A Comparative Study of Commercially Available Ultrasound Contrast Agents for Sub-harmonic-Aided Pressure Estimation (SHAPE) in a Bladder Phantom.

OBJECTIVE: The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. METHODS: Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB-saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. RESULTS: All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. CONCLUSION: Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE.

The Inequitable Experiences of Left-Handed Medical Students in Surgical Education.

PURPOSE: Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed-specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students' circumstances. METHOD: In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance. RESULTS: The authors identified 3 themes related to left-handed medical students' surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction. CONCLUSIONS: Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner's current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.

Ultrasound Contrast Stability for Urinary Bladder Pressure Measurement.

The goal of this study was to evaluate ultrasound contrast microbubbles (MB) stability during a typical cystometrogram (CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated. The results verified that air volume in intravenous (IV) bag headspace was not enough to have a significant effect on MB stability during a CMG. We also showed that higher MB dosage results in a more stable condition. Finally, the results indicated that the CMG infusion system adversely affects MB stability. In summary, to ensure MB stability during the entire duration of a CMG, lower filling rates (limited by estimated bladder capacity in clinical applications) and/or higher MB dosage (limited by FDA regulations and shadowing artifact) and/or the consideration of alternative catheter design may be needed.

Pressure Measurement in a Bladder Phantom Using Contrast-Enhanced Ultrasonography-A Path to a Catheter-Free Voiding Cystometrogram.

OBJECTIVES: The long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free. This is of importance because the CMG catheter, due to its space-occupying property and non-physiological effects, can undermine the reliability of the test during voiding and cause misdiagnosis. In this study, we tested this hypothesis and optimized the protocol in a controlled benchtop environment. MATERIALS AND METHODS: A bladder phantom was designed and built, capable of simulating clinically relevant bladder pressures. Laboratory-made lipid-shelled MBs (similar in composition to the commercial agent, DEFINITY) was diluted in 0.9% normal saline and infused into the bladder phantom using the CMG infusion system. A typical simulated CMG consists of 1 filling and 4 post-filling events. During CMG events, the bladder phantom is pressurized multiple times at different clinically relevant levels (small, medium, and large) to simulate bladder pressures. Simultaneous with pressurization, MB subharmonic signal was acquired. For each event, the change in MB subharmonic amplitude was correlated linearly with the change in bladder phantom pressure, and the SHAPE conversion factor (slope of the linear fit) was determined. In doing so, a specific signal processing technique (based on a small temporal window) was used to account for time-decay of MB subharmonic signal during a simulated CMG. RESULTS: A strong inverse linear relationship was found to exist between SHAPE and bladder phantom pressures for each of the CMG filling and post-filling events ( r2> 0.9, root mean square error < 0.3 dB, standard error <0.01 dB, and P < 0.001). SHAPE showed a transient behavior in measuring bladder phantom pressure. The SHAPE conversion factor (in dB/cm H 2 O) varied between filling and post-filling events, as well as by post-filling time. The magnitude of the SHAPE conversion factor tended to increase immediately after filling and then decreases with time. CONCLUSIONS: Microbubble subharmonic emission is an excellent indicator of bladder phantom pressure variation. The strong correlation between SHAPE signal and bladder phantom pressure is indicative of the applicability of this method in measuring bladder pressure during a CMG. Our results suggest that different SHAPE conversion factors may be needed for different events during a CMG (ie, at different time points of a CMG). These findings will help us better protocolize this method for introduction into human subjects and allow us to take the next step toward developing a catheter-free voiding CMG using SHAPE.

An Alternative Approach to Single-Stage Cloaca Repair: Image-Guided Anorectoplasty with Delayed Vaginoplasty.

BACKGROUND: Cloacal anomalies occur when a fetus's rectum, vagina, and urethra fail to separate and result in 1 common channel at birth. They are commonly managed by complex reconstruction in the first year of life. This manuscript presents an alternative approach to management in patients with absent or nondilated Mullerian structures. CASE: Image-guided, combined endoscopic and laparoscopic surgery (CELS) was used to perform an anorectal pull-through at 5 months of age on a patient with persistent cloaca and no definite vaginal or uterine structures seen on MRI and endoscopy. Urogenital reconstruction is delayed until adolescence. SUMMARY AND CONCLUSION: We hypothesize that performing a minimally invasive anorectoplasty on patients with complicated anatomy and low risk for hydrocolpos could potentially result in improved urologic function and better psychosocial outcomes. Delaying vaginoplasty will enable determination of the function of remnant Mullerian structures and allow the patient to direct the augmentation approach.

The effect of preoperative tamsulosin on ureteroscopic access in school-aged children.

INTRODUCTION: Flexible ureteroscopes are not tailored for pediatric ureteral size and may not pass at first attempt into the pediatric ureter. Administration of tamsulosin preoperatively in adults has been shown to facilitate ureteral access sheath placement. Several studies have shown tamsulosin to be safe and effective when utilized for medical expulsive therapy in pediatric patients, but its utility for preoperative ureteral dilation has not been studied to date. OBJECTIVE: We hypothesized that preoperative tamsulosin reduces failed ureteroscopic access in children. MATERIALS AND METHODS: We conducted a retrospective review of patients aged 0-18 years undergoing flexible ureteroscopy (URS) from 2014 to 2019 at a single institution. Patients were divided into those taking 0.4 mg of tamsulosin daily for at least 1 week prior to surgery and those not taking tamsulosin. The primary outcome was failure to pass a 7.95 Fr flexible ureteroscope on initial attempt, requiring stent placement and staged management. Patients undergoing URS or stent placement within the prior year, requiring semi-rigid URS, or with genitourinary anomalies were excluded. RESULTS AND DISCUSSION: A total of 49 patients met inclusion criteria. The tamsulosin group (n = 13) and non-tamsulosin group (n = 36) were similar with respect to demographic data. The percentage of prepubertal patients was 53% vs 33% (p = 0.19). The tamsulosin group had lower failed URS (38% vs 61%, p = 0.20). When stratified by age, both prepubertal and postpubertal patients in the tamsulosin group had lower failed URS (43% vs 67%, p = 0.67 and 33% vs 58%, p = 0.38). These clinically significant results suggest initial passage of a flexible ureteroscope is more successful in pediatric patients on preoperative tamsulosin. This study was largely limited by its low power and flaws inherent to its retrospective design. CONCLUSION: Our results have implications for prescribing tamsulosin preoperatively to reduce multiple procedures and anesthetics in children. Adequately powered prospective trials are warranted to confirm preoperative tamsulosin reduces failed first-attempt flexible URS in children.

Evaluation of outcomes following complete primary repair of bladder exstrophy at three individual sites prior to the establishment of a multi-institutional collaborative model.

PURPOSE: The Multi-Institutional Bladder Exstrophy Consortium (MIBEC) was established in 2013 to refine technical aspects of the complete primary repair of bladder exstrophy (CPRE), to decrease complications, and to improve outcomes. In order to place outcomes from the consortium into context of historic outcomes, we evaluated continence and dry intervals in children who were repaired prior to the beginning of the consortium at these institutions. We hypothesized that continence (voiding with dryness) is rarely achieved after primary CPRE and surgery following CPRE improves dryness but may hinder voiding per urethra. MATERIALS AND METHODS: We reviewed prospectively maintained IRB approved databases of children who underwent CPRE for classic bladder exstrophy (BE) between 5/1993 and 1/2013 at 3 institutions. Exclusion criteria included: lack of continence documentation, and lack of follow up subsequent to January 2014. We recorded age at closure, method of bladder emptying, bladder capacity and surgical history. We used a 3 part dryness scale for both patients who void volitionally and those on CIC. Children were considered dry if they could hold urine for over 3 h. An intermediate group was defined as having a dry interval of 2-3 h, with minimal dampness in between voids. If dry intervals were <2 h with frequent leakage, children were considered wet. RESULTS: A total of 54 of 73 (38 M) children met inclusion criteria. 35 of 54 (64.8%) children void per urethra, while 18 (33.3%) perform clean intermittent catheterization (CIC) and 1 underwent a vesicostomy due to incomplete emptying and UTI's. 25/35 (71.4%) of those voiding per urethra underwent CPRE only, while the remaining 10 underwent secondary continence procedures. In total, 26 of 54 (48.1%) are dry, that is either continent or not wet for > 3 h, while only 11/54 (20.4%) are truly continent, i.e., voiding per urethra. Only 9/54 (16.7%) are continent after a single surgery (CPRE). 14/54 children who are dry (25.9%) underwent a bladder neck procedure with or without augmentation and empty with CIC. DISCUSSION AND CONCLUSION: Granular detail about the specifics of emptying, surgical history, and dry intervals is crucial to understand the true outcomes from the repair of BE. Children with BE undergoing CPRE prior to the institution of MIBEC experienced variable results, with only 17% achieving continence while spontaneously voiding per urethra without additional reconstruction. We are now engaged in MIBEC to identify factors that contribute to continence and to attempt to render such findings reproducible.

Repair of injured urethras with silk fibroin scaffolds in a rabbit model of onlay urethroplasty.

