Journal of Surgical Oncology 2014;110:366–371
Overlapping Allograft for Primary or Salvage Bone Tumor Reconstruction DAE-GEUN JEON, MD,* WON SEOK SONG, MD, WAN HYEONG CHO, MD, CHANG-BAE KONG, SANG HYUN CHO, MD, SUNG WOO CHOI, MD, AND SOO-YONG LEE, MD
MD,
Department of Orthopedic Surgery, Korea Cancer Center Hospital, Seoul, Korea
Background: Compared with end‐to‐end allograft coaptation, overlapping allograft offer a superior union rate by increasing the contact area. However, reports on overlapping allograft are scarce. Therefore, we attempted to confirm the usefulness of this technique either after primary tumor resection or in salvaging a failed reconstruction. Methods: We analyzed the outcome of 35 overlapping allografts reconstructions. Indications were primary reconstruction of a skeletal defect (n ¼ 19) and salvage of a failed reconstruction (n ¼ 16). Graft survival, union rate, and time to union were evaluated as a function of clinical variables such as age, use of chemotherapy, type of junction, method of fixation, length of overlapped bone, and method of overlapping. Results: All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3–14 months). One allograft was removed with local recurrence at 19 months post‐operatively. Average length of overlapped bone was 3.5 cm (range, 1.4–6.5 cm). Patient age 40%, and (3) remaining host bone fragment is too short to accommodate a regular‐ length stemmed implant (initial tumor involvement is too extensive or after removal of a failed tumor prosthesis) [1,3–5]. Biologic (allograft, recycled autograft) and composite biologic (allograft‐ or recycled autograft–prosthesis composite) reconstruction were introduced to overcome the limitations of tumor prosthesis by supplementing bone stock. Nevertheless, they have shown limited success due to relatively high rates of non‐union, fracture, loosening, and infection [6–9]. Non‐union at the junction site seems to be a leading cause of mechanical failure. On the other hand, the telescoping (overlapping) allograft technique was introduced to preserve the adjacent joint, increase the bone apposition surface area compared with end‐to‐end techniques, reduce the frequency of non‐union, and reestablish bone length, minimizing the size of endoprosthesis needed for reconstruction [10,11]. Among the possible indications for overlapping allograft, Healey et al. [10] focused mainly on salvage of a short remnant of the proximal femur in revision of a failed distal femoral endoprosthesis with poor bone stock. Besides preserving the adjacent joints at risk for replacement, we attempted to confirm the usefulness of this technique, such as supplementing bone stock in pediatric patient, and arthrodesis in locations where tumor prosthesis is generally not advocated (distal tibia, distal radius). In this study, we asked whether overlapping allograft could achieve our surgical goals (sparing adjacent joint at risk, reconstitution of the diaphysis, arthrodesis) in terms of graft survival, graft‐related complications, and functional outcome. Our second question was to determine whether any clinical factors are related to graft union.
Between January 2007 and April 2013, 130 reconstructions with allograft were performed in our department. The types of overlapping allograft used were intercalary (two junctional sites for union) reconstruction in 35 patients, onlay graft in 44, and restoration of bone stock (one junction site for union) in 51. Among the 51 patients with overlapping allograft reconstruction, we extracted 35 patients. The exclusion criteria in this study were pelvic location (11 patients) and less than 12 months of follow‐up (5 patients). The indications for allograft reconstruction were; (1) primary reconstruction of a skeletal defect (19 patients), (2) salvage of a failed tumor prosthesis (9 patients), or pasteurized autograft (7 patients). There were 20 female and 15 male patients with an average age of 15 years (range, 5–49 years). There were 30 patients with osteosarcoma, 2 with Ewing’s sarcoma, 2 with giant cell tumor, and 1 with chondrosarcoma. Eighteen lesions were located in the femur, seven in the tibia, seven in the humerus, two in the radius, and one in the ulna (Table I). Enneking’s criteria were used to stage the tumors [12]. There were 33 stage IIB and 2 stage 3 tumors. The average follow‐up duration was 30 months (range, 16–60 months). Follow‐up duration was defined as the time from date of index surgery to date of final visit.
ß 2014 Wiley Periodicals, Inc.
Grant sponsor: KRP (KCCH Research Competence Promotion); Grant sponsor: Korea Institute of Radiological & Medical Sciences; Grant number: 50247‐2014. Conflict of interest: None. *Correspondence to: Dae‐Geun Jeon, MD, Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215‐4, Gongneung‐dong, Nowon‐ gu, Seoul 139‐706, Korea. Fax: þ82‐2‐970‐2403. E‐mail: [email protected] Received 27 March 2014; Accepted 13 May 2014 DOI 10.1002/jso.23669 Published online 2 June 2014 in Wiley Online Library (wileyonlinelibrary.com).
