Evaluation of Mathisen's technique for ureteral reimplantation in children with primary vesicoureteral reflux.

INTRODUCTION: Although cross-trigonal ureteral reimplantation (Cohen) is a commonly used technique in children, it represents a non-physiological transfer of the ureteral orifices and may prove challenging with regard to endoscopic ureteral operations in later life. In 1964, Mathisen described an alternative method of ureteral reimplantation with lateralization of the neohiatus, creating an orthotopic course of the submucosal ureter. We have evaluated success and complication rates of both techniques that were applied sequentially at our departments. METHODS: Forty-eight consecutive patients (83 ureters, 24 males/24 females) following Mathisen reimplantation were compared with 53 consecutive patients (98 ureters, 30 males/23 females) following Cohen reimplantation. Inclusion criteria were primary vesicoureteral reflux (VUR) and no previous intervention. Reflux grades (Mathisen 58 ureters/69.9% VUR ≥ III; Cohen 66 ureters/66.7% VUR ≥ III) and the occurence of other complicating factors (ureteroceles, megaureters, posterior urethral valves) in both groups were comparable. RESULTS: After Cohen's reimplantation there were no immediate complications requiring intervention; during follow-up (mean 28.2 months) three patients (5.6%) suffered febrile urinary tract infections (UTIs), of which one (1.8%) was diagnosed with a persisting VUR. Persistent hydronephroses (≥II SFU) were recorded in six patients (13.2%). After reimplantation using Mathisen's technique, two patients (4.1%) suffered significant intravesical bleeding; during follow-up (mean 23.06 months) four patients (8.3%) suffered febrile UTIs, and seven patients (14.5%) were diagnosed with persisting VUR after a mean follow-up of 10.8 months. The patients with persistent VUR had more commonly high-grade (IV and V) VUR initially, compared to the whole group. Two patients (4.1%) had persistent hydronephroses (≥II SFU). Mathisen's technique for ureteral reimplantation yielded a significantly (p = 0.0256 patients, p = 0.006 ureterorenal units) lower success rate (85.5% patients, 89.2% ureterorenal units) in comparison with Cohen's technique (98.2% patients, 99% ureterorenal units). Although there was no intervention for obstruction, persistent hydronephrosis was more common in the Cohen group (13.2% vs. 4.1%, n.s.). CONCLUSIONS: Despite the advantages of an orthotopic ureteral orifice close to the bladder neck, as achieved by Mathisen's reimplantation, cross-trigonal ureteral reimplantation proved more reliable for VUR correction. As regards optimizing the results, patient selection for either technique could prove essential. Nevertheless, as regards the difficulties with ectopic ureteral orifices in the Cohen technique in the long-term follow-up, the concept of anatomic, orthotopic ureteral reimplantation should be pursued and the technique should be further refined.

Clinical outcome after endoscopic therapy for occult vesicoureteral reflux in females: preliminary results of a retrospective case series.

OBJECTIVE: The aim of this study was to evaluate the clinical outcome after endoscopic therapy by injection of bulking agent in the treatment of occult vesicoureteral reflux (VUR) [no VUR on standard voiding cystourethrography (VCUG), but positive (99m)Tc-2,3-dimercaptosuccinic acid (DMSA) scan] in females who have recurrent febrile urinary tract infections (UTIs). MATERIAL AND METHODS: A case series was retrospectively identified of 24 females (mean age 15.5 years) with negative VCUG, but renal scars in one (n = 4) or both (n = 20) kidneys on DMSA scan. Endoscopic injection was performed bilaterally in 20 (83.3%) and unilaterally in four patients (16.7%). The incidence of postoperative UTIs was documented with a mean follow-up of 2.5 years (range 1-6 years). RESULTS: The mean renal part function (DMSA scan) on the left and right sides was 53.5% (15-74%) and 47.3% (26-85%), respectively. Twenty-one out of 24 patients (87.5%) showed no evidence of any febrile UTIs postoperatively. One patient (4.2%) experienced a further febrile UTI 6 months after treatment. Two other patients (8.3%) had one questionable afebrile UTI, 4 and 3 years after therapy. Pressure-flow electromyography confirmed a dysfunctional voiding pattern in 12 patients (50%) treated with pelvic floor therapy and behavioural interventions before endoscopic therapy. CONCLUSIONS: Injection of bulking agent seems to be a suitable treatment for occult VUR in females to prevent further febrile UTIs. Patients with occult VUR should undergo a careful evaluation of possible urodynamic disorders such as dysfunctional voiding. These findings should be studied in prospective trials before drawing any conclusions.

