In the last few decades the majority of patients with bone and soft tissue sarcomas have been treated with limb- salvage surgery.28,40 In addition to the use of biologic solutions, endoprostheses have gained increasing acceptance among orthopaedic oncology surgeons during the last 30 years.46 Modular systems have replaced one-piece prosthesis construction.45 Modern tumor endoprostheses have modularity, allowing for intraoperative flexibility of the reconstruction length and good functional results.3 During the last 30 years, the overall 5-year survival rate of endoprostheses has increased from 20% to 85%, which occurred despite better patient survival rates and high demands on the implants by young and physically active patients.28 Nevertheless, the use of endoprostheses as limb-saving therapy is accompanied by a high rate of late complications such as loosening, infection, and mechanical failure.9,10,38 The aim of this study was to assess the successful reduction of complications in limb salvage surgery using a new Modular Universal Tumor and Revision System (Mutars®) (Implantcast, Buxtehude, Germany).
MATERIALS AND METHODS
We retrospectively reviewed 250 patients (115 females, 135 males) treated for a bone or soft tissue sarcoma (including four patients with a transformed giant cell tumor) using a Mutars® (Implantcast) tumor endoprosthesis from 1992 to 2003. The mean age of the patients was 30.7 years (range, 7.4-80 years), and the mean followup was 45 months (range, 3-140 months). The indications for endoprosthetic replacement were: osteosarcoma (139 patients), chondrosarcoma (43 patients), Ewing's sarcoma (36 patients), osseous malignant fibrous histiocytoma (12 patients), parosteal osteosarcoma (six patients), osseous leiomyosarcoma (three patients), undifferentiated bone sarcoma (two patients), and fibrosarcoma of bone (one patient). Four patients had a soft tissue sarcoma with osseous involvement. At first presentation the Enneking13 disease stages included: Ia (two patients), Ib (35 patients), IIa (one patient), IIb (151 patients), and III (57 patients). Four patients had a transformed giant cell tumor.
Twenty-three patients (20 patients with Ewing's sarcoma) received chemotherapy and radiation therapy. One hundred fifty- eight patients received only chemotherapy and six patients received only radiation therapy. Sixty patients had no neoadjuvant treatments. Patients with osteosarcoma received chemotherapy according the Cooperative Osteosarcoma Study5 and patients with Ewing's sarcoma according the European Intergroup Cooperative Ewing's Sarcoma Study protocol.33
The osseous defect was reconstructed with a modular Mutars® (Implantcast) endoprosthesis. The endoprosthesis was titanium and the articulating areas were CoCrMo. The defect was reconstructed in 2-cm steps, and the modular components were fixed with screws (Fig 1). The rotation between the components can be changed in 5°-increments. Normally, the stem was implanted without cementation. However, we used gentamicin containing cement (Refobacin®-Palacos®, Biomet Europe, Berlin, Germany) for the implants that were cemented. Stems for uncemented implantation were 12 cm long, were hexagonal, and achieved good primary rotational stability (Fig 2). The stem has been coated with hydroxyapatite (HA) since 1997, but the femoral shaft preparation has changed. Previously, the medullary cavity was reamed concentrically before implanting the hexagonal stem. Since then it has been under-reamed to 1.5 mm less than the stem diameter. It was prepared to a hexagonal shape by a special rasp providing better contact between the HA coating and cortical bone. All prostheses were planned by using a digital radiograph (Fig 3). We used a rotating-hinge knee prosthesis in distal femoral and proximal tibia replacements.
After key soft tissue structures of the hip abductors, knee extensor mechanism, or rotator cuff were resected, they were reconstructed by fixation to a Trevira® tube (Implantcast, Buxtehude, Germany) placed around the prosthesis and fixed by sutures.16 In proximal tibia replacement, gastrocnemius flaps were used to provide adequate muscle coverage of the prosthesis and to reinforce the extensor mechanism reconstruction (Fig 4). The patellar tendon, which was sectioned 1-2 cm proximal to the tibial tubercle, was also sutured to the Trevira® tube (Implantcast). To allow tension-free skin closures, we used mesh grafts after proximal tibia replacement. In proximal femoral replacements, the hip was reconstructed using a bipolar cup or a socket.
We reconstructed the proximal humerus in 39 patients and the prosthesis was covered with a Trevira® (Implantcast) tube. Stem cementation was performed in 12 patients. We performed an extraarticular resection in 13 patients, which was combined with a Tikhoff-Linberg procedure in eight patients. We performed a distal humerus replacement in five patients and a total humerus replacement in seven patients.
