Purpose of this paper was to review the Rizzoli experience in prosthetic reconstruction of the knee after resection of bone tumors with special attention to major complications and functional outcome.

Material: 669 knee modular uncemented prostheses were implanted between 1983 and 2006 after resection of the distal femur, total femur or proximal tibia. These prostheses include 126 first generation Kotz prosthesis (KMFTR) and 543 second generation HMRS prostheses.

Methods: All patients are followed periodically in the clinic. Data for this study was obtained from clinical charts; imaging studies were reviewed with special attention to prosthesis related major complications requiring revision surgery. Revision for polyethylene wear was considered a minor complications, since it does not imply change of main prosthetic components, thus failure of the implant. Functional results were assessed according to the MSTS system.

Since abrupt data could be misleading due to the oncologic population and related deaths (although 2/3 of the patients were cured or long survivors), to censore the implant unrelated events a statistical analysis of the implant survival was performed and Kaplan-Meyer curves of implant survival were studied.

Results: In the 126 KMFTR group major complications included infection 13%, breakage of the stems 12%, aseptic loosening 8.7%, while revision for polyethylene wear rated 45%.

In 543 HMRS prostheses major complications were infection 8%, stem breakage 2%, aseptic loosening 4%, while revision for polyethylene wear components rated 7.4%.

Techniques of revisions were analyzed, as well as the outcome of revised cases, which showed that about 2/3 of the patients treated for major complications do well, although the risk for further complications is significantly incresed in revised implants.

Functional results were evaluated according to the MSTS system: in KMFTR prostheses were good or excellent in 80% of the patients, while in HMRS were good or excellent in 90% of the patients.

Discussion: The reduction of major complication rate with the newer designs of the modular prosthesis was statistically significant and this seems to confirm that newer materials and a modified stem design positively affected the implant survival. Also the wear of polyethylene component was dramatically decreased in the newer prosthetic design. Functional results were satisfactory in most of the patients that did not experience major complications, with a trend to improvement in the newer design. Revision surgery is technically demanding and sometimes newer ‘hybrid’ techniques are suggested, implying the use of bone allografts.

Appropriate timing of revisions is crucial. An early treatment of complications can improve the final outcome.

Purpose of this study is to report the preliminary results of the clinical experience of the Rizzoli with a new modular reconstructive tumor prosthesis for the lower limb (GMRS-Stryker).

Material and methods: based on the clinical experience and the review of 842 cases of modular tumor prosthesis for the lower limb, a new prosthetic design was introduced derived from the previous. It is a modular system with a rotating hinge mechanism for the knee and several possible options for the stems, including titanium and chromium-cobalt-molybdenum stems, cemented and uncemented, curved and straight-fluted, with or without hydroxyapatite coating. Moreover adaptors were available to revise older HMRS implants with GMRS components.

Between October 2003 and march 2006 this system was implanted at the Rizzoli in 85 cases. This series included 42 males and 43 females, ranging in age from 8 to 76 years. The sites of prosthetic reconstruction were distal femur in 60 cases, proximal femur in 7, total femur in 1, proximal tibia in 17 cases.

There were 79 oncologic and 6 non oncologic diagnoses. The histological diagnoses of the oncologic cases included 11 giant cell tumors and 68 malignant tumor: 52 osteosarcomas, 7 spindle cells sarcomas, 6 Ewing’s sarcoma, 3 chondrosarcomas. Of the 79 oncologic cases 55 were primary reconstructions with GMRS prosthesis and 24 secondary reconstructions for failure of a previous reconstruction.

In 16 cases HMRS/GMRS hybrid implants were used in reconstruction or revision, using adaptors.

All patients are periodically checked in the outpatient clinic of the Rizzoli.

Complications were reported and analyzed, x-rays were reviewed and pertinent information achieved for each patient. Functional results were assessed according to the MSTS system.

Results: at a short follow up (min 5 months, max 30 months) showed 76 patients NED (11 benign and 65 malignant), 1 NED1 after treatment of local recurrence, 4 NED1 after treatment of metastases.

