BACKGROUND:Neuroblastoma is the second most common solid pediatric tumor and the most common cancer to be detected in children younger than 12 months of age. To date, 2 different staging systems describe the extent of the disease: the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Risk Group Staging System (INRGSS). The INRGSS-system is characterized by the presence or absence of so called image-defined risk factors (IDRFs), which are described as surgical risk factors. We hypothesized that IDRFs correlate with surgical complications, surgical radicality, local recurrence and overall survival (OS).PATIENTS AND METHODS:Between 2003 and 2010, 102 patients had neuroblastoma surgery performed in our department. We analyzed medical records for IDRF-status and above named data.RESULTS:16 patients were IDRF-negative, whereas 86 patients showed one or more IDRF. Intra- or postoperative complications have been reported in 21 patients (21%). 19 of them showed one or more IDRF and 2 patients were IDRF-negative (p=n.s.). Patients who suffered from intra- or postoperative complications demonstrated a decreased OS (p=0.011). Statistical analysis revealed an inverse correlation between the extent of macroscopical removal and IDRF-status (p=0.001). Furthermore, the number of IDRFs were associated with a decreased likelihood of radical tumor resection (p<0.001). 19 patients had local recurrence; all of them were IDRF-positive (p=0.037).CONCLUSIONS:Pediatric surgeons should consider IDRFs as a useful tool for risk assessment and therefore planning for neuroblastoma surgery.

BACKGROUND:Internationally the need for neonatal ECMO is decreasing and the Extracorporeal Life Support Organization (ELSO) recommends that centres providing neonatal ECMO should treat at least 6 children per year.METHOD:After a one-year training programme and preparation of the clinical application, neonatal ECMO was established and subsequently 41 infants [median age 1 day (1-172 days), median weight 3.25 kg (1.27-5.79 kg)] with severe respiratory failure have been treated within a 6-year period (fall 2008-fall 2014). For rescue therapy we provide inhaled nitric oxide, high-frequency oscillation and other differentiated ventilator strategies. Parallel to the clinical use of ECMO all employees have been trained in a special programme at 3-monthly intervals.RESULTS:By establishing an elaborate training programme and concentrating the treatment of critically ill newborns in one centre, the expertise of both running and preventing of neonatal ECMO due to pulmonary failure can be achieved. The diagnoses correlate to those of other centres which perform neonatal ECMO. 13 infants needed ECMO. The resulting overall survival rate was 11/12 (91.7%) infants treated with ECMO with a curative approach. All patients could be weaned from ECMO.CONCLUSION:In the context of a specialised university hospital with all treatment options for critically ill newborns and with the establishment of a specialised training programme, neonatal ECMO for pulmonary failure can achieve equally good results in comparison to those of national and international ECMO centres.

Hintergrund: Das neonatale Lungenversagen geht mit hoher Morbidität und Mortalität einher. Zwei der drei häufigsten Diagnosen (Mekoniumaspirationssyndrom, congenitale Zwerchfellhernie und persistierender pulmonaler Hypertonus des Neugeborenen) treten perinatal unvorhersehbar auf. Der schnelle Transport in ein spezialisiertes Zentrum ermöglicht die Reduktion von Morbidität und Mortalität.

PURPOSE:The incidence of ureteropelvic junction obstruction (UPJO) and concomitant vesicoureteral reflux (VUR) ranges from 14 to 18 %. Therefore, different guidelines recommend a voiding cystourethrogram (VCUG) to identify cases of VUR early in the diagnostic process. Aim of this multicenter study was to reassess the incidence of concomitant VUR and the need for additional VCUG in a large cohort of patients with UPJO. Furthermore, we asked for clinical objectives that defined the need for VCUG with the intention of minimizing radiation exposure and the need for invasive diagnostic procedures.METHODS:Medical records for 266 patients (69 girls, 197 boys) with UPJO were analyzed retrospectively. Data were obtained on gender, clinical symptoms, results of pre- and postnatal ultrasound, VCUG and 99(m)Technetium-MAG3 (MAG3) scan. They were correlated with the incidence of concomitant VUR.RESULTS:One hundred and seventy-eight patients (67 %) underwent VCUG. Concomitant VUR was detected in 13 patients. Dilating VUR (dVUR) was observed in 11 patients. In our study, the overall incidence of a concomitant VUR was 7.3 %. In cases of proven VUR, we observed a positive predictive value for female gender, ureteral dilatation, renal insufficiency, and recurrent urinary tract infections (UTI). But there was no correlation between concomitant VUR and the severity of hydronephrosis.CONCLUSIONS:Our data suggest that the low incidence of concomitant VUR in cases of UPJO does not justify the routine use of VCUG as a routine diagnostic tool. Especially, ureteral dilatation and recurrent UTI have a positive predictive value for concomitant VUR.

Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models. Existing CF mouse models fail to reflect important aspects of human CF. We thus generated a CF pig model by inactivating the CFTR gene in primary porcine cells by sequential targeting using modified bacterial artificial chromosome vectors. These cells were then used to generate homozygous CFTR mutant piglets by somatic cell nuclear transfer. The homozygous CFTR mutants lack CFTR protein expression and display severe malformations in the intestine, respiratory tract, pancreas, liver, gallbladder, and male reproductive tract. These phenotypic abnormalities closely resemble both the human CF pathology as well as alterations observed in a recently published CF pig model which was generated by a different gene targeting strategy. Our new CF pig model underlines the value of the CFTR-deficient pig for gaining new insight into the disease mechanisms of CF and for the development and evaluation of new therapeutic strategies. This model will furthermore increase the availability of CF pigs to the scientific community.

Cystic fibrosis (CF), the most common inherited disease in the Caucasian population, is caused by mutations of the CFTR gene, coding for an anion channel responsible for chloride movement, determining transepithelial salt transport, fluid flow and ion concentrations. Cystic fibrosis is determined by chronic lung disease, marked by airway surface dehydration, reduced mucus clearance and increased mucus obstruction, impaired bacterial killing and inflammation and continuous destruction of the lung tissue. The lack of suitable CF mouse models has so far impeded the understanding of disease mechanisms and the development of novel therapies. Recently, a pig model reflecting the main hallmarks of the human disease in the respiratory, gastrointestinal and genital tracts has been reported (Rogers et al. 2008 Science 321, 1837–1841). In the present study, we generated a new CF pig model by disrupting the CFTR gene using an approach that differs in 3 major aspects from the previously published model: (1) gene targeting was achieved using a modified bacterial artificial chromosome (BAC) vector; (2) transcription of the CFTR gene was completely prevented; and (3) homozygous CFTR mutant pigs were derived by nuclear transfer from cells in which both alleles were inactivated by sequential BAC targeting. We characterised 2 cloned litters with a total of 13 piglets (including 4 stillborns). All piglets showed a characteristic CF multi-organ disease with severe meconium ileus, microcolon, microgallbladder, hypoplasia of the exocrine pancreas, congenital aplasia of the vas deferens and malformations of the trachea. In contrast to the recently published CF pig, where the majority of the intestinal obstructions occurred proximal to the ileocecal junction, we found obstructions exclusively distal to this site. We thus present a novel pig model for CF that reflects the main hallmarks of the human disease. It confirms the suitability of the CFTR mutant pig for cystic fibrosis research and increases the availability of CF models for molecular and translational CF research. The help by Prof. K. Heinritzi and his team from the Pig Clinic, LMU Munich, is gratefully acknowledged. This study was supported by Mukoviszidose e.V.