We performed a proximal femoral replacement in 41 patients. An extraarticular resection was performed in nine patients, and in six patients a proximal femur resection was combined with a P2-P3 hemipelvectomy. Thirteen patients had stem cementation, and a Trevira® tube (Implantcast) was used in 37 patients. Of 28 evaluable patients with an intraarticular resection, 16 had a bipolar cup and 12 had a socket.
We treated 103 patients with a distal femoral replacement; 16 patients had an extraarticular resection. A Trevira® tube (Implantcast) was used in four patients for extensor reconstruction. A gastrocnemius flap for better muscle coverage of the prosthesis was performed in 30 patients. Twenty-four patients had cemented stems.
We performed an intraarticular tumor resection in 12 patients with a total femoral replacement, and a Trevira® tube (Implant- cast) was used to reattach the muscles. A bipolar cup was used in 11 patients.
Forty-two patients received a proximal tibia replacement. A Trevira® tube (Implantcast) was used for attaching the gastrocnemius and patellar tendons. An extraarticular resection was performed in only two patients. Nine patients had mesh graft to allow a tension-free skin closure. Only one patient received a cemented tibia stem, and one patient received a total tibia replacement.
Postoperatively, all patients received intravenous cephalosporin for 3 to 7 days, followed by oral therapy until wound healing was achieved. They also received local antibiotic prophylaxis with a gentamicin-containing collagenous drug carrier. The shoulder was immobilized in a sling for 4 weeks after proximal humerus reconstructions.
In patients with a cementless implantation of the prosthetic stem of the lower extremity, weightbearing was restricted to 10 kg for 6 weeks followed by increasing weightbearing by 10 kg per week. The patients received a low molecular heparin during the period of no full weightbearing. The range of motion (ROM) was not restricted in patients treated with a proximal femoral replacement combined with a bipolar cup. However, patients with a socket were restricted to bed rest for 4 weeks. In the proximal tibia replacement or distal femoral replacement with an additional gastrocnemius flap, the knee was kept immobilized in a knee immobilizer for 4 weeks.
Survival data were compiled using the Kaplan-Meier survivorship analysis and analyzed using Statistical Package for the Social Sciences software (Version 11.0, SPSS Inc, Chicago, IL). Any event (eg, local recurrence or prosthetic failure) which led to ablative surgery was considered in the limb-survival analysis. In contrast, the end points for prosthetic failure were aseptic loosening, stem fracture, and infection. Radiographic signs of aseptic loosening were proven by surgery. Infection was diagnosed in the presence of pus or if the leucocyte count in the fluid aspirated from the periprosthetic cavity was elevated. In two patients infection was diagnosed only by chronic inflammatory tissue in histologic sections. We performed a multivariate Cox regression analysis to determine possible risk factors for prosthetic survival. Each factor was examined with a log-rank test based on Kaplan-Meier estimates. The influence of stem design on loosening and the influence of prosthesis type on infection rate were determined using the chi square test.
There were 203 patients alive at final followup (mean, 45 months; range, 3-140 months) despite 6.9% (14 patients) of patients presenting with metastatic disease and 0.5% (one patient) with local recurrence. One hundred eighty- nine patients remained alive with no evidence of disease at a mean of 50 months (range, 3-140 months). Forty-seven patients died of disease at a mean of 26 months (range, 3-100 months).
The 5-year limb survival in patients with tumors of the upper extremity and the lower extremity were 88.7% and 87.1%, respectively. Limb survival was 93.1% for distal femur tumors, 87.1% for proximal tibia tumors, and 82.6% for proximal femur tumors.
