Justus Lieber

ESIN in Forearm Fractures

Background and Purpose:Elastic stable intramedullary nailing (ESIN) is well established for stabilizing pediatric forearm fractures. To prevent uncritical use, it is necessary to evaluate the problems and complications of this common technique.Patients and Methods:Four pediatric surgical departments participated in a retrospective study analyzing the last 400 fractures treated with ESIN. Continuous documentation of treatment, postoperative course and follow-up formed the basis of evaluation. In this article forearm fractures (n = 163, 40.7%) are discussed, and epidemiology, indication, fracture types, intraoperative technique, postoperative management and problems, as well as complications and results are compared to those described in the literature.Results:Complete, transverse fractures of the midshaft (73%) were mainly seen. Indication for intervention was an intolerable axial deviation (85.9%). Intraoperative technique (operating and transillumination time, site of approach, material choice) and postoperative management (hospital stay, number of X-ray controls, and follow-up) differed highly depending on the hospital’s circumstances. Postoperatively, 3.0% of patients showed soft-tissue irritation due to sharp nail ends or wound infections. Complications (10.4%) included secondary rupture of a tendon in 3.7%, refracture with nails in situ in 2.5%, axial deviations > 10° or instability of osteosynthesis in 1.8%, delayed healing in 1.2%, migration of nails in 0.6%, and technical failure in 0.6%. Overall, a significant functional restriction (limitation of movement > 10°) was found in three cases only (1.8%) following radial neck fracture.Conclusion:ESIN in pediatric forearm fractures is an often used technique with clear indications and excellent results to be expected. Numerically, complications have not altered considerably, but they rather show a shifting of problems with optimization and refinement of technique and improvement of equipment. Thus, continuous evaluation of technical principles and procedural recommendations constitutes the mainstay in the prevention of problems and complications.

Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma cells†

An increased expression of anti‐apoptotic proteins is regularly found in malignant cells, contributing to their clonal expansion by conferring an improved survival ability. In Hepatoblastoma (HB) apoptosis regulation contributes to resistance and therapy failure, therefore we modulated apoptosis sensitivity of HB cells for an improved cytotoxic activity of commonly used drugs.

The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

BackgroundThe primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts.MethodsViability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).ResultsABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain.ConclusionsOur results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.

The Use of ESIN in Humerus Fractures Shaft Seldom, Subcapital Sometimes, Supracondylar Often

Background:The aim of this study was to collect data of patients treated by elastic stable intramedullary nailing (ESIN), regarding epidemiology, indications, results, and complications.Patients:Altogether, 400 patients with fractures of the humerus, the lower arm, the femur and the lower leg, treated with ESIN, were evaluated. The participating hospitals, each collecting 100 patients, were the Department of Pediatric Surgery, Inselspital of the University of Bern, Switzerland, the Department of Pediatric Surgery, University of Graz, Austria, the Department of Pediatric Surgery, St. Hedwig’s Hospital Regensburg, Germany, and the Department of Pediatric Surgery, Dr. von Hauner’s Children’s Hospital of the University of Munich, Germany. This study concentrates on 123 patients (30.8%) with humeral fractures. Of these, 29 had sustained proximal humeral fractures, 14 shaft fractures, and 80 distal humeral fractures.Results:In most cases good and excellent results with regard to functional and cosmetic outcome were observed. Rare, but typical problems and complications included implant dislocations, secondary axial deformations, and temporary nerve damages.Conclusion:ESIN of the humerus is now the standard operation to treat proximal and shaft fractures in childhood. ESIN of supracondylar fractures has advantages if performed by an expert, though the surgital technique is not simple.

Acute traumatic posterior elbow dislocation in children

Traumatic posterior dislocation of the elbow is often associated with significant morbidity and incomplete recovery. The aim of this study was to retrospectively analyse the outcome of 33 children (median age 10.8 years). Patients underwent reduction and assessment of stability under general anaesthesia. Pure dislocations (n=10) were immobilized, whereas unstable fractures (n=23) were stabilized. Refixation of ligaments was performed if stability was not achieved by fracture stabilization alone. Immobilization was continued for 26 (pure dislocations) or 35 days (associated injuries), respectively. Results were excellent (n=9) or good (n=1) after pure dislocation. Results were excellent (n=15), good (n=7) or poor (n=1) in children with associated injuries. Accurate diagnosis, concentric stable reduction of the elbow as well as stable osteosynthesis of displaced fractures are associated with good results in children with acute posterior elbow dislocations.

Developments in the Treatment of Pediatric Long Bone Shaft Fractures

Shaft fractures of the long bones are among the most common pediatric injuries. They are characterized by a limited potential for spontaneous correction because of the fractures--distance to the physis. Although conservative treatment has been practiced for many years with satisfying results, several aspects have led to an increase in the numbers of surgical procedures including changes of living, sports habits, economics, and patients-request to treatment. We reviewed the literature to describe developments of treatment concepts of pediatric shaft fractures. In shaft fractures of the upper extremities, increasing rates of surgical procedures have been reported preventing functional deficits of forearm prosupination and cosmetic deformities of the humerus. In fractures of the lower extremities maximizing stability shifted into the focus of interest to achieve early mobilization and to compensate heavier body weights of children and adolescents. Consecutively, the current gold standard of pediatric shaft fracture treatment--ESIN (elastic stable intramedullary nailing)--has been modified repeatedly using end caps, prebended nails, and optimized surgical techniques. In addition, new methods such as rigid locking nails and plates have been included in the treatment approaches for femur and tibia shaft fractures. All these methods of pediatric fracture care carry inherent advantages that require consideration for each clinical situation. On the other side, this has enlarged the spectrum of potential complications, which needs continuous evaluation to further improve treatment results.

Elastic Stable Intramedullary Nailing (ESIN) of Pediatric Metacarpal Fractures: Experiences with 66 Cases

INTRODUCTION Elastic stable intramedullary nailing (ESIN) is the first-choice surgical technique for stabilizing various pediatric diaphyseal and selected metaphyseal fractures of the long bones. This technique has increasingly been applied in fractures of the small bones. Here, we report experiences with ESIN in displaced fractures of the metacarpals in children. PATIENTS AND METHODS Retrospective data analysis of metacarpal fractures in children stabilized by ESIN in three pediatric trauma centers between 2003 and 2009. Indication for intervention was total displacement or axial deviation >10 degrees in the frontal plane and/or >30 degrees in the sagittal view. RESULTS A total of 66 cases of metacarpal fractures (51 right hand and 12 left hand) treated by ESIN were found in 63 children (mean age 13.3 years; range 4.0 to 16.1) over the study period. Of these, 55 fractures affected metacarpal 5, 6 fractures affected metacarpal 4, 3 fractures affected metacarpal 1, and 2 fractures occurred at metacarpal 2. Mean operating time was 21 minutes (range 5 to 54), titanium elastic nails were used with a diameter of 1.5 mm (n = 23), 2.0 mm (n = 42), and 2.5 mm (n = 1). Single ESIN implantation was performed in 63 cases; in 3 cases, two nails were implanted. Eleven patients received additional immobilization due to nondisplaced additional fractures of the phalanx (n = 2) or for analgetic treatment (n = 9). Five complications were registered (7.6%). In two cases recurrent fracture dislocation occurred, one of them requiring revision of the osteosynthesis. In other two cases irritation of the extensor tendons occurred, one of them requiring secondary tendon plasty. One persisting cutaneous hyposensibility after ESIN of a metacarpal 5 fracture was reported. All fractures healed uneventfully and metal removal was performed after a mean of 92 days (range 31 to 104). After a mean follow-up of 26 months (range 2 to 74), all patients had full range of movement and cosmetic results were described as good and satisfactory by all patients. CONCLUSION ESIN of the metacarpals is a safe, minimally invasive, and technically easy option in displaced fractures that warrant surgical intervention achieving excellent long-term results. Complications occurred when technical aspects to obtain stability were neglected or tendons and nerves of the hand had been injured. Stabilizing fractures of metacarpal 1 is technically challenging when compared with fractures of metacarpals 2 to 5.

Treatment of benign bone defects in children with silicate-substituted calcium phosphate (SiCaP).

BACKGROUND In children with benign bone defects, various treatment options are recommended. Whether these defects should be curetted, osteosynthetically stabilized and/or filled with allogenic or synthetic bone material is still a matter of controversy. METHODS The reported study presents preliminary results of five children with benign bone lesions of the lower extremity. Curettage and filling of the defect with a commercially available silicate-substituted calcium phosphate (SiCaP) (Actifuse® by ApaTech Ltd., Elstree, United Kingdom) was performed. Patients were followed-up in the outpatient clinic. The healing process was assessed according to the clinical and radiological criteria. RESULTS Clinical and radiological follow-up showed uneventful healing without intraoperative and short-term complications. All patients were capable of full weight bearing after a few weeks and currently did not experience any decreased range of movement among adjacent joints. Growth disturbances did not occur. In all patients increasing cancellous bone reconstruction of the defect, without signs of osteolysis could be shown radiologically. CONCLUSION SiCaP represents a good and safe alternative to hitherto existing therapies in the management of defined symptomatic benign bone defects in the pediatric age group.

ESIN in Femur Fractures: Exact Technique Is Important!

Background and Purpose:Elastic stable intramedullary nailing (ESIN) is gaining increasing popularity, but studies with high case loads are rare. It was the aim of four experienced pediatric trauma centers to give an update of indications for ESIN, postoperative management, and complications.Patients and Methods:Data of the last 100 ESIN cases of each department before June 30, 2003 were collected by reviewing the charts and X-rays. Among these 400 collected ESINs 65 femoral shaft fractures (16%) were found. The patients’ age ranged between 23/4 and 151/4 years. The middle third of the shaft was affected 42 times (65%), 13 fractures (20%) were in the proximal third of the diaphysis, and ten (15%) in the distal part of the femur, five dia- and five metaphyseal. Mainly transverse fractures were treated (52%), followed by 38% oblique or spiral fractures and 10% wedge or comminuted fractures. Two open reductions were required. Median hospitalization time was 6 days. Nails were extracted after a mean of 178 days.Results:Six skin irritations (wound infections, hematoma, seroma), one patient with myositis ossificans and one with constant pain at too long nail end were found. Three cosmetically relevant scarrings were observed during follow-up. Relevant axial deviations at fracture healing in two and shortening in one fracture could be seen, all caused by technical failure.Conclusion:ESIN meets all demands for an optimal fracture healing in children. Still, a considerable percentage of complications is observed, mainly caused by the surgeon himself, which can be avoided by exact indication and technique. Postoperative management has yet to be standardized.

Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737.

The response of standard-risk hepatoblastoma (HB) to neoadjuvant cisplatin (CDDP) chemotherapy is excellent; however, in high-risk HB, drug resistance remains a major challenge. Alternative therapeutic strategies may consider combining cytotoxic drugs with apoptosis sensitizers as this has shown additive effects in various types of malignancies. Analysis of published expression databases have revealed an anti-apoptosis state in HB samples. Herein, we evaluated the synergistic effects of ABT-737 as a modulator of apoptosis in combination with CDDP in HB. To this end, clonogenic assays were performed with HepT1 and HUH6 HB cells to evaluate the synergistic effects of CDDP and ABT-737. Combination treatment with CDDP and ABT-737 reduced the clonogenicity of HB cells more than 5-fold compared to treatment with CDDP alone. Furthermore, the HUH6 mixed-type HB cells showed higher sensitivity to CDDP and combination treatment compared to the HepT1 embryonal-type cells. Subcutaneous HUH6 tumors in NOD/LtSz-scid IL2Rγnull mice were treated with CDDP (1.25 and 3 mg/kg body weight, n=6), ABT-737 (100 mg/kg, n=5) and the combination of both agents (n=5). Combined treatment led to a significantly reduced tumor growth compared to CDDP treatment alone (p<0.02). When using higher doses of CDDP (3 mg/kg) alone or in combination with ABT-737, dose-dependent toxicity was observed in this mouse strain. In conclusion, our results demonstrated the enhancement of chemotherapy efficacy by using modulators of apoptosis together with cytotoxic agents. Additive effects of ABT-737 may allow reduction in CDDP dosages with maintenance of antitumor activity. Sensitizing HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.