Functional outcome and quality of life following resection of the proximal humerus performed for musculoskeletal tumors and reconstruction done by four different methods.

INTRODUCTION: The proximal humerus is a frequent site for both primary and secondary bone tumors. Several options are currently available to reconstruct the resected humerus, but there is no consensus regarding optimal reconstruction. The aim of this retrospective study was to compare the functional outcome, complications and patient compliance following four different types of reconstructive techniques. MATERIAL AND METHODS: The authors performed 90 proximal humerus resections due to primary and secondary bone tumors over the past 21 years. Four different procedures were performed for reconstruction following the resection: fibula autograft transplantation, osteoarticular allograft implantation, modular tumor endoprosthesis (hemiarthroplasty) and reconstruction of the defect with a reverse shoulder prosthesis-allograft composite. A retrospective analysis of the complications and patient's physical status was performed. Functional outcome and life quality was evaluated by using the MSTS and SF-36 scores. RESULTS: The best range of motion was observed following arthroplasty with a reverse shoulder prosthesis-homograft composite followed by a fibula autograft reconstruction. Revision surgery was required due to major complications most frequently in the osteoarticular allograft group, followed by the reverse shoulder prosthesis-allograft composite group, the autologous fibula transplantation group; the tumor endoprosthesis hemiarthroplasty group had superior results regarding revision surgery (40, 25, 24 and 14% respectively). MSTS was 84% on average for the reverse shoulder prosthesis-allograft composite group, 70% for the autologous fibula group, 67% for the anatomical hemiarthroplasty group and 64% for the osteoartricular allograft group. Using the SF-36 questionnaire for assessment no significant differences were found between the four groups regarding quality of life. DISCUSSION: Based on the results of our study the best functional performance (range of motion and patient compliance) was achieved in the a reverse prosthesis-allograft combination group-in cases where the axillary nerve could be spared. The use of an osteoarticular allograft resulted in unsatisfying functional results and high complication rates, therefore we do not recommend it as a reconstructive method following resection of the proximal humerus due to either primary or metastatic bone tumors. Young patients who have good life expectancy but a small humerus or intramedullar cavity reconstruction by implantation of a fibula autograft is a good option. For patients with a poor prognosis (i.g. bone metastases) or in cases where the axillary nerve must be sacrificed, hemiarthroplasty using a tumor endoprosthesis was found to have acceptable results with a low complication rate. According to the MSTS and SF-36 functional scoring systems patients compliance was nearly identical following all four types of reconstruction techniques; the underlying cause may be the complexity of the shoulder girdle. However, we recommend the implantation of a reverse shoulder prosthesis-allograft whenever indication is appropriate, as it has been demonstrated to provide excellent functional outcomes, especially in young adults.

Comorbidity clusters in generalized osteoarthritis among female patients: A cross-sectional study.

OBJECTIVES: To investigate the prevalence of comorbidities among female patients with generalized osteoarthritis (GOA) in comparison to an age- and sex matched control group. To identify clusters of comorbidities in both groups. METHODS: An observational, cross-sectional study was conducted. Consecutive female patients with hand and knee osteoarthritis according to the American College of Rheumatology (ACR) classification criteria were invited to participate in the study. A control group of participants without musculoskeletal symptoms, history or evidence of osteoarthritis or inflammatory rheumatic disease were also included. Cardiovascular, obstructive pulmonary, gastrointestinal, endocrine, neurological, malignant diseases and depression were recorded in both groups. In both study groups comorbidity cluster and factor analysis was performed. RESULTS: The study population included 200 GOA and 200 control participants. The following comorbidities were observed adjusted to Bonferroni correction with a significantly higher prevalence among individuals with GOA: hypertension, uterine leiomyoma, gastroesophageal reflux disease, diverticulosis, upper gastrointestinal tract ulcers, depression, diseases with vertigo (benign paroxysmal positional vertigo and vertebrobasilar insufficiency) and surgery due to otoclerosis. In the GOA group 5 clusters were identified with different comorbidity patterns. CONCLUSION: We report a high comorbidity rate in GOA. Cluster analysis allowed us to identify different comorbidity subsets for vascular, gastrointestinal and malignant gynaecological disorders. Further research is required to understand the links between GOA and non-musculoskeletal comorbidities.

On the presence of a metalloprotease in human skin fibroblasts that degrades the human skin elastic fiber system.

Succinyl-trialanine paranitroanilide, a specific synthetic substrate of elastases, was shown to be hydrolyzed by Triton X-100 extracts of human skin fibroblasts at near neutral pH. The neutral endopeptidase has been partially purified by ion exchange chromatography (DEAE Sephadex) and affinity chromatography using an AH-Sepharose (Ala)3 column. The enzyme has been purified 85-fold and appears to be a metalloprotease as shown by its inhibitory profile. In its partially purified form, the neutral endopeptidase was found inactive toward benzoyl arginine paranitroanilide, benzoyl tyrosine paranitroanilide, azocasein, type I collagen, and [3H]ligamentum nuchae-insoluble elastin. Structural glycoprotein microfibrils isolated from porcine aorta are extensively degraded by this neutral protease. It could also hydrolyze, but to a lesser extent, insoluble elastin purified from human aortas; it was, however, found inactive toward bovine ligamentum nuchae elastin. Its potentiality to degrade the human skin elastic fiber system (namely elastic fibers, oxytalan, and elaunin fibers) has been assessed by a morphometric analysis of the length of these fibers (on tissue sections appropriately stained to identify the components of the elastic fiber system) prior to and after enzyme action. Analysis of the data obtained by morphometry indicated that this neutral protease attacked rapidly both elaunin and oxytalan fibers of human dermis, but only slowly the mature elastic fibers.

Osteosarcoma over the age of forty.

The European Musculo Skeletal Oncology Society (EMSOS) has carried out a retrospective review of patients over the age of 40 years with osteosarcoma. 481 patients from 12 centres or multicentric groups were included. 42 patients had osteosarcoma arising in Paget's disease, median survival was 9 months. Patients with axial or metastatic tumours also did badly whilst 41 patients with radiation-induced osteosarcoma had a prognosis paralleling conventional osteosarcoma matched for patient age and site of the tumour. 238 patients had high grade non-metastatic osteosarcoma and had a survival of 46% at 5 years. Older patients had less chemotherapy and fared worse. Osteosarcoma in the elderly is a curable condition and warrants intensive treatment with chemotherapy and surgical resection.

Distribution of fibronectin and laminin in human liver tumors.

Two extracellular matrix and basement-membrane components, fibronectin (Fn) and laminin, were studied by the indirect immunoperoxidase technique in ten primary human liver cancers. Similar distributions of both Fn and laminin were detected in the well differentiated hepatocellular carcinomas with trabecular and tubular pattern. Two moderately differentiated hepatomas contained Fn only. Neither Fn nor laminin were present, however, in the parenchyma of one poorly differentiated hepatoma. In three cases of cholangiocarcinoma, laminin surrounded the tumorous ducts, while Fn appeared mainly in the reactive connective tissue stroma. The present findings indicate that bile-duct cancers synthesize laminin, and not Fn while differentiated hepatocellular carcinomas produce both Fn and laminin in vivo. The presence of Fn even in moderately differentiated types of liver cancer is in contrast to the findings for carcinomas developing from other organs and it may serve as a marker for primary hepatocellular carcinomas in the differential diagnosis.

Fibrous dysplasia associated with intramuscular myxoma (Mazabraud's syndrome): a long-term follow-up of three cases.

The association between of fibrous dysplasia and intramuscular myxomas is extremely rare. The authors summarize the characteristics of Mazabraud's syndrome, as well as its clinical course on the basis of 24 cases reported in the literature and 3 cases of their own. The syndrome is quite uniform, and mostly occurs in women. Usually the presentation of poliostotic fibrous dysplasia bilaterally in the lower limbs and pelvic bones is followed by the appearance of multifocal intramuscular myxomas in the adjacent muscles, mostly decades later. These hamartomas tend to recur locally or symmetrically in the ipsilateral muscle groups and may reach enormous size without treatment. Malignant transformation (osteosarcoma, fibrosarcoma) on the basis of fibrous dysplasia in Mazabraud's syndrome has been reported in the literature. In our cases, however, in spite of the many recurrences, and the enormous size of the tumours, no malignant transformation was noted in either the fibrous dysplasias or the intramuscular myxomas during the long follow-up time (31 years for fibrous dysplasia and 16 years for myxomas). Early wide surgical excision and a careful long-term follow-up for the often very late recurrences of the myxomas is suggested in Mazabraud's syndrome.

Calcitonin therapy of aneurysmal bone cysts.

Seven aneurysmal bone cysts (ABC) were treated with the hormone calcitonin. Six of the cysts, which were hypovascular responded well to the calcitonin administered directly into the cyst. Ossification and rebuilding of the ABC occurred after some months in every case. One hypervascularized ABC, however, failed to respond either to embolo-therapy or to the calcitonin hormone treatment. The authors recommend calcitonin administration as a useful non-invasive method for the treatment of hypovascular ABC.

Multicentric extraabdominal desmoid tumour: a case report.

The very rare condition of multicentric desmoid tumours involving two distant and apparently independent sites is reported in a 17-year-old man. The tumours grew simultaneously and reached approximately equal size. No evidence of familiar polyposis or any other feature of Gardner's syndrome were noted. The proximal desmoid tumour developed from the left hip region and extended into the femoral bone, whereas the distal mass was attached to the left popliteal fossa infiltrating the flexor muscles, the nerves and vessels. On the basis of the good results published recently in the literature and our own earlier experiences, the intralesional resection of the desmoid tumours was completed with postoperative fractionated radiotherapy.

Aneurysmal bone cyst: its pathogenesis based on angiographic, immunohistochemical and electron microscopic studies.

Based on angiographic, immunohistochemical as well as electron microscopic findings, authors outline a hypothesis for the etiopathogenesis of aneurysmal bone cysts. No changes were found at the arterial site in 16 studied aneurysmal bone cysts, with no signs of an arteriovenous shunt. In certain cases, however, dilated and tortous efferent veins became visible in the late venous phase. Due to the impedance of venous flow, the intracystic pressure increases and the small veins become dilated causing formation of aneurysmal slits. This is supported by the immunohistochemical finding that S-actin shows concentric arrangement around the aneurysmal cavities. Endothelial lining and basal membrane remnants were detectable in places, though the aneurysmal slits were devoid of continuous endothelial lining and basal membrane. We suggested that the aneurysmal bone cyst corresponds to a hemodynamic disturbance and is due to primary or secondary venous malformation of the bones.

Characterization of bone forming cells in posttraumatic myositis ossificans by lectins.

Lectins were used to characterize bone forming cells in posttraumatic myositis ossificans. The lectins applied were as follows: Arachis hypogaea (PNA): specific for beta-D-galactose (1,3)N-acetyl-D-galactosamine (Gal-1,3 GalNac), Canavalia ensiformis (Con A): specific for alpha-D-glucose (D-Glc) and alpha-D-mannose (D-Man) and Wheat germ (WGA): specific for N-acetyl(1,4)D-glucosamine (Glc-NaC) and neuraminic acid. The development of myositis ossificans was characterized by the appearance of a WGA binding cell population. The lectin-binding sites appeared as a cluster in the supranuclear cytoplasm, corresponding to the Golgi-complex. However, the WGA lectin-binding sites disappeared in the mature form of myositis ossificans. We assume that these lectin binding cells may be the bone marrow derived precursors of myofibroblast-like cells which are responsible for bone formation within the damaged muscle.

Intraosseous lipomatosis. A case report.

We report a case of systemic intraosseous lipomatosis involving the proximal femur, both ends of the tibia, and the tarsal and metatarsal bones. The lesions progressed during a five-year follow-up with a pathological fracture of the tibial plateau. CT scans were characteristic and helpful in diagnosis but MR imaging added little information. Intraosseous lipomatosis is a hamartomatous malformation due to hyperplasia of adipose tissue, and is fundamentally different from solitary benign intraosseous lipoma. Management involves reconstruction of any pathological fracture. Large progressive lesions should be treated by curettage and grafting in an attempt to prevent such fractures.

Tumor endoprostheses vs. bone grafts in bone tumor surgery: experiences in Hungary.

From 1981 through 1991, 76 bone tumor patients were treated by limb salvage operations at the Orthopaedic Department of the Semmelweis Medical University in Budapest. The bone defect was reconstructed with endoprostheses in 25 cases and with bone grafts in 51 cases. The mean follow-up period of 72 patients was 51 months (minimum 12 months). There were local recurrences in 11% of the patients. The functional rating of the tumor endoprostheses was "excellent" or "good" in 74%. Complications occurred in two cases. The most common complications with bone grafting were infection (9.8%), fracture (11.8%), which did not influence the end result, and nonunion (9.8%), which often occurred in homografts of resection-arthrodesis during chemotherapy. These complications were successfully managed without loss of the limb in all but two cases. The bone grafts were rated as functionally acceptable ("excellent" or "good") in 66% of the patients. The reconstruction of bone defect with bone grafting is suggested in cases of semimalignant and low malignant tumors; however, tumor endoprostheses implantation is preferred in high malignant tumors that need chemotherapy.

[Periosteal chondroma]. / Periostales Chondrom.

Ten cases of periosteal (juxtacortical) chondroma were observed in a series of 234 benign cartilaginous tumors of the hand recorded in the Bone Tumor Register of the Orthopaedic Department of the Semmelweis Medical School, Budapest. The X-rays and histology of this slowly growing, juxtacortical, locally active tumor may simulate a chondrosarcoma and may often lead to difficulties in the differential diagnosis. The adequate assessment of the X-ray and histological finding prevents overdiagnosis and unjustified radical surgical therapy.

Surgical treatment and prognostic factors in giant-cell tumor of bone.

The rate of local recurrence in the giant-cell tumor of bone (GCT) is influenced by many factors. GCT aggressiveness is related to mitotic activity, aneuploidy of tumor cells, chromosomal abnormality, excessive metalloproteinase expression and alterations in different oncogenes. Statistically, there was no correlation between the recurrence rate and the size and site of tumor, stage of disease and involvement of subchondral bone. However, statistical analysis revealed that the use of adjuvants (phenol, bone cement, etc) and the type of surgical intervention (en block resection versus curettage and grafting) were factors with a prognostic value. Although recurrence or malignant transformation in GCT cannot be predicted yet, about 96% of the patients can be cured. In the majority of cases, recurrences have no fatal consequences for the patient but may lead to various degrees of disability due to repeated and more radical surgical procedures. Joint-sparing surgery and careful curettage with the use of adjuvants should be the treatment of choice whenever possible. In the future, modern instruments of molecular biology will be used to aid the evaluation of primary and recurrent tumors and will have an increasing influence on surgical planning.

[Results with endoprostheses and bone transplantation in surgery for bone tumors]. / Eredményeink endoprotézisekkel és csonttranszplantációval a csonttumorsebészetben.

Seventy six bone tumor patients were treated by limb salvage operations at the Orthopaedic Department of the Semmelweis Medical School in Budapest from 1981 through 1991. The bone defect was reconstructed with endoprostheses in 25 cases and with bone grafts in 51 cases. The mean follow-up period of 72 patients was 51 months (min. 12 months). There were local recurrences in 11% of the patients. Two complications occurred at the tumor endoprostheses, which functional rating were excellent or good in 75%. The most common complications at the bone grafting were infection (9.8%), fracture (11.8%), which did not influence the end result, and nonunion (9.8%) occurring often in homografts of resection-arthrodesis during the chemotherapy. This complications could be managed in all but two cases without loss of the limb. The bone grafts performed acceptable (excellent or good) functional result in 66% of the patients. Authors suggest reconstruction of the bone defect with bone grafting in cases of semimalignant and low malignant tumors, prefer, however, tumor endoprosthesis implantation in high malignant bone tumors which need chemotherapy.

[Experience with surgical treatment of osteosarcoma]. / Osteosarcomák sebészi kezelésével szerzett tapasztalataink.

The authors treated 79 patients with osteosarcoma by surgery and chemotherapy 1975 through 1991. The appearance, localization and differential diagnosis are discussed. Attention is called to the doctor's delay. The effective pre- and postoperative chemotherapy decreased the incidence of the lung metastases and increased the survival rate (71% 3 years overall survival and 41% 5 years survival) and made the limb-sparing surgery possible. The development of the reconstructive surgical technique and new designs of tumor endoprostheses enabled us to perform limb-sparing surgery in more than one third of the cases at the same survival chance. The limb-sparing means a decisive change in the quality of the rehabilitation of the osteosarcoma patients.

[Dual fluorescence in situ hybridization analysis of synovial sarcoma]. / Synovalis sarcoma kettös jelölésü fluorescens in situ hibridizációs vizsgálata.

Synovial sarcoma have (about in 95% of the cases) the specific and characteristic reciprocal chromosomal translocation t(X; 18) (p11.2; q 11.2). Application of dual-colour fluorescence in situ hybridization (FISH) on interphase nuclei to identify the specific translocation has a diagnostic importance for daily pathological practice. For visualisation of the translocated chromosomal fragments of synovial sarcoma cells on imprint smears, chromosome X painting probes and chromosome 18 centromeric probes were used. Our present study indicates that the precise preoperative diagnosis of synovial sarcoma using dual-colour FISH is possible on smears and this possibility (to identify specific chromosomal translocations in soft tissue tumours) is a landmark in the preoperative diagnosis of soft tissue sarcomas.

[Results of limb-saving surgery and prognostic factors in patients with osteosarcoma]. / Végtagmegtartó mútétek eredményei és prognosztikai tényezók osteosarcomás betegeknél.

Ninety six patients with high-grade osteosarcoma of the extremities were treated between 1986 and 1997 in the authors institution. They were divided into three groups: in group I, all of 75 patients with non-metastatic OS received intensive chemotherapy and underwent surgery. In group II, 9 patients already had metastases at the time of referral. In group III, 12 patients received chemotherapy in delayed or suboptimal form. In group I, local recurrences occurred in 7 per cent (3 patients), metastases in 20 per cent of the patients with limb-saving, whereas these numbers were 3 per cent and 38 per cent in the amputation group. The 5-year disease free survival (DFS) was 72% v 69% in the limb-saving and amputation group, respectively. In groups II and III, 5-year DFS was extremely poor, 10 and 20% only. With univariate analysis, factors having a positive influence on the survival were: tumor volume < 60 cm3, wide or radical surgical margin, distal location of osteosarcoma, cartilagineous ground substance less than 20% and response to chemotherapy. The last 4 variables maintained their significance in the multivariate Cox model as well. Age > 30 showed indirect negative influence on the final outcome (enhanced intolerability to the drugs and less co-operability of the patients etc.). This data confirm the competence of the limb-saving surgery at certain indications beside the amputation.

Ethical standards for orthopaedic surgeons.

This paper offers a summary of the ethical guide for the European orthopaedic community; the full report will be published in the EFORT Journal.

Compromised bone healing following spacer removal in a rat femoral defect model.

PURPOSE: The clinical demand for bone grafting materials necessitated the development of animal models. Critical size defect model has been criticized recently, mainly for its inaccuracy. Our objective was to develop a dependable animal model that would provide compromised bone healing, and would allow the investigation of bone substitutes. METHODS: In the first group a critical size defect was created in the femur of adult male Wistar rats, and a non-critical defect in the remaining animals (Groups II, III and IV). The defect was left empty in group II, while in groups III and IV a spacer was interposed into the gap. Osteoblast activity was evaluated by NanoSPECT/CT imaging system. New bone formation and assessment of a union or non-union was observed by µCT and histology. RESULTS: The interposition model proved to be highly reproducible and provided a bone defect with compromised bone healing. Significant bone regeneration processes were observed four weeks after removal of the spacer. CONCLUSION: Our results have shown that when early bone healing is inhibited by the physical interposition of a spacer, the regeneration process is compromised for a further 4 weeks and results in a bone defect during the time-course of the study.