Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

Current Utilization and Perceptions of Formal Education of Point-of-care Ultrasound in Urology.

OBJECTIVE: To assess the extent of formal point-of-care ultrasound (POCUS) training, current utilization of POCUS, and contemporary perceptions of POCUS amongst urologists. METHODS: A survey including questions regarding demographics, prior ultrasound education, current ultrasound utilization in practice/training, perceived optimal POCUS utilization, and the perception of formal ultrasound training was developed. The survey was disseminated to residency program directors (PDs) via the SAU and members of AUA subsection organizations. Data were collected via Redcap. RESULTS: A total of 40 PDs and 159 other respondents completed the survey with approximately half (51%) in an academic practice and two-thirds (68%) with more than 10years in practice. PD response rate was 28%, and general response rate was 2%. Among all respondents, 95% (186/196) and 82% (160/194) agreed/strongly agreed formal POCUS training would be worthwhile during and after residency. Among urology residency PDs, 93% (37/40) agreed/strongly agreed that formal POCUS training is worthwhile in residency. The majority of respondents used some form of ultrasound in practice (77%, 154/199). However, only 37% (72/199) of all respondents had prior formal POCUS training, and 19% (5/26) of PDs reported formal training in their programs. Of respondents without formal training, 63% (80/127) reported interest in pursuing formal training. CONCLUSION: POCUS is widely utilized in many practices. Yet, most urologists have not participated in formal POCUS training and most programs do not have curricula. Urologists have favorable opinions of the utility, safety, and efficacy of POCUS and desire training.

Clinical Validation of an Adult-acquired Buried Penis Classification System Based on Standardized Evaluation of the Penis, Abdomen, and Scrotum.

OBJECTIVE: To clinically validate a previously developed adult-acquired buried penis (AABP) classification system that is based on a standardized preoperative physical examination that subtypes patients by their penile skin/escutcheon complex (P), abdominal pannus (A), and scrotal skin (S). METHODS: The Trauma and Urologic Reconstruction Network of Surgeons (TURNS) database was used to create an AABP cohort. Patients were retrospectively classified using the previously described PAS classification system. The frequency of subtypes, surgical methods utilized for AABP repair, and correlations between PAS classification and surgery subtypes were analyzed. RESULTS: The final cohort consisted of 101 patients from 10 institutions. Interrater reliability between two reviewers was excellent (κ = 0.95). The most common subtypes were P2c (contributory escutcheon+insufficient penile skin; 27%) and P2a (contributory escutcheon+sufficient penile skin; 21%) for penile subtypes, A0 (no pannus; 41%) and A1 (noncontributory pannus; 39%) for abdominal subtypes, and S0 (normal scrotal skin with preserved scrotal sulcus; 71%) for scrotal subtypes. AABP repair procedures included escutcheonectomy (n = 59, 55%), scrotoplasty (n = 51, 48%), split-thickness skin grafting (n = 50, 47%), penile skin excision (n = 47, 44%) and panniculectomy (n = 7, 7%). P, A, and S subtypes were strongly associated with specific AABP surgical techniques. CONCLUSION: The PAS classification schema adequately describes AABP heterogeneity, is reproducible among observers, and correlates well with AABP surgery types. Future work will focus on how PAS subtypes affect both surgical and patient-centered outcomes.

Thermal Infrared Camera Imaging to Aid Necrotizing Soft Tissue Infections of the Genitalia Management.

OBJECTIVE: To determine if imaging with a thermal infrared camera might aid clinicians with diagnosis of equivocal necrotizing soft tissue infections of the genitalia (NSTIG) cases and help surgeons when determining appropriate surgical resection margins. MATERIALS/METHODS: For 12 months at a single tertiary academic hospital, sequential patients already undergoing exploration for acute scrotum had preoperative photography with an infrared camera (FLIR C5). We compared infrared and standard preoperative photography with operative reports and postoperative photography to investigate if infrared photography corresponded with operative findings in severe scrotal infections-specifically the viability of the skin and the ultimate surgical resection margins. RESULTS: A total of 16 patients were included. The pre-operative infrared photos directly correlated with resection margins in 13 of 16 (81%) patients. Notably, areas with a relatively lower (cooler) infrared intensity corresponded well to both visibly necrotic tissue when discrete and areas with large underlying fluid collections. Diffuse warm signal relative to surrounding skin correlated with cellulitis and viable skin. CONCLUSION: In this observational study, infrared photography corresponded well with physical exam and operative findings. There may be a role for augmented temperature photography in the diagnosis and triage of scrotal infections. More research with standardized temperature gating of infrared signal and controls with normal or nonacute scrotums are needed to elucidate the clinical utility for infrared photograph.

Nephrostomy Balloon and Sheath Suprapubic Tube Placement-A Minimally Invasive Approach to Large Caliber Suprapubic Tube Placement.

