Department of Surgery, University of Melbourne, Department of Surgery and Orthopaedics, St. Vincent’s Hospital, Melbourne, Bone and Soft Tissue Sarcoma Service, Peter MacCallum Cancer Centre, Victoria.
The standard for local control of malignant bone and soft tissue tumours has been amputation. Advances in multimodality treatment have seen a shift towards preservation of the limb. Sophisticated techniques that employ combinations of prosthetic and biologic material now provide a greater opportunity for functional reconstruction of the limb. This review covers the principles of limb sparing surgery and highlights the importance of preoperative staging, adjuvant and neo-adjuvant treatments and surgical margins. Complications are common and should be pre-empted. Limb sparing surgery is a complex procedure that requires expert knowledge of the requirements and criteria for its use. It is an important part of multidisciplinary management of sarcoma and the success of such surgery is maximised when conducted in centres with specific interest and expertise in this field.
Bone and soft tissue sarcomas are rare mesenchymal malignancies that arise in two to four per 100,000 head of population.1,2 The limbs are the commonest sites for sarcoma, with over 50% of soft tissue and bone sarcomas occurring in the lower limb. The advent of multimodality treatment with advances in chemotherapy, radiotherapy and surgery, all supported by more sophisticated diagnostic and imaging techniques, has led to considerable improvement in long-term survival. Overall survival following treatment of primary sarcoma now approaches 75% at five years, and surgery remains the mainstay of treatment.1,2 Surgery to resect the tumour followed by reconstructions to preserve function, mobility and aesthetics (limb sparing surgery) has now replaced amputation as the primary form of surgical intervention.3-5
Limb sparing surgery may be considered when specific criteria are met, including:
Previously a sensate lower limb was thought to be mandatory for limb sparing surgery. Sacrifice of the sciatic nerve traditionally led to lower limb amputation for fear of developing chronic non-healing trophic ulceration of the foot. However, with better awareness of foot hygiene and shoe wear, limb sparing surgery is now practised despite the need to include the sciatic nerve in resections of proximal thigh or pelvic tumours.6,7
Limb sparing surgery is indicated when:
Limb sparing surgery is contraindicated when
Accurate diagnosis is critical to successful treatment. Appropriate choices of chemotherapy agents or radiotherapy depend on correct identification of the type of sarcoma.8-13 For example, chemotherapy differs between osteosarcoma, Ewing sarcoma and myxoid liposarcoma. Soft tissue sarcomas comprise a heterogeneous group and consensus on grade, type and subtype of sarcoma can be difficult to achieve.
Biopsy is fundamental to obtaining an accurate histological diagnosis. In principle, the same group that will be undertaking definitive treatment should perform biopsy of primary bone and soft tissue sarcomas. This is because the placement of the biopsy site and the avoidance of post-biopsy complications, such as haematoma orinfection, may influence the potential for undertaking limb sparing surgery. Biopsy, whether open or closed, should always be done in the line of the operative incision to allow inclusion of the biopsy site in the definitive resection. It is our preference to perform CT-guided core needle biopsies.14
Local staging of the tumour is important for planning surgery. The tumour size, site, shape, consistency, edge, capsule and adjacent structures are important information for planning the surgical margins and reconstructions after assessing response to neoadjuvant therapies. Imaging of the limb should include plain radiographs, CT, MRI, PET or thallium scans.15,16 In addition, CT scans of the chest are mandatory for assessing systemic spread, because pulmonary involvement is the commonest site for first metastases. Evidence of metastasis is likely to affect the nature of care and therefore all efforts to diagnose metastases should be undertaken.
Pre-operative (neoadjuvant) chemotherapy or radio-therapy is fundamental to managing bone and soft tissue sarcomas, respectively. The benefits of adjuvant therapy include:
These effects may aid the planning of surgical margins, improve the resectability of tumours and allow greater safety when dissecting close to vital neurovascular structures.
The response to neoadjuvant therapy may be critical for determining if limb sparing surgery or amputation should be performed. For example, there is a correlation between local recurrence and response to chemotherapy in osteosarcoma.17 Moreover, the risk for local recurrence rises substantially when margins of resection diminish.17 Therefore, if pre-operative imaging demonstrates that the response to neoadjuvant chemotherapy is poor and if planned surgical margins are expected to be close, then to avoid locally recurrent disease, amputation may be preferable over limb sparing surgery. This information is valuable in the pre-operative counselling of patients and for the obtaining of informed consent for surgery.
Adequacy of surgical margins correlates directly with the incidence of local recurrence and relates to the quality and quantity of tissue around the tumour that is included in the resected specimen.18-20 The definition of surgical margins are as follows:
The quality of the anatomic boundary is also relevant when determining the adequacy of the margin. The fascia lata is a very tough tissue, although it may be only a few millimetres thick. If the fascia lata is included as an uninvolved boundary, then the resection may be regarded as wide.
Intralesional and marginal margins are regarded as being inadequate surgical margins, while wide and radical margins are regarded as adequate surgical margins in the management of sarcoma. Marginal margins may be equivalent to wide margins alone when combined with radiotherapy or chemotherapy. Marginal margins are usually avoided, however may be important when having to preserve important neurovascular structures.
A wide variety of reconstructions are available for limb sparing surgery. These include:
Reconstructions may also be mobile or rigid. These refer to the preservation or fusion of a previously mobile joint at reconstruction.
Tumour prostheses take their origins from the evolution of standard joint prostheses. Advances in metallurgy, tribology and prosthetic fixation have allowed the development of modular implants that can be individualised to each patient, while exhibiting strength and durability.21-23 Prostheses for the hip and knee were the first to be developed and today, prostheses are also available for the shoulder joint, scapula, elbow, total humerus, ulnar, total femur, pelvis and the ankle.
Improvements in computer aided design of prostheses and manufacturing techniques now allow the custom creation of unique prostheses to accurately match the defect created by tumour resection. Such customised machining of prostheses is matched with computer guided surgery to ensure that the exact resection shape is created during surgery, to allow accurate matching of resection defect with the customised implant. These techniques require rigorous planning and dialogue between manufacturer, surgeon and imaging specialists.
One of the earliest attempts at limb sparing surgery was the arthrodesis of the knee after resection of tumours of the distal femur. In an attempt to span the gap between femur and tibia created by distal femoral resection, a segment of the ipsilateral tibia would be elevated and used to span the tibio-femoral gap in an arthrodesis procedure. Held by a long arthrodesis nail, the construct would permit full weight bearing after the bone graft united with the remnant femur and tibia.
The popularity of bone banks soon permitted harvest and storage of large structural allografts, which were then employed in place of autograft bone to fill the defect of tumour resection.24 Allograft bone had a number of advantages including:
The disadvantages of allograft bone included:
The availability of modern internal fixation devices has helped to support the allograft constructs and long-term results have been acceptable.
The fibula has been a versatile resource for reconstructing defects of up to 22 centimetres. The fibula may be used as a vascularised or non-vascularised graft and has been utilised in a number of innovative ways,25,26 including spanning defects, creating articulations, arthrodesis of joints and in combination with allografts.
Other innovative methods of biologic reconstruction include the role of extracorporeal radiotherapy to sterilise the tumour bearing bone immediately after resection, and then to reimplant the resected bone back into the resection site.27 This technique utilises established radiotherapy techniques to deliver up to 10 times the normal radiotherapy dose to tumour bearing bone in a single fraction. By performing this in an extracorporeal fashion, the anticipated toxicities of such high doses can be avoided. Moreover, the technique has the advantage of reconstructing the defect with a perfectly sized matched construct. To date, reported series have not encountered recurrent tumour following reconstruction using this technique.
Allograft prosthetic composites (APC) capitalise on the advantage of allograft bone to rebuild bone stock to the post-operative defect, while permitting the predictability of prosthetic joint replacement to regain stable joint motion. Large defects created by the resection of a joint and the adjacent diaphysis and metaphysis can be reconstructed by the use of allograft bone that includes a metaphyseo-diaphyseal segment, on to which a standard joint prosthesis may be cemented. The most common sites where APC are used include the hip (proximal femur), knee (distal femur or proximal tibia) and the shoulder (proximal humerus). Residual soft tissue attachments on the allograft allow host to allograft tendon and ligamentous reconstructions, which improve the stability and function of the reconstructed joint.
Salvaging limb sparing surgery after a complication is a complex task, but may be undertaken in certain circumstances. Careful planning and a multidisciplinary approach is required. Innovative techniques are available that may result in a functional limb.28,29
Limb sparing surgery is the technique of choice for surgical management of limb sarcomas. In comparison to amputation, limb sparing surgery:
Limb sparing surgery is a complex procedure that requires expert knowledge of the requirements and criteria for its use. It is an important part of multidisciplinary management of sarcoma. The success of such surgery is maximised when conducted in centres with specific interest and expertise in this field.
1. Choong, PF and HA Rudiger. Prognostic factors in soft-tissue sarcomas: what have we learnt? Expert Rev Anticancer Ther. 2008;8(2):139-46.
2. Clark, JC, CR Dass, and PF Choong, A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134(3):281-97.
3. Choong, PF and FH. Sim, Limb-sparing surgery for bone tumors: new developments. Semin Surg Oncol. 1997;13(1):64-9.
4. Federman N, Bernthal N, Eilber FC, Tap WD, The multidisciplinary management of osteosarcoma. Curr Treat Options Oncol. 2009;10(1- 2):82-93.
