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.

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.

Muscle regeneration is undisturbed by repeated polytraumatic injury.

INTRODUCTION: Clinical observations suggest that repeated injury within a week after a traumatic event impairs the regeneration of tissues. Our aim was to investigate the effect of repeated trauma on the proliferation of satellite cells in skeletal muscle tissue. MATERIALS AND METHODS: Cold lesion injury was performed in the soleus muscle and in the motor cortex of anesthetized male Wistar rats 0, 1, or 2 times with 7 day intervals between the interventions. Following the last operation, 5-bromo-2'-deoxyuridine was injected i.p. for 6 or 12 days to label dividing cells. Gut epithelium was used as positive control. Immunohistochemistry was performed 1 and 5 weeks after the last injury and the sections were analyzed with confocal microscopy. RESULTS: In the case of repeated trauma, the percentage of proliferating cells remained the same compared to single hit animals after 1 week (28.0 ± 2.5% and 29.6 ± 3.0%) as well as after 5 weeks (13.9 ± 1.8% and 14.5 ± 2.2%). CONCLUSION: The second hit phenomenon is probably due to systemic factors rather than to a diminished regenerating potential of injured soft tissues.

The dangers of intraosseous fibrosing agent injection in the treatment of bone cysts. The origin of major complications shown in a rabbit model.

Direct intraosseous injection of fibrosing agent is widely used in the treatment of aneurysmal bone cysts. The purpose of this study was to evaluate the consequences of fibrosing agent penetrating the medulla of bones. This may be the case when, by mistake, the fibrosing agent is administered into the medulla or when the wall of the cyst ruptures and fibrosing agent is able to drift into the medulla. Twelve rabbits were injected transcutaneously with a fibrosing agent directly into the proximal metaphysis of the tibia. Prior to injection 0.5 ml of liquid-like, bloody, intraosseal tissue was aspirated, then 0.5 ml of fibrosing agent was administered. Fibrosing agent was introduced slowly (20 s) to avoid overpressure. Nine rabbits (75%) died within minutes after the introduction of fibrosing agent. A full body roentgenogram was taken of each rabbit and the animals that died underwent autopsy to find the exact cause of death. Roentgenograms of the chest showed massive multiple pulmonary emboli confirmed in all lethal cases by the autopsy. This animal model was created to draw attention to the dangers of any leakage of the fibrosing agent into the medulla of bones.

Comparison of the degenerative changes in weight-bearing joints following cementing or grafting techniques in giant cell tumour patients: medium-term results.

The aim of this retrospective study was to compare and assess the effect of bone grafting and cementing techniques--two common applications used in the treatment of subchondral giant cell tumours of bone (GCTs)--on the development of degenerative changes in the weight-bearing joints of the lower extremity. Eighty patients were included in this follow-up study, 44 of whom underwent curettage followed by bone grafting, and 36 who had curettage followed by cementation. At the 24-month post-operative examination, significantly less degenerative change was found in patients with bone cement than in those with bone grafting. At the 50-month and later (range: 50-148 months) post-operative examination, however, no significant differences were found between the two groups, indicating that there was a significant acceleration of degenerative changes in the cemented group after the 24-month follow-up.

Functional outcome and life quality after endoprosthetic reconstruction following malignant tumours around the knee.

Between 1993 and 2002, we treated 43 patients with malignant musculoskeletal tumours of the knee region. All patients had partial resection of the femur or tibia together with endoprosthetic replacement. We were able to follow-up 23 patients with an average follow-up of 30 (12-97) months. Complications occurred in ten cases, of which one was a case of local recurrence. Most of the patients were completely satisfied with their condition, with a decreased walking distance as the only notable restriction. There was no correlation between the functional outcome and life quality assessment and the type of the implanted prosthesis, length of resected bone and type of resection. However, patients with tumours in the distal femur had significantly better functional and life quality outcome than those with a proximal tibial tumour.

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.

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.

[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.

[Malignant transformation of giant cell tumor in the distal radius. Value of the DNA cytophotometry]. / Die maligne Entartung eines Riesenzelltumors am distalen Radiusende. Wertigkeit der DNS-Zytophotometrie.

The GCT is a primary bone tumor of intermedia dignity, whereby the forecast of the biological behaviour and outcome is impossible on the base of the conventional histological diagnosis. The authors observed in one of their GCT-patients a malignant transformation of the formerly benign tumor. Through announcement of their case the authors want to call the attention to the importance of the DNA-Cytophotometry and to their possible future additional role in the diagnostics of the GCT and in the prediction of their biological behaviour.

Synovial neoformations and tumours.

An important group of soft tissue tumours and tumour-like lesions originates from the synovium of the joints, bursae and tendon sheaths. These include synovial chondromatosis, diffuse articular lipomatosis (lipoma arborescens), villonodular synovitis, synovial haemangioma, synovial chondroma and fibroma (intracapsular and peri-articular), primary chondrosarcoma originating from the synovium and synovial sarcoma. The main clinical symptoms of these tumours, such as pain, swelling, effusion and joint locking, are not specific, so the diagnosis can easily be missed in clinical practice. The most important clinical characteristics and the differential diagnostic clues for synovial tumours and tumour-like lesions are described in this chapter. In addition, the new results of genetic and histological studies are discussed, together with a summary of the available evidence-base for therapy.

The efficacy of a combination of etoposide, ifosfamide, and cisplatin in the treatment of patients with soft tissue sarcoma.

BACKGROUND: Successful chemotherapy for patients with soft tissue sarcoma (STS) has been limited by a lack of active drugs. The most effective single agents are doxorubicin, dacarbazine, and, more recently, ifosfamide. Previously the most widely used combination has been CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). In one randomized trial, ifosfamide was superior to cyclophosphamide; two nonrandomized studies also reported favorable results. Etoposide monotherapy was successful in 8%; the effectiveness of cisplatin was 5-23%. In view of these findings, the authors treated STS patients with an etoposide, cisplatin, and ifosfamide (VIP) combination. METHODS: The eligibility criteria included histologically confirmed, inoperable, metastatic or locally recurrent STS; a World Health Organization (WHO) performance status of 0-2; a maximum age of 75 years; and progressive, measurable disease. A total of 104 patients were treated from January 1990 to June 1997. The median age of the patients was 42.4 years. The patients were treated with a combination of etoposide (100mg/m(2) for 5 days), ifosfamide (2000 mg/m(2) for 2 days), and cisplatin (20mg/m(2) for 5 days) once a month via a peripheral vein. The treatment response and the toxicity were assessed according to WHO criteria. RESULTS: Of 104 evaluable patients, 47 responded. The overall response rate was 46% (complete response: 10%; partial response: 36%). In 43 patients the disease remained stable (41%). Remission duration was 4.6 months. Toxicity was moderate. The main adverse events were alopecia (100%), nausea and vomiting (73%), and leukopenia (29%). CONCLUSIONS: This new combination is promising for the treatment of patients with advanced STS.

Limb-saving surgery, survival, and prognostic factors for osteosarcoma: the Hungarian experience.

BACKGROUND AND OBJECTIVES: There are many factors thought to have an influence on the prognosis of osteosarcoma that have been reported in the literature. Their significance, however, still remains controversial in most cases. Experience with osteogenic sarcoma (OS) was reviewed in order to evaluate surgical results and survival and to determine the prognostic factors. METHODS: Ninety-six patients with high-grade osteosarcoma of the extremities were treated between 1986 and 1997 in the authors' institution. They were divided into 3 groups: In group I, all 75 patients with nonmetastatic OS received intensive chemotherapy (high-dose methotrexate, doxorubicin, ifosfamide, and cisplatin) 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. Results and Conclusions In group I, there were local recurrences in 3 patients (7%) and metastases in 8 patients (20%) with limb-saving, whereas these numbers were 1 (3%) and 14 (38%) in those who had amputation. The 5-year disease-free survival (DFS) was 72% and 69% in the limb-saving and amputation groups, respectively. In groups II and III, 5-year DFS was extremely poor, 10% and 20% only, underlining the importance of stage and intensity of chemotherapy, respectively. With univariate analysis, sex, duration of symptoms, and radiographic appearance of OS had no prognostic value, whereas tumor volume <60 cm(3), wide or radical surgical margin, distal location of OS, cartilagineous ground substance <20%, and response to chemotherapy were positive prognostic factors. The last 4 variables maintained their significance in the multivariate Cox model as well. Age >30 years showed indirect negative influence on the final outcome through enhanced intolerability to the drugs and less cooperability of the patients. The results on survival with limb-saving surgery were well comparable with those of amputation.

Mid-foot reconstruction following involvement of five bones by giant cell tumor.

We report on a patient who had giant cell tumor involving multiple bones of the mid-foot. The tumor originated from the navicular bone, but also destroyed the cuboid, and all cuneiform bones. This unusual presentation of giant cell tumor presented a therapeutic challenge for the surgeons. The patient was treated with en bloc resection and the bony defect replaced with a massive iliac crest graft which united within 9 months and has remained stable for 7 years without local recurrence, and with excellent function of the foot.

[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.

The prognostic significance of DNA cytophotometry and proliferation index (Ki-67) in giant cell tumors of bone.

We studied DNA ploidy by smear cytophotometry and proliferation activity by Ki-67 MIB immunohistochemistry in 69 primary and recurrent giant cell tumors (GCT) from 50 randomly selected patients. The obtained results were evaluated with comparisons made to the available clinical data. From the 46 primary tumors 63% showed diploidy and 37% aneuploidy. A significantly (P=0.026) higher recurrence rate (64%) was observed in aneuploid than in diploid tumors (31%). In the course of the recurrences, both the ratio of aneuploid tumors as well as the proliferation index of the tumors increased, though the degree of the latter was non-significant. Aneuploidy did not mean an unambiguous tendency towards malignant transformation; however, a close follow-up of recurrent aneuploid tumors, and wide excision of the recurrence instead of intralesional curettage are the recommended procedures. The DNA cytophotometry and proliferation index of GCTs--as compared to other histologic examinations--are of prognostic value in the evaluation of the recurrence potential of the GCTs.