There was 1 case of infection, treated with removal of the implant and spacer with antibiotics. There were 3 disruptions of the knee extensor apparatus, 1 patellar instability treated by revision of the prosthesis.

Functional result were evaluable in 59 cases and showed a function of 26% to 50% in 14% of pts, of 51% to 75% in 19%, over 76% in 67%. Results were considered good or excellent in 86% of the evaluated patients.

Conclusions: Although the results have been evaluated at a short term follow up, this prosthetic system is promising and it can also be used in some non oncological settings, such as challenging revisions of prosthetic failures with massive bone loss or some post-radiation non unions or allografts failures.

Introduction: The role of surgery for local control in the multimodal management of Ewing’s sarcoma has substantially increased during the past 20 years. However, selection bias due to location (extremities vs axial skeleton) and relatively non-homogeneous treatment received by patients in multi-institutional trials may limit objective evaluation and comparison of the relative role of surgery and radiation therapy in this setting. Purpose of this study was to review a large series of patients homogeneously treated at a single institution.

Methods: 268 patients with non-metastatic Ewing’s sarcoma of the extremities treated by contemporary multimodal management were reviewed. Chemotherapy was administered according to 4 sequential protocols of adjuvant (1) and neoadjuvant (3) treatment. Local control consisted of surgery in 136 patients, surgery and radiation therapy in 70 patients, and radiation therapy in 60 patients. Two patients underwent only chemotherapy.

Results: The 5-year event-free survival (EFS) and overall survival (OS) were 62 and 69 per cent respectively. The rates of 5-year EFS and local control were significantly lower in patients treated with radiation therapy compared to patients treated by surgery or surgery and radiation therapy (48 vs 66 per cent, p=0.002; 80 vs 94 per cent, p= 0,0001). In group 3 (Radiation Therapy only) there were also 6 secondary malignancies.

Conclusion: Surgery was associated with better survival and local control in this series. In our opinion, surgery should always be considered in the local treatment of Ewing’s sarcoma of the extremities. Postoperative Radiation Therapy must be added in cases of inadequate surgical margins.

Introduction: Secondary sarcomas of bone are a rare group of usually high-grade malignant tumors developing over different pre-existing bone conditions, historically associated with worse prognosis than their primary counterpart. Purpose of this study was to investigate the factors affecting the outcome, with emphasis modern multi-modal management.

Methods: From approximately 30000 bone tumor cases filed at our Institution, 87 patients with secondary sarcoma were identified. Secondary chondrosarcomas were not included and all the patients had an high-grade lesion. Patients were divided in 3 groups: radiation induced sarcomas (29), sarcomas in Paget’s disease (34), and sarcomas in benign lesions (24). Of these patients, 67 were admitted for treatment while 20 were consultations; of the 67 patients admitted, 44 had stage II while 23 had stage III disease. There were 57 males and 30 females, average age was 52. Most common histotype was osteosarcoma (81). Treatment varied from none to combined multimodal management including chemotherapy and surgery.

Results: Cumulative survival is 37% at 10 years. Survival was affected by stage of disease (II=54%, III=0%; p< 0.00005), site (extremities 44%, pelvis-spine 0%; p< 0.00005), inclusion of surgery in the treatment plan (yes 51%, no 0%; p< 0.00005), and type of treatment (combined chemotherapy and surgery 56%, surgery 39%; p=0.07). No differences were noted between the 3 main etiologic groups.

Conclusions: Secondary sarcomas are a rare group malignant tumors with heterogeneous clinical features. While stage and site are still the most relevant prognostic factors, modern multimodal management including neoadjuvant chemotherapy and surgery seems to favourably affect the outcome.

Introduction: The use of allograft prosthetic composite (APC) of the proximal tibia offers advantages over prosthetic replacement or osteoarticular graft with a better functional outcome since the possibility of a careful soft tissue reconstruction;

Materials and Methods: From 1994 to 2002, 62 APC of the proximal tibia were performed in our department after bone tumor resection (56 malignant bone tumors, 4 cases of previously failed knee implant and 2 stage 3 benign tumors). The patients median age was 18 yrs (range: 11–77 yrs) and the mean resected length was 13.2 cm (range: 8.5–28 cm). The median follow up was 59 months (range: 13–137 months)

Results: In three patients (4,8%) a recurrence was reported at 22, 33 an 40 months and amputation was performed.