INTRODUCTION:In some patients with Hirschsprung's disease (HD), the initial surgical procedure fails, and the patients suffer from repeated or persistent symptoms. These patients complain of severe inflammation, intestinal obstruction, fecal or urinary incontinence, abdominal pain or dystrophy. However, little data has been published on the long-term follow-up results after re-operations for HD.MATERIALS AND METHODS:We followed 8 cases between 2004 and 2006, of complicated HD requiring repeated surgery and recorded prior procedures, histological results, indications for re-operation, postoperative follow-up as well as long-term clinical outcomes including stool patterns, nutrition and micturition.RESULTS:The follow-up period ranged from 3.0 to 5.5 years (mean: 4.4 years). Indications for repeat procedures were as follows: blind rectal pouch after a Duhamel operation (n = 2), persistent aganglionosis (n = 4), long-segment stenosis (n = 1) after a Rehbein operation, and anal stenosis following TERPT (transanal endorectal pull-through) (n = 1). In one patient who had a Duhamel-Martin operation, extirpation of the rectum and a definitive terminal ileostomy was necessary. A Duhamel procedure was performed in five patients with a primary Rehbein and 1 patient with a primary Duhamel operation. Complete stool continence was achieved in 4 patients. Partial fecal incontinence persisted in one patient with associated trisomy 21. 1 patient with total colonic aganglionosis and 1 patient with a pelvic fistula and a previous subtotal colectomy reported soiling 1-2 times per week after a repeat operation. 4 patients in our series experienced postoperative complications following repeated surgery [perianal ulceration (n = 2), repeated botulinum toxin injection for sphincter achalasia (n = 1) and functionally impaired colonic transit without stenosis (n = 1)]. Micturition was normal in 7 patients, 1 patient with associated trisomy 21 was partially continent, and 1 patient reported infrequent urge incontinence.CONCLUSIONS:All patients improved after further surgical intervention. However, resolution of their symptoms was delayed and partial stool incontinence or soiling persisted in 3 patients. Most complications leading to repeat procedures are preventable, especially residual aganglionosis. Therefore, great efforts should be made to minimize complications when planning and performing the primary surgery.

BACKGROUND:The aim of this study was to examine the diagnostic and therapeutic yield of urine tests in epididymitis in children. Recently, urine examination in prepubertal epididymitis has been described as having little value for diagnostic or treatment. Yet, although urine cultures are often sterile, in clinical practice prepubertal boys with epididymitis are often treated with antibiotics.MATERIAL AND METHODS:A retrospective analysis of all boys with 1-episode epididymitis presenting to a single institution over a 5-year-period was performed. Results of laboratory tests (blood, urine) were collected.RESULTS:We found 151 consecutive patients. In 93 cases (62%), results of urine examinations were available. Only 1 patient (1%) showed bacteriuria in urine sediment, while urine culture in this patient was sterile. Urine cultures were done in 6 of 97 patients treated in hospital (6%), and all cultures were sterile. Surgical exploration was performed in 7 patients (5%); in 6 of them epididymal cultures were taken intraoperatively with negative microbiological results.CONCLUSION:In our group of children with epididymitis, almost all urine tests (urinalysis, urine culture) were negative. Epididymitis in prepubertal boys seems to be mostly idiopathic, and positive microbiological findings are rare. Antibiotic treatment in this age group should only be done in cases with positive urine tests.

Einleitung: Die endoskopische Refluxkorrektur beim vesico uretero renalen Reflux (VUR) bei Kindern gilt als anerkannte Behandlungsmöglichkeit des VUR und ist im Begriff, sich selbst bei hochgradigem VUR zur first-line Therapie zu entwickeln.

Es kommt nicht selten vor, dass (Kinder-)Chirurgen oder (Kinder-)Urologen von Personensorgeberechtigten mit dem Verlangen konfrontiert werden, eine Zirkumzision an einem Knaben vorzunehmen, obwohl die medizinische Indikation nicht vorhanden oder jedenfalls fraglich ist. Der vorliegende Beitrag macht deutlich, dass ein Arzt in derartigen Fällen Abstand von einem solchen Eingriff nehmen sollte, um später nicht Adressat von zivilrechtlichen Klagen zu werden oder gar Beschuldigter in einem Strafverfahren. Denn die Autoren kommen zu folgendem Ergebnis: Ein Arzt, der an einem minderjährigen und nicht einsichtsfähigen Jungen eine medizinisch nicht notwendige Zirkumzision vornimmt, macht sich nach § 223 Absatz 1 des Strafgesetzbuchs (StGB) strafbar, selbst wenn die Inhaber der Personensorge in den Eingriff einwilligen. Mangels Dispositionsbefugnis über das beeinträchtigte Rechtsgut (die körperliche Unversehrtheit des Kindes) ist diese Einwilligung nämlich unwirksam. Der Beitrag stellt nicht nur die aktuelle Rechtslage dar, sondern widmet sich auch eingehend den oft vorgetragenen Argumenten, die für die Rechtmäßigkeit einer Zirkumzision streiten sollen (Behandlung einer Phimose, Vorbeugung von Krankheiten, Religion).

