ARMS. Reconstruction of Large Femur and Tibia Defect with Free Vascularized Fibula Graft and Locking Plate INTRODUCTION.

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Original Article ARMS Archieves of Reconstructive Microsurgery pissn 2383-5257 eissn 2288-6184 Arch Reconstr Microsurg 2015;24(2):68-74 http://dx.doi.org/10.15596/arms.2015.24.2.68 Reconstruction of Large Femur and Tibia Defect with Free Vascularized Fibula Graft and Locking Plate Min Bom Kim, Young Ho Lee*, Jeong Kook Baek, Ho Sung Choi, Goo Hyun Baek Department of Orthopaedic Surgery, Seoul National University Hospital, Seoul, Korea Received October 29, 2015 Revised November 23, 2015 Accepted November 24, 2015 *Correspondence to: Young Ho Lee Department of Orthopaedic Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-4186 Fax: +82-2-764-2718 E-mail: orthoyhl@snu.ac.kr Financial support: None. Conflict of interest: None. Purpose: The reconstruction of femur and tibia defects following tumor resection remains a surgical challenge. The clinical outcome of free vascularized fibula graft (VFG) reconstruction with locking plate for massive femur and tibia defects of more than 10 cm that were secondary to skeletal tumor resection is reported. Materials and Methods: Thirteen patients with a mean follow-up of 3.3 years were reviewed. Seven patients received vascularized fibula grafts in the femur and six in the tibia. The mean bony defect of the femur and tibia was more than 10 cm and the length of the grafted fibula was more than 15 cm. All defects were stabilized with long locking plates. Results: All patients were free of disease at final follow-up; All VFGs were transferred successfully. All patients had a successful outcome with bony union. Stress fractures of the grafted fibula had occurred but the locking plate stabilized the fracture and healed until the last follow-up. All patients were able to walk without a brace after a mean of 9 months postoperatively. Conclusion: VFG with locking plate is a reliable reconstructive procedure for massive femur and tibia defects. Key Words: Free vascularized fibula graft, Reconstruction, Locking plate, Bone defect INTRODUCTION Recent advances in multimodality treatment with chemotherapy and wide surgical resection margins have improved the prognosis of patients with musculoskeletal sarcoma. Following wide resection of the tumor, several reconstructive procedures have been applied for large bony defects, including mega-prosthesis implantation, as well as allograft and vascularized bone grafts. In view of the long-term viability of spared limbs, the limited durability of prostheses is a major problem. Because of improved long- term survival rates for sarcoma patients, a 10-year lifespan of about 50% for primary prostheses is no longer satisfactory. 1 The principal disadvantages of intercalary allografts include the high incidence of non-union (17%~50%), fracture (17%~30%) and infection (10%~15%). 2 Our group aimed to achieve biological reconstruction with living bone autografts. Free vascularized fibular graft (VFG) has become an established procedure for the treatment of massive bone defects. 3 Fibula is probably the most suitable donor bone for large defects in long bones because of its length, geometrical shape and mechanical strength. On the other hand, the femur and tibia is probably the most difficult bone for reconstruction and limb salvage remains a high-risk endeavor. The most important problem is late stress fracture of FVFG due to a low initial mechanical strength. We used locking plates to protect CC This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2015 by the Korean Society for Microsurgery. All Rights Reserved. 68

Min Bom Kim, et al. Reconstruction of Large Femur and Tibia Defect with Free Vascularized Fibula Graft and Locking Plate Table 1. Patients and reconstruction procedure Case No. Gender/age (yr) Bone defect Type of artery Length of graft Follow-up Prognosis of Diagnosis Site and gender (cm) anastomosis (cm) (yr) tumor 1 F/8 Osteosarcoma Femur 13 End-to-side 17 6 NED 2 M/14 Osteosarcoma Femur 16 End-to-side 20 5 NED 3 F/22 Osteosarcoma Femur 25 End-to-end 30 3 NED 4 M/34 Osteosarcoma Femur 10 End-to-side 15 4 NED 5 F/13 Osteosarcoma Femur 14 End-to-end 19 5 NED 6 M/35 Osteosarcoma Femur 16 End-to-side 20 3 NED 7 F/10 Osteosarcoma Femur 10 End-to-side 15 4 NED 8 M/39 Osteosarcoma Tibia 20 End-to-side 25 3 NED 9 M/24 Nonossifying fibroma Tibia 22 End-to-side 27 3 NED 10 M/63 Osteosarcoma Tibia 15 End-to-side 20 2 NED 11 F/15 Osteosarcoma Tibia 12 End-to-side 15 3 NED 12 M/25 Giant cell tumor Tibia 15 End-to-side 19 2 NED 13 F/15 Giant cell tumor Tibia 13 End-to-side 18 4 NED F: female, M: male, NED: no evidence of disease. the stress-fractured fibula graft until bone healing. To our knowledge there have been only a few studies to date describing VFG for massive bone