Image-defined Risk Factors Correlate with Surgical Radicality and Local Recurrence in Patients with Neuroblastoma.

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.

[Establishment of a Neonatal ECMO Programme on the Basis of a Special Training Programme--A 6-year Analysis]. / Etablierung neonataler ECMO bei Lungenversagen auf der Grundlage eines speziellen Trainingsprogramms--Eine 6-Jahres-Analyse.

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.

Bladder augmentation with small intestinal submucosa leads to unsatisfactory long-term results.

PURPOSE: To evaluate the use of small intestinal submucosa (SIS) for bladder augmentation in a series of select patients. MATERIAL AND METHODS: Six patients (age 6.5-15.4, mean 9.8 years) underwent bladder augmentation with SIS: one after a cloacal exstrophy repair, one after multiple surgery of the bladder because of vesicoureteral reflux, two with spina bifida, two after bladder exstrophy repair. All suffered from a microbladder with a mean volume of 61.5 ml (range 15-120, 7-36% of expected bladder capacity for age). Preoperative bladder compliance ranged from 1.0 to 3.3 (mean 1.3) ml/cmH2O. RESULTS: Follow-up time ranged from 4.6 to 33.5 (mean 24.4) months. An increase of bladder volume was achieved in four patients (53-370 ml, 16-95% of expected bladder capacity for age). Bladder compliance postoperatively ranged from 0.9 to 5.6 (mean 3.0) ml/cmH2O. Histological examinations showed a complete conversion of SIS, leaving irregular urothelial lining and bladder wall containing muscular, vascular and relatively thick connective tissue in four patients and regular urothelium in two patients. Major complications were bladder stones in two patients and a bladder rupture in one patient. CONCLUSION: Bladder augmentation with SIS in humans failed to fulfill the hopes raised by animal studies. Due to the insufficient increase in bladder compliance and therefore failure to accomplish sufficient protection of the upper urinary tract, bladder augmentation with SIS cannot be recommended as a substitute for enterocystoplasty.

Children and adolescents with ureteropelvic junction obstruction: is an additional voiding cystourethrogram necessary? Results of a multicenter study.

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.

Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis.

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.

Re-operations for Hirschsprung's disease: long-term complications.

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.

Urinalysis in children with epididymitis.

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.

Fetal urinary bladder rupture and urinary ascites secondary to posterior urethral valves. A case report.

Megacystis is a typical prenatal sonographic finding in cases of lower urinary tract obstruction. Urinary bladder perforation represents a rare complication in this condition. We report on a boy with in utero bladder perforation and urinary ascites secondary to posterior urethral valves. The pre- and postnatal therapy is described and the current literature is reviewed.

[Enuresis in childhood]. / Serie Kindersprechstunde, Teil 2: Enuresis. "Mein Kind ist Bettnässer"!

In children with nocturnal bedwetting, the basic diagnostic evaluation to differentiate between monosymptomatic enuresis and organic or functional urinary incontinence is mandatory. When the diagnosis of monosymptomatic enuresis is set, a stepped therapeutic program is available, in which alarm/behavior therapy has a central role. Drug therapy of monosymptomatic enuresis in childhood is an established option and is reserved for certain indications.

Late obstruction after subureteral collagen injection.

We present a case with distal ureteral obstruction after a single subureteral collagen injection. Postnatally, the girl presented with bilateral vesicoureteral reflux (VUR). At one year of age, a bilateral subureteral collagen injection was carried out. Postoperatively, the girl was followed up regularly and showed no pathological findings. But three years later, hydronephrosis with a distal ureteral obstruction on the right side was found. An ureteral reimplantation was performed on that side and the histological finding was a ureteral stenosis, consisting of collagen with a knotty sclerosis and a histiocytic and granulomatous reaction. This is the first case with a late obstruction at the ureteral orifice three years after a single collagen injection. We found an inflammatory reaction against the collagen, which led to a sclerosis of the implant. Further surveillance of patients after subureteral injections should focus on this kind of complication.

