Frank J. Penna

Robotic Assisted Laparoscopic Mitrofanoff Appendicovesicostomy: Preliminary Experience in a Pediatric Population

PURPOSE Continent urinary diversion has a central role in treating various urinary tract conditions and traditionally has been performed as an open procedure. We report on 10 patients who underwent a robotic assisted laparoscopic Mitrofanoff procedure using the da Vinci surgical system. MATERIALS AND METHODS Patients had bladder dysfunction of various etiologies, including posterior urethral valves and neurogenic bladder. Preoperatively all patients unsuccessfully attempted clean intermittent catheterization via the urethra. RESULTS Mean operative time was 323 minutes (range 181 to 507). One case was converted to open surgery secondary to an inadequate appendix discovered intraoperatively. Mean estimated blood loss was 48.4 cc (range 5 to 200). Median hospitalization was 5 days. Median followup was 14.2 months. Urinary leakage developed postoperatively in 1 patient, requiring an open revision. Minor incontinence developed in 2 cases, of which 1 was corrected with dextranomer/hyaluronic acid injection and 1 resolved without intervention. CONCLUSIONS The robotic assisted laparoscopic Mitrofanoff procedure is feasible to perform, is associated with satisfactory outcomes and minimal complications, and has the benefits of a minimally invasive approach.

Assessment of Parental Satisfaction in Children Undergoing Voiding Cystourethrography Without Sedation

PURPOSE Approximately 50,000 children undergo voiding cystourethrography annually. There is a recent trend toward using sedation or delaying voiding cystourethrography due to the anticipated distress to the patient. We hypothesized that with adequate preparation and proper techniques to minimize anxiety, voiding cystourethrography can be performed without sedation. We assessed parental satisfaction associated with patient and parent experience of voiding cystourethrography without sedation. MATERIALS AND METHODS We used a 33-question survey to evaluate parental satisfaction with patient and parent experience of voiding cystourethrography without sedation. Children were divided into 3 groups according to toilet training status. Statistical analysis was performed using Stata®. RESULTS A total of 200 surveys were completed. Of the children 54% were not toilet trained. Of the parents 90% reported adequate preparation. More than half of parents classified the experience of voiding cystourethrography as equivalent to or better than a physical examination, immunization, ultrasound and prior catheterization. Most parents were satisfied with the ability of the child to tolerate the procedure and considered the experience better than expected. Children in the process of toilet training had the most difficulty with the procedure, correlating with lower levels of parental satisfaction. CONCLUSIONS Voiding cystourethrography performed with adequate preparation and support can be tolerated without sedation. Children in the process of toilet training and females tolerate the procedure least.

CKD and Bladder Problems in Children

Approximately 35% of children with CKD who require renal replacement therapy have a significant urological abnormality, including posterior urethral valves, a neuropathic bladder, prune belly syndrome, Hinman syndrome, or severe vesicoureteral reflux. In such children, abnormal bladder function can have a significant deleterious effect on the renal function. In children with bladder outlet obstruction, bladder compliance and capacity often are abnormal, and a sustained intravesical pressure of >40 cm H(2)O impedes drainage from the upper urinary tract. Consequently, in these conditions, regular evaluation with renal sonography, urodynamics, urine culture, and serum chemistry needs to be performed. Pediatric urological care needs to be coordinated with pediatric nephrologists. Many boys with posterior urethral valves have severe polyuria, resulting in chronic bladder overdistension, which is termed as valve bladder. In addition to behavioral modification during the day, such patients may benefit from overnight continuous bladder drainage, which has been shown to reduce hydronephrosis and stabilize or improve renal function in most cases. In children with a neuropathic bladder, detrusor-sphincter-dyssynergia is the most likely cause for upper tract deterioration due to secondary vesicoureteral reflux, hydronephrosis, and recurrent urinary tract infection (UTI). Pharmacologic bladder management and frequent intermittent catheterization are necessary. In some cases, augmentation cystoplasty is recommended; however, this procedure has many long-term risks, including UTI, metabolic acidosis, bladder calculi, spontaneous perforation, and malignancy. Nearly half of children with prune belly syndrome require renal replacement therapy. Hinman syndrome is a rare condition with severe detrusor-sphincter discoordination that results in urinary incontinence, encopresis, poor bladder emptying, and UTI, often resulting in renal impairment. Children undergoing evaluation for renal transplantation need a thorough evaluation of the lower urinary tract, mostly including a voiding cystourethrogram and urodynamic studies.

Safety Profile of Trocar and Insufflation Needle Access Systems in Laparoscopic Surgery

BACKGROUND The most common laparoscopic complications are associated with trocar insertion. The purpose of this study was to develop an objective method of evaluating the safety profile of various access devices used in laparoscopic surgery. STUDY DESIGN In 20 swine, 6 bladed and 2 needle access devices were evaluated. A force profile was determined by measuring the force required to drive the trocar or needle through the fascia and into the peritoneum, at 0 and 10 mmHg. The amount of tissue deformation, the length of blade exposed, and the duration of exposure were measured using a high-speed digital imaging system. RESULTS The needle system without the sheath required the least driving force and had the most favorable force profile. In contrast, the bladed, nonretractable trocar system required a higher driving force and a rapid loss of resistance. Insertion under a pneumoperitoneum did not significantly alter the force profile of the various access devices except for the amount of tissue deformation. With the bladed system, the blade itself was exposed for an average of 0.5 to 1.0 seconds for a distance of 4.5 to 5.0 cm. In comparison, the needle system was exposed for 0.2 seconds for a distance of 1.8 cm. CONCLUSIONS We developed a reproducible method of measuring the forces required to place the access systems, their pattern of resistance loss, and the characteristics of the blade exposure. These parameters may provide an adjunctive and objective measurement of safety, allowing for more direct comparison between various trocar designs.

Identifying Ureteropelvic Junction Obstruction by Fluorescence Imaging: A Comparative Study of Imaging Modalities to Assess Renal Function and Degree of Obstruction in a Mouse Model

PURPOSE Radiological imaging is the mainstay of diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children. MATERIALS AND METHODS We investigated the novel use of Genhance™ 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine renography, magnetic resonance imaging and fluorescence imaging were performed. RESULTS Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls. CONCLUSIONS Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.

Quality of life in children with vesicoureteral reflux as perceived by children and parents

PURPOSE Significant research has been dedicated to the management of vesicoureteral reflux (VUR). However, few studies have been published to evaluate the impact of this disease on quality of life. The aim of this study was a prospective examination of the health-related quality of life (HRQoL) in children with VUR who have either been treated medically (antibiotics or surveillance) or by ureteral reimplant (UR) using a validated patient satisfaction survey. MATERIALS AND METHODS A prospective, longitudinal study was conducted using a validated HRQoL questionnaire, the Pediatric Quality of Life Inventory (PedsQL™ 4.0 Generic Core). 353 children or parents of children with VUR, age 2-18 years, completed the survey. Statistical analysis was performed with significance set at p-value ≤ 0.05. RESULTS Children and parents of children with VUR did not score lower on total or subscale domains of HRQoL when compared to a historical healthy control. On univariate analysis, patients who underwent UR scored lower on total as well as physical, social, and school subscale HRQoL domains, compared to patients managed medically. When controlling for gender, ethnicity, age, reflux grade, and antibiotic use, there was no difference in total HRQoL between patients who underwent UR compared to those managed medically. CONCLUSIONS In terms of HRQoL, VUR is a benign clinical entity and neither antibiotic use nor UR is associated with lower HRQoL. Disease-specific quality of life surveys are needed to accurately evaluate patient and parent satisfaction in the management of VUR.

Ureteroureterostomy: An Alternative to Ureteroneocystostomy in Select Cases of Pediatric Renal Transplantation

Purpose: Ureteroneocystostomy is the standard mode of establishing urinary drainage in renal transplantation. However, donor‐to‐recipient ureteroureterostomy may be considered in the presence of a challenging bladder or an augmented bladder, or when the donor ureter might be compromised or is too short. This approach also preserves a nonrefluxing system with an orthotopic ureteral orifice. Materials and Methods: We retrospectively reviewed the records of all pediatric renal transplantations in which ureteroureterostomy was performed at a single tertiary care pediatric center over the 12‐year period from 2004 to 2015. Ureteroureterostomy was performed in end‐to‐side fashion from donor‐to‐recipient ureter. Patients with a history of symptomatic vesicoureteral reflux were excluded from ureteroureterostomy. Parameters were reviewed, including age, gender, source of renal transplantation (deceased or living donor), indications for ureteroureterostomy and complications. Results: Primary ureteroureterostomy was performed at 23 of the 213 renal transplantations (10.8%). At transplantation mean ± SD age was 11.7 ± 4.9 years and mean weight was 33.5 ± 18.9 kg. Two secondary ureteroureterostomies were done to salvage the ureter due to complications after ureteroneocystostomy. Of the patients 60% and 40% underwent ureteroureterostomy during deceased and living donor renal transplantation, respectively. The most common indications included a challenging small bladder due to anuria, a valve bladder and a neurogenic augmented bladder. Two urinary leaks (8%) occurred and no allografts were lost. Conclusions: Ureteroureterostomy is a safe alternative to standard ureteroneocystostomy in renal transplantation. Ureteroureterostomy should be considered a primary option in certain complex situations and secondarily as a salvage procedure when ureteral problems develop after ureteroneocystostomy in patients who undergo renal transplantation.

Improving Lymph Node Yield in Retroperitoneal Lymph Node Dissection Using Fluorescent Molecular Imaging: A Novel Method of Localizing Lymph Nodes in Guinea Pig Model

OBJECTIVES To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.

Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).

Host-pathogen interactions can induce epigenetic changes in the host directly, as well as indirectly through secreted factors. Previously, uropathogenic Escherichia coli (UPEC) was shown to increase DNA methyltransferase activity and expression, which was associated with methylation-dependent alterations in the urothelial expression of CDKN2A. Here, we showed that paracrine factors from infected cells alter expression of another epigenetic writer, EZH2, coordinate with proliferation. Urothelial cells were inoculated with UPEC, UPEC derivatives, or vehicle (mock infection) at low moi, washed, then maintained in media with Gentamycin. Urothelial conditioned media (CM) and extracellular vesicles (EV) were isolated after the inoculations and used to treat naïve urothelial cells. EZH2 increased with UPEC infection, inoculation-induced CM, and inoculation-induced EV vs. parallel stimulation derived from mock-inoculated urothelial cells. We found that infection also increased proliferation at one day post-infection, which was blocked by the EZH2 inhibitor UNC1999. Inhibition of demethylation at H3K27me3 had the opposite effect and augmented proliferation. CONCLUSION: Uropathogen-induced paracrine factors act epigenetically by altering expression of EZH2, which plays a key role in early host cell proliferative responses to infection.

Development and Initial Validation of a Disease Specific Quality of Life Survey for Children With Vesicoureteral Reflux

PURPOSE Vesicoureteral reflux is believed to be a largely asymptomatic condition. However, previous studies have failed to assess the precise impact of vesicoureteral reflux on quality of life. We created and validated a survey for assessment of quality of life in children with vesicoureteral reflux. MATERIALS AND METHODS Two surveys were created by a team of pediatric urologists and survey design specialists, 1 for general assessment and 1 for postoperative assessment in patients undergoing surgical treatment for vesicoureteral reflux. Cronbach alpha test was used to assess internal consistency reliability and the correlation coefficient for test-retest analysis. Surveys were distributed from November 2008 to January 2010 during routine office visits for vesicoureteral reflux. The postoperative survey was distributed 8 to 20 weeks following surgery. RESULTS The general survey yielded a Cronbach alpha of 0.64 and a correlation coefficient of 0.78, while the postoperative survey results were 0.58 and 0.84, respectively, for the same parameters. Complete general surveys were obtained from 216 patients. All but 4 categories, related to repeat testing, office visits and medicine intake, reached greater than 80% positive quality of life responses. The postoperative survey was completed by 104 patients. Bladder spasm was the only category with less than 86% rate of positive quality of life response. CONCLUSIONS Vesicoureteral reflux is shown to have little effect on quality of life in pediatric patients. These validated surveys should be applied to compare the effect of different management options on quality of life.