Cytokine Signaling in Pediatric Kidney Tumor Cell Lines WT-CLS1, WT-3ab and G-401.

Renal tumors comprise ~7% of all malignant pediatric tumors. Approximately 90% of pediatric kidney tumors comprise Wilms tumors, and the remaining 10% include clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, renal cell carcinoma and other rare renal tumors. Over the last 30 years, the role of cytokines and their receptors has been considerably investigated in both cancer progression and anti-cancer therapy. However, more effective immunotherapies require the cytokine profiling of each tumor type and comprehensive understanding of tumor biology. In this study, we aimed to investigate the activation of signaling pathways in response to cytokines in three pediatric kidney tumor cell lines, in WT-CLS1 and WT-3ab cells (both are Wilms tumors), and in G-401 cells (a rhabdoid kidney tumor, formerly classified as Wilms tumor). We observed that interferon-alpha (IFN-α) and interferon-gamma (IFN-γ) very strongly induced the activation of the STAT1 protein, whereas IL-6 and IFN-α activated STAT3 and IL-4 activated STAT6 in all examined tumor cell lines. STAT protein activation was examined by flow cytometry and Western blot using phospho-specific anti-STAT antibodies which recognize only activated (phosphorylated) STAT proteins. Nuclear translocation of phospho-STAT proteins upon activation with specific cytokines was furthermore confirmed by immunofluorescence. Our results also showed that both IFN-α and IFN-γ caused upregulation of major histocompatibility complex (MHC) class I proteins, however, these cytokines did not have any effect on the expression of MHC class II proteins. We also observed that pediatric kidney tumor cell lines exhibit the functional expression of an additional cytokine signaling pathway, the tumor necrosis factor (TNF)-α-mediated activation of nuclear factor kappa B (NF-κB). In summary, our data show that human pediatric renal tumor cell lines are responsive to stimulation with various human cytokines and could be used as in vitro models for profiling cytokine signaling pathways.

The Alexis Laparoscopic System as Minimally Invasive Surgical Technique in Operative Management of Huge Cystic Ovarian Tumors in Children and Young Adolescents: A Case Report.

BACKGROUND: The use of the Alexis wound protector-retractor (AWPR) could further improve the laparoscopic techniques for safely removing huge ovarian tumors in children. CASE: A 15-year-old patient presented to our emergency department with a history of weeks of persistent abdominal pain. Clinical examination and magnetic resonance imaging demonstrated a 25 × 21 × 21 cm cystic mass arising from the left ovary. An en block unilateral oophorectomy and salpingectomy with the use of a medium-sized AWPR was performed without complications. The patient was discharged on the second postoperative day. CONCLUSION: The AWPR is a safe and effective tool in treating such children and adolescents with huge ovarian tumors, preserving fertility, minimizing the postoperative pain and hospital stay, and providing an excellent cosmetic outcome.

Nonsurgical Treatment of Chest Wall Deformities: Contradiction or Complement?

For decades, open surgical repair was the only available method to treat congenital and acquired chest wall deformities (CWDs). In 1998, D. Nuss described a minimally invasive procedure for surgical repair of pectus excavatum (PE), and a few years later H. Abramson reported on his experience with the "reversed Nuss technique" for surgical repair of pectus carinatum (PC). Both procedures are performed with increasing frequency worldwide.However, nonsurgical measures such as vacuum bell (VB) therapy for conservative treatment of PE and more differentiated bracing systems for conservative treatment of PC were established 15 to 20 years ago. Nowadays, information on new therapeutic modalities circulates not only among surgeons and pediatricians, but also rapidly among patients. In particular, patients who refused operative treatment by previously available procedures now appear at the outpatient clinic and request to be considered for the new methods.Analyzing the increasing number of studies reporting on conservative treatment of CWDs as well as our own group of patients who visited a busy outpatient clinic in a small country within the last 15 to 20 years, we have to realize that the majority of patients asked for nonsurgical treatment of their CWD. Based on these experiences and results, we have to realize that nonsurgical treatment of CWD is no contradiction but a helpful complement to treat congenital and acquired CWDs and may be applied for the majority of patients suffering from a CWD.

Dynamic Compression System: An Effective Nonoperative Treatment for Pectus Carinatum: A Single Center Experience in Basel, Switzerland.

Background Several nonoperative treatments are currently available for the correction of pectus carinatum (PC). Objective The objective of this study is to report our single center experience with the dynamic compression system (DCS). Materials and Methods The DCS is a rigid aluminum brace. PC is reshaped into a normal appearance through anterior-posterior pressure and lateral expansion of the chest. Patients with chondrogladiolar PC were considered suitable for the nonoperative treatment with DCS. Results In this study, 53 of 68 children (78%) with chondrogladiolar PC were assessed retrospectively: 2 children were corrected by surgery, 12/53 (23%) treated by a conventional orthesis, 11/53 (21%) remained without therapy because of minor PC, and 36/53 (68%) were treated using the DCS. Of these 36 patients, 17 (47%) are already cured with a good (7/17) to excellent (10/17) cosmetic result after a median treatment period of 9 months (range, 2.5-16 months). The mean daily time of wearing of the device for those 17 patients was 9 hours (range, 5-18). None abandoned the treatment and there were almost no complications. Conclusions Lateral expansion of the chest and the possibility to measure the applied pressure seemed to be the key to DCSs success. We propose the DCS as first choice in the treatment of chondrogladiolar PC in children.