Surgeons and urologists (usually pediatric) are often confronted with the request to perform circumcision on a boy from parents or guardians in the absence of a medical indication. This review highlights the importance of refraining from such procedures to avoid being the possible addressee of a civil law claim or even being accused in a lawsuit a some later point. The attending physician who performs a circumcision without medical indication on a minor male incurs a penalty according to 223 para. 1 of the German Criminal Code, even in the case where the parent or guardian of the child has signed the informed consent to that procedure. In the absence of power of approval over the compromised legally protected interest of the child (physical inviolacy), the consent is invalid. The present article discusses not only the current German legal status, but also examines in depth the arguments often put forward to support the legitimacy of male circumcision (treatment of phimosis, disease prevention, religion).

Der vesikoureterale Reflux (VUR) kann als eine der häufigsten urologischen Anomalien durch rezidivierende Pyelonephritiden zu Nierenparenchymnarben, Hypertension und terminaler Niereninsuffizienz führen. Die Diagnostik bei präpartalem sonographischem Verdacht oder nach einem Harnwegsinfekt umfasst neben der Sonographie die Bestätigung der Diagnose im Röntgen-MCU und im ersten Lebensjahr die dynamische Nierenszintigraphie zum Ausschluss einer begleitenden Abflussstörung, jenseits des 1. Lebensjahrs meist eine statische Nierenszintigraphie zum Ausschluss von Nierenparenchymnarben nach Harnwegsinfekt. Die Therapie orientiert sich am Alter und Schweregrad des VUR. Im 1. Lebensjahr erfolgt in der Regel eine konservative Behandlung mit antibiotischer Dauerprophylaxe. Die operative Therapie (endoskopische Refluxkorrektur, Harnleiterreimplantation) ist beim Verbleiben des VUR über das 1. Lebensjahr hinaus, bei Ablehnung der konservativen Therapie oder beim Auftreten von Durchbruchsinfektionen unter der Antibiotikaprophylaxe indiziert. Der Langzeitverlauf ist abhängig von der Nierenschädigung.

Established bubble-jet printheads consist of an assembly of three layers, which are a CMOS substrate, a channel layer and a nozzle layer. The aim of the presented work was to simplify the setup of bubble-jet printheads by means of integrating channel and nozzle structures in one single three-dimensional laser-structured polyimide nozzle plate. Different bonding techniques for an assembly onto 1/3 inch standard CMOS printhead substrates are validated. The main challenges are a variety of bonding materials, an alignment accuracy of <5 μm and the prevention of blocking the 20 μm deep fluidic channels in the polyimide which have minimal lateral dimensions of 10 μm and a minimal pitch of 15 μm. In total, three bonding techniques, with and without additional adhesion layers, were developed and evaluated. One method applies a 4 μm thick layer of Epotec 353ND (Polytec), a standard two-component epoxy, in a specifically adapted rolling manner onto the film that is subsequently aligned to the silicon chip using a flip-chip-bonder. Screen-printing and dispensing processes of adhesives were investigated but failed due to insufficient structural resolution. The second method uses photolithographic processes to produce structured adhesion preforms in SU-8 resist. With a layer thickness of 3 μm and an adapted curing schedule, promising results concerning resolution and contour accuracy were obtained. Thirdly, bonding without additional adhesion layers was achieved in a micro-sealing process that takes advantage of the highly defined thermoplastic softening of polyimide KJ (DuPont). The different processes were compared regarding to yield, printing behavior of the assembled printheads and applicability to high volume productions. The hereby developed adhesion technology was applied on the assembly of large one inch printheads for special applications.