Tobias Renkawitz

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

BackgroundChondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro.MethodsResected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed.ResultsExpression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment.ConclusionsThese findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.

A new short uncemented, proximally fixed anatomic femoral implant with a prominent lateral flare: design rationals and study design of an international clinical trial

BackgroundAnatomic short femoral prostheses with a prominent lateral flare have the potential to reduce stress-shielding in the femur through a more physiological stress distribution to the proximal femur. We present the design rationale of a new short uncemented, proximally fixed anatomic femoral implant and the study design of a prospective multi-centre trial to collect long-term patient outcome and radiographic follow up data.MethodsA prospective surveillance study (trial registry NCT00208555) in four European centres (UK, Italy, Spain and Germany) with a follow up period of 15 years will be executed. The recruitment target is 200 subjects, patients between the ages of 18 and 70 admitted for primary cementless unilateral THA will be included. The primary objective is to evaluate the five-year survivorship of the new cementless short stem. The secondary objectives of this investigation are to evaluate the long term survivorship and the clinical performance of the implant, the impact on the subjects health related Quality of Life and the affect of the prosthesis on bone mineral density. Peri- and postoperative complications will be registered. Clinical and radiographic evaluation of prosthesis positioning will be done post-operatively and at 3, 6, 12, 24, 60, 120 and 180 months follow up.DiscussionShortening of the distal stem can maximise bone and soft tissue conservation. New stem types have been designed to improve the limitations of traditional implants in primary THA. A new, uncemented femoral short stem is introduced in this paper. A long-term follow up study has been designed to verify stable fixation and to research into the clinical outcome. The results of this trial will be presented as soon as they become available.

Measuring leg length and offset with an imageless navigation system during total hip arthroplasty: is it really accurate?

A novel imageless measurement algorithm to assess leg length (LL) and offset (OS) changes during total hip arthroplasty (THA) has been established, the purpose of this study was to describe the process and establish whether or not it is accurate.

Fractured neck of femur--internal fixation versus arthroplasty.

BACKGROUND Surgery is the treatment of choice for fractured neck of femur. For middle-aged patients (aged ca. 40 to 65), there is considerable debate over the indications for arthroplasty or internal fixation. The choice of surgical technique varies widely from one region to another. In this article, we discuss the main criteria that should be used in making this decision. METHODS We selectively reviewed the literature on the diagnosis and treatment of fractured neck of femur, including the current guideline of the German Society for Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie, DGU) and recent findings from the field of health services research. RESULTS The treatment of middle-aged patients with dislocated fractures should be based on rational decision-making. The patients level of activity before the accident should be judged in terms of his or her previous mobility, independence in daily activities, and mental status. Internal fixation is recommended if the fracture can be adequately repositioned, the bone is of good quality, and there is no evidence of osteoarthritis. Fractures that are more than 24 hours old should be treated with total hip arthroplasty. Hemiprostheses are appropriate for very old patients. Physically frail, bedridden, and/or demented patients should undergo internal fixation of the fracture. For non-displaced or impacted fractures, functional treatment (i.e., prophylactic securing of the fracture with screws or nails) is indicated. Rapid diagnosis and a short time in bed before surgery lower the rate of complications. Internal fixation with preservation of the femoral head should ideally be performed within the first 6 hours of trauma, and within the first 24 hours at most. CONCLUSION Despite the increasing scarcity of resources, treatment should still be based on well-founded clinical guidelines. Minimally invasive surgery enables better function in the early postoperative phase and can thereby lower complication rates. An interdisciplinary concept for the postoperative care of elderly patients also has a major effect on the outcome.

Stem torsion in total hip replacement

Background and purpose The clinical results of THR may be improved by correct femoral torsion. We evaluated the stem position by postoperative CT examination in 60 patients. Methods 60 patients requiring total hip arthroplasty were prospectively enrolled in this study. Minimally invasive THR was performed (anterior approach) in a lateral decubitus position and each patient underwent a postoperative CT examination. The position of the stem was evaluated by an independent external institution. Results Stem torsion ranged from –19° retrotorsion to 33° antetorsion. Normal antetorsion (i.e 10–15° according to Tönnis) was present in 5 of 60 patients, so the prevalence of abnormal stem antetorsion was 92% (95% CI: 82–97). We found a stem antetorsion outside the range of 0–25° in 21 of 60 hips. Women had a higher mean stem antetorsion (8.0° (SD 11)) than men (1.5° (SD 10)). Interpretation Postoperative stem antetorsion shows a high variability and is gender-related. We suggest precise assessment of stem antetorsion intraoperatively by means of computer navigation, preparing the femur first. In abnormal stem antetorsion, the cup position can be adjusted using a combined anteversion concept; alternatively, modular femoral components or stems with retroverted or anteverted necks (“retrostem”) could be used.

Computer-assisted total hip arthroplasty: coding the next generation of navigation systems for orthopedic surgery

This article outlines the scientific basis and a state-of-the-art application of computer-assisted orthopedic surgery in total hip arthroplasty (THA) and provides a future perspective on this technology. Computer-assisted orthopedic surgery in primary THA has the potential to couple 3D simulations with real-time evaluations of surgical performance, which has brought these developments from the research laboratory all the way to clinical use. Nonimage- or imageless-based navigation systems without the need for additional pre- or intra-operative image acquisition have stood the test to significantly reduce the variability in positioning the acetabular component and have shown precise measurement of leg length and offset changes during THA. More recently, computer-assisted orthopedic surgery systems have opened a new frontier for accurate surgical practice in minimally invasive, tissue-preserving THA. The future generation of imageless navigation systems will switch from simple measurement tasks to real navigation tools. These software algorithms will consider the cup and stem as components of a coupled biomechanical system, navigating the orthopedic surgeon to find an optimized complementary component orientation rather than target values intraoperatively, and are expected to have a high impact on clinical practice and postoperative functionality in modern THA.