Infection was reported in 15 patients (24.2%): 2 early infections (healed with surgical debridment), 1 femoral stem septic loosening (treated with early revision with cemented stem); in 8 cases removal of the infected APC was required followed by implant of a new prosthetic device after cement spacer; two infections did not healed and patient underwent amputation; in two cases a good functional result was achieved removing the infected graft and covering the proximal tibia with cement and no other surgery was required.

Non union of the graft was observed in 8 patients (12.9%): in 4 patients autologous bone grafting was necessary to heal the osteotomy line. In other 3 cases non union was associated with graft fracture. In one case non union was associated with tibial stem loosening and revision of the whole implant was done.

Polyethylene wear was assessed in 5 patients (8%) and revision of the polyethylene components was always required.

Nine patellar tendon rupture (14.5%) were assessed and repaired was performed in seven cases.

The functional outcome of 42 patients with more than two years of follow up was excellent in 25 cases, good in 13, fair in 2 and poor in 2.

Discussion: APC of the proximal tibia is an effective alternative to osteoarticular graft and modular prosthesis because it allows good to excellent results in most of the patients (90.4%). The major concern is infection rate (24.2%) that usually lead to amputation (80%). Non union does not usually represent a problem because it’s tendency to spontaneous or bone grafting induced healing. Aseptic loosening of the tibial or femoral stem is rare. Patellar tendon rupture rate (14.5%) is similar to modular prosthetis rate and can be lowered using a femoral component with patellar groove.

Introduction: Giant Cell Tumor (GCT) is rarely associated with lung metastases (1–4%). No prognostic factors have been reliably associated with the occurrence of lung metastases.

Since high levels of urokinase-type plasminogen activation system have been associated with cancer metastasis, purpose of this study was to investigate its expression in patients with giant cell tumor and the relationship with outcome.

Materials and Methods: Expression of urokinase-type plasminogen activation system was evaluated by immunohistochemistry in the primary lesion of 65 patients with GCT. This included urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type 1 (PAI-1), and u-PA receptor (u-PAR). Patient population consisted of 12 cases that developed lung metastases and 53 cases that did not show metastases at last follow-up. Clinical outcome of the 2 groups was retrospectively reviewed and correlated with u-PA, PAI-1 and u-PAR expression levels.

Results: Overexpression of u-PA, PAI-1 and u-PAR was more frequent in the metastatic (92%) than non-metastatic (21%) group (p< 0.0005). Incidence of local recurrence was higher in the metastatic (67%) than non-metastatic (30%) group (p=0,024). Risk of re-recurrence after 1st local recurrence was more than 4 times higher in the metastatic than non-metastatic group (p=0.05). No differences were observed in the 2 groups with respect to age, sex, site, stage, treatment, follow-up and mortality.

Conclusions: Overexpression of urokinase-type plasminogen activation system in this study associated with an increased risk of lung metastases, local recurrence and local re-recurrence. Evaluation of urokinase-type plasminogen activation system expression levels may identify a subgroup of patients with increased risk of relapse

Introduction: Allograft-Prosthesis Composite represents a reliable option for proximal femur replacement after resection for bone tumor. It provides advantages over megaprostheses because of better soft tissue repair and superior abduction strength, quality of gait, hip stability, and load transfer by healed bone rather than prosthetic stem, with potential impact on implant survival. Purpose of this paper was to review details of the surgical technique and results.