Overlapping Allograft Reconstruction TABLE I. Patients Demographics Variables Age Mean (range) 15 year >15 year Gender Male Female Diagnosis Osteosarcoma Ewing’s sarcoma Chondrosarcoma Giant cell tumor Location Femur/tibia Humerus/radius/ulna Enneking stage 3 IIB Surgical goal Reconstitute the diaphysis Preserve adjacent joint at risk Reestablish original bone length Percentage of initial defect 40 (19.6–40%) >40 (42–77%) Types of fixation Stem of prosthesis Intramedullary nail Plate or screw Length of allograft (cm) 12 (6.3–12 cm) >12 (12.2–23 cm) Length of overlapping (cm) 3 (1.4–2.7 cm) >3 (3.2–6.5 cm) Types of host–allograft junction Diaphysis–diaphysis Diaphysis–metaphysis Metaphysis–diaphysis Types of overlapping Circumferential Partial Total
Number of patient (%)
14.2 (5–49) 23 (65.7%) 12 (34.3%) 15 (42.9%) 20 (57.1%) 30 2 1 2
(85.7%) (5.7%) (2.9%) (57.1%)
18/7 (71.4%) 7/2/1 (28.6%) 2 (5.7%) 33 (94.3%) 18 (51.4%) 11 (31.4%) 6 (17.2%) 9 (25.7%) 26 (74.3%) 18 (51.4%) 10 (28.5%) 7 (20.1%) 11 (31.4%) 24 (68.6%) 11 (31.4%) 24 (68.6%)
bone remaining for stem fixation was 4.7 cm (range, 3–9 cm). The location of six arthrodesis was the distal tibia in three patients, distal radius in two, and distal ulna in one. We used fresh frozen allograft under sterile conditions (allografts were stored at 80°C in a bone bank). Proper selection and preparation of the allograft are important to create a stable construct. In general, when selecting a graft, a larger diameter is better. According to the osteotomy site and outer diameter of the host bone, there are two types of overlapping. One is either the allograft medullary canal is placed over the host bone or it is impaled into the medullary canal of the existing host bone (circumferential overlapping). The other is, when outer diameter of the host bone is too thick, the allograft is shaped with a tong‐like outer sleeve and placed outside the host bone (partial overlapping) (Fig. 1). The steps listed subsequently describe the procedure for the most common indication, reconstruction of the femoral diaphysis. After tumor resection, (1) muscle was detached 3–5 cm proximal to the osteotomy site of the host bone leaving the periosteum untouched, (2) the periosteal outer diameter of the remaining host bone was measured and an allograft with an endosteal inner diameter large enough to allow an overlap distance of at least 2 cm was selected (the upside down distal femoral allograft provides an example), (3) the defect and amount of overlapping was considered to allow a provisional allograft cut at 2 cm proximal to the level of epicondyle, (4) cancellous bone was hollowed out from the allograft using a rigid reamer and high‐speed burr, (5) after trial impacting of the allograft over the host bone, the allograft was cut to a length that restored the desired amount of diaphysis, (6) to prevent the allograft cortical shell from cracking or the prosthesis stem from jamming, over‐reaming of the allograft medullary canal was performed, (7) fixation was performed with a plate or intramedullary device. Although, we prefer non‐cemented fixation, we performed cemented fixation in following situations; (1) prosthesis type designed for cemented fixation, (2) failed previous cemented implant, (3) fixation for short remnant of the proximal femur or distal tibia. To make stable allograft–host construct, there are two points to be considered. One is property of the host–allograft interface. To minimize allograft collapse after weight bearing, use of thicker cortical portion of
17 (48.5%) 17 (48.5%) 1 (3.0%) 28 (80.0%) 7 (20.0%) 35 (100%)
In 15 patients, allograft reconstruction was performed during neoadjuvant or adjuvant chemotherapy. The bone was resected at 3 cm from any sign of involvement as determined by MRI. However, for low‐grade lesions, the resection margin was set at up to 1 cm. The percentages of bone resected ranged from 20% to 77% (mean 53%). Except for one case with a metaphyseal junction, the remaining 34 osteotomy sites were diaphyseal. The surgical goals of reconstruction were; (1) reconstitution of the diaphysis (18 patients), (2) preservation of the adjacent joint at risk (11 patients), and (3) arthrodesis (6 patients). Of the 18 patients with a goal of minimizing the length of tumor prosthesis, 12 underwent diaphyseal reconstruction at the time of tumor resection while the remaining 6 were revision cases (failed pasteurized autograft in 4, junctional osteolysis after tumor prosthesis in 2). The location of diaphyseal reconstruction was the femur in 11 patients, humerus in 5, and tibia in 2. Of the 11 patients with an adjacent joint at risk, all except one patient were revision cases (failed tumor prosthesis in 5, failed pasteurized autograft in 3, failed bone cement spacer in 2). The adjacent joint at risk was the hip in seven patients, elbow in 2, and ankle in 2. The average distance from the osteotomy site to the corresponding joint line was 11.8 cm (range, 8–21.7 cm), while the average length of cortical Journal of Surgical Oncology
367
Fig. 1. A: Plain lateral radiograph of a 17‐year‐old girl showing osteosarcoma of the distal femur. B: Post‐operative radiograph showing resection and overlapping allograft fixed with an intramedullary nail. Note the tong‐like allograft sleeve for partial overlapping (arrow). C: Radiograph taken 3 years post‐operatively, showing solid union of the graft.