defects of the femur following tumor resection. In the current study, a series of 13 patients treated for femur and tibia reconstruction by VFG and locking plate was reviewed retrospectively. The clinical results and complications are assessed and the hypertrophy and late stress fracture of FVFG are discussed. MATERIALS AND METHODS Patients Thirteen patients who had undergone a vascularized free fibular transfer procedure for massive femur and tibia defect secondary to extensive skeletal tumor resection were reviewed, and their characteristics are summarized in Table 1. The seven men and six women had a mean age of 30 years (8~63 years) and the mean follow-up period was 3.3 years (1~6 years). Tumor diagnoses were ten osteosarcomas, two giant cell tumors and one nonossifying fibroma. The bone defect site was from the distal third to the proximal third. All osteosarcoma patients underwent preoperative neoadjuvant chemotherapy and multiple bone reconstruction procedures, which proved to be failed (Fig. 1). Fig. 1. Radiographs of case 1 preoperatively. An 8-year-old female with an osteosarcoma of the distal femur. A 13-cm femur defect was shown. She underwent chemotherapy and multiple osteosynthesis procedures, which proved as failure. Surgical procedures Skeletal fixation of the femur and tibia was performed with a locking plate and screws ( Johnson and Johnson synthes, Paoli, PA, USA) in all patients. VFGs were transferred and placed as www.e-arms.org 69

Arch Reconstr Microsurg Vol. 24. No. 2. November 2015 an in-lay (intramedullar) graft and fixated with locking plate with screws to enhance the graft stability. The minimal length of bone defect was 10 cm (range 10~25 cm) and the minimal length of FVFG was 15 cm (15~30 cm). The donor peroneal artery was anastomosed to the branch of the femoral artery by the end-to-end technique in three and in four it was by the end-to-side anastomosed directly to the femoral artery. The peroneal veins were anastomosed to the vanae comitantes of the recipient artery and/or the saphenous vein by end-toend anastomosis technique (Fig. 2). In the tibia, donor artery was anastomosed to the anterior tibial artery by end-to-side technique in all 6 cases. Additional autologous bone graft from iliac bone was performed around VFG. Evaluation Graft survival was evaluated by bone scan in all cases. Bony union and hypertrophic changes of VFG and the occurrence of stress fractures were confirmed by plain radiographs obtained monthly for one year after surgery. Functional recovery was evaluated at final follow-up using the system proposed by the A B Fig. 2. Images of 17-cm free vascularized fibula graft harvested with long vein graft. The vein graft was harvested to facilitate vessel anastomosis to the recipient vessel in the deep site (A). Vessel pedicle of free vascularized fibula graft was connected to a looped vein graft. Artery and vein are identified with surgical marker to consider for the vein valves (B). Table 2. Clinical outcomes and complications Case No. Survival of graft Proximal union Distal union Follow-up (mo) MTS score Complication Graft stress fracture onset 1 Yes 5 7 10 80 Graft stress fracture 6 months after VFG procedure 2 Yes 7 9 11 85 3 Yes 6 6.5 9 73 4 Yes 5.5 8 9 85 Graft stress fracture 3 months after VFG procedure 5 Yes 3 9 10 80 6 Yes 4 5 7 85 7 Yes 5 7 8 85 8 Yes 6 8 10 80 Graft stress fracture 5 months after VFG procedure 9 Yes 7 8 9.5 70 10 Yes 3 5 8 85 11 Yes 4 5 11 80 12 Yes 6 8 10 80 13 Yes 5 7 85 MTS: Musculoskeletal Tumor Society, VFG: vascularized fibular graft. 70

Min Bom Kim, et al. Reconstruction of Large Femur and Tibia Defect with Free Vascularized Fibula Graft and Locking Plate A B Fig. 3. Graft insetting images. Fibular graft was inset inlay method (A) and lateral long locking plate was applied to protect and fixed the bone defect (B). Fig. 4. The immediate postoperative X-ray images of the femur. The inlay fibula graft was fixed with locking plate. Musculoskeletal Tumor Society (MTS).8 Fig. 5. During the follow-up period, fibular graft underwent a stress fracture under the protection of lateral locking plate. Oncological outcome There was no local recurrence of malignant bone tumor and patients showed no evidence of disease at the final follow-up. RESULTS The clinical outcomes and complications per case are summarized in Table 2. Graft survival In total, all VFGs were successfully transferred (Fig. 3, 4). Vascular complications were not correlated with preoperative www.e-arms.org 71