Diagnosis and management of pediatric urethral injuries.

OBJECTIVE: The incidence of urethral injuries in children is rare due to the fact that the urethra is short, mobile and protected by the pubic bone. The management of urethral trauma in childhood remains controversial because of the limited expertise of most urologists. MATERIAL AND METHODS: We performed a literature review by searching the Medline database for articles published between 1975 and 2010 based on clinical relevance. Electronic searches were limited to the keywords 'pediatric', 'urethral injury', 'trauma' and 'reconstruction'. RESULTS: Retrograde urethrography is considered the gold standard for diagnosis of urethral injuries. The initial management should ensure drainage of the bladder either by suprapubic cystostomy or urethral realignment if possible: in complete anterior urethral disruption as well as in children with life-threatening pelvic and intra-abdominal injuries after posterior urethral injuries, a deferred repair after 3 months is necessary. Immediate primary suturing of disrupted and dislocated urethral ends should be avoided because of high complication rates. Primary repair, however, of the defect is possible in girls avoiding a 2-stage approach. CONCLUSION: The aim of therapy is minimizing remote damages such as urethrocutaneous fistulae, periurethral diverticulae, strictures, incontinence and impotence with different therapeutic management depending on classification of the injury and the presence of life-threatening injuries.

Endoscopic treatment of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer in children: results of postoperative follow-up with real-time 3D sonography.

OBJECTIVES: We evaluated whether real-time 3D ultrasound (4D-US) together with clinical evaluation is an alternative to voiding cystourethrography (VCUG) after endoscopic treatment of vesicoureteral reflux (VUR) in children at postoperative follow-up. MATERIAL AND METHODS: We reviewed 178 children who underwent endoscopic therapy with dextranomer/hyaluronic acid copolymer in grade II or III VUR between 2002 and 2005. 4D-US was performed in all patients 1 day and 3, 9 and 18 months after endoscopic therapy. Only children with postoperative urinary tract infections (UTIs) and/or nonorthotopic position of the bulking agent were referred for VCUG. RESULTS: In 93% of the ureteral units, the depot could be detected in the orthotopic position after 3, 9 and 18 months. None of these children developed UTIs in the postoperative follow-up. Twelve children demonstrated a shifting of the depot, indicating a possible therapy failure. Eight of these 12 patients (66.7%) presented a positive VCUG, and 50% of them sustained UTIs. CONCLUSIONS: 4D-US seems to be a sufficient protocol in the follow-up of children after endoscopic treatment of low-grade VUR. VCUG should be performed in cases of a shifted position of the depot; invasive investigations are unnecessary in asymptomatic children with orthotopic bulk.

MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity.

Following homozygosity mapping in a single kindred, we identified nonsense and missense mutations in MYO5B, encoding type Vb myosin motor protein, in individuals with microvillus inclusion disease (MVID). MVID is characterized by lack of microvilli on the surface of enterocytes and occurrence of intracellular vacuolar structures containing microvilli. In addition, mislocalization of transferrin receptor in MVID enterocytes suggests that MYO5B deficiency causes defective trafficking of apical and basolateral proteins in MVID.

Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson's disease in children.