Prosthetic survival without any reoperation was 60.4% at 5 years and 42.3% at 10 years postoperatively (Fig 5). Excluding minor revision surgeries, the prosthesis survival rate was 79.9% at 3 years and 71.2% at 5 years postoperatively. Patients with chondrosarcoma had the best 5-year survival rate at 93% (mean survival, 93 months; 95% confidence interval [CI], 86-101) compared with survival in patients with osteosarcoma (70.4%; mean survival, 87 months; CI, 77-97) (p = 0.02) and Ewing's sarcoma (67.4%; mean survival, 72 months; CI, 59-85) (p = 0.05). Prosthetic survival was adversely influenced by radiation therapy and chemotherapy. The 5-year survival rate was 73.6% (mean survival, 96 months; CI, 88- 105) without and 57.9% (mean survival, 64 months; CI, 50-79) (p = 0.16) with radiation therapy. Patients without chemotherapy had prosthetic survival of 82.5% (mean survival, 107 months; CI, 96-119) compared with 67.6% (mean survival, 85 months; CI, 76-94) (p = 0.17) for patients treated with chemotherapy. Radiation therapy did not influence outcome in patients treated with chemo- therapy and without chemotherapy, nor did age. The 5-year prosthetic survival was 69.4% for patients 0-20 years old, 76.4% for patients 21-40 years old, 72.7% for patients 41-60 years old, and 73.6% for patients older than 61 years. The replacement site had the most important influence on survival. Based on Kaplan-Meier estimates, the 5-year survival rate was 89.7% for endoprostheses of the upper extremity. Proximal humerus replacement had an even better 5-year survival rate at 93.6%. The results of a proximal humerus replacement were better (p < 0.05) than in any other site. The 5-year survival rate was 68.5% for endoprostheses of the lower extremity. Proximal femoral replacement revealed better survival rate (5-year survival rate, 78.7%) than distal femoral replacement (5-year survival rate, 65.9%) (p = 0.40) or proximal tibia replacement (5-year survival rate, 61.7%) (p = 0.25) (Fig 6). Prosthetic survival was better (p = 0.0036) for patients with an intraarticular distal femur resection (73.1% at 5 years) than for patients with an extraarticular distal femur resection (34.4% at 5 years).
The most common complication was deep prosthetic infection (30 patients; 12%). The type of prosthetic replacement did not influence infection rates. However, predilection sites were a proximal femoral replacement in eight patients (19.5%), a proximal tibia replacement in seven patients (16.7%), and a distal femoral replacement in 12 patients (11.7%). Extraarticular resection with distal femoral replacement resulted in a 6.2-fold higher (p = 0.004) infection risk compared with intraarticular resection.
Twenty patients (8%) had obvious aseptic loosening as defined in Materials and Methods. The most common site was the distal femoral replacement with femoral stem loosening in 15 of 103 patients (14.6%). Excluding one of these patients, in whom loosening was caused by a CoCr allergy, loosening was obvious in 13.6% of patients. This patient had revision surgery using a titanium-niob coating of the articulating surfaces which resulted in stable implant fixation. Loosening was associated with implantation of a CoCr stem without HA coating and without hexagonal shaft preparation (conventional technique). Loosening occurred in nine of 27 (33.3%) such patients with a mean followup of 76 months, compared with four of 52 patients (7.7%) treated with the new implantation technique at a mean followup of 40 months (p < 0.006). Extraarticular resection of the knee resulted in a loosening rate of 25% (four of 16 patients). Loosening after intraarticular resection occurred in 11 of 87 patients (12.6%). Loosening of an uncemented tibial stem occurred three of 42 patients with a proximal tibial replacement (7.1%).
The prosthetic stem broke in four patients (1.6%) at a mean of 43.3 months (range, 21-70 months) postoperatively. Three of 103 patients (2.8%) with a distal femoral replacement had femoral stem breakage. One of 42 patients (2.4%) with a proximal tibial replacement had tibial stem breakage. All stem diameters were 12 mm or less. Two of three femoral stems were cemented, but the tibial stem was uncemented.
Cranial subluxation of a proximal or total humerus replacement occurred in only two patients (4.3%). Only three patients (7.3%) with proximal femoral replacements had a dislocation. One patient who had dislocation in the first postoperative week did not have a Trevira® tube (Implantcast). All patients with dislocations had socket implantations. There was no dislocation of a bipolar cup in combination with the Trevira® tube (Implantcast) in patients with an intraarticular proximal femur resection.
Eight of 103 patients (7.8%) who had a distal femoral replacement had polyethylene bushing wear develop. The polyethylene was changed at a mean of 28 months (range, 6-70 months) postoperatively. An avulsion of the patella tendon with development of patella alta and an extension deficit of 20° occurred in one patient with a proximal tibia replacement. The patient did not accept the immobilization for 4 weeks. In all other patients the extensor mechanism allowed active knee extension with a mean extension lag of 5° (range, 0°-20°).
The functional score, as described by Enneking et al,14 was a mean of 25 of 30 points for patients with a proximal tibia replacement (83%; range, 13-30 points), 24 points for patients with a distal femoral replacement (80%; range, 8-30 points), 23 points for patients with a distal humerus replacement (77%; range, 18-27 points), 21 points (70%) for proximal femoral (range, 14-29 points) and humerus (range, 1-25 points) replacements, 20 points for total femoral replacements (67%; range, 13-27 points) and 19 points for total humerus replacements (63%; range, 18-20 points).
Limb-sparing surgery with tumor endoprostheses has steadily increased during the last decades as endo- prosthetic survival has improved because of advances in prosthetic design with modular components, manufacturing, surgical techniques (eg, muscles flaps), and experience using endoprostheses.29 However, the complication rate after endoprosthetic replacement is still high (eg, aseptic loosening, stem fracture, infection, and dislocation).22,25,28,29,35,41 We evaluated the complication rate and functional outcome of the newly developed Mutars® (Implantcast) tumor endoprosthesis system. The new hexagonal-shaped design of the stem should provide good rotational stability with reduced loosening rates and less stem breakage. Using the Trevira® tube (Implantcast) should decrease dislocation and improve functional results.
The current retrospective study has inherent limitations. Some patients could not be included in the study because of incomplete data. Furthermore, it was not possible to contact all patients many years postoperatively. Therefore, a selection bias cannot be excluded.
Aseptic loosening remains a major problem after prosthetic replacement of large bone defects.18,29,39,42,46 Its occurrence depends on the endoprosthetic reconstruction site, with the highest rates of loosening occurring for a distal femoral replacement.29 Mittermayer et al29 and Plotz et al34 favored cementless fixation and reported aseptic
loosening in 8.4%-11% of patients with a tumor endoprosthesis of the lower extremity. Our results suggest preparing the medullary cavity with a hexagonal rasp and implanting the HA-coated titanium stem led to good primary rotation stability and excellent secondary osseo- integration, with a loosening rate of only 7.7% for distal femoral replacement. The shape of the distal femur stem is important. Anatomically curved femoral stems achieve a long press-fit stem anchorage (Fig 2).28,46 In contrast to constrained prostheses, using rotating-hinge knee prostheses that allow limited external and internal rotations, rotational stress is resorbed mainly by the joint instead of the stem. Therefore, aseptic loosening has been reported to be reduced.3,8,17,29
We think that there are some indications for cemented- stem implantations. Cement is indicated in patients with a poor prognosis, and it allows older patients to be bear full weight immediately, therefore optimizing quality of life and reducing complications from reduced weightbearing. With metadiaphyseal resection of the distal femur, a cementless press fit-stem implantation often is not possible, requiring the use of cement to achieve stable fixation (Fig 7).
The most common implant failure resulting in prosthetic removal is a stem fracture (3.3%-16% of patients).28,34,45 However, stem breakage can be reduced by replacing the thick macroporous surface coating with a thinner macroporous surface allowing a larger minimal diameter of 11 mm.34 Our excellent results emphasized the stability of forged titanium stems for distal femoral replacement with only a thin HA coating, making a larger core stem diameter possible.46 The only stems that broke were smaller than 12 mm in diameter, therefore we now implant only stems with a minimal diameter of 12 mm.