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allograft (meta‐diaphyseal or diaphyseal portion) is recommended for host–allograft coaptation. The other is compression between host and allograft should be made by tapping the allograft with mallet. If the host– allograft construct shows stability without fixation, the overlapping is adequately performed. At time of primary reconstruction, no patient received additional autogenous bone graft in the host–allograft space and this procedure was reserved for non‐union. There are cases with morselized cancellous allograft on overlapped space. In tight telescope type fit (diaphyseal–diaphyseal) case, there was no space for cancellous allograft. However, in some cases with diaphyseal (host)–metaphyseal (allograft) contact, we added some morselized cancellous allograft. The extremity was immobilized in a cast or brace, usually for 6 weeks, with range of motion exercise permitted thereafter. Functional outcome was assessed using the Musculoskeletal Tumor Society System [13]. We recorded clinical variables including: age, gender, location of defect, use of chemotherapy, percentage of initial defect, length of allograft, type of host–allograft junction (diaphyseal– diaphyseal or others), method of fixation (intramedullary stem or others), length of overlapped bone, and method of overlapping (circumferential or partial). Bimonthly plain anteroposterior and lateral radiographs were obtained and examined until 3 years after the index operation. Radiographic union at the junction sites (35 sites in 35 patients) was judged by two of the authors (WSS, DGJ). The osteotomy site was considered radiographically healed when callus was seen bridging the site or blurring was seen between the cortex of the host bone and the allograft on plain radiographs. For patients who showed resorption of the allograft or loosening of internal fixation, additional onlay allograft or temporary brace fitting was performed. The primary end points of this study were union and subsequent remodeling. Allograft failure was defined as the need for graft removal. Student’s t‐test was used to compare mean time to union of the osteotomy sites. Significance was set at P < 0.05.
RESULTS Except for one case with local recurrence, no allografts was removed due to infection, fracture, or non‐union. All 35 patients achieved our surgical goals and reconstruction related outcomes are summarized in Table II. In 29 patients (18 with diaphyseal reconstruction, 11 with adjacent joint at risk), the average defect was 57.6% (range, 33.8–77%), which decreased to a mean of 25.6% (range, 5–57.8%) after overlapping allograft reconstruction (Fig. 2). The percentage of bone stock recovery was largest at humerus and smallest at the distal tibia (Fig. 3). All weight
Fig. 2. A: Plain radiograph of an 11‐year‐old girl showing osteosarcoma of the distal femur. B: Post‐operative radiograph, showing overlapping allograft to reconstitute the diaphysis. Initial bone defect of 48% after tumor resection decreased to 20% after reconstruction with an upside down adult proximal femur. C: Radiograph taken 2 years post‐operatively, showing union, and remodeling of the allograft.
bearing bone (lower extremity) was fixed with a prosthesis stem or intramedullary nail while non‐weight bearing bone (upper extremity) was fixed with a plate, screw, and prosthesis stem. Cemented fixation was performed in two reverse shoulder–allograft composite reconstructions and three failed cemented fixation (two in the proximal femur and one in the distal tibia) (Fig. 4). The average length of overlapped bone showed little difference according to patient age, defect location, and primary or revision cases. Location at the distal tibia showed longer time to union. Two patients required additional surgery. One patient with distal tibial reconstruction underwent below‐
TABLE II. Outcome of Overlapping Allograft Reconstruction According to the Surgical Goals
Surgical goal Restoration of diaphysis
Spare adjacent joint at risk
Arthrodesis
Number of patients
Average patient age (year)
18
10 (6–15)
Femur (11)
22 (14–41)
Humerus (5)
12 (11–13) 20 (11–38)
Proximal tibia (2) Femur (7)
10 (8–12) 35 (26–43)
Humerus (2) Distal tibia (2)
15 (14–17) 13 (12–14) 49
Distal tibia (3) Distal radius (2) Distal ulna (1)
11
6
IM nail, intramedullary nail.
Journal of Surgical Oncology
Location
Type of fixation
Percentage of initial defect
Percentage of defect after allograft
Average overlapping length (cm)
Non‐cemented stem (9)
53 (34–65)
24 (12–34)
3.7 (1.9–5.6)
4.5 (3–7)
47 (36–65)
12 (5–18)
3.5 (2.3–6)
5.6 (4–7)
54 (46–62) 64 (56–74)
24 (16–33) 36 (20–58)
4.9 (4.6–5.2) 3.3 (1.4–6.5)
3.5 (3–4) 6.1 (3–7)
75 (74–76) 75 (74–77)
5 55
2.4 (1.5–3.3) 4.7 (4.1–5.4)
3.5 (3–4) 13 (12–14)
28 (27–30) 46 (42–50) 20
0 0 0
2.4 (1.4–3.2) 4.2 (3.7–4.7) 1.8
7.6 (5–9) 5.5 (3–8) 8
IM nail (2) Screw (3) Cemented stem (2) IM nail (2) Non‐cemented stem (5) Cemented stem (2) Screw (2) Cemented stem (1) Non–cemented stem (1) IM nail (3) Plate (2) IM nail (1)
Time to Union (months)
Overlapping Allograft Reconstruction
369
(range, 1.4–6.5 cm). Patient age 12 cm (P ¼ 0.014) shortened the average time to union (Table III). The percentage of initial defect, location of defect (upper vs. lower extremity), use of chemotherapy, fixation method, length of overlapped bone, and type of host–allograft junction (diaphyseal– diaphyseal vs. diaphyseal–metaphyseal) did not affect the time to union.
DISCUSSION
Fig. 3. A: Plain radiograph of a 7‐year‐old girl showing osteosarcoma of the humerus with long intramedullary extension of the tumor. B: Post‐ operative radiograph showing reconstruction with an adult femur and fixation with a screw. C: Radiograph taken 5 years post‐operatively, showing complete union, and remodeling of the graft.
knee amputation with local recurrence 19 months post‐operatively. This patient showed union at 9 months post‐operatively and was in excellent functional state before the development of local recurrence. The other patients showed union at 7 months post‐operatively, but displayed progressive resorption of the graft. This patient underwent onlay allograft 3‐years after the initial operation. The average Musculoskeletal Tumor Society functional score was 26.6 (88.7%) of 30 points in 34 patients. All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3–14 months). The average length of overlapping was 3.5 cm
Fig. 4. A: Plain radiograph of a 19‐year‐old lady showing low‐grade osteosarcoma of the proximal humerus. B: Post‐operative radiograph showing reverse shoulder‐overlapping allograft composite reconstruction. C: Radiograph taken 2 years post‐operatively, showing solid union at the allograft–host junction. Journal of Surgical Oncology
Currently, the three most popular methods for reconstruction of large bone defects after tumor resection are tumor prosthesis, biologic, and biologic–composite reconstruction. To improve the outcome of these three methods, understanding the underlying cause of failure is a prerequisite. Amount of bone resection is one of the main causes of prosthesis failure [1,3–4]. In pediatric patient, bone stock loss or osteoporosis may imperil subsequent lengthening procedure or switching to adult type modular prosthesis. Therefore, restoration of bone stock at time of primary reconstruction may decrease the rate of mechanical complication. Biologic reconstruction is limited by relatively high rate of junction non‐union and allograft fracture [14– 16]. Therefore, to improve the outcome of these three reconstructive options, novel use of allograft, which shows lower rates of non‐union and fracture than traditional size‐matched end‐to‐end allograft is essential. In this regard, overlapping allograft reconstruction is an excellent method in terms of primary union rate and time to union [10– 11,17]. Although, our cohort was not large in number, no case showed non‐union. Moreover, the time to union of overlapping allograft was comparable to that of long‐bone fracture [18]. Finally, use of an
TABLE III. Associations Between Time to Union and Clinical Variables
Variables Age 50% Length of allograft 12 cm >12 cm Fixation method IM nail or prosthesis stem Others Overlapping length 3 cm >3 cm Overlapping method Circumferential Partial Types of host–allograft junction Diaphysis–diaphysis Others IM nail, intramedullary nail.