Methods: A retrospective study of 62 patients who had resection of the proximal femur because of a bone tumor and reconstruction with an Allograft-Prosthesis Composite was undertaken. The basic surgical technique consisted of an uncemented tapered long stem prosthesis (i.e. Wagner or Wagner-type stem) cemented in the allograft and press-fitted in the host bone, achieving bone-bone contact through a transverse osteotomy. Details of the surgical technique included: 1) accurate preoperative planning, canal sizing and implant selection; 2) under-reaming of the proximal 5–10 mm of the host medullary canal, depending upon bone quality and diameter of the selected stem; 3) allograft preparation and prosthesis cementation in the allograft; 4) introduction of the composite implant, pressfitted in host medullary canal, until bone-bone contact is achieved; 5) careful repair of abductors and iliopsoas to corresponding allograft tendon insertions.

Key points for successful fixation are absolute rotational stability and satisfactory circumferential bone-bone contact at the time of surgery.

Postoperative regimen consisted of hip, followed by progressive bracing and toe-touch weight-bearing for 6 weeks, weight-bearing.

Results: There were 2 septic failures. Two patients developed asymptomatic nonunion. There were no dislocations. Most common complication was fracture of the allograft greater trochanter (30%), which required surgery in only 1 case and never substantially affected function. The incidence of trochanteric fracture decreased from 63% in the first 27 patients to 5% in the following 35 patients by switching implant design from a valgus 145° neck angle to 135° neck angle, improving offset and abductors function. Bone grafting of the allograft-host union was required in 10% of the cases.

According to MSTS, results were satisfactory in 90% of the patients, with average score 91% (75%–96%).

Discussion and Conclusion: Allograft-Prosthesis Composite is a successful procedure for reconstruction of the proximal femur. Careful surgical technique is the key to excellent function and low complication rate.

Multiple Hereditary Exostoses is a rare skeletal chondrodysplasia characterized by the presence of a variable number of osteochondromas, usually mostly affecting the long bones but possibly located anywhere. Appearance and growth of exostoses is parallel to the patient’s growth, essentially ending when skeletal maturity is reached.

Its clinical expression is well known and may vary from asymptomatic to severe deformities and is rarely complicated by trasformation to secondary chondrosarcoma (0.5–2%). Research in the field of genetics has lead to identification of 2 responsible genes, EXT1 and EXT2, located respectively on chromosome 8 and 11, both coding for transmembrane glycoproteins involved in the synthesis of heparan-sulfate chains.

A third rare abnormality (EXT3) has been located on chromosome 19 but the responsible gene has not been identified yet.

Seems logical to investigate the genetic basis of the disease and the correlation with clinical aspects, either severity of the deformities and consequent functional impairment and potential for chondrosarcoma.

At the authors’ Institution a total of 550 patients with Multiple Hereditary Exostoses are presently filed. Genetic screening by DHPLC (Denaturing High Performance Liquid Chromatography) and clinicoradiographic orthopedic evaluation has been carried out on 200 patients. So far, 45 mutations have been identified (35 in EXT1 and 10 in EXT2) in 167 patients, 20 of which presented with negative family history and are therefore considered “de-novo” mutations.

Comparison of the clinical data and prospective long term follow-up will possibly clarify different prognosis and risk of secondary chondrosarcoma for different genotypes.

We reviewed 124 patients with a conventional pelvic chondrosarcoma who had been treated over a period of 20 years. We recorded the type of tumour (central or peripheral), type of operation (limb salvage surgery or hemipelvectomy), the grade of tumour, local recurrence and/or metastases, in order to identify the factors which might influence survival.

More satisfactory surgical margins were achieved for central tumours or in those patients treated by hemipelvectomy. However, grade 1 tumours, whatever the course, did not develope metastases or cause death, while grade 3 tumours had the worst outcome and prognosis.

Central, high-grade tumours require aggressive surgical treatment in order to achieve adequate surgical margins, particularly in those lesions located close to the sacroiliac joint. By contrast, grade 1 peripheral chondrosarcomas may be treated with contaminated margins in order to reduce operative morbidity, but without reducing survival.

Aim: This study wants to investigate whether the administration of stromal stem cells (SSC) in a platelet-rich plasma (PRP) scaffold could promote angiogenesis which resulted in a better allograft integration.

Methods: surgery: A monolateral resection of 3cm segment of the metatarsus, was perfomed in 10 adult cross-breed sheep (3–4 years old), weighting 60–70 kg.