Infection is the most serious complication in limb salvage with tumor prostheses.11,12,23,35,41 Infection rates are between 1% to 36%, with lower rates for the upper extremity and higher rates around the knee, especially for the proximal tibia replacement.17,22,28,34,44,45,46 Routine use of a gastrocnemius flap when performing proximal tibia replacement reduced the infection rate in our patients to 16.7%, and from 36% to 12% in patients in the study by Grimer et al.17 Furthermore, the development of smaller implants, especially for very young children, made soft tissue coverage of the prosthesis easier.34 However, despite these improvements, reported infection rates in addition to the rate in our patients are still high. We hope to reduce the infection rate in the future by using an antimicrobial silver coating.15
Complications have led to prosthetic removal, but wear of the load-bearing surfaces usually can be treated by minor revision surgery.28 Failure of the polyethylene bushes was reported in as much as 42% of patients by using fixed-hinged knee prostheses with one-block polyethylene bushings.7 However, this complication can be reduced to less than 10% by using rotating-hinge knee mechanisms and two-block bushings,28,34,45 Early repair of the worn bushing is necessary, however, to prevent aseptic loosening from the debris.28
Dislocation is the most common complication after proximal and total femoral endoprosthetic reconstructions,2 with rates varying from 1.7% to 20%.2,9,22,24,43 Use of a tube for muscle reattachment and reconstruction of the joint capsule was not reported in any of these studies. In our study, dislocation could be reduced to 0% by a surgical technique of acetabular preservation and reconstruction of the joint capsule with a Trevira® tube (Implantcast) on which the abductor mechanism and the iliopsoas muscle are reattached to avoid a persistent limp. Good functional results were achieved.9 These data emphasize that the use of a bipolar cup offers additional stability and lessens the risk of dislocation.9,16,30 In the study of Bickels et al,2 the same operative technique resulted in a dislocation rate of 1.7%. Donati et al9 described acetabular wear after proximal femoral replacement with a bipolar cup in only two of 25 patients after a followup greater than 10 years. In proximal humerus replacement, the Trevira® tube (Implantcast) reduced the high dislocation rates reported in previous studies6,36 by reattaching the remaining muscles to the tube.1,26
In proximal tibia replacement one major technical difficulty is restoring the extensor mechanism.17 The absence of a powerful extensor mechanism results in poorer functional results.17 Zeegen et al46 reported the extensor mechanism ruptured in one of eight patients with a proximal tibia replacement. They did not use a tube for fixation of the patella tendon. Plotz et al34 reconstructed the extensor mechanism with a Trevira® (Telos, Marburg, Germany) band with augmentation by the patella tendon which was fixated at the prosthesis by a screw; a screw broke in one of 10 patients. Bickels et al4 reconstructed the extensor mechanism by reattaching the patellar tendon to the prosthesis with a Dacron tape-reinforced autologous bone graft. With this technique 14.5% of patients required a secondary reinforcement of the patellar tendon.4 Twenty percent of patients had an extension lag greater than 20°.4 In contrast to these results, by using the Trevira® tube (Implantcast) for reattaching the patellar tendon, only one patient had an extension lag greater than 20°. Because of tight fixation of the extensor mechanism to the Trevira® tube (Implantcast) with augmentation with a gastrocnemius flap, the functional outcome in proximal tibia replacement is better (Enneking score of 83%) than reported in other studies.4,34
In addition to the followup duration, prosthetic survival depends on the site and type of replacement. Reconstructions in the shoulder and hip have greater survival rates than endoprostheses around the knee.19,20,27,30,35,46 The survival rates of the Mutars® (Implantcast) system were excellent, with 5-year prosthetic survival rates of 93% for proximal humeral replacements, 78% for proximal femoral replacements, 66% for distal femoral replacements, and 61% for proximal tibial replacements.
The lower survival rate for proximal femoral replacements (78% in our study; 89%-100% reported in the literature19,30,46) can be explained by the large number of patients with Ewing's sarcoma receiving radiation therapy. Of these patients, four of eight had infections develop, necessitating prosthetic removal. Routine use of gastrocnemius flaps and strong fixation provided by the Trevira® tube (Implantcast) were important factors contributing to improved 5-year prosthetic survival rates (61% in our study; 54% reported by Horowitz et al20) for proximal tibia replacements.
The survival rates for distal femoral replacements have been reported as 59% to 87%.19,21,35,37,46 Our overall 5-year prosthetic survival for distal femoral replacements was lower at 65.9%. However, these results were negatively influenced by the number of extraarticular resections, which had worse results. Excluding these patients, the 5-year prosthetic survival was 73.1%.
In addition to prosthetic survival, it is important for patients to have as few revision surgeries as possible. Using the Mutars® system, no reoperation was necessary in 60.4% of patients at 5 years and in 42.3% at 10 years. In contrast, Plotz et al34 reported the probability of survival of the prostheses without any reoperation as 34% after 5 years and 25% after 10 years.
The Mutars® system (Implantcast) has some advantages compared with other systems. First, using a Trevira® tube (Implantcast) makes muscle and tendon refixation much easier, resulting in a reduced dislocation rate of the hip and better functional results in proximal femoral and tibia replacements. Second, using a hexagonal-shaped, forged stem and a special preparation technique of the medullary canal in distal femoral replacements reduced the aseptic loosening rate. Third, we hope to reduce the infection rate with the newly developed antimicrobial silver coating.15
We thank Sam Patton, MD, Department of Orthopaedic Surgery, Edinburgh University, for revising the paper as a native-speaking orthopaedic surgeon specializing in orthopaedic oncology.
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