BACKGROUNDS/AIMS: A urinary copper (Cu) >25 micromol/24 h following penicillamine had a reported specificity of 98.2% and sensitivity of 88.2% in diagnosing Wilson's disease (WD). We have re-evaluated this test. Ninety-eight subjects were studied at presentation. METHODS: Thirty-eight (19 girls, 19 boys; median age 10.3 years; range 5-16 years) had an ultimate diagnosis of WD. Sixty (24 girls, 36 boys; median age 10.1, range 2.3-15 years) had other liver disorders. Urinary Cu was estimated for 24h before (basal Cu) and for 24h whilst giving penicillamine 500 mg orally 12 hourly x 2 (post-penicillamine Cu). RESULTS: Both basal Cu and post-penicillamine Cu differed significantly between WD patients and controls (basal Cu: median 6.5 micromol/24 h, range 0.9-109 micromol/24 h, versus median: 0.8 micromol/24 h, range 0.1-19.5, p<0.0001; post-penicillamine Cu: median 36.9 micromol/24 h, range 1.98-219 micromol/24 h, versus median 12.35 micromol/24 h, range 0.5-49.8 micromol/24 h, p<0.0001). A post-penicillamine Cu >25 micromol/24 h was observed in 29/38 patients with WD and in 4/60 controls. 25/38 WD patients were symptomatic. Twenty-three of these and 6/13 asymptomatic siblings had a positive test. The test had a sensitivity of 76% (95% confidence interval [CI], 59.8-88.6%) and a specificity of 93% (95% CI, 83.8-98.2%). Sensitivity was better in symptomatic patients (92%, [95% CI; 74-99%]) than asymptomatic (46%, [95% CI; 19.2-74.9%]). CONCLUSIONS: This test is valuable in the diagnosis of WD with active liver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings.

Growth curves of the fetal prostate based on three-dimensional reconstructions: a correlation with gestational age and maternal testosterone levels.

OBJECTIVE: To create a nomogram of the fetal growth of the human prostate corresponding to gestational age, and to investigate the relationship between the expansive growth of the fetal prostate and the maternal testosterone surge during pregnancy. MATERIALS AND METHODS: In all, 27 fetal prostates at 11-40 weeks of gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed. Serial sections of prostates were immunostained and examined using light microscopy. After modular image acquisition the volumes were calculated using three-dimensional reconstruction. The prostate volumes were correlated with gestational age, and related to reference testosterone levels during pregnancy. RESULTS: There was exponential growth of the fetal prostate with gestational age. The increasing volume of the prostate during the fetal period corresponded with maternal testosterone levels. In the second trimester there was a significant increase in prostate volume in relation to the bladder. In infants, macroscopically there was an inverse proportion between bladder size and prostate volume. CONCLUSIONS: Starting from the second trimester there is distinct growth of the fetal prostate, obviously triggered by the maternal testosterone surge. In neonates there is an inversion of the dimensions between bladder and prostate. These results indicating exponential growth of the fetal prostate provide evidence of a gender-related transient infravesical obstruction in human fetuses.

Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis.

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury.

Cerebrospinal fluid leakage after lumbar puncture in neonates: incidence and sonographic appearance.

OBJECTIVE: The purpose of this article is to review the incidence and sonographic appearance of cerebrospinal fluid leakage after lumbar puncture in the neonatal period. Thirty-three neonates underwent spinal sonography after diagnostic lumbar puncture. A total of 21 of these patients showed cerebrospinal fluid leakage into the epidural space extending from the level of the cauda equina to the lumbar (n = 9), the thoracic (n = 8), or the cervical (n = 4) region. In eight patients, the subarachnoid space was markedly compressed by the epidural fluid collection. CONCLUSION: Cerebrospinal fluid leakage into the epidural space is a frequent complication of lumbar puncture in neonates and has a characteristic appearance on sonograms. Leakage after lumbar puncture must be differentiated from cerebrospinal fluid leakage due to perinatal meningeal injury. If cerebrospinal fluid leakage at the puncture site compresses the subarachnoid space, sonography assists in the performance of subsequent lumbar puncture.