Number
Time to union (month)
23 12
4.6 (3–9) 7.4 (4–14)
0.001
15 20
5.9 (3–14) 5.3 (3–9)
0.519
25 10
5.4 (3–14) 5.9 (3–12)
0.568
16 19
5.3 (3–9) 5.8 (3–14)
0.587
13 22
5.7 (3–9) 5.5 (3–14)
0.832
10 25
7.2 (4–14) 4.9 (3–9)
0.014
28 7
5.9 (3–14) 5.2 (3–9)
0.378
11 24
5.2 (3–9) 5.8 (3–14)
0.546
28 7
4.7 (3–8) 9.0 (5–14)
0.011
17 18
6.2 (3–14) 5.0 (3–8)
0.187
P value
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Jeon et al.
oversized allograft frees us from finding a size‐matched allograft and is generally stronger. Our study is limited by the small number of patients and short follow‐ up. We also did not include concurrent controls, therefore, we can compare our results only with observations or data in the literature. However, the number of patients allowed us to assess graft survival and union of those who underwent this reconstructive procedure. Additionally, this study group had some inherent heterogeneity in terms of patient age, diagnosis, use of chemotherapy, amount of overlapping, type of internal fixation, and types of overlapping, all of which could affect union. In terms of graft survival and graft‐related complications, our surgical goals were met. Except for one case with local recurrence, no allograft had to be removed due to infection, fracture, or non‐union. Compared with the reported infection rate of 5–29% in end‐to‐end method, 0% infection rate in our study may be explained by the low proportion of revision cases (16/35, 45.7%), the small percentage of patients undergoing chemotherapy at the time of reconstruction (17/35, 48.6%), low proportion of proximal tibial location (7/35, 20%), the use of cortical shell type allograft, and relatively short follow‐up period [9,19–20]. Furthermore, because average age in our cohort was 15 years (median, 12.5 years), there is a possibility that small patient size can be one reason for the low complication rates compared with historical control. Allograft fracture is another cause of failure. The reported incidence of allograft fracture has ranged from 6% to 50% [6,21,22]. Type of fixation, non‐union, and resorption of bone can contribute to graft fracture. Plate constructions show higher incidence of fracture due to residual screw holes in the allograft [23]. Use of irradiated allograft also is a factor for increased rate of allograft fracture or resorption [9,24]. Although, the 0% fracture rate in our study remains to be verified due to the short follow‐up period, use of strong, oversized fresh‐frozen allograft, fixation of weight‐bearing bone with an IM nail or prosthesis stem, and, above all, early solid union by using an overlapping method may have contributed to the excellent outcome in our study. How to increase the primary union rate and decrease the risk of resorption or fracture are issues in biologic or composite biologic reconstruction. The reported risk of allograft non‐union and resorption range from 13% to 70% and 7% to 46%, respectively [9,19,20,25,26]. When junctional union is not obtained, the load‐sharing properties of the allograft are minimal, and eventually, the longevity of the allograft– prosthesis composite is threatened. To enhance junctional union in end‐ to‐end allograft procedures, such strategies as autogenous bone grafting, step‐cut osteotomy, and compressible IM nailing have been attempted,
with reported benefits and limitations [27–29]. Meanwhile, the overlapping allograft method improves the intrinsic stability of the construct and markedly increases the apposed bone surface area. In terms of primary union rate and time to union, overlapping allograft shows superior results compared with traditional end‐to‐end coaptation (Table IV). Moreover, this method frees us from finding a size‐matched allograft, which may expand the use of allograft (especially in pediatric cases). However, there are several practical points to discuss. First, regarding the length of overlapping, Healey et al. [10] stressed at least 5 cm of overlapping to optimize stability and promote healing. However, average overlapping length in our study was 3.5 cm and this variable did not affect the time to union. We believe the quality of contact (stout cortex‐to‐cortex coaptation) is more important than mere length of overlapping. In our study, a 9‐year‐old girl who had cortical‐cancellous contact (incomplete removal of allograft cancellous bone) showed delayed union followed by progressive graft resorption; eventually, onlay allograft was inevitable. Second, Healey et al. recommended use of a temporary circumferential wire or bone‐holding clamp to prevent cracking of the thin allograft cortical shell at the overlapping junction. However, we did not experience any allograft cracking without such protective procedures. Instead, in cases without over‐reaming of the allograft medullary canal, we noted cracking of the allograft cortex at prosthesis–allograft interface during the impaction process. Third, regarding factors related to time to union, it is reasonable that age 12 cm also showed shorter time to union should be interpreted carefully. Because the average age of patients with an allograft >12 cm (12 years) was younger than that of patients with an allograft
