Knock-down of oncohistone H3F3A-G34W counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells.

Giant cell tumors of bone (GCTB) are semi-malignant tumors associated with extensive osteolytic defects and massive bone destructions. They display a locally aggressive behavior and a very high recurrence rate. Recently, a single mutation has been identified in GCTB affecting the H3F3A gene coding for the histone variant H3.3 (H3.3-G34W). The aim of this study was to investigate whether H3.3-G34W is sufficient to drive tumorigenesis in GCTB. Initially, we confirmed the high frequency of this mutation in 94% of 84 analyzed tissue samples. Using a siRNA based approach we could selectively knockdown H3.3-G34W in primary neoplastic stromal cells isolated from tumor tissue (GCTSC). H3.3-G34W knockdown caused a significant inhibition of cell proliferation, migration and colony formation capacity in vitro. Xenotransplantation of GCTSCs onto the chorioallantoic membrane of fertilized chicken eggs further demonstrated a significant impact of H3.3-G34W knockdown on tumor engraftment and growth in vivo. Our data indicate that H3.3-G34W is sufficient to drive tumorigenesis in GCTB. Apart from the application of H3.3-G34W screening as diagnostic tool, our data suggest that H3.3-G4W represents a promising target for the development of new GCTB therapies.

Radiation Dose Reduction in Digital Plain Radiography of the Knee after Total Knee Arthroplasty.

PURPOSE: To reduce radiation exposure of frequently performed radiographs of the knee in follow-up of total-knee arthroplasty ensuring accurate assessment by using objective quality control criteria. MATERIALS AND METHODS: In this prospective randomized study 278 radiographs of the knee in follow-up of total-knee arthroplasty were performed with standard and 37% reduced radiation dose. The evaluation of the plain-radiographs was conducted using the following criteria: bone-implant interface, implant-surface character, implant-implant discrimination and periarticular heterotopic ossification. Two radiologists evaluated these criteria using a score ranging from 1 (definitely assessable) to 4 (not assessable). If a single criterion had been evaluated with a score ≥ 3 or more than 2 criteria with ≥ 2 points, the radiograph was score das "not assessable". The study was designed as non-inferiority-trial. RESULTS: 100% of examined radiographs were scored as assessable, hence no statistical inferiority between the examinations with standard and reduced dose could be observed. Singular assessment of the defined criteria was likewise dose-independent. CONCLUSION: Plain-radiography of the knee following total-knee arthroplasty can be performed with 63% of standard dose without loss of diagnostic validity. KEY POINTS: Due to the non-inferiority of digital radiographs of the knee joint after total-knee arthroplasty done with 37% reduced image receiver dose we recommend the tested speed class of SC 800 as a new reference value for digital radiographs with this indication.

Distal Rectus Femoris Tendon Transfer for the Correction of Stiff-Knee Gait in Cerebral Palsy.

INTRODUCTION: Distal rectus femoris tendon transfer is the standard surgical procedure for the treatment of stiff-knee gait in patients with cerebral palsy and is commonly performed during single-event multilevel surgery. STEP 1 POSITIONING AND APPROACH: With the patient supine, make a 3 to 4-cm longitudinal incision 2 to 3 cm above the patellar proximal pole. STEP 2 PREPARATION OF THE RECTUS FEMORIS TENDON: Separate the rectus femoris tendon from the vasti; avoid releasing the entire quadriceps at all cost. STEP 3 PREPARATION OF THE GRACILIS OR SEMITENDINOSUS TENDON FOR TRANSFER: Isolate the gracilis tendon proximally, release it from its muscle belly, and pull it out distally through a small incision at the pes anserinus insertion. STEP 4 TRANSFERRING THE GRACILIS TENDON TO THE RECTUS FEMORIS TENDON: Insert a long tendon passer above the fascia and beneath the sartorius muscle belly from anterior to posterior to the mini-incision in the pes anserinus region to grasp and transfer the gracilis tendon to the anterior approach. STEP 5 TENDON TENSIONING AND SUTURING: Weave the gracilis tendon into the released rectus femoris tendon with the interlacing technique described by Pulvertaft. RESULTS: Various studies have demonstrated good initial results, with an improvement in peak knee flexion in swing phase and knee motion in swing phase, following distal rectus femoris tendon transfer. WHAT TO WATCH FOR: IndicationsContraindicationsPitfalls & Challenges.

Pigmented villo-nodular synovitis and giant-cell tumor of tendon sheaths: a binational retrospective study.

AIM: Pigmented villonodular synovitis is rare. Thus, we initiated a retrospective multi-center study regarding symptoms, location, type of disease, type of surgery, number of recurrences, use of adjuvant therapies and functional outcome. RESULTS: Ten centers contributed. Data from 173 patients were sampled. The disease was seen predominantly in joints, less frequently in tendon sheaths and bursae. Patients with articular lesions suffered mainly from the diffuse type. In tendon sheaths, the relation "diffuse versus nodular" was nearly 50 % each, in bursae most often the nodular type was found. Anatomically, mostly the knee was affected. Institutions with more than 20 patients had a lower rate of recurrence than those with less than 20 cases. Regarding the knee, there were less recurrences in joints treated with open synovectomy than in those treated arthroscopically. CONCLUSIONS: Since the rate of recurrence has been rather high, the use of adjuvant treatments (radiosynoviorthesis or radiotherapy) is recommended. In our study, the rate of their application was quite low. Patients who received an adjuvant therapy after primary surgery did not show any recurrence. In 14 % of patients in whom an adjuvant therapy had been used, after at least one recurrence, further recurrences were observed. Functional results were excellent in 84 % of patients. LEVEL OF EVIDENCE: Prognostic multi-center study, Level III.

CT-guided percutaneous radiofrequency ablation in osteoid osteoma: re-assessments of results with optimized technique and possible pain patterns in mid-term follow-up.

PURPOSE: To re-assess radiofrequency ablation (RFA) of osteoid osteoma (OO) with an optimized technique and to evaluate patterns of post-interventional pain important for the detection of recurrence. MATERIALS AND METHODS: 44 consecutive patients with OO treated with precise inclusion criteria by RFA were examined retrospectively. RFA was performed with an optimized technique. Technical success (TS), primary and secondary clinical success (PCS/SCS) and minor and major complications (MIC/MAC) were evaluated. Pain patterns defined as "osteoid osteoma-specific pain" (OOSP) and "unspecific pain" (UP), "limitations in daily activity" (LDA) and "patient satisfaction" (PS) were evaluated using a numeric rating scale (0 - 10; 0 = no pain, 0 = no limitation, 10 = fully satisfied). The pain intensity before and after RFA was compared. The mean follow-up time was 35 months (n = 40, range 2 - 60 months). RESULTS: TS was 100 % (n = 44), PCS 98 % (n = 44), and SCS 100 % (n = 40). MIC and MAC were 0 % (n = 44). OOSP was 0 after RFA in all 44 patients. UP was 0 in 24 of 40 patients (60 %), 1 in 11 patients (28 %) for up to 7 days and 1 - 4 in 5 patients (13 %) for 30 - 180 days. LDA was 0 in 39 of 40 patients (98 %), and 1 in 1 patient. PS was 10 in all patients. The pain after RFA was significantly less than before RFA (p < 0.0001). CONCLUSION: Using an optimized technique primary clinical success rates in the high nineties have to be expected. Unspecific pain of low intensity is not unusual after RFA and has to be distinguished from pain caused by recurrent disease.

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

BACKGROUND: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. PATIENTS AND METHODS: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. RESULTS: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. CONCLUSIONS: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Medium to long-term results after reconstruction of bone defects at the knee with tumor endoprostheses.

BACKGROUND AND OBJECTIVES: Limb salvage and reconstruction with tumor endoprostheses is considered as therapeutic standard in the treatment of bone defects at the knee. Few studies report long-term results so far. METHODS: Seventy-seven patients who had a cementless or cemented MUTARS endoprosthesis implanted were followed-up for a mean period of 46 months (3-128 months). The defects were due to primary tumor lesions in 69 cases or metastases in 8 cases. The distal femur (n = 49) or the proximal tibia (n = 28) was reconstructed predominantly with cementless implants (femur: 69%, tibia: 92%). The resection of the tumor was intraarticular in 46 and extraarticular in 31 patients. RESULTS: After 10 years probability of limb salvage was 92% with a recurrence rate of 3%. Complications were frequent with a revision rate of 58% and lead to a cumulative probability of survival of the initially implanted prosthesis of 57% after 5 years. Locking mechanism failure (n = 15) and aseptic loosening (n = 13) were the most frequent failure modes. CONCLUSIONS: Regardless of achieving a low recurrence rate and satisfactory functional results, we found a high complication rate after implantation of a megaprosthesis. This was particularly evident for extraarticular resections and cemented fixation, which should be avoided when possible.

[Development of orthopedics over the next 20 years]. / Entwicklung der Orthopädie in den nächsten 20 Jahren.

The combination of orthopedic and traumatology surgery in one specialization allows the coexistence of specialized surgical subgroups. The long term morbidity forecast predicts an increased demand for orthopedic procedures for the next 20 years. The excellent training level must be maintained for the following generation of orthopedic and trauma surgeons. Besides the physicians, health care providers and hospitals as well as politics should help in mastering this difficult challenge. Orthopedic surgery and traumatology with a multitude of subspecialties remain an attractive specialty with a promising future.

[Current short- and long-term results of lumbar disc replacement : update 2008]. / Lumbale Bandscheibenendoprothetik - Update 2008 : Metaanalyse der Kurz- und Langzeitergebnisse.

Lumbar total disc replacement is an increasingly common way of treating degenerative lumbar disc disease while preserving mobility. The aim of this analysis was to survey evidence-based data to classify the procedure. Based on a MEDLINE inquiry, 38 clinical trials dealing with lumbar total disc replacement were selected and analyzed by the criteria of indication, preoperative procedure, and clinical follow-up. These data represent 3,180 patient-related evaluations with follow-up of 5.9 to 204 months. We also included ten retrospective studies. Patient satisfaction was a mean of 90.73%, and the Oswestry Disability Index and Visual Analog Scale were significantly lower. High rates of revision surgery, explantation surgery, and secondary fusions are linked to wrong preoperative indication. According to evidence criteria, the results show that lumbar total disc replacement is a safe procedure with a high rate of success. There is clear evidence that both imprecise indication and the choice of too-small implants significantly reduce the prospect of surgical success and increase the rates of reintervention.

[Experience in orthopaedic surgery with minimum provider volumes]. / Erfahrungen mit Mindestmengen in der Orthopädie.

The implementation of minimum provider volumes in orthopaedic surgery appears to be logically evident. A general volume outcome relationship could be found for total knee and hip replacement on a high level of evidence, but no definite threshold value could be identified. For other orthopaedic procedures the evaluated data hint at a volume outcome relationship but do not prove one. Preliminary model calculations on the effects of a regulation based on volume outcome considerations concerning medical care in Germany show that, though for total hip and knee replacement quite a large number of hospitals would be excluded from medical care, the number of patients to be reallocated would be small. Since 1 January 2007 a minimum provider volume of 50 total knee replacements per year per hospital has been mandatory in Germany. The further application of a minimum requirement regulation based on volume outcome considerations in the German health care system must be performed very carefully, because significant effects are to be expected.

[The cemented MS-30 stem. A multi-surgeon series of 333 consecutive cases]. / Der zementierte MS-30-Schaft : Ergebnisse einer Multi-surgeon-Serie von 333 konsekutiven Fällen.

INTRODUCTION: So far there is only one peer-reviewed long-term publication from the inventors' clinic for the MS-30 stem. MATERIAL AND METHODS: In a retrospective study we followed the first 333 consecutive MS-30 stems. All patients with 5- to 11-year follow-up were clinically and radiographically evaluated. At the time of implantation the criteria of modern cementing techniques were not implemented. Clinical evaluation was done using the scores of Harris and Merle d'Aubigné and Postel. Radiographic evaluation included quality of the cement mantle (true lateral radiographs taken under fluoroscopy), stem subsidence, loosening signs, and the risk for pending failure. RESULTS: At follow-up 12 hips had undergone femoral revision: 3 for aseptic loosening, 6 for infection, 1 for periprosthetic fracture, and 2 for recurrent dislocation. The overall survival for all reasons at 10 years was 96.1%; survival with aseptic loosening as an end point was 99.0%. The median Harris Hip Score at follow-up was 80 (26-100) points. Radiological evaluation revealed a thin cement mantle (<2 mm) in approximately 2/3, predominantly on the lateral views (Gruen zones 8/9). One-third of all reviewed prostheses were considered at risk for pending failure, which strongly correlated with the initial quality of the cement mantle. CONCLUSION: Midterm results with the MS-30 stem are encouraging and an even better long-term outcome can be expected with a better cement technique.

A novel model for the investigation of orthotopically growing primary and secondary bone tumours using intravital microscopy.

Here is reported the development of an experimental model using intravital microscopy as a tool to orthotopically investigate malignant bone tumours. Although up to 85% of the most frequently occurring malignant solid tumours, such as lung and prostate carcinomas, metastasize into the bone, and despite the knowledge that a tumour's course may be altered by its surrounding tissue, there is no adequate experimental model available enabling the investigation of orthotopically grown bone tumours in vivo. Intravital microscopy is an internationally accepted experimental method, used in various acute and chronic animal models, that enables qualitative and quantitative analysis of the angiogenesis, microcirculation, growth behaviour, etc. of various benign and malignant tissues. Non-invasive investigations of up to several weeks are possible. Additionally, tissue samples can be taken after termination of the in vivo experiments for further ex vivo investigation (histology, immunohistochemistry, molecular biology, etc.), elucidating the mechanisms that underlie the in vivo observations. Severe combined immunodeficient mice were fitted with a cranial window preparation where the calvaria served as the site for orthotopic implantation of the solid human tumours Saos-2 osteosarcoma (primary) and A 549 lung carcinoma and PC-3 prostate carcinoma (secondary). In all preparations, the take rate was 100%. Histological assessment confirmed the data obtained in vivo, showing typical tumour growth with infiltration of the surrounding osseous and soft tissues. This novel model serves as a valuable tool in understanding the biology of primary and secondary bone tumours in physiological and pathophysiological situations, with implications for the most areas of tumour therapy such as chemotherapy, radiation and antiangiogenesis.

Equal quality of life after limb-sparing or ablative surgery for lower extremity sarcomas.

This study investigated quality of life (QoL) and function of 124 patients with lower extremity sarcoma who underwent either amputation or limb-salvage surgery (LSS) in order to assess potential differences in subjective treatment outcome. The results reflect similar QoL in both treatment groups. However, in contrast to patients with LSS, who described QoL in terms of a high physical performance status with sports and recreational activities, amputees' QoL was strongly associated with their social acceptability. High QoL in amputees brings into question the expectations held with time-consuming advanced technical skills for LSS by physicians.