Arch Reconstr Microsurg Vol. 24. No. 2. November 2015 impairment of the donor limb. DISCUSSION Fig. 6. Stress fracture of the graft showed hypertrophic bone healing and bony union between the graft and host bone was achieved within 7 months postoperatively. Fully weight bearing was permitted 10 months. chemotherapy or type of anastomosis. There were no complications from infection or wounds at either of the recipient or donor sites. Bony union All patients showed bone healing after the procedure. Late stress fractures were observed in three patients during followup period even though the weight bearing was not permitted, but stress fractures were healed eventually and made the graft hypertrophic. Fracture in the proximal junction between the recipient and graft occurred in one patient. Two fracture in the distal junction occurred as the illustrated case (Fig. 5). Although the exact time to bony union was difficult to diagnose using only plain radiographs, the proximal junctions were united by five months postoperatively at least. More than 6 months were necessary at the distal junction (Fig. 6). Functional outcome The time required for patients to walk without braces was a mean of 9 months (range 7~11 months). The MTS score was classified as good and the mean score was 81 points (range 70~85 points). No patient reported serious functional Massive femur and tibia defects resulting from bone tumors present a major challenge because of limitations with the available reconstructive methods. Although the role of VFG for difficult long bone defects has been well recognized, there are problems with long bone reconstruction. The first problem is the technically demanding nature of this procedure. The femur is located deeper than other long bones and has few main vessels suitable for microsurgical anastomosis. Monitoring of graft vascularity is troublesome because the peroneal flap used for this purpose sometimes fails to reach the skin surface. Few papers have clearly provided demonstration of graft survival. Yajima et al. 4 reported that femur reconstruction using VFG was successful in 19 out of 20 patients (95.0%), and that vascular complication of the monitoring peroneal flap occurred in 5 cases (three overstretched flaps and two thromboses). It is thought that an important factor for graft survival is not the mode of anastomosis, but rather the selection of recipient vessels. 5 Preoperative planning is easier in tumor cases compared to traumatic cases because any scar formation at the site of vascular anastomosis is usually minimal. Careful preoperative selection of recipient vessels and postoperative observation of the monitoring flap are essential. However, our cases received chemotherapy and multiple osteosynthesis procedures, which caused scar contracture and poor vessel condition because of malignant bone tumor. This makes it more difficult to transfer VFG and locking plating. The second problem with massive bone defects is the rate of bony union between VFG and long bone. Union rates of more than 80% have been reported after successful transfer. Jupiter et al. 6 were the first to report reconstruction of femur defects with FVFG. Primary bony union was achieved with single VFG in five out of seven patients with post-traumatic infection or non- union. Wood 7 reported the largest series (n=35) of femur reconstruction with VFG. Overall, 69% of patients were healed with single VFG and 83% following additional operations. These authors recommended using VFG for the reconstruction of massive femur defects greater than 10 cm. Yajima et al. 4 also demonstrated a high rate of bony union (95%) at an average time of 6.4 months after surgery. Hsu et al. 8 reported that overall 72

Min Bom Kim, et al. Reconstruction of Large Femur and Tibia Defect with Free Vascularized Fibula Graft and Locking Plate bony union with FVFG reconstruction was achieved in 90% of the cases after an average post-operative period of 7.6 months. The overall union rate in the current study compares favorably to other reports and supports the use of VFG with locking plate as a stable procedure for femur and tibia reconstruction. It is recommend to use long enough to cover the whole length of the long bone to prevent the stress concentration fracture at the end of the locking plate. The third problem encountered in femur and tibia reconstruction with VFG is late stress fracture. The fibula normally contributes only 1/7 to 1/10 of the total weight bearing. Its anatomic configuration, therefore, cannot be compared with the femur in terms of size or biomechanical strength. Late stress fracture is probably prevented by locking plate construct. Stress fracture causes hypertrophic changes in the VFG under the protection of locking plate. Without the locking plating, stress fractures might result in nonunion of fractured graft and graft failure. One of the major advantages of using a living fibula transfer is its ability to hypertrophy. 