BACKGROUND: Preclinical validation of scaffold-based technologies in animal models of urethral disease is desired to assess wound healing efficacy in scenarios that mimic the target patient population. This study investigates the feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously damaged urethras in a rabbit model of onlay urethroplasty. MATERIALS AND METHODS: A focal, partial thickness urethral injury was created in adult male rabbits (n = 12) via electrocoagulation and then onlay urethroplasty with 50 mm2 BLSF grafts was carried out 2 wk after injury. Animals were randomly divided into three experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1 (n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were performed preoperatively and at 2 wk after injury in all groups as well as at 1 or 3 mo after scaffold grafting and included urethroscopy, retrograde urethrography (RUG), and histological and immunohistochemical analyses. RESULTS: At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses of repaired urethral segments demonstrated a 39% reduction in urethral stenosis detected following electrocoagulation injury. Histological and immunohistochemical analyses revealed the formation of innervated, vascularized neotissues with α-smooth muscle actin+ and SM22α+ smooth muscle bundles and pan-cytokeratin + epithelium at graft sites. CONCLUSIONS: These results demonstrate the feasibility of BLSF matrices to support the repair of previously damaged urethral tissues.

Tissue Engineering and Conduit Substitution.

Radical cystectomy (RC) with urinary diversion is associated with significant morbidity, much of which arises from the interposition of bowel segments in the urinary system. A tissue-engineered alternative for urinary diversion could dramatically reduce the perioperative and long-term morbidity associated with RC. Attempts at developing a tissue-engineered incontinent urinary conduit (TEUC) have involved mechanical scaffolds and promoting tissue growth within them. Despite some preclinical success, significant obstacles remain before a TEUC is ready for clinical use. A further understanding of tissue and materials engineering may help overcome these obstacles or help to develop a new approach to tissue engineering entirely.

Pediatric medical device development by surgeons via capstone engineering design programs.

BACKGROUND: There is a need for pediatric medical devices that accommodate the unique physiology and anatomy of pediatric patients that is increasingly receiving more attention. However, there is limited literature on the programs within children's hospitals and academia that can support pediatric device development. We describe our experience with pediatric device design utilizing collaborations between a children's hospital and two engineering schools. METHODS: Utilizing the academic year as a timeline, unmet pediatric device needs were identified by surgical faculty and matched with an engineering mentor and a team of students within the Capstone Engineering Design programs at two universities. The final prototypes were showcased at the end of the academic year and if appropriate, provisional patent applications were filed. RESULTS: All twelve teams successfully developed device prototypes, and five teams obtained provisional patents. The prototypes that obtained provisional patents included a non-operative ureteral stent removal system, an evacuation device for small kidney stone fragments, a mechanical leech, an anchoring system of the chorio-amniotic membranes during fetal surgery, and a fetal oxygenation monitor during fetoscopic procedures. CONCLUSIONS: Capstone Engineering Design programs in partnership with surgical faculty at children's hospitals can play an effective role in the prototype development of novel pediatric medical devices. LEVELS OF EVIDENCE: N/A - No clinical subjects or human testing was performed.

Ten-Year Review of Perioperative Complications After Transurethral Resection of Bladder Tumors: Analysis of Monopolar and Plasmakinetic Bipolar Cases.

OBJECTIVES: To evaluate the rate of perioperative complications after plasmakinetic bipolar and monopolar transurethral resection of bladder tumor (BTURB and MTURB). In addition, the study identifies patient and procedure characteristics associated with early complications. PATIENTS AND METHODS: Retrospective review was conducted on patients undergoing transurethral resection of bladder tumor procedures at a single institution from 2003 to 2013 to assess the 30-day complication rates associated with BTURB and MTURB. RESULTS: Four hundred twenty-seven patients met inclusion criteria and underwent 586 procedures (379 BTURB and 207 MTURB). Baseline patient demographics, tumor stage, and tumor grade were similar in BTURB and MTURB cohorts. The overall complication rate was 34.3% for MTURB and 26.7% for BTURB. The most frequent complications were acute urinary retention (AUR) 11%, hematuria 8%, and urinary tract infection (UTI) 7%. There was no statistical difference in rates of AUR, hematuria, UTI, or readmission for continuous bladder irrigation or hemostasis procedures between BTURB and MTURB cohorts. There was a trend toward lower perforation rate during BTURB (2.6% vs 5.8%). In multivariate logistic regression analysis, MTURB, male gender, and large resections were predictive of overall complications. Male gender was associated with hematuria and AUR. Large bladder tumor resection size was also associated with increased risk of overall complications and AUR. CONCLUSION: BTURB was associated with a lower risk of overall complications, but there was no difference in the rate of hematuria in the two cohorts. Male gender and large tumor size are associated with higher risk of early complications.

Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2B pathway.

Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions. In isolated tissue assays, inosine (1 mM) significantly decreased the amplitude of spontaneous activity (SA) in SCI bladder muscle strips. This effect was prevented by a pan-adenosine receptor antagonist CGS15943, but not by A1 or A3 receptor antagonists. The A2A antagonist ZM241385 and A2B antagonist PSB603 prevented the effect of inosine. The effect of inosine was mimicked by the adenosine receptor agonist NECA and the A2B receptor agonist BAY60-6583. The inhibition of SA by inosine was not observed in the presence of the BK antagonist, iberiotoxin, but persisted in the presence of KATP and SK antagonists. These findings demonstrate that inosine acts via an A2B receptor-mediated pathway that impinges on specific potassium channel effectors.

Cystectomy and Urinary Diversion for the Management of a Devastated Lower Urinary Tract Following Prostatic Cryotherapy and/or Radiotherapy.

INTRODUCTION: We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. METHODS: Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. RESULTS: Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). CONCLUSION: Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract.

Clinical pathway for early discharge after complete primary repair of exstrophy and epispadias by using a spica cast.

INTRODUCTION/OBJECTIVE: Secure closure of the pubic diastasis during bladder exstrophy and epispadias repair decreases the abdominal wall tension at the time of reconstruction. Pelvic osteotomies are routinely performed at the time of abdominal wall and bladder reconstruction in order to more easily facilitate pubic symphyseal diastasis approximation. Postoperative pelvic immobilization is performed by methods that include modified Buck's traction, modified Bryant's traction, and spica casting. People undergoing closure often require inpatient hospitalization for 2-8 weeks because of the pelvic immobilization. The present study examined the findings from a clinical pathway for early discharge after complete primary repair of exstrophy (CPRE) and proximal epispadias repair with spica casting. METHODS: The present study is a retrospective review of patients that underwent pelvic osteotomies with spica casting at the time of CPRE or proximal epispadias repair from November 2006 to March 2013. All patients had anterior innominate osteotomies and spica cast pelvic immobilization. RESULTS: Pelvic osteotomies and spica cast pelvic immobilization were performed on 17 children. The median postoperative stay was 6.0 days and the subdivided results are in Table. No children experienced an abdominal or orthopedic complication. A few children required minor cast adjustments to relieve pressure. After cast removal, no skin breakdown, pressure necrosis, or nerve palsy were found. The median length of casting without pinning was 31 (26-48) days. DISCUSSION: The use of spica cast pelvic immobilization after exstrophy and epispadias repair is safe and allows for earlier discharge when compared to other methods of pelvic immobilization. However, although the family appreciates early discharge and additional bonding, the priority is the success of the closure. The present findings demonstrate, and are corroborated by other spica cast publications, that spica casting is as effective as modified Bryant's traction or modified Buck's traction. The success rates for CPRE with spica casting are similar to published staged repairs and have the benefit of allowing for bladder cycling, which potentially enables better bladder growth and development. If success and complication rates are comparable amongst the different pelvic immobilization groups, then variables including hospital length of stay and cost become appropriate comparisons. CONCLUSION: The shortened discharge time, along with a significant decrease in acuity of care leads to significant decreases in hospital costs. Additional hospital stay when using modified Bryant's traction or modified Buck's traction with external fixation will accrue significant hospital costs.

V-Loc urethro-intestinal anastomosis during robotic cystectomy with orthotopic urinary diversion.

INTRODUCTION: Robotic-assisted radical cystectomy (RARC) is an emerging minimally invasive alternative for the treatment of invasive bladder cancer. The V-loc (Covidien, Mansfield, MA) suture is a unidirectional barbed suture that provides even distribution of tension. We determined the rate of urinary leak at the urethro-intestinal anastomosis following orthotopic neobladder construction performed with V-loc suture. METHODS: We retrospectively reviewed charts on all patients that underwent RARC with orthotopic neobladder urinary diversion performed with a V-loc suture from February 2010 to February 2012. The urethro-intestinal anastomosis was evaluated for urinary leak by cystogram at 3 to 4 weeks, postoperatively. RESULTS: In total, 11 patients were available for analysis. The mean patient age was 57.2 years (range: 47-71). The average clinical follow-up was 8 months (range: 4-15). On surgical pathology, 8 (73%) patients had pT2 or less disease, 3 (27%) had pT3/T4 disease, and 1 (9%) had N+ disease. The mean intraoperative blood loss was 315 mL (range: 150-600) and the average operative time was 496 minutes (range: 485-519). No patient (0%) demonstrated a urinary leak at the urethro-intestinal anastomosis on postoperative cystogram. Eight patients (73%) were continent by 4 months, postoperatively. CONCLUSIONS: Orthotopic neobladder urethro-intestinal anastomosis can be performed effectively and safely with V-loc suture with an acceptably low urinary leak rate.