Isolation and ex-vivo expansion of SSC: nucleated cells were isolated with density gradient and expanded ex-vivo with alpha-MEM containing 20% FCS.

Radiographic and histomorphometric analysis: Radiographs were made after surgery and after 1, 2 and 4 months. Histomorphometric studies were carried out to study the defect and the new bone formation at the implant site

Results: Union had occurred in all the 5 animals of the SSC group after 4 months as observed radiographically and morphologically, while in the control group the osteotomy line was still visible. Histomorphometric analysis demonstrated a higher % of new-bone formation in both the host (%section quadrant) and the grafted bone in SSC animals.

Conclusions: Results presented suggest that SSC in PRP-based scaffold have improved allograft integration. In conclusion the application of this surgical approach may result in an increased and accelerated bone graft integration, reducing the time required for bone healing and increasing the chances of a successful bone implant.

Bone reconstruction in pediatric oncology always has to face two major problems: the frequent unavailability of small prosthetic tools and the difficulty in finding bone allografts of adequate size.

Aim of this work is to present the research lines in this field, currently active in our institution to improve the planning and the results of reconstructive tumor surgery in children. Starting from patient’s CT data sets, subject-specific 3D models of bone segments can be created and compared with the similar models obtained by the CT analysis of massive allografts stored in the Rizzoli Bone Bank.

In the same time the computer modelling technologies allow the development of three-dimensional environment, where the surgeon can navigate and exploit both artificial (prostheses, metallic plates and screws) or biological tools (bone allografts or autografts).

The presented method has been utilized with success in 10 children (mean age 8, range 4–13) that underwent a skeletal reconstruction of the limbs in the last year (proximal humerus 1, diaphyseal humerus 1, total humerus 1, distal radius 1, proximal femur 3, diaphyseal femur 1, proximal tibia 1, diaphyseal tibia

Aims: Purpose of this study was to obtain long term follow-up in patients with Osteofibrous Dysplasia (OFD), in order to investigate natural history of the disease, late results of treatment, and potential risk of Adaman-tinoma development in this setting. Methods: A retrospective study of 48 patients with histologically proven OFD observed at our Institution between 1900 and 1997 was undertaken. Clinico-pathologic features of all cases were reviewed and found consistent with OFD. A clinical status update and current radiographs were obtained in all patients. A subgroup of 21 patients with minimum follow-up of 20 years (21 to 44 years, average 27) was analysed for functional result and adamantinoma development. Functional result according to MTS-ISOLS score correlated with surgical aggressiveness. Results: Best results were observed in patients that received a single biopsy or curettage; worse results were seen after multiple resections or osteotomies and associated with complications as infection or compartment syndrome. No patients had current symptoms or significant symptoms changes nor physical findings, radiographic clues or subsequent radiographic changes suggesting adamantinoma development. Conclusions: OFD is a benign condition; the natural history of the disease has minimal consequences in the adult life. Surgical treatment is usually not necessary and may actually worsen the result because of the potential for severe complications.

The relationship with adamantinoma remains unclear, follow-up is suggested.

Aims: Purpose of this study was to evaluate the results of a staged revision technique in the treatment of deep infection after limb salvage surgery for bone tumors and to identify factors possibly affecting the outcome. Methods: A retrospective study of 19 consecutive patients with an infected bone tumor reconstruction treated at our Institution in the period 1986–1997 was undertaken. All the patients underwent staged revision (two stages in 13 cases, three stages in 5, four stages in 1) using one or more antibiotic loaded cement spacers after debridement and partial (10 cases) or complete (9 cases) removal of the original implant. Postoperatively, all the patients received oral or parenteral antibiotics for a minimum of 4 weeks. Delayed reimplantation was performed in 15 cases, average time to reimplantation being 7 months (4–14). A minimum follow up of 3 years was available in all patients. Cultures identiþed S. Epider-midis in 12 cases (63%), S. Aureus in 4 (21%), mixed organisms in 2 (11%), and were negative in 1 case (5%) despite clinical evidence of infection. Results: At a minimum follow-up of 3 years, 13 patients were continuously infection-free (68%) while 6 relapsed (32%). Two of the 6 relapses were cleared by amputation while 4 remained infected. Average functional result of infection-free patients according to the International Society Of Limb Salvage (ISOLS) was 71% (21.2 points), ranging from 60% to 80% (18 to 24 points). Conclusions: Staged revision with antibiotic loaded cement spacer for infected bone tumor reconstruction is a demanding and expensive technique requiring prolonged inability. Overall success rate in this series approaches 70%. Complete removal of the infected implant, microbiology, appropriate antibiotic selection, and negative cultures before reimplantation are crucial.

