Adam B. Hittelman

Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance

BACKGROUND Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals. METHODS Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Childrens Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Students t-tests. RESULTS One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant. CONCLUSIONS In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.

Surface modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer

Penetration of the bladder permeability barrier (BPB) is a major challenge when treating bladder diseases via intravesical delivery. To increase transurothelial migration and tissue and tumor cell uptake, poly(lactic-co-glycolic acid; PLGA) nanoparticles (NP) were modified by addition of a low molecular weight (2.5 or 20 kDa) positively charged mucoadhesive polysaccharide, chitosan, to the NP surface. In designing these NPs, we balanced the adhesive properties of chitosan with the release and bioactivity of the siRNA. Chitosan-functionalized NPs demonstrated increased binding to and uptake in intravesically instilled mouse bladders and human ureter at 10 times the level of unmodified NPs. Furthermore, we extended the bioactivity of survivin siRNA in vitro for up to 9 days and demonstrated a decrease in proliferation when using chitosan-modified NPs relative to unmodified NPs. In addition, treatment of xenograft tumors with chitosan-modified NPs that encapsulate survivin siRNA (NP-siSUR-CH2.5) resulted in a 65% reduction in tumor volume and a 75% decrease in survivin expression relative to tumors treated with blank chitosan NPs (NP-Bk-CH2.5). Our low molecular weight chitosan delivery system has the capacity to transport large amounts of siRNA across the urothelium and/or to the tumor site, thus increasing therapeutic response. Mol Cancer Ther; 13(1); 71–81. ©2013 AACR.

Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C.

What’s known on the subject? and What does the study add?

Does Severity of Renal Scarring on DMSA Scan Predict Abnormalities in Creatinine Clearance

OBJECTIVES To examine the relationship between severity of renal scarring and creatinine clearance. Existing studies on renal scarring and functional outcomes have focused on the presence or absence of scarring. METHODS Patients with a history of urinary tract infection leading to the diagnosis of vesicoureteral reflux were recruited. These subjects were admitted to a pediatric research center for an in-patient collection of 24-hour urine to be sent for creatinine and protein. DMSA scans performed at least 6 months after documented urinary tract infection were graded by 3 independent, blinded pediatric urologists for renal scarring according to the Randomized Intervention for Children with Vesicoureteral Reflux study criteria. RESULTS Twenty-nine subjects (14 girls, 15 boys) with a median age of 7 years were recruited. Scar grading was reliable between the observers with a Kappa score of 0.66-0.75. On DMSA scan, 10% were scar-free, 62% had unilateral scars, and 28% had bilateral scars. Mean creatinine clearance was 123 for those with unilateral disease and 100 for those with bilateral disease (P = .048). Median proteinuria (58 mg/dL) and serum creatinine (0.5 mg/dL) were similar between the 2 groups. Creatinine clearance did not differ according to average scar grade, taking both kidneys into account. CONCLUSIONS In children with vesicoureteral reflux, although those with bilateral scarring have a significantly lower creatinine clearance than those with unilateral scarring, the severity of scar grade alone does not predict overall creatinine clearance with short-term follow-up.

Pediatric incidental appendectomy: a systematic review

Incidental appendectomy is the removal of the vermiform appendix accompanying another operation, without evidence of acute appendicitis. It is generally performed to eliminate the risk of future appendicitis. The risks and benefits of incidental appendectomy during various operations in children have been debated for over a century, but need to be revisited in light of innovations in medical practice, including minimally invasive surgery, improved imaging techniques, and use of the appendix as a tubular conduit for reconstruction. A detailed review was undertaken of the techniques, pathology, risks of appendectomy, utility of the appendix, and incidental appendectomy in the treatment of specific pediatric medical conditions. A comprehensive literature search was performed, and retrieved results were reviewed for relevance to the topic. The decision to perform a pediatric incidental appendectomy relies on informed consideration of the individual patient’s co-morbid conditions, the indication for the initial operation, the future utility of the appendix, and the risk of future appendiceal pathology. The discussion includes a variety of situations and comorbid conditions that may influence a surgeon’s decision to perform incidental appendectomy.

An unusual destination for magnetic foreign bodies.

Rare earth metal magnets (Buckyballs and similar products) remain an important public health risk for children. We report the presentation, course, and treatment of a boy who inserted a string of 30 magnets through his urethra into his bladder and review the diagnostic as well as the therapeutic options for foreign bodies inserted into the pediatric urogenital tract.

Distinguishing pediatric and adolescent renal cell carcinoma from other renal malignancies

Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors.

House Staff Communication Training and Patient Experience Scores

Objective: To assess whether communication training for house staff via role-playing exercises (1) is well received and (2) improves patient experience scores in house staff clinics. Methods: We conducted a pre–post study in which the house staff for 3 adult hospital departments participated in communication training led by trained faculty in small groups. Sessions centered on a published 5-step strategy for opening patient-centered interviews using department-specific role-playing exercises. House staff completed posttraining questionnaires. For 1 month prior to and 1 month following the training, patients in the house staff clinics completed surveys with Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) questions regarding physician communication, immediately following clinic visits. Preintervention and postintervention results for top-box scores were compared. Results: Forty-four of a possible 45 house staff (97.8%) participated, with 31 (70.5%) indicating that the role-playing exercise increased their perception of the 5-step strategy. No differences in patient responses to CG-CAHPS questions were seen when comparing 63 preintervention surveys to 77 postintervention surveys. Conclusion: Demonstrating an improvement in standard patient experience surveys in resident clinics may require ongoing communication coaching and investigation of the “hidden curriculum” of training.

Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting.

Clitoral Epidermoid Cyst Presenting as Pseudoclitoromegaly of Pregnancy

Objective Acquired clitoromegaly is rare and may result from hormonal and nonhormonal causes, and evaluation of the pregnant patient with clitoromegaly invokes a specific set of differential diagnoses. Methods Case report. Results We describe the case of a young woman with pregnancy-associated clitoral enlargement whose hormonal evaluation proved negative. Further investigation concluded that an epidermoid cyst was the culprit of her pseudoclitoromegaly. The patient underwent successful surgical resection and has had no recurrence at her subsequent pregnancy. Conclusion We review the differential diagnosis of clitoromegaly, including hormonal and nonhormonal causes, with focus on the evaluation of pregnancy-associated clitoromegaly.