Overlapping Allograft for Primary or Salvage Bone Tumor Reconstruction DAE-GEUN JEON, MD,* WON SEOK SONG, MD, WAN HYEONG CHO, MD, CHANG-BAE KONG, SANG HYUN CHO, MD, SUNG WOO CHOI, MD, AND SOO-YONG LEE, MD
MD,
Department of Orthopedic Surgery, Korea Cancer Center Hospital, Seoul, Korea
Background: Compared with end‐to‐end allograft coaptation, overlapping allograft offer a superior union rate by increasing the contact area. However, reports on overlapping allograft are scarce. Therefore, we attempted to confirm the usefulness of this technique either after primary tumor resection or in salvaging a failed reconstruction. Methods: We analyzed the outcome of 35 overlapping allografts reconstructions. Indications were primary reconstruction of a skeletal defect (n ¼ 19) and salvage of a failed reconstruction (n ¼ 16). Graft survival, union rate, and time to union were evaluated as a function of clinical variables such as age, use of chemotherapy, type of junction, method of fixation, length of overlapped bone, and method of overlapping. Results: All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3–14 months). One allograft was removed with local recurrence at 19 months post‐operatively. Average length of overlapped bone was 3.5 cm (range, 1.4–6.5 cm). Patient age 40%, and (3) remaining host bone fragment is too short to accommodate a regular‐ length stemmed implant (initial tumor involvement is too extensive or after removal of a failed tumor prosthesis) [1,3–5]. Biologic (allograft, recycled autograft) and composite biologic (allograft‐ or recycled autograft–prosthesis composite) reconstruction were introduced to overcome the limitations of tumor prosthesis by supplementing bone stock. Nevertheless, they have shown limited success due to relatively high rates of non‐union, fracture, loosening, and infection [6–9]. Non‐union at the junction site seems to be a leading cause of mechanical failure. On the other hand, the telescoping (overlapping) allograft technique was introduced to preserve the adjacent joint, increase the bone apposition surface area compared with end‐to‐end techniques, reduce the frequency of non‐union, and reestablish bone length, minimizing the size of endoprosthesis needed for reconstruction [10,11]. Among the possible indications for overlapping allograft, Healey et al. [10] focused mainly on salvage of a short remnant of the proximal femur in revision of a failed distal femoral endoprosthesis with poor bone stock. Besides preserving the adjacent joints at risk for replacement, we attempted to confirm the usefulness of this technique, such as supplementing bone stock in pediatric patient, and arthrodesis in locations where tumor prosthesis is generally not advocated (distal tibia, distal radius). In this study, we asked whether overlapping allograft could achieve our surgical goals (sparing adjacent joint at risk, reconstitution of the diaphysis, arthrodesis) in terms of graft survival, graft‐related complications, and functional outcome. Our second question was to determine whether any clinical factors are related to graft union.
Between January 2007 and April 2013, 130 reconstructions with allograft were performed in our department. The types of overlapping allograft used were intercalary (two junctional sites for union) reconstruction in 35 patients, onlay graft in 44, and restoration of bone stock (one junction site for union) in 51. Among the 51 patients with overlapping allograft reconstruction, we extracted 35 patients. The exclusion criteria in this study were pelvic location (11 patients) and less than 12 months of follow‐up (5 patients). The indications for allograft reconstruction were; (1) primary reconstruction of a skeletal defect (19 patients), (2) salvage of a failed tumor prosthesis (9 patients), or pasteurized autograft (7 patients). There were 20 female and 15 male patients with an average age of 15 years (range, 5–49 years). There were 30 patients with osteosarcoma, 2 with Ewing’s sarcoma, 2 with giant cell tumor, and 1 with chondrosarcoma. Eighteen lesions were located in the femur, seven in the tibia, seven in the humerus, two in the radius, and one in the ulna (Table I). Enneking’s criteria were used to stage the tumors [12]. There were 33 stage IIB and 2 stage 3 tumors. The average follow‐up duration was 30 months (range, 16–60 months). Follow‐up duration was defined as the time from date of index surgery to date of final visit.
ß 2014 Wiley Periodicals, Inc.
Grant sponsor: KRP (KCCH Research Competence Promotion); Grant sponsor: Korea Institute of Radiological & Medical Sciences; Grant number: 50247‐2014. Conflict of interest: None. *Correspondence to: Dae‐Geun Jeon, MD, Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215‐4, Gongneung‐dong, Nowon‐ gu, Seoul 139‐706, Korea. Fax: þ82‐2‐970‐2403. E‐mail: [email protected] Received 27 March 2014; Accepted 13 May 2014 DOI 10.1002/jso.23669 Published online 2 June 2014 in Wiley Online Library (wileyonlinelibrary.com).
Overlapping Allograft Reconstruction TABLE I. Patients Demographics Variables Age Mean (range) 15 year >15 year Gender Male Female Diagnosis Osteosarcoma Ewing’s sarcoma Chondrosarcoma Giant cell tumor Location Femur/tibia Humerus/radius/ulna Enneking stage 3 IIB Surgical goal Reconstitute the diaphysis Preserve adjacent joint at risk Reestablish original bone length Percentage of initial defect 40 (19.6–40%) >40 (42–77%) Types of fixation Stem of prosthesis Intramedullary nail Plate or screw Length of allograft (cm) 12 (6.3–12 cm) >12 (12.2–23 cm) Length of overlapping (cm) 3 (1.4–2.7 cm) >3 (3.2–6.5 cm) Types of host–allograft junction Diaphysis–diaphysis Diaphysis–metaphysis Metaphysis–diaphysis Types of overlapping Circumferential Partial Total
Number of patient (%)
14.2 (5–49) 23 (65.7%) 12 (34.3%) 15 (42.9%) 20 (57.1%) 30 2 1 2
(85.7%) (5.7%) (2.9%) (57.1%)
18/7 (71.4%) 7/2/1 (28.6%) 2 (5.7%) 33 (94.3%) 18 (51.4%) 11 (31.4%) 6 (17.2%) 9 (25.7%) 26 (74.3%) 18 (51.4%) 10 (28.5%) 7 (20.1%) 11 (31.4%) 24 (68.6%) 11 (31.4%) 24 (68.6%)
bone remaining for stem fixation was 4.7 cm (range, 3–9 cm). The location of six arthrodesis was the distal tibia in three patients, distal radius in two, and distal ulna in one. We used fresh frozen allograft under sterile conditions (allografts were stored at 80°C in a bone bank). Proper selection and preparation of the allograft are important to create a stable construct. In general, when selecting a graft, a larger diameter is better. According to the osteotomy site and outer diameter of the host bone, there are two types of overlapping. One is either the allograft medullary canal is placed over the host bone or it is impaled into the medullary canal of the existing host bone (circumferential overlapping). The other is, when outer diameter of the host bone is too thick, the allograft is shaped with a tong‐like outer sleeve and placed outside the host bone (partial overlapping) (Fig. 1). The steps listed subsequently describe the procedure for the most common indication, reconstruction of the femoral diaphysis. After tumor resection, (1) muscle was detached 3–5 cm proximal to the osteotomy site of the host bone leaving the periosteum untouched, (2) the periosteal outer diameter of the remaining host bone was measured and an allograft with an endosteal inner diameter large enough to allow an overlap distance of at least 2 cm was selected (the upside down distal femoral allograft provides an example), (3) the defect and amount of overlapping was considered to allow a provisional allograft cut at 2 cm proximal to the level of epicondyle, (4) cancellous bone was hollowed out from the allograft using a rigid reamer and high‐speed burr, (5) after trial impacting of the allograft over the host bone, the allograft was cut to a length that restored the desired amount of diaphysis, (6) to prevent the allograft cortical shell from cracking or the prosthesis stem from jamming, over‐reaming of the allograft medullary canal was performed, (7) fixation was performed with a plate or intramedullary device. Although, we prefer non‐cemented fixation, we performed cemented fixation in following situations; (1) prosthesis type designed for cemented fixation, (2) failed previous cemented implant, (3) fixation for short remnant of the proximal femur or distal tibia. To make stable allograft–host construct, there are two points to be considered. One is property of the host–allograft interface. To minimize allograft collapse after weight bearing, use of thicker cortical portion of
17 (48.5%) 17 (48.5%) 1 (3.0%) 28 (80.0%) 7 (20.0%) 35 (100%)
In 15 patients, allograft reconstruction was performed during neoadjuvant or adjuvant chemotherapy. The bone was resected at 3 cm from any sign of involvement as determined by MRI. However, for low‐grade lesions, the resection margin was set at up to 1 cm. The percentages of bone resected ranged from 20% to 77% (mean 53%). Except for one case with a metaphyseal junction, the remaining 34 osteotomy sites were diaphyseal. The surgical goals of reconstruction were; (1) reconstitution of the diaphysis (18 patients), (2) preservation of the adjacent joint at risk (11 patients), and (3) arthrodesis (6 patients). Of the 18 patients with a goal of minimizing the length of tumor prosthesis, 12 underwent diaphyseal reconstruction at the time of tumor resection while the remaining 6 were revision cases (failed pasteurized autograft in 4, junctional osteolysis after tumor prosthesis in 2). The location of diaphyseal reconstruction was the femur in 11 patients, humerus in 5, and tibia in 2. Of the 11 patients with an adjacent joint at risk, all except one patient were revision cases (failed tumor prosthesis in 5, failed pasteurized autograft in 3, failed bone cement spacer in 2). The adjacent joint at risk was the hip in seven patients, elbow in 2, and ankle in 2. The average distance from the osteotomy site to the corresponding joint line was 11.8 cm (range, 8–21.7 cm), while the average length of cortical Journal of Surgical Oncology
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Fig. 1. A: Plain lateral radiograph of a 17‐year‐old girl showing osteosarcoma of the distal femur. B: Post‐operative radiograph showing resection and overlapping allograft fixed with an intramedullary nail. Note the tong‐like allograft sleeve for partial overlapping (arrow). C: Radiograph taken 3 years post‐operatively, showing solid union of the graft.
