Ernst Horcher

Trends in Hypospadias Surgery: Results of a Worldwide Survey

BACKGROUND Hypospadias is a challenging field of urogenital reconstructive surgery, with different techniques currently being used. OBJECTIVE Evaluate international trends in hypospadias surgery. DESIGN, SETTING, AND PARTICIPANTS Paediatric urologists, paediatric surgeons, urologists, and plastic surgeons worldwide were invited to participate an anonymous online questionnaire (http://www.hypospadias-center.info). MEASUREMENTS General epidemiologic data, preferred technique in the correction of hypospadias, and preferred technique in the correction of penile curvature were gathered. RESULTS AND LIMITATIONS Three hundred seventy-seven participants from 68 countries returned completed questionnaires. In distal hypospadias (subcoronal to midshaft), the tubularised incised plate (TIP) repair is preferred by 52.9-71.0% of the participants. Meatal advancement and glanuloplasty (MAGPI) is still a preferred method in glandular hypospadias. In the repair of proximal hypospadias, the two-stage repair is preferred by 43.3-76.6%. TIP repair in proximal hypospadias is used by 0.9-16.7%. Onlay flaps and tubes are used by 11.3-29.5% of the study group. Simple plication and Nesbits procedure are the techniques of choice in curvature up to 30°; urethral division and ventral incision of the tunica albuginea with grafting is performed by about 20% of the participants in severe chordee. The frequency of hypospadias repairs does not influence the choice of technique. CONCLUSIONS In this study, we identified current international trends in the management of hypospadias. In distal hypospadias, the TIP repair is the preferred technique. In proximal hypospadias, the two-stage repair is most commonly used. A variety of techniques are used for chordee correction. This study contains data on the basis of personal experience. However, future research must focus on prospective controlled trials.

Regression and progression in neuroblastoma. Does genetics predict tumour behaviour

Neuroblastoma (NB) is a heterogeneous disease. The clinical course may range from spontaneous regression and maturation to very aggressive behaviour. Stage 4s is a unique subcategory of NB, generally associated with good prognosis, despite skin and/or liver involvement and the frequent presence of tumour cells in the bone marrow. Another type of NB is the locally invasive tumour without bone and bone marrow involvement which can also have a good prognosis, irrespective of lymph node involvement. Unfortunately, there is only limited biological information on such tumours which have not been treated with cytotoxic therapy despite lymph node involvement, residual tumour mass after surgery and/or bone marrow infiltration. In order to find specific genetic changes common to NBs with a benign clinical course, we studied the genetic abnormalities of these tumours and compared them with highly aggressive tumours. We analysed a series of 54 localised and stage 4s tumours by means of in situ hybridisation performed on fresh cells or on paraffin embedded tissues. In addition, we performed classical cytogenetics, Southern blotting and PCR analysis on fresh tumour tissue. The majority of patients had been treated with surgery alone, and in a number of patients tumour resection was incomplete. Deletions at 1p36 and amplifications of the MYCN oncogene were absent, and diploidy or tetraploidy were not seen in any case, with residual localised tumours possessing a favourable outcome. Unexpectedly, one patient with a tetraploid 4s tumour without any genetic structural changes not receiving any cytotoxic treatment, did well. Interestingly, this genetic spectrum contrasted with that of progressing tumours, in which most had genetic aberrations, the deletion at 1p36 being the most common event. These data, although limited, suggest that an intact 1p36 (recognised by D1Z2), the absence of MYCN amplification and near-triploidy (at least in localised tumours), represent prerequisites for spontaneous regression and/or maturation.

Intratumoural heterogeneity of 1p deletions and MYCN amplification in neuroblastomas.

BACKGROUND At least three genetic hallmarks identify aggressive tumour behaviour in neuroblastomas; amplification of the oncogene MYCN; deletion (loss of heterozygosity [LOH]) at the short arm of chromosome 1 (del1p36), seen in approximately 28% of the cases; and di-tetraploidy. The MYCN oncogene is amplified in approximately 23% of all neuroblastomas and becomes important for the stratification of therapy in localised and 4s tumours. Up to now, it has been believed that the genetic constellation of neuroblastic tumours is stable and does not alter during tumour evolution or during tumour progression. PROCEDURE Using fluorescence in situ hybridisation techniques (FISH) to investigate different tumour areas on touch preparations and histological sections, we show that genetic heterogeneity can be detected in neuroblastomas, especially in tumours detected by urinary mass screening. CONCLUSION The identification of such cell clones is important, because the MYCN amplification and/or the deletion at 1p36 appear to be responsible for aggressive local growth and development of metastases.

Monocyte phagocytosis as a reliable parameter for predicting early-onset sepsis in very low birthweight infants.

BACKGROUND Septic complications lead to a high mortality rate in very low birthweight infants (VLBWI). Therefore, prognostic markers for the development of sepsis attach importance to start an efficient therapy as early as possible. AIMS Functional and phenotypical variables of blood monocytes in the cord and peripheral blood were investigated to evaluate the parameters for predicting early-onset and late-onset sepsis (nosocomial infections). STUDY DESIGN In a prospective study, 25 VLBWI were investigated. METHODS In the cord blood taken immediately after birth, the capacity of the monocytes to phagocytose non-opsonized E. coli bacteria by flow cytometry and the ex-vivo production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 (enzyme-linked immunoassay (ELISA)) after lipopolysaccharide (LPS) stimulation were measured. At the third day, the HLA-DR expression on the monocytes (flow cytometry) and the LPS-induced cytokine production were measured from the peripheral blood. RESULTS Five VLBWI already developed early septic complications after 24-72 h, while the other three infants had late-onset sepsis 10-18 days after birth. The prognostic significance for early-onset sepsis was highest for the decreased monocyte phagocytic capacity (sensitivity and specificity: 100%) and for the LPS-induced formation of TNF-alpha and IL-1 beta in cord blood. Moreover, in septic VLBWI, the HLA-DR expression on the monocytes was lowered on day 3 after birth. The prognostic significance for late-onset sepsis was highest for TNF-alpha and IL-1 beta levels in the peripheral blood on the third day after birth. CONCLUSIONS The determination of phagocytosis in the cord blood seems to be a reliable parameter for predicting early-onset sepsis and offers the possibility for a forward start of an antibiotic therapy.

Perforating appendicitis: An indication for laparoscopy?

AbstractBackground: This pilot study was performed to reassess the widespread postulate that laparoscopic surgery is contraindicated in cases of perforating appendicitis. Methods: A total of 75 children (appendiceal perforation: n= 67; perityphlic abscesses and peritonitis: n= 8) were analyzed in a prospective nonrandomized trial. Ten of them were treated by laparoscopic appendectomy. Results: In the laparoscopy group, both pain and hospitalization were less time-consuming (i.e., by 50% and 19%, respectively). Antibiotics use was down from 2.6 over 6 days to 2.2. over 5.5 days, while the duration of surgery was up by 52%. Wound healing disturbances occurred in 10% (n= 1) and postoperative fever in 50% (n= 5) of patients, compared to 14% (n= 9) and 15% (n= 10) in the group treated by open surgery. All severe complications requiring reintervention (10%; massive subcutaneous abscess, n= 3; retrocolic abscess, n= 2; adhesion-related ileus, n= 3; appendicular stump, n= 1) were associated with open surgery. Conclusions: There was not a single major complication in the laparoscopy group. These unexpected results are in contrast to previous reports and have prompted us to initiate a prospective randomized trial.

Pulmonary echinococcosis (hydatidosis) in children: Results of surgical treatment

From 1986–1996, 33 children with 49 pulmonary hydatid cysts underwent surgical treatment in Vienna and Istanbul. Cysts were unilateral in 28 and bilateral in 5 cases; unruptured cysts (URC) were diagnosed in 19 patients, and 14 children presented with ruptured cysts (RC). Ten patients had cysts in other organs (liver, spleen, central nervous system) in addition to pulmonary cysts. Diagnosis was primarily based on chest X‐ray and computed tomography scan. In Austrian children, a new combination of serological tests was used successfully (71% positive).

Clinical and Immunological Correction of DOCK8 Deficiency by Allogeneic Hematopoietic Stem Cell Transplantation Following a Reduced Toxicity Conditioning Regimen

Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality.