Influence of Immobilization Time on Functional Outcome in Radial Neck Fractures in Children.

Background Radial neck fractures represent 20 to 30% of elbow fractures in children. Incorrect treatment can lead to significant permanent functional impairment. Posttraumatic avascular necrosis may cause a deformity of the radial head and neck. Deformation of the radial head and neck can be more severe after open rather than closed reduction or orthopedic treatment without reduction. The aim of our study was to analyze the influence of immobilization time on functional outcome. Patients and Methods Retrospective, descriptive study of all children who had been treated for a radial neck fracture between 1999 and 2013 at the University Children's Hospital Basel. Patients were allocated to two groups (group 1: patients treated between 1999 and 2008, group 2: patients treated between 2009 and 2013). The fractures were classified according to the classification of Metaizeau. The primary endpoint was the percentage of patients who reached the full range of elbow motion at the end of the treatment period or the last follow-up. Secondary endpoints were immobilization time and number of patients with persistent physical restrictions of the elbow range of motion as well as the type of restrictions and subjective complaints. Results A total of 67 patients treated for radial neck fracture were included in the first group (1999-2008). A total of 47 patients were allocated to the second group (2009-2013). Overall, 59 patients in group 1 and 39 patients in group 2 were treated nonoperatively. Average immobilization time was 22.7 days (range, 6-60 days) in group 1 and 13.2 days (range, 0-27 days) in group 2. Full range of motion was observed in 50 to 72.7% of patients in group 1 and in 71.4 to 92% of patients in group 2, depending on the grade of fracture displacement. Overall, 21 patients (31%) of group 1 showed a persistent functional restriction. In group 2, only six patients (12%) suffered from a persistent functional restriction of the elbow range of motion. Conclusion Aside from the severity of fracture displacement and treatment modality (conservative vs. operative, closed vs. open reduction), the duration of immobilization may also influence the functional outcome. Further prospective studies are required to confirm our results.

Laparoscopy-Assisted Single-Port Appendectomy in Children: Safe Alternative also for Perforated Appendicitis?

Because of its low complication rate, favorable safety, cost-effectiveness, and technical ease, mono-instrumental, laparoscopy-assisted single-port appendectomy (SPA) has been the standard therapy for appendicitis in our department since its introduction 10 years ago. We report our experience with this technique and compare its outcome to open appendectomy (OA). The records of all children who underwent appendectomy at our institution over a period of 8 years were analyzed retrospectively. Patient baseline data, markers of inflammation, operative time, length of hospital stay, complication rate according to the classification of Clavien-Dindo, and histologic grading were assessed to compare the 2 surgical techniques (SPA and OA). The chi square test, the Student's t test and the Wilcoxon-Mann-Whitney test were used to analyze the data and the comparisons of the mean values. A P value < 0.05 was considered significant. Overall, 975 patients were included in the study. A total of 555 children had undergone SPA and 420 had been treated by OA. Median operative time of SPA was longer than that of OA (60.8  min vs 57.4  min; P < 0.05). Length of hospital stay after SPA was shorter than after OA (4.4 days and 5.9 days, respectively; P < 0.001). The overall complication rate was lower for SPA than that for OA (4.0% vs 5.7%), but the difference of complications for SPA and OA was not statistically significant (P < 0.22). SPA was successfully performed in 85.9% of children. In 53.8% of patients with perforated appendicitis, no conversion was required. In the group of children with perforated appendicitis, the complication rate of ∼20% was independent of the surgical technique applied. With respect to operative time, length of hospital stay, and postoperative complication rate, SPA is not inferior to OA. SPA is safe and efficient, even in the management of perforated appendicitis.

Prospective study on central venous line associated bloodstream infections.

OBJECTIVE: To prospectively assess the incidence rates and characteristics of central venous line associated bloodstream infections (CLABSI) in one institution. METHODS: All patients with indwelling central venous catheters (CVC) between 1 April 2008 and 31 March 2009 were enrolled. The medical records of patients were reviewed and information on relevant characteristics entered into a standardised questionnaire. Central laboratory records were regularly checked for positive blood cultures in study patients. RESULTS: There were 209 CVC for a total of 14752 CVC days in 152 patients (88 males, 58%) including neonates and patients with surgical conditions and haemato-oncological and other underlying diseases. Median age at CVC insertion was 3 months (IQR 0-56 months). Fourteen CLABSI occurred in 13 patients. Overall CLABSI incidence (per 1000 CVC days) was 0.95 (9.71 for silastic percutaneous CVC, 7.65 for other CVC, 1.97 for Broviac, 0.18 for Port-a-cath). CVC remained in place for ≤ 14 days in 109 (52%) instances, 15-90 days in 45 (22%) instances and > 90 days in 55 (26%) instances. The incidence of CLABSI in these three categories was 3.36, 4.36 and 0.47, respectively. Predominating cultured organisms were coagulase-negative staphylococci (N=3), S. aureus (N=3), and Enterococcus spp. (N=3). CONCLUSIONS: CLABSI incidence varied by type of catheter and type of patient, with the highest risk in neonates (with silastic percutaneous CVC) and by far the lowest risk for Port-a-cath CVC. Prophylactic measures to reduce CLABSI should be tailored to individual types of catheters and patient characteristics.