In vitro investigation of the influence of pelvic tilt on acetabular cup alignment.

This study investigates the influence of pelvic tilt on conventional alignment of acetabular cups. Cementless cups were aligned into a synthetic replica of the pelvis 300 times at different pelvic tilts. At +10 degrees pelvic tilt, average cup inclination was 46.2 degrees (32 degrees to 65 degrees ; +/-7.0 degrees ), and average cup anteversion was 19.8 degrees (4 degrees to 37 degrees ; +/-9.1 degrees ). At neutral pelvic tilt, inclination was 44.5 degrees (28 degrees to 59 degrees ; +/-7.2 degrees ), and anteversion was 15.6 degrees (-5 degrees to 33 degrees ; +/-8.1 degrees ). At -10 degrees pelvic tilt, inclination was 42.6 degrees (25 degrees to 61 degrees ; +/-7.2 degrees ), and anteversion was 10.5 degrees (-10 degrees to 37 degrees ; +/-12.2 degrees ). Overall, 50% of the cups were positioned outside the safe zone: 46% in pelvic inclination, 42% in neutral position, and 63% in pelvic reclination (P = .007). This study shows the considerable inaccuracies of conventional cup implantation by experienced and trainee surgeons and shows the influence of pelvic tilt on acetabular cup alignment.

Is the acetabular cup orientation after total hip arthroplasty on a two dimension or three dimension model accurate

PurposeMalposition of the acetabular component in total hip arthroplasty (THA) is a common surgical problem that can lead to hip dislocation, reduced range of motion and may result in early loosening. The aim of this study is to validate the accuracy and reproducibility of a single x-ray image based 2D/3D reconstruction technique in determining cup inclination and anteversion against two different computer tomography (CT)-based measurement techniques.MethodsCup anteversion and inclination of 20 patients after cementless primary THA was measured on standard antero-posterior (AP) radiographs with the help of the single x-ray 2D/3D reconstruction program and compared with two different 3D CT-based analyses [Ground Truth (GT) and MeVis (MV) reconstruction model].ResultsThe measurements from the single x-ray 2D/3D reconstruction technique were strongly correlated with both types of CT image-processing protocols for both cup inclination [R²=0.69 (GT); R²=0.59 (MV)] and anteversion [R²=0.89 (GT); R²=0.80 (MV)].ConclusionsThe single x-ray image based 2D/3D reconstruction technique is a feasible method to assess cup position on postoperative x-rays. CT scans remain the golden standard for a more complex biomechanical evaluation when a lower tolerance limit (+/-2 degrees) is required.

The influence of hip rotation on femoral offset in plain radiographs.

Background and purpose — Adequate restoration of femoral offset (FO) is critical for successful outcome after hip arthroplasty or fixation of hip fracture. Previous studies have identified that hip rotation influences the projected femoral offset (FOP) on plain anteroposterior (AP) radiographs, but the precise effect of rotation is unknown. Patients and methods — We developed a novel method of assessing rotation-corrected femoral offset (FORC), tested its clinical application in 222 AP hip radiographs following proximal femoral nailing, and validated it in 25 cases with corresponding computed tomography (CT) scans. Results — The mean FORC was 57 (29–93) mm, which differed significantly (p < 0.001) from the mean FOP 49 (22–65) mm and from the mean femoral offset determined by the standard method: 49 (23–66) mm. FORC correlated closely with femoral offset assessed by CT (FOCT); the Spearman correlation coefficient was 0.94 (95% CI: 0.88–0.97). The intraclass correlation coefficient for the assessment of FORC by AP hip radiographs correlating the repeated measurements of 1 observer and of 2 independent blinded observers was 1.0 and 1.0, respectively. Interpretation — Hip rotation affects the FOP on plain AP radiographs of the hip in a predictable way and should be adequately accounted for.

Comparison of two accelerated clinical pathways - after total knee replacement how fast can we really go?

Objective: To evaluate whether a further optimization of an existing accelerated clinical pathway protocol after total knee replacement is feasible and improves postoperative outcome. Design: Prospective, parallel group design. Setting: Orthopaedic University Medical Centre. Patients: A total of 143 patients, scheduled for unilateral primary total knee replacement under perioperative regional analgesia. Intervention: Sixty-seven patients received an optimized accelerated clinical pathway including patient-controlled regional analgesia pumps, ultra-early/doubled physiotherapy and motor-driven continuous passive motion machine units. Seventy-six patients received a standard accelerated clinical pathway. Main measures: Feasibility was defined as the proportion of patients successfully completing the assigned pathway. Early postoperative pain on a visual analogue scale, consumption of regional anaesthetics, knee range of motion, time out of bed, non-stop walking distance/stair climbing, circumference measurement and Knee Society Score on the operated leg. Possible discharge according to an own discharge checklist. Results: All patients assigned to both groups successfully completed this pathway. Patients in the optimized pathway showed significant benefits regarding stair climbing/walking distance/time out of bed/circumference measurements of the thigh/Knee Society function score on the fifth postoperative day and stair climbing/ circumference measurements of the thigh on the eighth postoperative day, and reduction of the consumption of regional anaesthetics. No significant reduction in length of stay was observed. Conclusions: Early postoperative functional process indicators tended to be higher within the optimized pathway group, but the main effects flattened over the course of the first eight postoperative days.