Functional imaging for determination of nephroblastoma: an obligatory diagnostic program.

In Europe, 1.7 % of children with predicted nephroblastoma undergo neoadjuvant chemotherapy without being correctly diagnosed. It is necessary to reduce the number of misdiagnoses. In a girl who was referred to our institute with the diagnosis of nephroblastoma of the right kidney, DMSA scan revealed a hypertrophic compensation of the contralateral nephropathy in the lower part. Functional imaging studies of the kidney should be performed in patients in whom the type of pathology of a suspect mass in the kidney region is unclear, including a careful scrutiny of the MRI scan.

Surgical complications in the treatment of Wilms' tumor.

We present our data on the treatment of Wilms' Tumor (WT) with an emphasis on both the positive effect and the adverse effect of preoperative chemotherapy with regard to surgical intervention. From 1980 to 2000 70 children were treated. 57 % received preoperative chemotherapy (ChTx) and 43 % were operated on primarily. 75 % of the tumors responded to ChTx with significant shrinkage of the size. After preoperative ChTx 54 % of the cases were regrouped as stage I, whereas after primary operation 46 % of the patients were grouped as stage I, thus indicating a downstaging with preoperative ChTx. In 8 % of the patients with preoperative chemotherapy intraoperative complications occurred with a rupture of the tumor in 1 case. In contrast, there were intraoperative complications in 25 % of the patients with a primary operation with rupture of the tumor in 3 cases. 1 child (1.5 %) was treated with chemotherapy who did not have a Wilms' tumor but a benign nephroma (CMN). 3 cases had a clear cell sarcoma (CCSK) and in one case histology revealed a rhabdoid tumor (MRTK). In one case of CCSK only histology of the metastases disclosed the correct diagnosis. The rate of postoperative complications such as ileus was the same for both groups. Irrespective of the known adverse effects such as changing tumor histology, which may affect the correct staging, and the remaining risk of an initial inadequate treatment, our data show that the regimen of preoperative chemotherapy as proposed by the SIOP study should not be abandoned. However, the relatively small number of our patients does not allow a significant statement to be made but confirms the results of past SIOP studies.

Tubularized incised plate (TIP) urethroplasty (Snodgrass) in primary hypospadias repair.

In the past TIP urethroplasty became a preferred technique for distal hypospadias repair, and subsequently gained worldwide popularity and acceptance. The procedure gives good functional results and a cosmetic appearance that is superior to that obtained by flip-flap or onlay preputial flap repairs. In addition, this procedure is associated with a fairly low rate of complications. From 06/2000 to 04/2004 we performed 100 primary TIP urethroplasties in patients with distal hypospadias. The age of the patients at the time of surgical correction was 16 months to 10 years with a mean of 41.4 months. All patients underwent the procedure under general anesthesia supplemented by additional pain management with a penile block anesthesia or caudal anesthesia. The surgical technique is described. During follow-up (23.5 months) we observed 2 types of complications: formation of a urethrocutaneous fistula (5 pts., 5 %) and formation of meatal stenosis (17 pts., 17 %) with a steady decrease with no stenosis formation in the last 8 months of this series. A key point might be the length of the dorsal incision of the urethral plate which should not touch the dorsal lip of the anticipated neomeatus. There were no other complications, and the cosmetic results were good in all cases.

Incomplete duplication of the bladder. A case report.

Duplication of the bladder is an unusual congenital anomaly and is usually associated with other anomalies. We report an unusual case of duplicated bladder in a 8-year-old boy resulting from a septum in the sagittal plane. This malformation was associated with dysplasia of the left kidney and agenesis of the left testicle. The basic defects that lead to duplication of the lower urinary tract are unknown.

Ureterocystoneostomy (UCN) and subureteral collagen injection (SCIN): combined one-stage correction of high-grade bilateral vesicoureteral reflux (VUR) in children.

