Feasibility of Enhanced Recovery After Surgery (ERAS) implementation in Pediatric Urology: Pilot-phase outcomes of a prospective, multi-center study.

INTRODUCTION/BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a fundamental shift in perioperative care that has consistently demonstrated an improved outcome for a wide variety of surgeries in adults but has only limited evidence in the pediatric population. OBJECTIVE: We aimed to assess the success with and barriers to implementation of ERAS in a prospective, multi-center study on patients undergoing complex lower urinary tract reconstruction. STUDY DESIGN: Centers were directed to implement an ERAS protocol using a multidisciplinary team and quality improvement methodologies. Providers completed pre- and post-pilot surveys. An audit committee met after enrolling the first 5 patients at each center. Pilot-phase outcomes included enrollment of ≥2 patients in the first 6 months of enrollment, completion of 90 days of follow-up, identification of barriers to implementation, and protocol adherence. RESULTS: A total of 40 patients were enrolled across 8 centers. The median age at surgery was 10.3 years (IQR 6.4-12.5). Sixty five percent had a diagnosis of myelomeningocele, and 33 % had a ventriculoperitoneal shunt. A bladder augmentation was performed in 70 %, Mitrofanoff appendicovesicostomy in 52 %, Monti ileovesicostomy in 15 %, and antegrade continence enema channel in 38 %. The most commonly perceived barriers to implementation on the pre-pilot survey were "difficulty initiating and maintaining compliance with care pathway" in 51 % followed by a "lack of time, money, or clinical resources" in 36 %. The pre-pilot study experience, implementation, and pilot-phase outcomes are provided in the Table. All primary and secondary outcomes were achieved. DISCUSSION: The findings of the present study were similar to several small comparative studies with regard to the importance of a multidisciplinary team, strong leadership, and continuous audit for successful implementation of ERAS. Similar barriers were also encountered to other studies, which primarily related to a lack of administrative support, leadership, and buy-in from other services. The limitations of the present study included a relatively small heterogeneous cohort and absence of a comparative group, which will be addressed in the larger exploratory phase of the trial. The findings may also not be generaziable due to the need for sustainable processes that were unique to each center as well as an absence of adequate volume or resources at smaller centers. CONCLUSIONS: ERAS was successfully implemented for complex lower urinary tract reconstruction across 8 centers through a multidisciplinary team, structured approach based on the local context, and focus on a continuous audit.

Reoperative Anorectal Procedures in Patients with Anorectal Malformations - Is Bladder Function Affected?

BACKGROUND: Anorectal malformations (ARM) are associated with neurogenic bladder. The traditional surgical ARM repair is a posterior sagittal anorectoplasty (PSARP), which is believed to have a minimal effect on bladder dynamics. However, little is known about the effects of reoperative PSARP (rPSARP) on bladder function. We hypothesized that a high rate of bladder dysfunction existed in this cohort. METHODS: We performed a retrospective review of ARM patients undergoing rPSARP at a single institution from 2008 to 2015. Only patients with Urology follow-up were included in our analysis. Data was collected regarding original level of ARM, coexisting spinal anomalies and indications for reoperation. We assessed urodynamic variables and bladder management (voiding, CIC or diverted) before and after rPSARP. RESULTS: A total of 172 patients were identified, of which 85 met inclusion criteria with a median follow-up of 23.9 months (IQR, 5.9-43.8 months). Thirty-six patients had spinal cord anomalies. Indications for rPSARP included mislocation (n = 42), posterior urethral diverticulum (PUD; n = 16), stricture (n = 19) and rectal prolapse (n = 8). Within 1 year following rPSARP, 11 patients (12.9%) had a negative change in bladder management, defined as need for beginning intermittent catheterization or undergoing urinary diversion, which increased to 16 patients (18.8%) at last follow-up. Postoperative bladder management changed in rPSARP patients with mislocation (p < 0.0001) and stricture (p 0.005) but not for rectal prolapse (p 0.143). CONCLUSIONS: Patients who undergo rPSARP warrant especially close attention for bladder dysfunction as we observed a negative postoperative change in bladder management in 18.8% of our series. LEVEL OF EVIDENCE: Level IV.

Outpatient Robotic Surgery in Pediatric Urology: Assessment of Feasibility and Short-Term Safety.

PURPOSE: Robotic reconstructive and extirpative procedures have been widely utilized for surgical management of various conditions in pediatric urology. Outpatient laparoscopic surgery has become the standard in cases of orchidopexy, inguinal hernia repair and varicocelectomy. There is a growing body of evidence that robotic surgery for more complex conditions can also be performed in an outpatient setting. The aim of the study was to assess the short-term safety and feasibility of robotic reconstructive and extirpative procedures for various pediatric urological conditions as scheduled outpatient procedures. MATERIALS AND METHODS: Demographic information and perioperative data were prospectively collected in an institutional database for all pediatric patients undergoing outpatient robotic surgery from June 2012 to December 2019. Primary outcomes included rates of 30-day complications, emergency room visits and readmissions. RESULTS: A total of 135 pediatric patients underwent robotic procedures in an outpatient setting. The majority underwent pyeloplasty (62) or extravesical ureteral reimplantation (55). Ten patients underwent ureteroureterostomy and 8 patients underwent extirpative procedures (nephrectomy, hemi-nephrectomy). Median age at surgery was 62 months (IQR, 27-99), median weight was 20 kg (IQR, 12-30) and median body mass index was 17 (IQR, 15-18). During the 30-day followup period there were 9 complications (6.7%), of which only 1 (0.7%) was high grade (Clavien-Dindo 3). There were 9 emergency room visits (6.7%) including 5 cases of readmission (3.7%). CONCLUSIONS: Robotic reconstructive and extirpative procedures in pediatric urology can be safely performed as scheduled outpatient procedures in the majority of patients, obviating the need for routine inpatient care.

Diagnosis, management and recurrence rates of Mitrofanoff polyps.

BACKGROUND: Intraluminal polyps are a known complication following creation of a urinary continent catheterizable channel (Mitrofanoff). These polyps can lead to difficult catheterizations in addition to symptomatic bleeding. However, there is limited data available regarding management and outcomes of these polyps. We aim to describe clinical presentation and management of a large series of polyps occurring in a Mitrofanoff channel. METHODS: We performed a retrospective review of all patients that were treated for polyps in a Mitrofanoff at our institution. Information was collected regarding presenting symptoms, management and recurrence rates of the polyps. RESULTS: A total of 24 patients were identified that fulfilled inclusion criteria. The majority of these polyps developed in channels composed of appendix (87%), while only 3 patients (13%) had polyps develop in an ileal composed channel. Thirteen (54%) of these polyps were incidentally diagnosed while 11 patients presented with a variety of symptoms such as difficulty in catheterization, bleeding with catheterization or both difficulty catheterizing and bleeding. For management of the polyps, a cystoscopy was performed and snaring the polyp with stone basket was performed in 37%, energy was applied to base to remove polyps in 33%, 16% were fulgurated and only 13% were left in situ. All procedures were performed under general anesthesia and all of the pathology was benign showing chronic inflammatory tissue. Eight polyps (33%) recurred after initial treatment. DISCUSSION: We did not observe an asymptomatic channel polyp convert to a symptomatic during our follow up period. Our experience has led us to not intervene on all asymptomatic Mitrofanoff polyps encountered during cystoscopy under assumption they will inevitably become symptomatic. Although we admit our follow up period may not be long enough to make this a universal declaration of best practice when any Mitrofanoff polyp is diagnosed. Endoscopic treatment was effective minimally invasive method to address the symptomatic polyp rather than excision and construction of new channel. CONCLUSIONS: This is the largest series to date of polyps developing in urinary continent catheterizable channels. The majority of these polyps were encountered incidentally however symptomatic polyps presented with difficulty with catheterizations. Symptomatic polyps can be managed endoscopically but recurrence of the polyp can occur.

Clinical urologic and urodynamic outcomes in patients with anorectal malformation and absent vagina after vaginal replacement.

INTRODUCTION AND OBJECTIVES: Anorectal malformations (ARMs) represent a complex spectrum of anorectal and genitourinary anomalies and a paucity of evidence is available on long-term urologic outcomes in all ARM subtypes. It was our subjective bias from being a referral center for ARM patients that the subtype of rectovestibular fistula and absent vagina had higher risk of renal and bladder abnormalities than typical rectovestibular fistula patients. Therefore, to confirm or refute our clinical suspicions, the purpose of this study was to review this specific cohort of ARM patients and describe both the clinical urological and urodynamic outcomes. METHODS: A retrospective cohort study was performed for 120 patients who were treated for ARM and vaginal replacement at our institution between 1991 and 2017. Fifteen patients with rectovestibular fistula and absent vagina were included in our review. Demographic and clinical data were abstracted from their medical records, including urodynamic findings, need for clean intermittent catheterization (CIC), urinary continence, and renal function. RESULTS: Vaginal replacement surgery was undertaken concomitantly with ARM repair in 10 of the 15 patients (67%). One patient was lost to follow up, and mean follow up postoperatively was 39 months. In all but one patient, rectum or colon was used as the substrate for vaginal replacement. Of the 15 patients, 13 had continence data available. A total of 10 patients (77%) were able to achieve social continence. Overall six patients used CIC to manage their bladder and 40% of continent patients used CIC. Urinary continence outcomes in patients who had partial vaginal replacement compared to those with total vaginal replacement did not reveal a clinically significant difference. Continence was achieved in 3/4 patients (75%) with a history of tethered cord compared to 7/9 patients (78%) without a history of tethered cord release. Urodynamics were performed postoperatively in 7 of the 157 patients (47%). Uninhibited detrusor contractions (UDCs) were present in 3 out of 7 patients, and a cystometric capacity greater than expected was noted in 4 patients. Additionally, 2 patients had end filling detrusor pressure greater than 40 cm H2O. GFR data were available for 13 of the 15 patients and (85%) were classified as chronic kidney disease (CKD) stage I or not having any significant loss of renal function. CONCLUSIONS: In this cohort of rectovestibular fistula and absent vagina, 77% reported achieving urinary continence. However CIC was employed in 40% of the patients which is higher than prior published noncloaca female ARM patient population. Urodynamic abnormalities were noted when performed and led to change in bladder management. Renal function measured with GFR was normal in 85%. Patients with rectovestibular fistula and absent vagina benefit from urologic screening given higher rates of lower urinary tract dysfunction that can require CIC to protect the upper urinary tract and achieve urinary continence. TYPE OF STUDY: Case series. LEVEL OF EVIDENCE: Level IV.

Risk of Reaugmentation after Enterocystoplasty Using a Reconfigured Bowel Segment in Patients with Spina Bifida: A Bi-Institutional Cohort Study.

PURPOSE: Reaugmentation cystoplasty rates vary in the literature but have been reported as high as 15%. It is likely that bladders augmented with detubularized and reconfigured bowel are less likely to require reaugmentation. We assessed the incidence of reaugmentation among patients with spina bifida at 2 high volume reconstruction centers. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with spina bifida who underwent enterocystoplasty before age 21 years (1987 to 2017). Those who did not undergo augmentation with a detubularized and reconfigured bowel segment were excluded from analysis. Data on demographic and surgical variables were collected. Reaugmentation was the main outcome. One analysis was performed using the entire cohort and another analysis was restricted to patients with ileocystoplasty performed in the last 15 years (2002 to 2017). Survival analysis was used. RESULTS: A total of 289 patients were identified. Enterocystoplasty was performed in patients at a median age of 8.1 years (median followup 11.3, IQR 5.2-14.9). Most initial augmentations were performed using ileum (93.4%), followed by sigmoid (6.2%). Seven patients underwent reaugmentation, including 6 with initial augmentation using ileum and 1 with initial augmentation using sigmoid. On survival analysis risk of reaugmentation was 1.1% at 5 years and 3.3% at 10 years after the original surgery. All reaugmentations occurred within the first 9 years of followup. In the more contemporary cohort (162, median followup 7.0 years) only 1 patient underwent reaugmentation at 2.0 years. CONCLUSIONS: The risk of reaugmentation after enterocystoplasty with a detubularized and reconfigured bowel in the spina bifida population is lower than that reported in initial series.

Is anuria prior to pediatric renal transplantation associated with poor allograft outcomes?

INTRODUCTION: Anuria from end-stage renal disease leads to a defunctionalized bladder and may pose technical challenges at the time of renal transplantation. Anuria's effect on bladder function after renal transplantation is considered to be minimal in adults, although a paucity of evidence is available in children. The purpose of this study was to examine the effects of anuria prior to pediatric renal transplantation for ESRD due to medical renal disease on allograft outcome. METHODS: We performed a retrospective review of pediatric patients who underwent renal transplantation for medical renal disease at our institution between 2005 and 2016. Demographics and clinical data were assessed. We also compared GFR at 1 year post-transplant for medical renal patients with history of anuria and those without. RESULTS: Twenty-one patients fulfilled our inclusion criteria with median duration of anuria was 10 months. Preoperative VCUG was available in five patients and their bladder capacity was 29% of expected bladder capacity for age (range 8%-41%). Anticholinergic therapy was prescribed in six patients (28%) for a mean duration of 5 months (range 1-16 months). Comparison of GFR at 1 year post-transplant in anuria group and those without anuria showed no difference (69 vs 75 mL/min, P = 0.37). No correlation was observed between duration of anuria and post-transplant GFR. CONCLUSION: The majority of children in our pretransplant anuria cohort did not develop bladder dysfunction after renal transplantation. No difference was observed between GFR at 1 year when comparing anuric to non-anuric transplant recipients of medical renal disease etiology.

Hidden incision endoscopic surgery (HIdES) trocar placement for pediatric robotic pyeloplasty: comparison to traditional port placement.

Robotic assisted laparoscopy pyeloplasty (RALP) has been associated with shorter recovery, less pain and improved cosmesis. To minimize visible scars, the hidden incision endoscopic surgery (HIdES) trocar placement has been previously developed. Our aim was to compare outcomes between the HIdES and traditional port placement (TPP) for pediatric RALP. A retrospective study was performed on patients under 15 years of age who underwent RALP at a single institution between August 2011 and November 2013. Patient demographics, intraoperative details, narcotic administration, and complications were reviewed. A total of 49 patients were identified (29 in HIdES, 20 in TPP). There was no difference in median age (p = 0.77) or median height (p = 0.88) between the two groups. Median operative time was 180 min for HIdES and 194 min for TPP (p = 0.27). Eleven patients (11/29, 37.9%) in the HIdES group and fourteen patients (14/20, 70%) in the TPP group received postoperative narcotics (p < 0.05). Median follow-up was 42 months for HIdES and 41 months for TPP (p = 0.96). There were two complications (2/29, 6.9%) with HIdES, and one complication (1/20, 5.0%) with TPP (p = 1.00). The success rates were 96.6% (28/29) for HIdES and 100% (20/20) for TPP (p = 1.00). HIdES trocar placement for pediatric robotic pyeloplasty is a safe and viable alternative to TPP. HIdES is comparable to TPP regarding operative time, narcotic administration, hospital stay, and complication rate, without compromising success.

A Non-Narcotic Pathway for the Management of Postoperative Pain Following Pediatric Robotic Pyeloplasty.

PURPOSE: The purpose of this study is twofold: first, to describe the non-narcotic pathway (NNP) for the management of postoperative pain after robotic pyeloplasty (RP); second, to compare perioperative outcomes for children undergoing RP whose postoperative pain was managed with and without the NNP. PATIENTS AND METHODS: A retrospective review was performed on 96 consecutive patients from October 2011 to December 2015 who underwent RP by three primary surgeons at a single pediatric institution. Children managed with an NNP received alternating doses of scheduled intravenous acetaminophen and ketorolac every 3 hours throughout the postoperative course. Perioperative outcomes were compared after grouping patients according to the type of postoperative pain management pathway. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the two-tailed chi-squared test. RESULTS: A total of 49 (51.0%) patients were managed with the NNP, and 47 (49.0%) patients were managed without the NNP. A larger proportion of patients in the NNP did not receive postoperative narcotic medications (71.4% vs 25.5%; p < 0.001). Patients in the NNP were administered less narcotics (median 0.000 mg vs 0.041 mg morphine equivalents/kg/day; p < 0.001) and had a shorter length of stay (median 1.0 day vs 2.0 days; p < 0.001). There was no significant difference in the proportion of patients with postoperative complications (p = 0.958) or surgical success (p = 0.958). CONCLUSIONS: An NNP following pediatric RP is a viable and effective analgesic regimen that is associated with less narcotic use. It may also facilitate a shorter hospital stay. The majority of patients managed with this pathway had adequate pain control without being subject to the potential adverse effects of narcotic medications.

Early urologic considerations in patients with persistent cloaca.

Cloacal malformations represent one of the most complex conditions among anorectal malformations. Urologic conditions occur with an increased frequency in cloaca patients compared to patients with other types of ARM. The morbidity of the upper and lower urinary tract dysfunction/malformations at times can be severe; manifested by urinary tract infection, lower urinary tract symptoms, urinary incontinence, chronic kidney disease, and even end stage renal disease. Long-term follow-up of patients with cloaca has described significant chronic kidney disease and end-stage renal disease. Whether this rate of chronic kidney disease is a function of intrinsic renal dysplasia or acquired renal injury from neurogenic bladder is currently unknown. However, it is well known that severe lower urinary tract dysfunction, no matter the etiology, poses significant risk to the upper tracts when untreated. Neonatal assessment of the urinary tract accompanied by early identification of abnormal structure and function is therefore fundamental to minimize the impact of any urologic condition on the child's overall health. Adequate management of any associated bladder dysfunction is essential to preserving renal function, minimizing risk of urinary tract infection, and potentially avoiding need for future reconstructive surgery. This article summarizes our institution's approach to the ongoing early urologic management in patients with cloaca.

Epididymitis in patients with anorectal malformations: a cause for urologic concern.

INTRODUCTION: Epididymitis in patients with anorectal malformation (ARM) represents a unique problem because unlike the general population, an underlying urinary tract problem is frequently identified. We review our experience with epididymitis in ARM population with an emphasis on examining urologic outcomes. MATERIALS AND METHODS: We performed a retrospective review of male patients with ARM cared for from 1980 to 2010. Clinical and pathologic variables recorded included age at presentation, recurrence, associated urologic anomalies, incidence of ureteral fusion with mesonephric ductal structures, glomerular filtration rate and urodynamic parameters. RESULTS: Twenty-six patients were identified with documented episodes of epididymitis. Renal injury was noted in five patients (19%), all of whom were diagnosed with neurogenic bladder (NGB) several years after anorectoplasty. NGB was found in ten patients (38%) in our series. Ectopic insertion of ureter into a mesonephric ductal structure was discovered in five patients (19%). Twelve patients (46%) had recurrent episodes of epididymitis, with seven of these patients (58%) being diagnosed with NGB. Two patients in the pubertal group presented with a history of epididymitis and complained of ejaculatory pain. CONCLUSION: Epididymitis in a patient with ARM warrants a comprehensive urologic investigation, particularly in recurrent episodes. Attempts at surgical intervention (e.g. vasectomy) should be avoided until functional assessment of the urinary tract has occurred. Failure to recognize this association may lead to potentially avoidable complications and morbidity. Long term urological follow up of these patients is warranted to identify at risk patients and minimize renal deterioration.

Epididymitis in Patients with Anorectal Malformations: A Cause for Urologic Concern

Introduction Epididymitis in patients with anorectal malformation (ARM) represents a unique problem because unlike the general population, an underlying urinary tract problem is frequently identified. We review our experience with epididymitis in ARM population with an emphasis on examining urologic outcomes. Materials and Methods We performed a retrospective review of male patients with ARM cared for from 1980 to 2010. Clinical and pathologic variables recorded included age at presentation, recurrence, associated urologic anomalies, incidence of ureteral fusion with mesonephric ductal structures, glomerular filtration rate and urodynamic parameters. Results Twenty-six patients were identified with documented episodes of epididymitis. Renal injury was noted in five patients (19%), all of whom were diagnosed with neurogenic bladder (NGB) several years after anorectoplasty. NGB was found in ten patients (38%) in our series. Ectopic insertion of ureter into a mesonephric ductal structure was discovered in five patients (19%). Twelve patients (46%) had recurrent episodes of epididymitis, with seven of these patients (58%) being diagnosed with NGB. Two patients in the pubertal group presented with a history of epididymitis and complained of ejaculatory pain. Conclusion Epididymitis in a patient with ARM warrants a comprehensive urologic investigation, particularly in recurrent episodes. Attempts at surgical intervention (e.g. vasectomy) should be avoided until functional assessment of the urinary tract has occurred. Failure to recognize this association may lead to potentially avoidable complications and morbidity. Long term urological follow up of these patients is warranted to identify at risk patients and minimize renal deterioration .

Infant robotic bilateral upper urinary tract surgery.

We describe a case of robot-assisted laparoscopic bilateral upper urinary tract surgery in a 4-month-old infant for complex bilateral upper urinary tract duplication anomalies.

Creation of an appendicovesicostomy Mitrofanoff from a preexisting appendicocecostomy utilizing the spilt appendix technique.

Continent catheterizable channels have revolutionized reconstructive surgery to achieve both urinary and fecal continence. The Mitrofanoff and Malone antegrade continent catheterizable channels offer improved quality of life relative to permanent incontinent stomas. A frequently employed surgical option for creating a Mitrofanoff when an existing appendicocecostomy exists involves harvesting a separate piece of intestine. If however the Malone has preceded the creation of a Mitrofanoff, we describe a surgical technique that may avoid the need for a bowel harvest and resultant anastomosis. We report our series of patients utilizing a novel alternative strategy in the select clinical circumstance of an existing appendicocecostomy to expand the armamentarium of the urologic reconstructive surgeon.

Infant robot-assisted laparoscopic upper urinary tract reconstructive surgery.

OBJECTIVE: Our aim was to assess the outcomes of infant robot-assisted laparoscopic (RAL) upper urinary tract reconstruction. MATERIALS AND METHODS: The medical records of all infants who underwent RAL upper urinary tract reconstruction were reviewed. Patients less than 1 year of age at surgery were included. Patient demographics, intraoperative details, narcotic usage, and complications were reviewed. RESULTS: Ten infants met the study criteria. There were five right and five left-sided procedures. Eight pyeloplasties (4 right, 4 left) and two ureteroureterostomies (1 right single system, 1 left duplex system) were performed. The median age was 8 months (range 3-12 months). Median weight was 7.7 kg (range 5.8-10.9 kg). Median operative time was 128 min (range 95-205 min). There was no significant blood loss or intraoperative complications. One (10%) patient received a regional block. Eight (80%) patients did not receive postoperative narcotics. Median hospital stay was 1 day (range 1-2). Median follow-up was 10 months (range 3-18 months). Complications included one urinary leak, one ileus, and one urinary tract infection. Hydronephrosis improved in all patients. CONCLUSIONS: Infant RAL upper urinary tract reconstruction is technically feasible, safe, and effective. It can be applied for duplication anomalies and single system obstructions in infants.

Outcomes following Malone antegrade continence enema and their surgical revisions.

BACKGROUND/PURPOSE: The Malone antegrade continence enema (MACE) channel is an effective means to manage patients with neurogenic bowel; however, complications may occur that may require surgical revision. Specific reports of the outcomes of these interventions are limited. We describe our clinical results following revision of MACE. METHODS: We retrospectively identified patients undergoing MACE revision for at our institution between 1997 and 2009. Type of MACE (in situ appendicocecostomy (AC = 247), ileocecostomy (IC = 25), cecal flap (CF = 10)) performed was recorded, time from creation to revision, site of revision, and need for repeat surgical revision were recorded. RESULTS: Of a total of 282 patients that underwent creation of MACE during the study period, 49 patients (17%) required surgical revision. Of these 49 patients, 42 had undergone AC, four had IC and three had CF. Mean time from MACE creation to revision was 19 months. Sixty-eight revision procedures were performed in the 49 patients. Skin level or endoscopic procedures accounted for 52/67 (78%) procedures. Sixteen patients (33%) required more than one revision and three patients (6%) required more than two procedures. CONCLUSIONS: Skin level revisions accounted for over three-fourths of MACE revisions. In our series, two thirds of patients requiring revision required only a single procedure, but one third required more than one revision.

Renal IL-18 production is macrophage independent during obstructive injury.

BACKGROUND: Interleukin 18 (IL-18) is a pro-inflammatory cytokine that mediates fibrotic renal injury during obstruction. Macrophages are a well-known source of IL-18; however, renal tubular epithelial cells are also a potential source of this cytokine. We hypothesized that IL-18 is predominantly a renal tubular cell product and is produced during renal obstruction independent of macrophage infiltration. METHODS: To study this, male C57BL6 mice were subjected to unilateral ureteral obstruction (UUO) vs. sham operation in the presence or absence of macrophage depletion (liposomal clodronate (1 ml/100 g body weight i.v.)). The animals were sacrificed 1 week after surgery and renal cortical tissue harvested. Tissue levels of active IL-18 (ELISA), IL-18 receptor mRNA expression (real time PCR), and active caspase-1 expression (western blot) were measured. The cellular localization of IL-18 and IL-18R was assessed using dual labeling immunofluorescent staining (IFS). RESULTS: Immunohistochemical staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. IL-18 production, IL-18R expression, and active caspase 1 expression were elevated in response to renal obstruction and did not decline to a significant degree in the presence of macrophage depletion. Obstruction-induced IL-18 and IL-18R production localized predominantly to tubular epithelial cells (TEC) during obstruction despite macrophage depletion. CONCLUSION: These results demonstrate that renal tubular epithelial cells are the primary source of IL-18 production during obstructive injury, and that tubular cell production of IL-18 occurs independent of macrophage infiltration.

Interleukin-18 stimulates a positive feedback loop during renal obstruction via interleukin-18 receptor.

PURPOSE: Interleukin-18 is a proinflammatory cytokine that is an important mediator of obstruction induced renal tubulointerstitial fibrosis independent of tumor necrosis factor-α and ß1 activity. We hypothesized that interleukin-18 stimulates a positive feedback loop during obstruction via interleukin-18 receptor to increase interleukin-18 gene expression and protein production. MATERIALS AND METHODS: Male C57BL6 interleukin-18 receptor knockout (The Jackson Laboratory, Bar Harbor, Maine) and control wild-type mice underwent unilateral ureteral obstruction or sham operation and were sacrificed 1 week after surgery. Renal cortical tissue samples were harvested and analyzed for interleukin-18 protein by enzyme-linked immunosorbent assay, and for interleukin-18 and interleukin-18 receptor gene expression by quantitative polymerase chain reaction. The specific cellular localization of interleukin-18 and interleukin-18 receptor expression during obstruction was assessed using dual labeling immunofluorescence staining. RESULTS: Renal interleukin-18 receptor expression increased significantly in wild-type mice in response to obstruction but remained at sham operation levels in interleukin-18 receptor knockout mice. Similarly while interleukin-18 protein and gene expression were significantly increased in wild-type mice in response to obstruction, interleukin-18 levels and gene expression were significantly decreased during obstruction in knockout mice. Obstruction induced interleukin-18 and interleukin-18 receptor production were localized predominantly to tubular epithelial cells and to a lesser extent to the renal interstitium. CONCLUSIONS: Results reveal that interleukin-18 stimulates a positive feedback loop via interleukin-18 receptor during renal obstruction to stimulate interleukin-18 production and gene expression. The predominant cellular source of interleukin-18 production during renal obstruction appears to be tubular epithelial cells rather than infiltrating macrophages.

Extravesical implantation of a continent catheterizable channel.

PURPOSE: Extravesical ureteral reimplantation provides results equivalent to those of the open technique with the advantage of less postoperative morbidity from a large cystotomy. Surgical series describing the technique and efficacy of extravesical implantation of continent catheterizable channel are lacking. We reviewed our results to determine the efficacy of this technique with an emphasis on continence and the need for revision. MATERIALS AND METHODS: We reviewed the records of 394 patients who underwent a bladder continent catheterizable channel procedure from 1999 to 2009. Operative records describing an extravesical technique were noted. Briefly, a 3 to 6 cm incision is made in the detrusor and seromuscular flaps are created. The continent catheterizable channel is laid in the tunnel and the flaps are brought anterior to the channel and sutured to each other. Fixation of the bladder wall to the abdominal wall preserves tunnel length and minimizes the risk of angulation. The type of continent catheterizable channel, stomal continence and the need for revision were recorded. RESULTS: The extravesical implantation technique of a continent catheterizable channel was done in 84 of 394 patients (21%). The channel was an appendix in 47 cases and Monti ileovesicostomy in 37. Stomal continence was achieved in 79 of 84 cases (94%). At a mean followup of 45 months 22 patients (26%) required a total of 30 surgical revisions, of which most were skin level or endoscopic procedures at a mean of 26 months after channel creation. CONCLUSIONS: The extravesical technique for continent catheterizable channel implantation is effective. If intravesical surgery is not necessary, avoidance of a large cystotomy and longer operative time may expedite postoperative recovery when using an extravesical implantation technique to create a continent catheterizable channel.

Split-appendix technique for simultaneous appendicovesicostomy and appendicocecostomy.

PURPOSE: Surgical treatment of urinary and fecal incontinence with appendicocecostomy (AC) and appendicovesicostomy (AV) has high success in achieving continence. Usually, the appendix can only be used for one of these, requiring the second channel to be constructed from alternative tissue. We describe our outcomes using the split-appendix technique for simultaneous creation of AC and AV. METHODS: We reviewed records for all patients that underwent simultaneous AC and AV from the appendix alone from 1999 to 2009. When anatomy permitted, the appendix was divided into 2. The proximal end was kept in continuity with the cecum for an AC, whereas the distal end was used for AV. The appendiceal length, continence status, and subsequent need for surgical revision were recorded. RESULTS: Of 394 children who underwent reconstructive surgery with a Mitrofanoff channel, 43 patients (11%) used the split-appendix technique. After a mean follow-up of 40 months, 43 of 43 ACs and 41 of 43 AVs are continent. Of the 86, 16 (19%) channels created required surgical revision. CONCLUSIONS: The channels created from split-appendix technique have outcomes and revision rates comparable with those of other described techniques. This technique is applicable to a minority of children undergoing continent reconstruction; however, it has the benefit of avoiding a bowel resection and its accompanying risks.