9 Although the causes of satisfactory hypertrophy are not completely understood, the high incidence of graft hypertrophy observed here was probably related to the mechanical stimulation provided by weight-bearing. Interestingly, the intercalary inlay graft in this series showed marked hypertrophy compared to the non- weight-bearing onlay fibula. These results demonstrate that hypertrophy of the fibula graft is associated with mechanical stimulation from weight bearing. The inlay FVFG should be placed in the correct anatomical alignment following proper fixation of the femur. In the study by Wood, 7 late stress fractures occurred in two patients and other authors have also reported a rate of approximately 10% (7%~16%) for late stress fractures of grafted fibula. 4,6 Muramatsu et al. 10 previously reported stress fracture of FVFG in cases with post- traumatic non-union of the femur. They thought that the main reason for late fracture was misalignment of FVFG of more than 15 degrees from the anatomical direction of the femur. In an attempt to minimize the risk of graft fracture, they recommended to take careful note of the following three points: double VFG, rigid internal fixation and proper alignment of inlay FVFG. However, we could draw a satisfactory result with single-barrel long VFG and locking plating. To raise the primary mechanical strength of fibula grafts, the VFG was fixed as an inlay graft within the medullary canal to support weight-bearing, while the second was locking plate that provided stable support. The locking plate provide a believable stability to the defected long bone and could function as permanent prosthesis. We aligned and stabilized the host bone with locking plate. After then, free VFG was overlapped in the host bones and linked with the locking plate using locking screws for graft protection. It was easy to achieve both the hostgraft construct stability and the procedural convenience during microsurgical vessel anastomosis of the VFG with this method. There are some reports that double-barrel VFG should be used for the bone defect of significant size mismatch situation between host and graft, but this method is double-edged sword. It could endanger the graft pedicle continuity. We assert that it is the uniqueness of our article to use the single-barrel VFG protected with locking plate. As the case illustrated, the size mismatch between the host and graft could be overcome with our method. It could be thought that VFG with locking plate is the alternative option for femur reconstruction, but we have no direct experience with alternative treatments. Tsuchiya et al. 11 used the distraction osteogenesis technique for limb salvage following skeletal tumor resection. Their results suggest that this technique may provide sufficient biomechanical strength and durability and is especially beneficial in growing children. Araki et al. 12 and Kubo et al. 13 used extra-corporeally-irradiated autograft and demonstrated good clinical results. This technique can be combined with VFG protected by locking plate to raise the mechanical strength. However, the results from our series demonstrate that VFG with locking plate is a safe procedure for femur and tibia reconstruction. Even though the stress fracture of fibula graft, locking plate protect the fracture and hypertrophic union, and the bone defects were resolved without influencing the final outcome. REFERENCES 1. 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Arch Reconstr Microsurg Vol. 24. No. 2. November 2015 Surg Am 1979;61:98-104. 4. Yajima H, Tamai S, Mizumoto S, Ono H. Vascularised fibular grafts for reconstruction of the femur. J Bone Joint Surg Br 1993; 75:123-8. 5. Muramatsu K, Ihara K, Doi K, Shigetomi M, Hashimoto T, Taguchi T. Reconstruction of massive femur defect with free vascularized fibula graft following tumor resection. Anticancer Res 2006;26:3679-83. 6. Jupiter JB, Bour CJ, May JW Jr. The reconstruction of defects in the femoral shaft with vascularized transfers of fibular bone. J Bone Joint Surg Am 1987;69:365-74. 7. Wood MB. Femoral reconstruction by vascularized bone transfer. Microsurgery 1990;11:74-9. 8. Hsu RW, Wood MB, Sim FH, Chao EY. Free vascularised fibular grafting for reconstruction after tumour resection. J Bone Joint Surg Br 1997;79:36-42. 9. de Boer HH, Wood MB. Bone changes in the vascularised fibular graft. J Bone Joint Surg Br 1989;71:374-8. 10. Muramatsu K, Ihara K, Shigetomi M, Kawai S. Femoral reconstruction by single, folded or double free vascularised fibular grafts. Br J Plast Surg 2004;57:550-5. 11. Tsuchiya H, Wan SL, Sakayama K, Yamamoto N, Nishida H, Tomita K. Reconstruction using an autograft containing tumour treated by liquid nitrogen. J Bone Joint Surg Br 2005;87:218-25. 12. Araki N, Myoui A, Kuratsu S, Hashimoto N, Inoue T, Kudawara I, et al. Intraoperative extracorporeal autogenous irradiated bone grafts in tumor surgery. Clin Orthop Relat Res 1999;(368):196-206. 13. Kubo T, Sugita T, Shimose S, Tanaka H, Nobuto H, Tanaka K, et al. Acetabular osteosarcoma treated by irradiation-vascularized hybrid bone graft. Anticancer Res. 2004;24:1889-92. 74