The treatment of vesicoureteral reflux (VUR) is still a controversial issue. The efficacy of medical treatment appears to be equal to that of operative procedures in avoiding new formation of renal scars. However, there are generally accepted indications for operative procedures including bilateral high-grade VUR, especially in young patients. Ureteral reimplantation (UCN) is the operative treatment of choice in cases with high-grade VUR. Alternatively in cases with lower-grade VUR, injection of bulking agents under the refluxive orifice can be performed. It is also generally accepted that UCN with extravesical preparation of the ureter and the bladder should not be done bilaterally in a one-stage procedure. Postoperative bladder dysfunction may result due to detrimental neurogenic effects. In this study we report on our operative procedure in cases with bilateral high-grade VUR, during which we perform intra/extravesical UCN (mod. Leadbetter-Politano) of the higher-grade refluxive ureter, and (open) subureteral collagen injection (SCIN) of the lower-grade refluxive orifice as a combined one-stage procedure. In this study 50% of the patients had no VUR on either side after the first combined procedure. 15% of the patients showed significant down-grading of VUR of the injected side. These patients underwent a 2nd endoscopic SCIN. 35% of the patients showed no change of VUR of the injected side after the first procedure; these patients underwent reimplantation of this side in another operation. Accordingly, 50% of patients with bilateral high-grade VUR required a 2nd operative procedure under full anesthesia to achieve loss of VUR on both sides. None of the patients showed bladder dysfunction postoperatively. Mean follow-up after the last operative correction was 29.9 months (6 - 84 months).

Fibroadenoma of the breast in an 11-year-old girl.

Fibroadenoma is the main cause of unilateral breast mass in teenagers and adolescents. 4% of these are a special form described as giant or juvenile fibroadenoma. For primary diagnosis, ultrasound is the method of choice. The MRI allows exact evaluation of size and location. The fibroadenoma must be distinguished from the phylloid tumour, which can be malignant. The latter occurs in patients of all ages, but peaks between the ages 40 and 50 years. Only 2% of all primary malignant breast lesions are found in women aged under 25. Metastases of other primary tumours must be excluded, especially with a history of prior malignancies. When planning the surgical excision, the final cosmetic result is important. Although the main reason of an asymmetrical breast enlargement of young girls is a benign mass, an early surgical excision is efficient with regard to the best possible cosmetic outcome.

Critical validation of colour Doppler ultrasound in diagnostics of acute scrotum in children.

Acute scrotum in children is generally a symptom. Several pathologies of the testis, scrotum or groin may cause it, including inflammatory as well as ischaemic processes. Testicular torsion with ischaemia of the testis is an emergency requiring prompt surgical intervention. Even experienced paediatric surgeons and urologists may have difficulties differentiating an ischaemic from an inflammatory aetiology solely on the basis of clinical signs and symptoms. In cases of aetiologic uncertainty, operative exploration has to be performed to rule out ischaemia, which led in the past to a high rate of surgery. More recently, colour Doppler ultrasonography (CDUS) has become an imaging modality for the examination of the acute scrotum with the purpose of detecting ischaemia, thus reducing the need for explorative surgery. In this study we examined the reliability of CDUS, comparing the sonographical diagnoses with both the intraoperative findings and the clinical course. We present here 132 consecutive cases of acute scrotum in children, who were admitted from 01/98 through 10/02 to our hospital. All patients underwent CDUS. Patients with ultrasonographic signs of ischaemia of the testis (group A) and patients with demonstrated perfusion and suspicious or severe clinical symptoms (group B) were operated immediately. Patients with demonstrated perfusion without suspicious or severe symptoms (group C) were treated conservatively. Thirty-eight patients (28.8%) were treated operatively. Eleven cases of testicular torsion in group A (12 pat.) could be confirmed intraoperatively, in one case there was no testicular torsion but a severe inflammation of the testis with torsion of the appendix testis. In group B (26 pat.) operative exploration revealed one case of testicular torsion. In group B two cases of sonographically suspected torsions of the appendix testis also emerged as epididymitis intraoperatively. In the other cases postoperative diagnosis was in agreement with the preoperative CDUS. The clinical course of 94 conservatively treated patients (71.2%) (group C) confirmed in all cases a non-ischaemic aetiology. There was a total of 12 cases (9.1%) where acute scrotum was caused by testicular torsions. This relatively low rate underlines the necessity to differentiate between ischaemic and other aetiologies, thus avoiding operation in many patients. 71.2% of our patients could be treated conservatively. However, it is essential to exclude an ischaemic cause before opting for conservative therapy. Even though CDUS is a very valuable diagnostic tool in this sense, this exclusion cannot be ensured in every case and is highly dependent on the expertise and technique of the investigator. Therefore in cases with any doubts an operative exploration has to be performed to avoid the most dreaded complication in the treatment of acute scrotum.

