, Sweden) (SC) provides a new, non-invasive, and efficient technique for out-patient, office based Rezum procedures.  Through local administration of an analgesic around the prostate base, the SC has been shown to reduce pain, procedure times, and bleeding during MISTs.  Herein, we evaluated the analgesic efficacy of TUIA via the SC in a cohort of 10 patients undergoing in-patient RT for BPH.

Peri-prostatic nerve block using Clarius EC7 HD3 handheld ultrasound guidance.

Transrectal ultrasound (TRUS) is a common modality used during urological procedures that require real-time visualization of the prostate, such as prostate biopsy and peri-prostatic nerve blocks (PNB) for surgical procedures. Current practice for TRUS-guided PNB requires use of costly, fixed, and non-portable ultrasound machinery that can often limit workflow. The Clarius endocavity EC7 probe, a digital, handheld and pocket-sized endocavity ultrasound (US) device, is an alternative, portable technology which was recently shown to accurately visualize and measure prostate dimensions and volume. Moreover, in recent years, there has been a renaissance of office-based treatments for minimally invasive surgical therapies (MIST) for the treatment of benign prostate hyperplasia (BPH). More specifically, the Rezum procedure has been demonstrated to offer men a short, outpatient therapy with excellent 5-year outcomes in durability and preservation of antegrade ejaculation. While other anesthetic techniques have been described for Rezum, including inhaled methoxyflurane (Penthrox), nitrous oxide, IV sedation and general anesthesia (which often mandate the presence of an anesthesiology team), US-guided local blocks offer the urologist an independent method for pain management. While most urologists may not have direct access to expensive, cart-based ultrasound systems, point of care ultrasound (POCUS) technology, such as Clarius (Vancouver, BC, Canada) and Butterfly (Butterfly Network, Inc, Guilford, CT, USA), can provide high-resolution imaging in combination with smart phone technology. Herein, we sought to describe the technique for using Clarius EC7 for TRUS-guided PNB and its use in urological application with the Rezum BPH procedure.

Synthesis and secretion of Nerve Growth Factor is regulated by Nitric Oxide in bladder cells in vitro under a hyperglycemic environment.

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 µM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 µM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2'-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome.