Analysis of Factors Associated with Patient or Caregiver Regret following Surgery for Fecal Incontinence.

PURPOSE: Malone antegrade continence enema has been a successful and widely used procedure for achieving fecal continence in children. We present data on the previously uninvestigated issue of patient and caregiver regret following surgery for intractable constipation and fecal incontinence. MATERIALS AND METHODS: We reviewed all patients undergoing antegrade continence enema or cecostomy creation at a single institution between 2006 and 2016. Patients and caregivers were assessed for decisional regret using the Decisional Regret Scale. Results were correlated with demographics, surgical outcomes and complications. RESULTS: A total of 81 responses (49 caregivers and 32 patients) were obtained. Mean followup was 49 months. Decisional regret was noted in 43 subjects (53%), including mild regret in 38 (47%) and moderate to severe regret in 5 (6%). No statistical difference in regret was noted based on gender, complications or performance of concomitant procedures. On regression analysis incontinence was strongly associated with decisional regret (OR 4.4, 95% CI 1.1-18.1, p <0.001) and regret increased as age at surgery increased, particularly when patients were operated on at age 13 to 15 years (OR 2.6, 95% CI 1.0-6.4 for age 13 years; OR 2.9, 95% CI 1.1-7.8 for age 14 years; OR 3.1, 95% CI 1.1-8.8 for age 15 years). CONCLUSIONS: This is the first known study describing decisional regret following surgery for fecal incontinence. Surgical factors aimed at achieving continence may be effective in decreasing postoperative regret. The finding of increased regret in teenage patients compared to younger children should be shared with families since it may impact the age at which surgery is pursued.

Antimicrobial prophylaxis for children with vesicoureteral reflux.

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PURPOSE: Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. MATERIALS AND METHODS: Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. RESULTS: Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. CONCLUSIONS: Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy.

Temporal expression of hyaluronic acid and hyaluronic acid receptors in a porcine small intestinal submucosa-augmented rat bladder regeneration model.

INTRODUCTION: Hyaluronic acid (HA), a non-sulfated glycosaminoglycan, is an essential component of the extracellular matrix (ECM). Since HA is involved in many phases of wound healing and may play a key role in tissue repair and regeneration, this study was intended to understand temporal and spatial expression of HA and HA receptors (HARs) during the course of bladder regeneration in rats. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to partial cystectomy followed by augmentation with porcine small intestinal submucosal (SIS) prepared from distal sections of the small intestine. SIS-augmented bladders were harvested between postoperative days 2 and 56. RESULTS: Bladder regeneration proceeded without complications. All augmented bladders had complete urothelial lining and smooth muscle bundles by day 56 post-augmentation. Temporal and spatial distributions of HA and HARs were studied by immunohistochemistry in regenerating bladders. The strongest HA immunoreactivity was observed in the ECM on postoperative days 28 and 56. Cluster of differentiation 44 (CD44) immunoreactivity was detected in the cytoplasm of urothelial cells on day 56; and LYVE-1 immunoreactivity was exclusively limited to lymphatic vessels on days 28 and 56. CONCLUSIONS: We demonstrated that HA was synthesized throughout the course of bladder wound healing and regeneration; and HA deposition coincided with urothelial differentiation. Expression of CD44 and LYVE-1 followed the same temporal pattern as HA deposition. Therapeutic modalities through local delivery of exogenous HA to improve the outcome of SIS-mediated bladder regeneration might need to be coordinated with HAR expression in order to achieve maximal regenerative responses as opposed to fibrosis.

Update on tissue engineering in pediatric urology.

Pediatric urology patients often present with congenital or acquired tissue and organ dysfunction that requires surgical reconstruction to recreate the normal genitourinary systems functions. The traditional methods have varying degrees of donor site morbidity or inherent side effects. Tissue engineering is a developing field that aims to replace or regenerate these dysfunctional tissues and organs with cells, biomaterials, or a combination thereof. A tremendous amount of work has been done to these ends in terms of preclinical work, and some clinical trials have resulted. This review highlights the status of these studies in pediatric urology for the use of tissue engineering and reconstruction of the corporal bodies, urethra, and bladder.

Total and partial urogenital mobilization: focus on urinary continence.

PURPOSE: Total and partial urogenital mobilization procedures are the most common contemporary vaginoplasty surgeries for patients with congenital adrenal hyperplasia, urogenital sinus and cloacal anomalies. There is controversy regarding the urinary continence outcomes of these procedures. We reviewed the urinary continence outcomes of children who underwent total or partial urogenital mobilization at our institution and reviewed the literature to determine the continence rates of these procedures. MATERIALS AND METHODS: We retrospectively reviewed 25 patients who underwent total or partial urogenital mobilization with a focus on postoperative continence status. Continence was defined as parental report of full toilet training with no accidents during the day and rare accidents (fewer than 2 per month) at night after age 3 years. RESULTS: A total of 14 congenital adrenal hyperplasia, 5 urogenital sinus and 6 cloacal anomaly cases were managed by total (18) or partial (7) urogenital mobilization procedures with a mean followup of 4.41 years (range 0.21 to 12.1). In our cohort 21 of 22 patients (95.5%) were continent by age 3 years and there were no urinary complications. A total of 111 patients were identified in the literature with congenital adrenal hyperplasia or urogenital sinus, with 107 in 7 studies being continent (96.4%) by age 3 to 4 years. In 4 studies 32 patients were identified with cloacal anomalies who underwent total or partial urogenital mobilization, of whom 28 (87.5%) were continent by age 3 to 4 years. CONCLUSIONS: There was no significant difference between total and partial urogenital mobilization procedures regarding postoperative urinary continence in our cohort and the literature. The urinary continence rate was 96% in the congenital adrenal hyperplasia/urogenital sinus group and 89.5% in the cloacal group.

Re-epithelialization of demucosalized stomach patch with tissue-engineered urothelial mucosa combined with Botox A in bladder augmentation.

UNLABELLED: Re-epithelialization demucosa stomach patch is important to prevent the patch being exposed to urine that might cause patch shrinkage and fibrosis formation due to urine-derived chemical irritation. Additionally, Botox A acts by blocking the transmission of nerve impulses to smooth muscles and so paralysing the muscles, which is commonly used to relax muscle for treatment of oesophageal achalasia due to overactive smooth muscle and sphincters of gastrointestinal tract. We fabricated in vitro tissue engineered urothelial mucosa with multi-layers of urothelium and smooth muscle layers seeded on SIS scaffold and then used this cell-scaffold construct to cover nuke gastro patch combining with Botox A for gastrocystoplasty in a canine model. OBJECTIVE: To evaluate the demucosalized stomach patch covered with tissue-engineered urothelium for gastrocystoplasty and to determine whether or not injections of Botox A into the re-epithelialized stomach patch can protect the graft from contraction in a canine bladder reconstruction model. MATERIALS AND METHODS: Gastrocystoplasty was performed in 10 adult beagles after hemi-cystectomy using five types of stomach patch (n = 2 per group): entire stomach patches (group I); demucosalized patches (group II); demucosalized patches covered with cell-free small intestinal submucosa (SIS) (group III); demucosalized patches with urothelial and smooth muscle cell-seeded SIS (group IV); and demucosalized patches with the cell-seeded SIS combined with injections of Botox A (group V). The bladder volume/pressure and the graft sizes were measured before surgery and again 10 weeks after bladder augmentation. The graft tissues were examined both histologically and using immunohistochemistry. RESULTS: All dogs survived and their gastric grafts were all vital with a good blood supply. Gastric metaplasia of urothelium appeared on the top of stomach mucosa patches in two animals in group I. There was calcification formation at the centre of the graft in one animal in group II. As compared with urothelium that was partially covered over with stomach patches in groups II and III, stratified urothelium completely covered the demucosalized gastric patches in groups IV and V. There was less shrinkage of the stomach grafts in groups I and V, which shrank to half of their original size, than of the stomach grafts in groups II, III, and IV, which shrank significantly to one-quarter of their original sizes. CONCLUSIONS: Botox A injections appear to protect the graft contraction in the re-epithelialized stomach flaps. The gastrocystoplasty using demucosalized patches covered with tissue-engineered urothelial mucosa combined with an injection of Botox A could have clinical potential for use in bladder reconstruction.

Comparison of endoscopic ureterocele decompression techniques. Preliminary experience--is the watering can puncture superior?

PURPOSE: The optimal endoscopic technique to manage an obstructing ureterocele would reliably relieve obstruction without creating de novo vesicoureteral reflux. The classic incision achieves decompression but invariably creates new vesicoureteral reflux. We compared a new endoscopic puncture technique to assess its superiority to endoscopic incision. MATERIALS AND METHODS: We retrospectively reviewed 27 consecutive endoscopic ureterocele procedures at our institution. Patients who underwent an endoscopic incision or watering can puncture procedure had their records reviewed for preoperative radiological and clinical data, operative description, and postoperative radiological and clinical outcomes. RESULTS: Of the 15 patients with endoscopic ureterocele incision 11 underwent a watering can puncture. All ureteroceles were associated with grade 3 or 4 hydronephrosis. Incision successfully decompressed the ureterocele in 14 of 16 cases (87.5%) and hydronephrosis in 14 (87.5%) on postoperative renal ultrasound. De novo reflux was detected in 12 of 16 patients (75.0%) on postoperative voiding cystourethrogram. Puncture successfully decompressed the ureterocele in 10 of 11 cases (90.9%) and hydronephrosis in 9 (81.8%). De novo vesicoureteral reflux was detected in 4 of 11 patients (36.4%). CONCLUSIONS: Our initial review shows that the endoscopic watering can procedure successfully decompresses the obstructing ureterocele and its associated hydronephrosis. This technique also results in a decreased incidence of de novo vesicoureteral reflux and ultimately in fewer invasive procedures for the patient.

Voiding cystourethrogram--are our protocols the same?

PURPOSE: Voiding cystourethrogram is the gold standard for evaluating and diagnosing vesicoureteral reflux. Reflux detection can potentially be affected by many parameters during voiding cystourethrogram. MATERIALS AND METHODS: A 29-item survey was sent via e-mail through SurveyMonkey® to the chairperson of pediatric radiology at 65 national pediatric hospitals. This survey included questions on institutional protocols for performing voiding cystourethrogram. RESULTS: Responses were received from 41 institutions from across North America, including 17 of 19 Randomized Intervention for Children with Vesicoureteral Reflux study sites. Many aspects of the reports of voiding cystourethrogram protocols were similar with 90% or greater agreement in allowing parents in the room, contrast infusion by gravity, catheter or feeding tube use without balloons, no contrast dilution and voiding without a catheter in place. The height at which contrast medium was raised for infusion was 40, 60, 80, 100 and greater than 100 cm at 2.4%, 17.1%, 17.1%, 39.0% and 12.2% of sites, respectively, while the height was not measured or it varied at 12.2%. The infilling phase stopped when the bladder appeared full at 2.4% of sites, infusion stopped itself at 12.2%, patient voided at 61.0%, volume attained age expected capacity at 12.2%, the patient was uncomfortable at 4.9% and results varied at 7.3%. CONCLUSIONS: Data reveal that voiding cystourethrogram is performed differently across North America and no standard protocol exists for the procedure. These differences could significantly impact voiding cystourethrogram results among institutions and taint our ability to compare results in the literature.

Bladder regeneration in a canine model using hyaluronic acid-poly(lactic-co-glycolic-acid) nanoparticle modified porcine small intestinal submucosa.

OBJECTIVE: • To determine if hyaluronic acid (HA) can be incorporated into porcine small intestinal submucosa (SIS) through poly (lactide-co-glycolide-acid) (PLGA) nanoparticles to improve the consistency of the naturally derived biomaterial and promote bladder tissue regeneration. METHODS: • Beagle dogs were subjected to 40% partial cystectomy followed by bladder augmentation with commercial SIS or HA-PLGA-modified SIS. • Urodynamic testing was performed before and after augmentation to assess bladder volume. • A scoring system was created to evaluate gross and histological presentations of regenerative bladders. RESULTS: • All dogs showed full-thickness bladder regeneration. • Histological assessment showed improved smooth muscle regeneration in the HA-PLGA-modified SIS group. • For both groups of dogs, urodynamics and graft measurements showed an approximate 40% reduction in bladder capacity and graft size from pre-augmentation to post-regeneration measurements. • Application of the scoring system and statistical analysis failed to show a significant difference between the groups. CONCLUSIONS: • SIS can be modified through the addition of HA-PLGA nanoparticles. The modified grafts showed evidence of improved smooth muscle regeneration on histological assessment, although this difference was not evident on a novel grading scale. • The volume loss and graft shrinkage experienced are consistent with previous models of SIS bladder regeneration at the 10-week time point. • Additional research into the delivery of HA and the long-term benefits of HA on bladder regeneration is needed to determine the full benefit of HA-PLGA-modified SIS. In addition, a more objective biochemical characterization will be needed to evaluate the quality of regeneration.

Application of a continent fecal reservoir in patients with cloacal exstrophy.

PURPOSE: Initial enteric diversion in cloacal exstrophy is achieved by ileostomy or end colostomy with formal reconstruction in the form of hindgut pull-through performed in select patients. Those who are not candidates for a pull-through procedure are often left with a permanent incontinent stoma. Additionally due to congenitally deficient intestinal length, some patients with cloacal exstrophy experience short bowel syndrome. We present our surgical technique and clinical experience in 2 patients who were successfully treated with a novel continent cutaneous fecal reservoir. MATERIALS AND METHODS: We devised a fecal reservoir in 2 patients with end ileostomies who were deemed poor candidates for pull-through of the hindgut segment. One of the patients exhibited short bowel syndrome before undergoing reconstruction. A continent cutaneous fecal reservoir was created from all available hindgut and a segment of ileum. A flap valve mechanism was used to create a continent catheterizable channel. RESULTS: Seven years postoperatively both patients are continent of stool and neither has experienced complications attributable to enteric diversion. The patient with short bowel syndrome demonstrated significant improvement in nutritional status as evidenced by rapid weight gain and improvement in serum albumin level. Both patients and their families are highly satisfied with the surgical outcome. CONCLUSIONS: Hindgut and ileum can be combined to create a novel continent fecal reservoir. As an alternative to diverting ileostomy or colostomy, continent diversion offers potential metabolic and social advantages. Select patients with cloacal exstrophy will benefit from this form of enteric reconstruction.

Regional variations in small intestinal submucosa evoke differences in inflammation with subsequent impact on tissue regeneration in the rat bladder augmentation model.

OBJECTIVE: To examine the histological differences in the inflammatory response and regenerative outcomes of distal vs proximal porcine small intestinal submucosa (SIS) grafts in the rat bladder, as SIS from distal small intestine yields reliable and reproducible bladder regeneration, while SIS from proximal portions of small intestine does not provide similar results. MATERIALS AND METHODS: In all, 30 Sprague-Dawley rats underwent hemi-cystectomy followed by anastomosis of a bladder patch of SIS prepared from either distal or proximal small intestine. After bladder harvest, immunohistochemistry was used to quantify mast cells, eosinophils, macrophages, and neutrophils (PMNs). Total cell count per unit area was compared across the time course in univariate and logistic regression modelling. RESULTS: There were more eosinophils and mast cells in proximal SIS grafts, while there were more macrophages and PMNs in distal SIS grafts (all P < 0.05). Trichrome analysis showed increased collagen deposition in proximal SIS grafts and little smooth muscle regeneration. There was also significant graft contracture in proximal SIS grafts compared with distal SIS grafts (P < 0.05). CONCLUSIONS: We conclude that the location of SIS origin may evoke different inflammatory responses, which results in altered bladder tissue regeneration.

Unique patterns of molecular profiling between human prostate cancer LNCaP and PC-3 cells.

BACKGROUND: Human prostate cancer LNCaP and PC-3 cell lines have been extensively used to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer, respectively, there is limited information regarding gene expression patterns between these two cell lines and its relationship to prostate cancer. METHODS: Comprehensive gene expression analysis was performed. Total RNA was isolated from cultured cells and hybridized to Illumina human BeadChips representing 24,526 transcripts. Bioinformatics analysis was applied to identify cell line specific genes as well as biological mechanisms, pathways, and functions related to the genes. RESULTS: A total of 2,198 genes were differentially expressed between LNCaP and PC-3 cells. Using a robust statistical analysis and high significance criteria, 115 and 188 genes were identified to be unique to LNCaP and PC-3 cells, respectively. LNCaP cells maintained various metabolic pathways including a gene cluster that encodes UDP-glucuronosyltransferases. Several transcription factors including Tal alpha/beta, GATA-1, and c-Myc/Max may be responsible for regulating LNCaP cell specific genes. By contrast, PC-3 cells were characterized by their unique expression of cytoskeleton-related genes and other genes including VEGFC, IL8, and TGF beta 2. CONCLUSIONS: This study showed that LNCaP and PC-3 cells represent two distinct prostate cancer cell lineages. LNCaP cells retain many prostate cell specific properties, whereas PC-3 cells have acquired a more aggressive phenotype. Future studies for prostate cancer research need to consider similarities and differences between these two cells and their relationship to prostate cancer.

L stent for stomal stenosis in catheterizable channels.

PURPOSE: Stomal stenosis in patients with catheterizable channels can be a difficult problem that is managed by surgical revision or dilation. The L stent is a short, knotted catheter that lies flush with skin. The stent is used for any stomal narrowing, typically overnight for several days. The stent bridges the area of stenosis without passing into bowel or bladder lumen. We assessed whether the L stent is effective for preventing and managing stomal stenosis. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with catheterizable channels. A telephone survey and chart review were done to identify patients who required an L stent and those with stomal stenosis. Patient satisfaction was evaluated with Likert scale questions. RESULTS: We identified 50 patients with a total of 66 catheterizable urinary and enteric channels. Eight patients with a total of 11 (17%) affected stomas had stomal stenosis. Seven of 8 patients used the L stent for management and 100% reported improvement in stenosis. Six of 7 patients used the stent or catheterization with topical betamethasone cream. Four of 7 patients used the L stent greater than 6 months postoperatively and 3 reported that stenosis occurred immediately postoperatively. All patients who used the L stent reported intermittent self-directed stent use as a prophylactic measure to prevent recurrence. CONCLUSIONS: Conservative management for stomal stenosis with an L stent is a simple, effective and well tolerated technique. This patient centered management significantly decreases the risk of surgical revision.

Body mass index as a predictive value for complications associated with reconstructive surgery in patients with myelodysplasia.

PURPOSE: Patients with myelodysplasia often have urological pathology, with 25% to 40% requiring reconstructive procedures to achieve urinary and/or fecal continence. Complication rates from these major reconstructive procedures range between 10% and 50%. Additionally many of these patients have significant comorbidities, including a nonambulatory status that leads to an increased body mass index. It is currently unknown whether a high body mass index is associated with increased surgical complications. In this study we compare body mass index and postoperative complications. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients with myelodysplasia undergoing urinary or fecal reconstructive procedures. We analyzed data for body mass index and any documented complication occurring during hospitalization or at any time during followup. Patients were categorized based on body mass index as normal weight (less than 85th percentile), overweight (85th to 95th percentile) or obese (greater than 95th percentile). Statistical analyses using chi-square and Fisher's exact tests were then performed. RESULTS: Reconstructive procedures were carried out in 66 patients with myelodysplasia between 1997 and 2005. A total of 48 bladder augmentations were performed with a total of 101 stomas created. Mean followup was 39 months. Height and weight were available for body mass index calculation in 60 patients. Obesity was common in our patients with myelodysplasia, affecting 33% of the population (20 of 60 patients). We found a total of 53 complications in 31 patients (52%). There was a significant association between presence of complications and weight category, with complications occurring in 40% of normal weight, 40% of overweight and 75% of obese patients (p = 0.0380). An association between stomal stenosis and weight category was also found (p = 0.0373). In addition, multiple complications were more prevalent in obese patients. Of the 15 patients (25%) with 2 or more complications 10 (67%) were obese (p = 0.0066). CONCLUSIONS: Patients with myelodysplasia have a high incidence of obesity. Since obesity is associated with a higher complication rate, weight loss programs are highly recommended for obese patients with myelodysplasia before and after any reconstructive surgery.