Management of the primary obstructed megaureter (POM) and indication for operative treatment.

Presented is the diagnostic and therapeutic management of the primary obstructed megaureter (POM). 42 patients presented with 53 ureteral units (UU) of POM (5 females, 37 males, 36 neonates and 6 children aged 3 to 8 years). Of the 53 megaureters 10 UU (19%) were on the right and 27 UU(51 %)were on the left. 8 patients (19%)with 16 UU (30%)showed a bilateral abnormality. In 41% of the patients, hydronephrosis had been discovered by prenatal ultrasound. All patients were evaluated postnatally by ultrasound (US), voiding cysturethrogram (VCUG), intravenous pyelogram (IVP) and diuresis renogram (MAG-3) (DR). Due to the percentage of urinary drainage,the renogram results were classified into different categories:no obstruction, functional obstruction, equivocal and obstruction. A partial renal function was also calculated. Follow-up of the patients ranges between 5 to 48 months (mean: 22.1). All patients underwent serial US and serial DR were obtained in 36 patients. Initially, 9 (17%) UU showed a functional obstruction, 34 (64.2%) an equivocal and 10 (18.8%) an obstructive urinary drainage pattern. 2 kidneys showed a significant decreased partial function of 20, respectively 26%. Surgery was performed in an initial im-paired renal function with an obstructive pattern or in cases with normal function and at least equivocal urinary drainage pattern with no improvement or deterioration of the urinary drainage and/or function in the follow-up. Considering these criteria, 5(9.6%) patients needed surgery. No loss of kidney function has been observed in follow-up. DR is the most valuable diagnostic tool. Criteria interpreting the results are demonstrated in this article.

Clinical impact of differential renal function to indicate and assess pyeloplasty and the significance of coexisting vesicoureteral reflux.

PURPOSE: In patients with ureteropelvic junction obstruction (JPJO) who are conservatively treated, 5% to 10% of them show a deterioration of renal function without recovery after delayed pyeloplasty. Should surgery be indicated based on observed deterioration of differential renal function (DRF)? Can we expect improvement of the DRF after pyeloplasty? What other influencing parameters may affect DRF? MATERIALS AND METHODS: In this study, the authors examined 85 ureterorenal junctions that had undergone the Anderson-Hynes technique for surgical correction of UPJO. Based on the values obtained from the preoperative DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three categories: group I had poor DRF (less than 11% of total renal function [TRF]), group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF (more than 33% of TRF). Twelve months after surgery, renal function was reassessed. The results were correlated with age at surgery, symptoms, coexisting vesicoureteral reflux, and drainage. RESULTS: Seven ureterorenal junctions (8%) comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III. After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and 1% exhibited diminished function. In 50% of the renal cases with preoperative DRF less than 33%, postoperative improvement was seen. In follow-up renal scans, 30 cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent of the patients with impaired DRF improved after pyeloplasty performed within the first 3 months of life, compared with 42.8% of patients in whom surgery was performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the patients with preoperative impaired DRF compared with 11% with normal DRF. Forty-five percent of the patients with impaired DRF and no improvement after surgery had coexisting vesicoureteral reflux, compared with 9% of those with postoperative improvement. CONCLUSIONS: Sustained renal impairment after pyeloplasty is likely as a result of preexisting renal dysplasia with vesicoureteral reflux. Moderate delayed drainage after surgery does not affect DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except very low DRF) or the age at the time of diagnosis.