George Chiang

Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo

Histone deacetylase inhibitors (HDACis) are emerging as a promising new class of anticancer agents displaying growth‐inhibitory activity and low toxicity in vivo. In this study, we examined the effect of sodium butyrate (NaB) and trichostatin A (TSA) on the growth of human bladder carcinoma cell lines in culture and TSA on the growth of EJ and UM‐UC‐3 human bladder xenografts in nude mice. NaB and TSA suppressed the growth of bladder cell lines at millimolar (1.5–4.3 mM) and micromolar (0.03–0.33 μM) concentrations, respectively, inducing concentration‐dependent cell death. Bladder carcinoma cells within the experimental panel displayed the phenotype of late‐stage bladder lesions expressing N‐cadherin in the absence of E‐cadherin accompanied by low levels of plakoglobin expression. Exposure of these cells to HDACis resulted in upregulation of plakoglobin with no change in E‐cadherin expression. A 2‐hr exposure to TSA was the minimal time required to upregulate plakoglobin in cells with downregulation to baseline levels occurring within 24 hr following drug removal. In mice bearing EJ and UM‐UC‐3 bladder xenografts, TSA (500 μg/kg/day) caused suppression of tumor growth compared with mice receiving vehicle alone. A > 70% reduction in mean final tumor volume was recorded in both bladder xenograft models with no detectable toxicity. The results suggest that TSA inhibits bladder carcinoma cell growth and may be a useful, relatively nontoxic agent for consideration in the treatment of late‐stage bladder tumors.

The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt†

To evaluate PP2 as a modulator of the cadherin/catenin complex in late‐stage bladder carcinoma cells, and to assess its potential invasion‐suppressor activity in this model.

Early experience with laparoendoscopic single-site surgery in the pediatric urology patient population.

BACKGROUND AND PURPOSE To present our initial experience with single-incision laparoscopy in the pediatric urologic population. PATIENTS AND METHODS Four patients underwent eight single-incision laparoscopic procedures. One patient underwent bilateral nephrectomies, a hernia repair, and an orchiectomy. The remaining three patients underwent unilateral nephrectomies. All procedures were performed in children using the Covidien SILS port system via an umbilical incision. RESULTS Procedures in three of four patients, representing seven of eight cases, were successfully performed via a single incision. Operative times ranged from 114 minutes to 360 minutes. There were no conversions to traditional laparoscopy. One nephrectomy was converted to an open procedure secondary to bleeding. There were no complications postoperatively, and at follow-up, all wounds were well healed. CONCLUSIONS Single-incision laparoscopic urologic surgery is safe and feasible in the pediatric population. The umbilical (trans or peri) approach confers improved cosmesis over traditional laparoscopy, and the scar is essentially concealed.

Comparison of Laparoendoscopic Single-Site, Conventional Laparoscopic, and Open Nephrectomy in a Pediatric Population

INTRODUCTION We provide a single-institution comparison of open, conventional laparoscopic (CL) and laparoendoscopic single-site (LESS) nephrectomy in children. METHODS We identified all nephrectomy cases occurring at Rady Childrens Hospital from July 2007 to March 2010. Exclusion criteria included redo/bilateral operations, malignancy, transplant nephrectomy, or complex urogenital anomalies. We compared patient demographics, total operative times, estimated blood loss (EBL), length of stay (LOS), complication rates, postoperative pain score, narcotic usage, and total hospital costs. RESULTS We identified 7 LESS, 11 CL, and 8 open nephrectomy patients who met our criteria. The mean age of patients was 8.5, 7.3, and 4.2 years for LESS, CL, and open nephrectomy, respectively (P=.217). Operative times were 192.2, 219.3, and 127.4 minutes for LESS, CL, and open nephrectomy, respectively (P=.076). EBL was 15, 13.2, and 12.5 mL, respectively, for these groups (P=.871). There were no complications in any of the groups, although 1 LESS patient required conversion to open nephrectomy for bleeding. Mean LOS was 46.8, 36.9, and 33.8 hours in the LESS, CL, and open nephrectomy groups (P=.308). Mean pain scores on postoperative day 1 were 2.3, 1.8, and 1.6 in each group, respectively (P=.518). Hospital costs were comparable between the LESS and CL groups. The mean cost for open nephrectomy was 54.4% the mean cost for CL, however (P=.001). CONCLUSIONS LESS nephrectomy in children is safe and overall comparable with CL. In our experience, no modality confers a distinct advantage except for the decreased cost associated with open surgery.

Shunted Hydrocephalus Has a Significant Impact on Quality of Life in Children With Spina Bifida

To determine which clinical (health status) and nonclinical (demographic) factors may affect perceptions of quality of life in children with spina bifida and their parents.

Early clean intermittent catheterization may not prevent dimercaptosuccinic acid renal scan abnormalities in children with spinal dysraphism

OBJECTIVES To determine whether early initiation of clean intermittent catheterization is associated with increased renal preservation in children with spinal dysraphism based on dimercaptosuccinic acid (DMSA) renal scans. METHODS A retrospective review was performed of 100 patients from a pediatric spinal defects clinic from June 2007 to October 2011 who were followed with routine studies including DMSA scans, voiding cystourethrograms, renal/bladder ultrasounds, and urodynamics. DMSA scans were reviewed for evidence of renal cortical loss as defined by presence of scarring or difference in differential function greater than 15%. Multivariate analysis was performed for risk factors for upper tract damage. RESULTS Renal cortical loss on DMSA scan was found in 43/100 (43%) of patients. CIC was started at birth in 17/100 (17%) of patients with the rest starting at a median age of 5 years (IQR 3-9). Upon multivariate regression analysis, age at DMSA scan (OR 1.21; 95% CI 1.08-1.36), history of VUR (OR 8.64; 95% CI 2.52-29.57), history of hydronephrosis (OR 3.44; 95% CI 1.12-10.5), and CIC from birth (OR 9.26; 95% CI 1.99-43.18) were statistically significant predictors of kidney damage. CONCLUSION Early initiation of CIC may not reduce the incidence of DMSA abnormalities in pediatric patients with spinal dysraphism.

Ureteroscopy in Pediatric Patients with Spinal Abnormalities

BACKGROUND AND PURPOSE Ureteroscopy (URS) is considered a safe and effective treatment modality for ureteral stones in the pediatric population. Patients with scoliosis or spinal hardware, however, may have anatomic variability that makes URS challenging because of ureteral deviation or tortuosity. We reviewed 130 ureteroscopic procedures at our institution to determine if presence of spinal hardware or severe spinal deformities was associated with increased complications or worsened treatment efficacy. PATIENTS AND METHODS A retrospective chart review was performed on 130 ureteroscopic procedures in 102 patients. Patients were divided into two groups: Those with normal spinal anatomy and those with spinal abnormalities including spinal hardware or moderate to severe scoliosis. Parameters evaluated included patient demographics, stone burden, intraoperative complications (including urinary extravasation, bleeding, or need to abort procedure), and stone-free status. RESULTS Of 130 ureteroscopic procedures between 2002 and 2010, 25 URS were performed for purposes other than stone disease (gross hematuria, filling defects, or encrusted ureteral stents). The remainder of URS (105) were performed for stone disease. Nine patients had spinal hardware or significant spinal deformities including moderate to severe scoliosis. When comparing both the intraoperative complications as well as stone-free status, there was a difference between those patients with spinal abnormalities and those without. Of 90 URS performed for stones in normal anatomy patients, the stone-free rate was 61%, compared with 35.7% in patients with spinal deformities. There were 13 total complications (Satava grade I or II): 40% in spinal deformity patients compared with 6.1% in normal anatomy patients. CONCLUSION Spinal hardware and spinal deformities contribute to increased complications and worsened stone-free rates during pediatric URS compared with pediatric patients with normal anatomy. Our experience with URS in patients with spinal deformities suggests it may not be as safe or efficacious as in the general pediatric population but it can still be used as a primary modality.

Laparoendoscopic single-site (LESS) bilateral nephrectomy in the pretransplant pediatric population.

Marietti S, Holmes N, Chiang G. Laparoendoscopic single‐site (LESS) bilateral nephrectomy in the pretransplant pediatric population.
Pediatr Transplantation 2011: 15: 396–399.

Urologic findings on computed tomography of the abdomen and pelvis in a pediatric population

OBJECTIVES (1) Determine the number of urologic conditions diagnosed by computed tomography (CT) in children in the emergency department setting. (2) Identify which diagnoses were incidental. (3) Determine how often there was urologic follow-up by a local pediatric urologist. PATIENTS AND METHODS We reviewed the charts and radiologist interpretations of all CT scans of the abdomen and pelvis performed within 2 days of admission via our emergency department from July 2007 to June 2009. Patients were included if the diagnosis was new. If a urologic finding was noted on final read, the CT was re-examined by one of our urologists to verify the finding. RESULTS Among 2991 CT scans (one CT scan per patient), there were 213 (7%) new urologic findings: 124 were incidental; 144 patients (68% of patients with urologic findings) did not receive follow-up. Renal abnormalities were present in 127. The most common finding was renal cyst (69 patients). Ureteral abnormalities were present in 47. The most common ureteral finding was hydroureteronephrosis (40). Other anomalies identified included bladder (7) and scrotal (14) abnormalities, stones (13), and adrenal lesions (5). CONCLUSION Many urologic diagnoses are revealed during CT scans of the abdomen and pelvis. The majority are cysts, hydroureteronephrosis, and pyelonephritis. Many incidental findings have also been revealed in the emergency department setting.

Do Overweight and Obese Pediatric Stone Formers Have Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers?

OBJECTIVE To determine if 24-hour urinary parameters in children with nephrolithiasis across 4 institutions were influenced by body mass index (BMI). MATERIALS AND METHODS The 24-hour urinary parameters obtained from children with nephrolithiasis between 2000 and 2013 were stratified by BMI percentile ≥85th and <85th (overweight and obese patients vs healthy weight, respectively). A total of 206 children were included in the study. Exclusion criteria included patients with a history of spina bifida, neurogenic bladder, and cerebral palsy, and patients on medical treatment before the first 24-hour urine collection. RESULTS Overweight and obese patients consisted of 35.4% of the cohort (n = 73). Metabolic abnormalities were present in 130 children (63.1%). The most common abnormality present in the <85th percentile was hypercalciuria (32.3%), and in the ≥85th percentile, hyperoxaluria (37.0%). Univariable and multivariable analyses revealed that overweight and obese children were more likely to have low urinary volume and elevated uric acid compared to normal-weight children. CONCLUSION Although there is a link between stone formation and BMI in adults, no definitive conclusions have been proven in the pediatric literature. Our study indicates that stone-forming children who are overweight or obese have low urinary volume and elevated uric acid compared to normal-weight stone-forming children.