5. Papagelopoulos, P.J., Galanis EC, Vlastou C, Nikiforidis PA, Vlamis JA, Boscainos PJ, et al. Current concepts in the evaluation and treatment of osteosarcoma. Orthopedics. 2000;23(8):858-67;quiz 868-9.
6. Jones, KB, Ferguson PC, Deheshi B, Riad S, Griffin A, Robert S Bell, et al. Complete femoral nerve resection with soft tissue sarcoma: functional outcomes. Ann Surg Oncol. 2010;17(2):401-6.
7. Melendez M, Brandt K, Evans GR. Sciatic nerve reconstruction: limb preservationafter sarcoma resection. Ann Plast Surg. 2001;46(4):375-81.
8. Choong, PF, Petersen IA, Nascimento AG, Sim FH. Is radiotherapy important for low-grade soft tissue sarcoma of the extremity? Clin Orthop Relat Res. 2001(387);191-9.
9. Ek ET, Choong PF. The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Rev Anticancer Ther. 2006;6(2):225-37.
10. Hui AC, Ngan SY, Wong K, Powell G, Choong PFM. Preoperative radiotherapy for soft tissue sarcoma: the Peter MacCallum Cancer Centre experience. Eur J Surg Oncol, 2006. 32(10):1159-64.
11. Reynoso, D, Subbiah V, Trent JC, Guadagnolo BA, Lazar AJ, Benjamin R. et al. Neoadjuvant treatment of soft-tissue sarcoma: a multimodality approach. J Surg Oncol. 101(4): 327-33.
12. Ta, HT, Dass CR, Choong PFM, Dunstan DE. Osteosarcoma treatment: state of the art. Cancer Metastasis Rev. 2009;28(1-2):247-63.
13. Vincenzi B, Frezza AM, Santini D, Tonini G. New therapies in soft tissue sarcoma. Expert Opin Emerg Drugs.2010;15(2):237-48.
14. Altuntas AO, Slavin J, Smith1 PJ, Schlict SM, Powell GJ, Ngan S. Accuracy of computed tomography guided core needle biopsy of musculoskeletal tumours. ANZ J Surg. 2005;75(4):187-91.
15. Hicks RJ, Toner GC, Choong PFM. Clinical applications of molecular imaging in sarcoma evaluation. Cancer Imaging, 2005;5(1):66-72.
16. Ilaslan H, Schils J, Nageotte W, Lietman SA, Sundaram M. Clinical presentation and imaging of bone and soft-tissue sarcomas. Cleve Clin J Med. 2010;77(Suppl 1): S2-7.
17. Picci, P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994;12(12):2699-705.
18. Choong, PFM, Surgical margins for soft tissue sarcoma: size does matter. ANZ J Surg. 2006;76(3):97.
19. EnnekingWF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res.1980(153);106-20.
20. Liu CY, Chen WM, Chen TH, Chen PCH, Wu HTH, Shiau CY, et al. Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence. Ann Surg Oncol. 2010;17(8):2102-11.
21. Choong PFM. Reconstructive surgery following resection of primary and secondary tumours of the hip [Review article]. J Orthop Surg (Hong Kong). 2000;8(2):83-94.
22. Choong PFM, Franklin H, Pritchard DJ, Rock MG, Chao EYS. Megaprostheses after resection of distal femoral tumors. A rotating hinge design in 30 patients followed for 2-7 years. Acta Orthop Scand. 1996;67(4):345-51.
23. Shin DS Choong PFM, Edmund YH Chao, Sim FH. Large tumor endoprostheses and extracortical bone-bridging: 28 patients followed 10-20 years. Acta Orthop Scand. 2000;71(3):305-11.
24. Choong PFM. The role of allografts in tumour surgery. Acta Orthop Scand Suppl, 1997;273:89-94.
25. Akiyama, T, Clark JCM, Miki Y, Choong PFM The non-vascularised fibular graft: a simple and successful method of reconstruction of the pelvic ring after internal hemipelvectomy. J Bone Joint Surg Br. 2010;92(7):999-1005.
26. Pollock R, Stalley P, Lee K, Pennington D. Free vascularized fibula grafts in limb-salvage surgery. J Reconstr Microsurg. 2005;21(2):79-84.
27. Davidson AW, Hong A, McCarthy SW, Stalley PD. En-bloc resection, extracorporeal irradiation, and re-implantation in limb salvage for bony malignancies. J Bone Joint Surg Br. 2005;87(6):851-7.
28. Kong GY, Rudiger HA, Ek ET, Morrison WA, Choong PFM. Reconstruction after external hemipelvectomy using tibia-hindfoot rotationplasty with calcaneo-sacral fixation. Int Semin Surg Oncol. 2008;5:1.
29. Sim IW, Tse LF, Ek ET, Powell GJ, Choong PFM. Salvaging the limb salvage: management of complications following endoprosthetic reconstruction for tumours around the knee. Eur J Surg Oncol. 2007;33(6):796-802.