Suprapubic tubes (SPT) are a vital tool in the management of complex urologic voiding conditions. There are numerous methods of SPT placement, each with pros/cons: peel-away kits are easy to place, but often have small caliber SPTs, that is, 12 or 14 Fr, prone to kinking, that require serial upsizing to achieve the desired caliber; open SPT placements permit an initial large caliber SPT but are more invasive, particularly in obese patients. This video demonstrates a minimally invasive technique for SPT placement in patients with preserved urethral access to the bladder that safely allows for initial, precise placement of large caliber (>20F) catheters using the Nephromax nephrostomy balloon/sheath (NBS-SPT). Technique: A 6″ 17G Tuohy spinal needle is placed percutaneously 3 cm above the pubis (generally in the abdominal crease), 1-2 cm off midline towards the side the patient prefers to keep the drainage bag. The needle is angled to enter the bladder dome in the midline, which is visualized cystoscopically with a full bladder. The angling will allow the catheter to lie flat and decrease kinking. The stylette is removed and a stiff wire is advanced. A 2 cm horizontal skin incision is made. A 24 Fr NBS is advanced into the bladder under vision and inflated to 18 ATM. The balloon is then deflated/removed and the SPT is passed through the sheath into the bladder. Once inflated, the sheath removed and the SPT is secured to the skin. Study: A 10-year retrospective review of NBS-SPT placements at a single institution was performed, analyzing patient characteristics, surgical details, and surgical outcomes. NBS-SPT was attempted 65 times over the study period. The most common indications included acquired/congenital neurogenic bladder (48%) and urinary retention (25%). A simultaneous additional procedure (eg, cytolitholapaxy, bladder neck incision) was performed in 31% of NBS-SPTs. Median body mass index was 29.5 (interquartile range: 25-33.9) and 34% had prior abdominal procedures. Median operative time (NBS-SPT only) was 16 minutes (interquartile range: 14-20). All procedures were successful in placing a catheter 20F. Thirty-day Clavien I/II complication rate was 18% (hematuria n = 3; cellulitis n = 4; early SPT exchange for clogging n = 5); A Clavien IIIb complication occurred in one patient with hematuria requiring fulguration. First SPT exchange in clinic was successful in 95%, with 2 patients requiring replacement under anesthesia. NBS-SPT is a safe and efficient minimally invasive technique for initial, precise placement of large caliber SPT in patients with urethral bladder access.

Surgical management for giant bladder leiomyosarcoma.

While urothelial carcinoma is the most common histologic type of bladder cancer in the United States, leiomyosarcoma is a rare and aggressive variant. The rarity of bladder leiomyosarcoma results in uncertainty regarding the optimal treatment pathway. We report on a patient with a giant non-metastatic bladder leiomyosarcoma effectively managed with primary surgical intervention without chemoradiation.

Antenatal Presentation of Wilms' Tumor.

Tumors discovered antenatally are rare and the prognosis is generally poor. We present a case of a fetal left renal mass, initially discovered via routine prenatal ultrasound. The mother was an otherwise healthy gravida 4 para one 30-year-old female with 2 previous miscarriages, reportedly secondary to septate uterus. Further imaging and subsequent genetic testing was consistent with an antenatal Wilms' tumor with a mutation in the NPHP1 gene. The newborn received chemotherapy and had no evidence of recurrence at 3 months follow-up.

A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department.

BACKGROUND: Opioids are commonly prescribed in the emergency department (ED) for the treatment of acute pain. Analgesic alternatives are being explored in response to an epidemic of opioid misuse. Low-dose ketamine (LDK) is one opioid alternative for the treatment of acute pain in the ED. OBJECTIVES: This systematic review and meta-analysis sought to quantify whether LDK is an effective and safe opioid alternative for acute pain reduction in adults in the ED setting. (PROSPERO Registration Number CRD42017065303). METHODS: This was a systematic review of randomized controlled trials comparing intravenous opioids to LDK for relief of acute pain in the ED. Studies where the control group initially received opioids prior to ketamine were excluded. A research librarian designed the electronic search strategy. Changes in visual analog scale or numeric rating scale pain scales were analyzed to determine the relative effects of LDK and opioids in the treatment of acute pain. RESULTS: Three studies met the criteria for inclusion in this meta-analysis. Compared to pain scale reduction with morphine, ketamine was not inferior (relative reduction = 0.42, 95% confidence interval = -0.70 to 1.54). No severe adverse events were reported in any study, but higher rates of nonsevere adverse events were observed with ketamine. CONCLUSIONS: Ketamine is noninferior to morphine for the control of acute pain, indicating that ketamine can be considered as an alternative to opioids for ED short-term pain control.

Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates.

The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization.