Cartilage repair procedures associated with high tibial osteotomy in varus knees: clinical results at 11 years' follow-up.

BACKGROUND AND AIM: In this study, the authors retrospectively compared the clinical outcome of middle-aged active patients affected by a varus knee with medial unicompartmental osteoarthritis: the treatment was isolated high tibial osteotomy (HTO) for one group or HTO associated with a cartilage repair procedure, that was autologous chondrocyte implantation (ACI) for one group (HTO+ACI) and microfracture (MFX) for the other group (HTO+MFX). The purpose of this study was to analyse the clinical outcomes at long-term follow-up. The hypothesis was that a cartilage repair procedure may add some benefit to isolated axial correction. METHODS: 56 patients affected by medial osteoarthcritis in a varus knee were retrospectively investigated: 20 patients were treated by HTO, 18 by HTO+ACI and 18 by HTO+MFX. All patients underwent clinical assessment following HSS and WOMAC rating scores and a radiographic study was performed preoperatively and at follow-up. The statistical analysis confirmed that the three groups of patients were homogeneous regarding clinical, radiographical and anatomopathological patterns; differences have been reported in body mass index (BMI). RESULTS: At final follow-up, improvements in clinical and radiographical results were obtained in all patients. HTO and HTO+ACI series showed significantly higher scores compared to the HTO+MFX series. CONCLUSIONS: At more than 11 years of follow-up, isolated HTO and HTO+ACI treatments showed satisfactory results similar to those reported in the literature with no evidence of superiority of the addition of ACI to isolated HTO. MFX associated with HTO provided the worst results in the series.

Autologous chondrocytes implantation: indications and results in the treatment of articular cartilage lesions of the knee.

Articular cartilage lesions of the knee constitute a frequent event and one that is difficult to treat. In time, different surgical methods have been used with results that are often contradictory. The authors report the indications and results of different methods used in the treatment of cartilage lesions: in particular, the experience initiated in 1997 with autologous chondrocytes implantation is discussed. Between 1997 and 2000, a total of 40 patients were submitted to autologous chondrocytes implantation injected in suspension under a periosteal flap. This method includes wide exposure of the joint lesion by arthrotomy. Between 1999 and 2001, a total of 30 patients were submitted to autologous chondrocytes implantation using a tridimensional matrix. The availability of biomaterial simplified the implant method and made arthroscopy possible. All of the patients were submitted to serial clinical follow-ups. MRI was also conducted for a second arthroscopic look. The results obtained in both series after a mean follow-up of 4 years (range 2 to 6 years) are good, and confirm the effectiveness of the method that allows for complete morphological and structural repair of lesions of the joint cartilage.

Hip prosthesis revisions with LS stem: indications and results.

The authors present a study that includes 350 patients affected with loosening of hip arthroplasty and submitted to revision with a Wagner LS stem at the 4th Division of the Rizzoli Orthopaedic Institute. Several different types of cotyle (Fitek, Wagner, Standard Cup, cemented cotyle with support ring, Octopus system) were used depending on the anatomopathologic findings, combined with autoplastic grafts. Staging and grading of loosening were based on the four G.I.R. grades. A clinical evaluation of results was based on the Merle D'Aubigné parameters modified by Charnley. For radiographic evaluation the De Lee Charnley areas were studied for cotyle, the Gruen areas for the femoral stem. Overall, good results were obtained in 175 patients, fair in 137, poor in 38.

Hip arthroplasty in coxarthrosis secondary to Paget's disease.

A total of 5 hip arthroplasties implanted between 1997 and 2000 in 5 patients affected with coxarthrosis secondary to Paget's disease were reviewed. The quality of the pagetic bone (sclerotic and very vascularized) resulted in a slightly longer amount of time required for surgery because of the difficulty preparing prosthetic placement and intra- and postoperative blood loss exceeding the norm. Complications were not observed. Clinical results were good in 100% of cases. Radiographically, 2 stems were assembled in varus.

Osteoblasts and stromal cells isolated from femora in rheumatoid arthritis (RA) and osteoarthritis (OA) patients express IL-11, leukaemia inhibitory factor and oncostatin M.

We investigated both in vitro and ex vivo the role of mature osteoblasts (OB) and bone marrow stromal cells (BMSC) in RA and OA by analysing the expression of the following IL-6-type cytokines: IL-11, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and IL-6. OB and BMSC were isolated from femora of RA, OA and post-traumatic (PT) patients, cultured in vitro in the presence or absence of IL-1beta and tumour necrosis factor-alpha (TNF-alpha), and assessed for the production and mRNA expression of IL-6-type cytokines. Trabecular bone biopsies were obtained from the inner portions of femoral heads and used for cytokine in situ immunostaining. Cultured OB and BMSC from different patients constitutively secreted IL-11 and IL-6 but not OSM. LIF was secreted only by BMSC, at very low levels. Interestingly, IL-11 basal production was significantly higher in BMSC than in OB in all three groups tested. IL-1beta and TNF-alpha strongly stimulated IL-6-type cytokine release (except for OSM) by both OB and BMSC. OSM was expressed only at mRNA levels in all groups studied. Cytokine immunostaining on bone biopsies confirmed the data obtained on cultured cells: IL-11, IL-6 and LIF proteins were detected both in mesenchymal (BMSC and OB) and mononuclear cells; OSM was found only in mononuclear cells. These data demonstrate that IL-6-type cytokines are constitutively expressed in the bone compartment in RA, OA and PT patients and can be secreted by bone cells at different stages of differentiation (BMSC and OB). This suggests that these cytokines may be involved in the mechanisms of bone remodelling in OA and RA.

Chemokine expression by subchondral bone marrow stromal cells isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) patients.

We analysed the spontaneous and cytokine-stimulated production and expression in vitro of IL-8, GROalpha, MCP-1, RANTES, MIP-1alpha, MIP-1beta, by subchondral bone marrow stromal cells (BMSC) isolated from RA, OA, post-traumatic (PT) patients and normal donors (ND). BMSC were cultured in vitro in the presence or absence of IL-1beta and tumour necrosis factor-alpha (TNF-alpha), and assessed for chemokine production, expression and immunolocalization. BMSC from different sources constitutively released MCP-1, GROalpha and IL-8, but not MIP-1alpha or MIP-1beta, while BMSC from ND constitutively released only IL-8 and MCP-1. IL-8, GROalpha and RANTES production in basal conditions was significantly higher in RA patients than in ND. RANTES production was also higher in OA and RA than in PT patients. The combination of TNF-alpha and IL-1beta synergistically increased the production of all chemokines tested except for RANTES. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that all chemokines not detectable in the supernatants were expressed at the mRNA level. Chemokine immunostaining was localized around the nuclei. This work demonstrates that BMSC from subchondral bone produce chemokines and indicates that these cells could actively participate in the mechanisms directly or indirectly causing cartilage destruction and bone remodelling.

Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To evaluate whether subchondral osteoblasts (OB) are involved in the production of cytokines and chemokines in rheumatic diseases. METHODS: OB were isolated from subchondral bone of rheumatoid arthritis (RA), osteoarthritis (OA) and post-traumatic (PT) patients, cultured in vitro in the presence or absence of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and assessed for the production, immunolocalization, and mRNA expression of proinflammatory cytokines (IL-1alpha, IL-1beta, TNF-alpha) and alpha and beta chemokines [IL-8, growth related gene product (GRO-alpha), monocyte chemoattractant protein 1 (MCP-1), RANTES, and macrophage inflammatory proteins MIP-1alpha, MIP-1beta]. RESULTS: Cultured OB from different patients did not release IL-1alpha, IL-1beta, or TNF-alpha, and constitutively secreted IL-8, GRO-alpha, and MCP-1, while RANTES, MIP-1alpha, MIP-1beta were undetectable or near the lower level of sensitivity of the immunoenzymatic assay. GRO-alpha was significantly higher in RA than in OA and PT patients. IL-1beta and TNF-alpha alone or in combination strongly stimulated chemokine release by OB. Only RANTES production was not increased by the combination of the 2 cytokines. IL-1alpha, IL-1beta, and TNF-alpha were expressed as cytoplasmic proteins and were not secreted by OB even after stimulation. CONCLUSION: OB from subchondral bone release chemokines that could be involved in the mechanisms that directly or indirectly cause bone remodelling and cartilage destruction.

Knee prosthesis in rheumatoid patients.

Total knee arthroplasty is a reliable means to improve the quality of life not only in osteoarthritis, but also in rheumatoid patients. Specific aspects, like the low mechanical quality of bone tissue, the contemporary damage of several joints and the higher risk of complications, have to be taken into account in rheumatoid arthritis. The experience with 24 prostheses in 21 rheumatoid patients is reported and confirms the efficacy of this operation. Among the technical details discussed, stress is placed on the conservation of the posterior cruciate ligament, the use of cement, the procedure of patelloplasty instead of prosthetic replacement. Careful preoperative planning is required and resections, especially in the tibia, should be economical. The evaluation of the results according to the protocol of the America Knee Society shows a satisfactory increase both of the articular score (average from 36 to 88) and the functional score (average from 34 to 68).

Clinical setting of patients with systemic sclerosis by serum autoantibodies.

Associations of antinuclear (ANA) and anticardiolipin (aCL) antibodies with clinical manifestations were analyzed in patients with systemic sclerosis (SSc). We studied 105 SSc patients: 28 had limited cutaneous SSc (lcSSc) involving fingers; 36 had intermediate cutaneous SSc involving limbs and face; 33 had diffuse cutaneous SSc (dcSSc) involving the trunk; 8 had a sclerosis sine scleroderma. Clinical manifestations and instrumental and laboratory findings were considered to calculate a disease score. Serum anticentromere (ACA), anti-topoisomerase I (anti-topo I) antibodies, and aCL (of IgG/IgA/IgM classes) were investigated by conventional methods. ACA positive patients (n=18), compared to ACA negative, showed higher prevalence of IcSSc (p < 0.001), lower prevalence of restrictive ventilatory defect (p=0.006), and lower disease score (p=0.008). Anti-topo I positive patients (n= 70) showed lower prevalence of lcSSc (p =0.001) compared to anti-topo I negative. In aCL positive patients (n=27) widespread skin and visceral involvement occurred more frequently than in aCL negative. The association with myocardial ischemia or necrosis (p=0.010) was significant. Occurrence of ACA excluded the coexistence of anti-topo I (p < 0.001), and aCL (p=0.037). aCL positive patients showed higher disease score in comparison with ACA positive patients (p=0.003). In conclusion ACA recognize patients with a mild disease. aCL in contrast to ACA are better than anti-topo I in recognizing the most severe pictures of SSc.

Clinical significance of anticardiolipin antibodies in patients with systemic sclerosis.

One hundred and three patients suffering from systemic sclerosis (SSc), with different extent of skin involvement, were retrospectively examined to investigate the correlations between clinical manifestations and anticardiolipin antibodies (aCL). aCL of IgG, IgA, and IgM classes were measured in the patients' sera by enzyme linked immunosorbent assay. aCL were found in 26 patients (25.2%). A significant association was found between aCL and myocardial ischaemia or necrosis (p = 0.011). No patient showed the clinical picture of the antiphospholipid syndrome. On the basis of clinical manifestations, a protocol for disease score was drawn. Patients with IgG-aCL and with IgA-aCL showed a disease score higher than aCL negative patients (p = 0.008 and p = 0.022 respectively). Thus, the finding of aCL can be considered a useful serological index for the most severe forms of SSc.

Complications and surgical indications in 144 cases of nonmetastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy.

From September 1986 to December 1989, 144 patients with osteosarcoma of the extremities were treated with combined surgery and neoadjuvant chemotherapy. The disease-free survival was 79% for good responders (necrosis greater than 90%) and 72% for poor responders (necrosis less than 90%), and the local recurrence rate was low. Improvement in long-term prognosis and the increase of limb-sparing surgery determine a higher rate of immediate and late complications. Most of the complications were observed in limb-salvage procedures; 63% of these procedures presented one or more complications. In nine rotationsplasties, there were four complications, and in 13 amputations no complications were observed. Therefore, 55% of patients were affected by surgical complications. Twenty-eight complications were considered minor (not requiring surgery), whereas 77 complications were major. Functional results, evaluated according to Enneking's new system, were higher than 50% in two thirds of the limb-salvage procedures. Complications in limb-salvage procedures are more influenced by the type of reconstruction than by the surgical procedure used. Probably the most troublesome consequence of surgical complications in osteosarcoma is the deviation or delay in administering postoperative chemotherapy, which jeopardizes survival.

Solid variant of aneurysmal bone cyst.

BACKGROUND AND METHODS: Of the 200 cases of ABC in the Rizzoli Institute files, 15 had solid features on both gross and histologic examination. Inasmuch as fibrous proliferation with giant cell and bone production along with fibromyxoid areas and small aneurysmal spaces were found in the solid parts of the aneurysmal bone cyst, a grossly solid and radiographically osteolytic bone lesion with these microscopic features was called a solid aneurysmal bone cyst. Some authors call the same lesion extragnathic giant cell reparative granuloma. RESULTS: Sixty percent of the patients were female. The metaphysis was the preferred location in the long bones (8/11). Radiographic appearance was not specific, and sometimes a malignant lesion was very difficult to rule out. In seven patients, the lesion was considered radiographically "aggressive." Intralesional excision (curettage) in 12 patients and marginal resection in 3 patients with diaphyseal location was effective in controlling the lesion. No recurrence was detected after a mean follow-up of 59 months. CONCLUSIONS: High proliferative activity of the benign-appearing proliferative spindle cells, often with fairly abundant mitoses, associated with benign giant cells and immature bone production are the features of this pseudosarcomatous hyperplastic lesion. It is sometimes is mistaken for a malignant tumor.

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.

Systemic mastocytosis with skeletal involvement.

Systemic mastocytosis is a rare disease. The observation of one case characterized by clinical and radiographic bone involvement encouraged the authors to review the literature on the subject. The classification and most recent pathogenetic hypotheses correlated with various radiographic pictures, the different histological aspects, and most frequent differential diagnoses are reported.

The management of malignant bone tumors in children and adolescents.

A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection. Sixty-five percent of all patients were alive at 30 months and were considered disease free. The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases. In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%. On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result. This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth.

Bone tumors of the foot: epidemiology and diagnosis.

The authors reviewed 260 cases of bone tumors localized in the foot and treated at the Tumor Center of the Rizzoli Orthopaedic Institute: 191 were benign and 58 malignant and 11 metastasis. There was predilection for the hindfoot (57%), followed by the forefoot (33%) (prevalently the metatarsals). Localizations in the midfoot were rare (10%). Osteoid osteoma was observed in 26% of all of the tumors of the foot and in 35% of the benign forms. Among malignant neoplasms Ewing's sarcoma (27.5%) was the most frequent. Conservative surgery, which was always carried out in benign tumors, was also performed in some of the malignant ones, having an early diagnosis and a correct preoperative study. The indications and the limits of the different imaging techniques available are reported (bone scan, arteriography, CAT, MRI), and the role of biopsy in the definitive diagnosis of these neoplasms in discussed.

Supracondylar process of the humerus: four cases.

Four cases of supracondylar process of the humerus are presented. Two of the patients were asymptomatic and in one of these the supracondylar process was fractured. In a third there was median nerve compression and in the last there was ulnar nerve entrapment. The anatomical features, clinical symptoms and therapy are described. Good results were obtained after resection of the supracondylar process; neurological symptoms regressed one month after surgery.