Purpose of this study is to examine the long-term follow-up in prosthesis reconstruction after proximal humerus resections.

Material and methods From February 1975 to December 1990, 144 patients have been operated for a musculoskeletal tumor of the shoulder girdle with resection and reconstruction using a modular cemented prosthesis. The MRS prosthesis is assembled in three parts with a ball shaped rotating head stitched to the glenoid and acromium. Seventy patients died and 3 patients were lost to follow-up: 71 achieved a follow-up more than 10 years (123–259, av 175 mo). Age ranged from 9 to 73 years (mean 29.7). The resection was intrarticular in 44 cases, in 12 more the glenoid was resected along with the proximal humerus (extrarticular resection) and in 15 cases we performed a Tikhoff –Lindberg procedure.

Infection occurred in 7 patients (10%) from 1 to 144 months (median 12 mo): in 6 patients prosthesis removal was needed to achieve healing.

Mechanical complications were present in 19 patients (27%): 15 (21%) had prosthetic head instability (5 surgically treated), 2 breakage of the prosthetic stem and 2 prosthetic disassembly.

Results: A detailed roentgen graphic analysis has been developed to better define the long-term course of the cement bone interface. Only 3 aseptic stem loosening were detected at 1, 3 and 11 years (after a supercondylar fracture occurred 8 months before). Eighteen patients were reoperated (25%); in 4 cases with minor surgery. Failure of the system occurred in 11 cases (15%).

Conclusion: The long durability of this cemented prosthesis has been demonstrated with very few cases of stem loosening in the early follow-up time. The problem of a good prosthetic head suture is still under concerning particularly in Tikhoff-Lindberg procedure.

We have studied 560 patients with osteosarcoma of a limb, who had been treated by neoadjuvant chemotherapy, in order to analyse the incidence of local and systemic recurrence according to the type of surgery undertaken. Of these, 465 patients had a limb-salvage procedure and 95 amputation or rotationplasty.

At a median follow-up of 10.5 years there had been 225 recurrences. The five-year disease-free survival and overall survival rates were 60.7% and 68.5%, respectively, with no significant difference between patients undergoing amputation and those undergoing resection. The incidence of local recurrence was the same for patients treated by either amputation or limb salvage and correlated significantly with the margins of surgical excision and the histological response to chemotherapy. The outcome for patients with a local recurrence was significantly worse than for those who had recurrent disease with metastases only.

We conclude that limb-salvage procedures are relatively safe in osteosarcoma treated by neoadjuvant chemotherapy. They should, however, only be performed in institutions where the margins of surgical excision and the histological response to chemotherapy can be accurately assessed. If the margins are inadequate and the histological response to chemotherapy is poor an immediate amputation should be considered.

We describe 25 patients who were treated for a tumour of the proximal femur by resection and replacement with an uncemented, bipolar, modular prosthesis. When followed up after more than ten years four prostheses (16%) had required revision. Two joints showed wear and another necrosis of the acetabulum. One patient with loosening of the stem had been treated by radiotherapy to the femur. Articular cartilage seemed to be a reliable barrier to acetabular wear. Very few signs of the formation of particulate debris were observed. The most obvious feature in the bone-stem relationship was stress shielding, seen as osteoporosis of the proximal part of the femur around the stem in 68%. Functional activity was satisfactory in 68% of the patients. A better system of reattachment of the soft tissues is needed to avoid pain and a persistent limp.