All patient analysis was conducted with regard to survivorship, complications, site of complication, functional outcomes, and fixation method. Statistical outcomes were measured using the chi-square test and t-test for two proportions with a level of significance set at p < 0.05. All statistical analyses were performed using GraphPad Prism Software (Version 6; GraphPad Software, Inc, La Jolla, CA, USA).
Overall, there were 12 implant-related complications (27%) with 11 of these being either Type II or Type III failures (Table 2). Of these 11, five cases (11%, Patients 7, 14, 15, 20, and 23) had Type II (aseptic loosening) failure, which occurred at the distal stem of the prosthesis at the bone-stem interface and six cases (14%, Patients 5, 6, 16, 26a, 40a, and 40b) had Type III (structural) failures, which occurred at the clamp-rod interface. Four of the five cases of Type II failure were associated with breakage of the distal locking screw (Patients 7, 14, 15, and 20). Of the six cases of Type III failure, three patients had failure of the reducing bushing within the prosthesis (Patients 5, 26a, and 40a) and were revised with a new spacer clamp (Fig. 2). One patient (Patient 40b) experienced a second failure of the spacer clamp and was converted to an autograft-nail construct. Two other failures in this group occurred after a traumatic fall causing loosening of the clamp spacer and malrotation in one (Patient 6), which was corrected through revision surgery, and breakage of a connecting spacer in the other (Patient 16) requiring conversion to a total femoral replacement. One patient who previously experienced a Type III failure and was revised with a new clamp subsequently experienced a Type IV failure (infection), which required removal of the implant and conversion to a total femur replacement (Patient 26b). There was one case of local recurrence in a patient with metastatic renal cell carcinoma who required an above-knee amputation as a result of disease progression (Patient 37). We classified this patient as having a Type V (local recurrence) failure.
All 12 nononcologic complications occurred in patients with femoral implants. When compared with other anatomic sites, complications were more common in femoral sites (12 of 21 procedures [57%]) than in either tibial or humeral sites (0 of 23 procedures; odds ratio [OR], 62; 95% confidence interval [CI], 3-1154; p < 0.0001). Complication rate was not associated with resection size or intramedullary stem dimensions.
Overall, patients in this series had a mean MSTS score of 77% (humerus = 83%, tibia = 77%, femur = 75%) and additional detail for MSTS scoring can be seen in Table 1. Patients with cemented implants had higher MSTS scores than those with noncemented fixation (84% versus 66%, p = 0.0017). To assess the potential role of increased followup and implant age on functional scores, MSTS scores and subscores were grouped by anatomic site and then by duration of followup into 2 groups: (1) cases with less than 1 year followup and (2) cases with 1 year of followup or more. Duration of followup was not associated with MSTS scores for any anatomic sites. Resection size and intramedullary dimensions were not associated with either overall MSTS scores or subscores as assessed by the MSTS system.
The complication rate was 33% in noncemented cases and 21% in cemented cases (p = 0.39). In cases of noncemented fixation, all five nononcologic failures were Type II failures and occurred at the bone-stem interface. In cases of cemented fixation, all six nononcologic failures were Type III failures and occurred at the clamp-rod implant interface. Noncemented fixation of femoral reconstructions was associated with Type II failure and cemented fixation in the femur was associated with Type III failure (OR, 143; 95% CI, 2.413-8476; p = 0.0022).
Reconstruction of segmental skeletal defects in long bones after oncologic resection presents a challenge for orthopaedic surgeons. There are several methods of reconstruction for these defects, which include autografts, allografts, and endoprostheses. The goals of surgery are to relieve pain, achieve tumor control, and preserve function. Ideally, the reconstruction would provide immediate stability, preservation and early motion of adjacent joints and survival for the lifespan of the patient [10, 13, 35]. This study presents the functional outcomes of 44 reconstructive operations in 41 patients using a modular intercalary endoprosthesis. These results are comparable to similar studies involving intercalary endoprostheses and the inclusion of 41 patients (44 implants) from three musculoskeletal oncology centers makes this one of the largest studies to date using this type of reconstruction [1, 2, 9, 10, 18, 24, 31, 33] (Table 3).
This study has several limitations which bear discussion. First, this is a retrospective study and as such is subject to recall and selection bias. Notably, this may have contributed to our inability to find a difference in complication rate based on the use of cemented PMMA versus press-fit stems for fixation. Second, this study lacks a true control group because all cases included in this study fall under a single clinical indication and only one treatment was used for this indication; thus, we cannot directly compare our results with other types of implants, biologic reconstructions, or other more conservative treatments for other indications such as radiation alone or radiation combined with internal fixation. Third, the types of tumors included in this study as well as our patient population includes both cases of primary bony tumors and metastatic lesions in patients with notably different life expectancies as a result of variation in age and tumor stage at the time of treatment. Fourth, three (7%) of our patients were lost to followup and we cannot account for the lifespan of these implants in our final analysis.
We found a 27% overall nononcologic complication rate (12 of 44 procedures experienced complications) in our patients treated with this intramedullary endoprosthesis, which is similar when compared with the other options currently available. Published reports in the literature have complication rates ranging from 14% to 50% with mechanical failure of the prosthesis and aseptic loosening of the proximal or distal stem as the most common complications [1, 9]. Intercalary allografts allow attachment of soft tissues and come in various sizes, but patients are subject to a longer period of postoperative immobilization to protect the reconstruction until graft union . They are also associated with complications, including nonunion (18%-64%) [12, 15, 22, 23], fracture of the allograft (15%-51%) [5, 12, 23, 25], and a risk of infection of up to 30% [12, 15, 26]. In these studies of intercalary allografts, most patients were treated for primary bone sarcomas and are not directly comparable to the majority of patients in this study. Vascularized autografts are another option and may heal and hypertrophy under mechanical loads, but it may take several years before the graft will allow full weightbearing . Additionally, these grafts may have size limitations and are associated with donor site morbidity [7, 29]. Extracorporeally irradiated autografts can be used as an alternative to allografts to reconstruct a defect but require a longer time to incorporate and are therefore subject to nonunion, fracture, and infection . In addition, the potential loss of structural integrity of the resected bone segment limits the use of this technique. Distraction osteogenesis and bone transport may provide adequate biomechanical strength but may be time-consuming (1 mm/day) and has the drawbacks of external fixation with pin tract problems, which may pose an increased infection risk, especially in patients receiving adjuvant radiotherapy and chemotherapy [13, 36]. Reconstruction with an endoprosthesis avoids the prolonged period of immobilization associated with auto- and allograft reconstructions and allows early weightbearing. Early endoprostheses were limited by the lack of modularity. Lap joint endoprostheses are capable of using various stem-body lengths to create the prosthesis, but the segments are a one-piece design and sizes are more limited [9, 10]. Custom-made prostheses require several weeks to fabricate. In contrast, the IDSF system provides a modular design allowing the surgeon to intraoperatively adjust the implant to the proper size with various stem and spacer dimensions to fill the defect and correct any limb length discrepancy . A recent biomechanical study has demonstrated systematically equivalent or greater load resistance of modular segmental endoprostheses in all types of loading (axial compression, four-point bending, internal and external torsion) when compared with other fixation techniques .
Complications in our study were limited to patients with femoral implants. Although the overall incidence of complications in this study is 27%, which is similar to other studies [1, 2, 4, 9, 10, 18, 24, 31, 33] (Table 3), 57% of femoral reconstructions developed complications in this series.
We observed that the average functional results of all patients as measured by MSTS scores was 77% and this is comparable to that seen in other studies of intercalary endoprosthesis [9, 18, 24, 31, 33]. This approach seemed to provide adequate pain relief and maintenance of function, most notably with respect to the reduced postoperative time until full weightbearing could be permitted, in a group of patients who have a relatively short expected lifespan.
The use of PMMA for fixation of this intercalary endoprosthesis may be advantageous because our results and other studies have demonstrated increased postoperative function as measured by MSTS scores in patients with cemented implants [16, 21]. Failure of this implant remains a concern in cases of femoral reconstruction and this study demonstrates that cemented reconstructions are associated with failure at the clamp-rod interface (Type III), whereas noncemented fixation is associated with aseptic loosening and stem failure (Type II). Cemented fixation may also be beneficial because revision of stem (Type II) failure is surgically more challenging than revision at the clamp-rod interface.
The surgeon and patient need to consider the various options of treatment and especially whether to goal is palliation versus an attempt to increase disease control in patients with metastatic carcinoma. This prosthesis has value in patients with a solitary bony metastasis in a long bone with shortened expected longevity. Various autografts, allografts, and prostheses have all been proposed, each with its own advantages and disadvantages. The results of this study and those of similar studies indicate that the IDSF endoprosthesis can be used with results that seem similar to those of reported with other reconstructions. Because there has been an emphasis on early weightbearing and return to normal activity in patients with limited life expectancy, immediate stability provided by an intercalary endoprosthesis makes this a reasonable alternative to consider. In conclusion, the authors recommend caution in its use at the femoral site as a result of its high rate of complication. For cases of solitary tumors in the humerus and tibia, which cannot be otherwise reconstructed using biologic options, we recommend the use of the IDSF system with PMMA for fixation.
1. Abudu A, Carter SR, Grimer RJ. The outcome and functional results of diaphyseal endoprostheses after tumour excision. J Bone Joint Surg Br.
2. Ahlmann ER, Menendez LR. Intercalary endoprosthetic reconstruction for diaphyseal bone tumours. J Bone Joint Surg Br.
3. Aksnes LH, Bauer HC, Jebsen NL, Folleras G, Allert C, Haugen GS, Hall KS. Limb-sparing surgery preserves more function than amputation: a Scandinavian sarcoma group study of 118 patients. J Bone Joint Surg Br.
4. Aldlyami E, Abudu A, Grimer RJ, Carter SR, Tillman RM. Endoprosthetic replacement of diaphyseal bone defects. Long-term results. Int Orthop.
5. Alman BA, Bari A, Krajbich JI. Massive allografts in the treatment of osteosarcoma and Ewing sarcoma in children and adolescents. J Bone Joint Surg Am.
6. Brien EW, Terek RM, Healey JH, Lane JM. Allograft reconstruction after proximal tibial resection for bone tumors. An analysis of function and outcome comparing allograft and prosthetic reconstructions. Clin Orthop Relat Res.
7. Chang DW, Weber KL. Use of a vascularized fibula bone flap and intercalary allograft for diaphyseal reconstruction after resection of primary extremity bone sarcomas. Plast Reconstr Surg.
8. Chen TH, Chen WM, Huang CK. Reconstruction after intercalary resection of malignant bone tumours: comparison between segmental allograft and extracorporeally-irradiated autograft. J Bone Joint Surg Br.
9. Damron TA, Leerapun T, Hugate RR, Shives TC, Sim FH. Does the second-generation intercalary humeral spacer improve on the first? Clin Orthop Relat Res.
10. Damron TA, Sim FH, Shives TC, An KN, Rock MG, Pritchard DJ. Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. Clin Orthop Relat Res.
11. Deijkers RL, Bloem RM, Kroon HM, Lent JB, Brand R, Taminiau AH. Epidiaphyseal versus other intercalary allografts for tumors of the lower limb. Clin Orthop Relat Res.
12. Donati D, Liddo M, Zavatta M, Manfrini M, Bacci G, Picci P, Capanna R, Mercuri M. Massive bone allograft reconstruction in high-grade osteosarcoma. Clin Orthop Relat Res.
13. Dormans JP, Ofluoglu O, Erol B, Moroz L, Davidson RS. Case report: Reconstruction of an intercalary defect with bone transport after resection of Ewing's sarcoma. Clin Orthop Relat Res.
14. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res.
15. Gebhardt MC, Flugstad DI, Springfield DS, Mankin HJ. The use of bone allografts for limb salvage in high-grade extremity osteosarcoma. Clin Orthop Relat Res.
16. Habermann ET, Sachs R, Stern RE, Hirsh DM, Anderson WJ Jr, The pathology and treatment of metastatic disease of the femur. Clin Orthop Relat Res.
17. Han CS, Wood MB, Bishop AT, Cooney WP 3rd, Vascularized bone transfer. J Bone Joint Surg Am.
18. Hanna SA, Sewell MD, Aston WJ, Pollock RC, Skinner JA, Cannon SR, Briggs TW. Femoral diaphyseal endoprosthetic reconstruction after segmental resection of primary bone tumours. J Bone Joint Surg Br.
19. Henderson ER, Groundland JS, Pala E, Dennis JA, Wooten R, Cheong D, Windhager R, Kotz RI, Mercuri M, Funovics PT, Hornicek FJ, Temple HT, Ruggieri P, Letson GD. Failure mode classification for tumor endoprostheses: retrospective review of five institutions and a literature review. J Bone Joint Surg Am.
20. Hornicek FJ, Gebhardt MC, Tomford WW, Sorger JI, Zavatta M, Menzner JP, Mankin HJ. Factors affecting nonunion of the allograft-host junction. Clin Orthop Relat Res.
21. Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: state of the art. J Orthop Trauma.
22. Makley JT. The use of allografts to reconstruct intercalary defects of long bones. Clin Orthop Relat Res.
23. Mankin HJ, Gebhardt MC, Jennings LC, Springfield DS, Tomford WW. Long-term results of allograft replacement in the management of bone tumors. Clin Orthop Relat Res.
24. McGrath A, Sewell MD, Hanna SA, Pollock RC, Skinner JA, Cannon SR, Briggs TW. Custom endoprosthetic reconstruction for malignant bone disease in the humeral diaphysis. Acta Orthop Belg.
25. Muscolo DL, Ayerza MA, Aponte-Tinao L, Ranalletta M, Abalo E. Intercalary femur and tibia segmental allografts provide an acceptable alternative in reconstructing tumor resections. Clin Orthop Relat Res.
26. Ortiz-Cruz E, Gebhardt MC, Jennings LC, Springfield DS, Mankin HJ. The results of transplantation of intercalary allografts after resection of tumors. A long-term follow-up study. J Bone Joint Surg Am.
27. Palumbo BT, Henderson ER, Groundland JS, Cheong D, Pala E, Letson GD, Ruggieri P. Advances in segmental endoprosthetic reconstruction for extremity tumors: a review of contemporary designs and techniques. Cancer Control.
28. Refaat Y, Gunnoe J, Hornicek FJ, Mankin HJ. Comparison of quality of life after amputation or limb salvage. Clin Orthop Relat Res.
29. Rose PS, Shin AY, Bishop AT, Moran SL, Sim FH. Vascularized free fibula transfer for oncologic reconstruction of the humerus. Clin Orthop Relat Res.
30. Rougraff BT, Simon MA, Kneisl JS, Greenberg DB, Mankin HJ. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am.
31. Ruggieri P, Mavrogenis AF, Bianchi G, Sakellariou VI, Mercuri M, Papagelopoulos PJ. Outcome of the intramedullary diaphyseal segmental defect fixation system for bone tumors. J Surg Oncol.
32. Sakellariou VI, Mavrogenis AF, Babis GC, Soucacos PN, Magnissalis EA, Papagelopoulos PJ. Comparison of four reconstructive methods for diaphyseal defects of the humerus after tumor resection. J Appl Biomech.
33. Sewell MD, Hanna SA, McGrath A, Aston WJ, Blunn GW, Pollock RC, Skinner JA, Cannon SR, Briggs TW. Intercalary diaphyseal endoprosthetic reconstruction for malignant tibial bone tumours. J Bone Joint Surg Br.
34. Simon MA, Aschliman MA, Thomas N, Mankin HJ. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg Am.
35. Simon MA, Springfield DS. Surgery for Bone and Soft-tissue Tumors
1998;Philadelphia, PA, USALippincott-Raven Publishers.
36. Tsuchiya H, Tomita K, Minematsu K, Mori Y, Asada N, Kitano S. Limb salvage using distraction osteogenesis. A classification of the technique. J Bone Joint Surg Br.