Interleukin 8 correlates with intestinal involvement in surgically treated infants with necrotizing enterocolitis

PURPOSE The aim of this study was to test the predictive value of interleukin (IL) 8 in the assessment of intestinal involvement in necrotizing enterocolitis (NEC). METHODS Forty infants with surgically treated NEC were classified into 3 groups based on intestinal involvement during laparotomy: focal (n = 11), multifocal (n = 16), and panintestinal (n = 13). Preoperatively obtained serum levels of IL-8, C-reactive protein, white blood cell count, and platelet count were correlated with intestinal involvement using logistic regression models. RESULTS Interleukin 8 correlated significantly with intestinal involvement in infants with surgically treated NEC (odds ratio, 1.74; confidence interval, 1.27-2.39; P < .001). An exploratory IL-8 cutoff value of 449 pg/mL provided a specificity of 81.8% and sensitivity of 82.8% to discriminate focal from multifocal and panintestinal disease. An IL-8 cutoff value of 1388 pg/mL provided a specificity of 77.8% and a sensitivity of 76.9% to discriminate panintestinal disease from focal and multifocal disease. CONCLUSIONS To our knowledge, this is the first study to demonstrate a significant correlation of IL-8 with intestinal involvement in advanced NEC in a large patient population. Our results indicate that IL-8 may be a promising biomarker for assessing intestinal involvement in infants with advanced NEC.

First experience with prognostic factors in unselected neuroblastoma patients. The Austrian neuroblastoma 87 study

Between January 1987 and December 1993, 117 patients were registered in the Austrian A-NB87 study. The male/female ratio was 1.18, with 50 patients below the age of 1 year at diagnosis. Patients were assigned to stage according to the result of primary surgery in localised disease. Age, ferritin and neuron specific enolase were used in addition in stage III disease for risk-adapted treatment. Adrenal or pelvic primary tumour sites were mainly associated (81%) with advanced disease. The median observation time of the study is 3.5 years. The overall survival at 3 years was excellent in low stage disease and IVs patients, i.e. 100% for stage I and IIA (20 patients), 92% in stage IVs (13 patients), 81% in stage IIIA (18 patients) and 69% in stage IIB (8 patients). Stage IV (38 patients) showed a survival rate of 51%, whereas stage IIB (10 patients) had the worst outcome in this study, i.e. 20%, due to treatment-related toxicity. Significant unfavourable prognostic factors were neuron specific enolase (NSE) > 100 ng/ml, ferritin > 300 micrograms/ml and amplified MYCN. This study achieved a better survival rate in stage IV patients and a subgroup of stage III in comparison to our previous study (Pädiatrie und Pädologie 1986, 21, 269) and gives the basis to further reduce treatment intensity in low-risk disease based on biological factors. However, prognosis for high-risk cases was still poor in spite of a very aggressive treatment concept.

Tumor disease and associated congenital abnormalities on prenatal MRI.

OBJECTIVE Fetal tumors can have a devastating effect on the fetus, and may occur in association with congenital malformations. In view of the increasing role of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), we sought to demonstrate the visualization of fetal tumors, with regard to congenital abnormalities, on MRI. MATERIALS AND METHODS This retrospective study included 18 fetuses with tumors depicted on fetal MRI after suspicious US findings. An MRI standard protocol was used to diagnose tumors judged as benign or malignant. All organ systems were assessed for tumor-related complications and other congenital malformations. Available US results and histopathology were compared with MRI. RESULTS There were 13/18 (72.2%) benign and 5/18 (27.8%) malignant tumors diagnosed: a cerebral primitive neuroectodermal tumor in 1/18, head-neck teratomas in 4/18; ventricular rhabdomyomas in 4/18; a cardiac teratoma in 1/18; a hepatoblastoma in 1/18; neuroblastomas in 2/18; a cystic hemorrhagic adrenal hyperplasia in 1/18; a pelvic leiomyoma in 1/18; sacrococcygeal teratomas in 3/18. Tumor-related complications were present in 13/18 (72.2%) cases; other congenital abnormalities in 3/18 (16.7%). MRI diagnosis and histology were concordant in 8/11 (72.7%) cases. In 6/12 (50%) cases, US and MRI diagnoses were concordant, and, in 6/12 (50%) cases, additional MRI findings changed the US diagnosis. CONCLUSION Our MRI results demonstrate the visualization of fetal tumors, with frequently encountered tumor-related complications, and other exceptional congenital abnormalities, which may provide important information for perinatal management. Compared to prenatal US, MRI may add important findings in certain cases.