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allograft (meta‐diaphyseal or diaphyseal portion) is recommended for host–allograft coaptation. The other is compression between host and allograft should be made by tapping the allograft with mallet. If the host– allograft construct shows stability without fixation, the overlapping is adequately performed. At time of primary reconstruction, no patient received additional autogenous bone graft in the host–allograft space and this procedure was reserved for non‐union. There are cases with morselized cancellous allograft on overlapped space. In tight telescope type fit (diaphyseal–diaphyseal) case, there was no space for cancellous allograft. However, in some cases with diaphyseal (host)–metaphyseal (allograft) contact, we added some morselized cancellous allograft. The extremity was immobilized in a cast or brace, usually for 6 weeks, with range of motion exercise permitted thereafter. Functional outcome was assessed using the Musculoskeletal Tumor Society System [13]. We recorded clinical variables including: age, gender, location of defect, use of chemotherapy, percentage of initial defect, length of allograft, type of host–allograft junction (diaphyseal– diaphyseal or others), method of fixation (intramedullary stem or others), length of overlapped bone, and method of overlapping (circumferential or partial). Bimonthly plain anteroposterior and lateral radiographs were obtained and examined until 3 years after the index operation. Radiographic union at the junction sites (35 sites in 35 patients) was judged by two of the authors (WSS, DGJ). The osteotomy site was considered radiographically healed when callus was seen bridging the site or blurring was seen between the cortex of the host bone and the allograft on plain radiographs. For patients who showed resorption of the allograft or loosening of internal fixation, additional onlay allograft or temporary brace fitting was performed. The primary end points of this study were union and subsequent remodeling. Allograft failure was defined as the need for graft removal. Student’s t‐test was used to compare mean time to union of the osteotomy sites. Significance was set at P < 0.05.
RESULTS Except for one case with local recurrence, no allografts was removed due to infection, fracture, or non‐union. All 35 patients achieved our surgical goals and reconstruction related outcomes are summarized in Table II. In 29 patients (18 with diaphyseal reconstruction, 11 with adjacent joint at risk), the average defect was 57.6% (range, 33.8–77%), which decreased to a mean of 25.6% (range, 5–57.8%) after overlapping allograft reconstruction (Fig. 2). The percentage of bone stock recovery was largest at humerus and smallest at the distal tibia (Fig. 3). All weight
Fig. 2. A: Plain radiograph of an 11‐year‐old girl showing osteosarcoma of the distal femur. B: Post‐operative radiograph, showing overlapping allograft to reconstitute the diaphysis. Initial bone defect of 48% after tumor resection decreased to 20% after reconstruction with an upside down adult proximal femur. C: Radiograph taken 2 years post‐operatively, showing union, and remodeling of the allograft.
bearing bone (lower extremity) was fixed with a prosthesis stem or intramedullary nail while non‐weight bearing bone (upper extremity) was fixed with a plate, screw, and prosthesis stem. Cemented fixation was performed in two reverse shoulder–allograft composite reconstructions and three failed cemented fixation (two in the proximal femur and one in the distal tibia) (Fig. 4). The average length of overlapped bone showed little difference according to patient age, defect location, and primary or revision cases. Location at the distal tibia showed longer time to union. Two patients required additional surgery. One patient with distal tibial reconstruction underwent below‐
TABLE II. Outcome of Overlapping Allograft Reconstruction According to the Surgical Goals
Surgical goal Restoration of diaphysis
Spare adjacent joint at risk
Arthrodesis
Number of patients
Average patient age (year)
18
10 (6–15)
Femur (11)
22 (14–41)
Humerus (5)
12 (11–13) 20 (11–38)
Proximal tibia (2) Femur (7)
10 (8–12) 35 (26–43)
Humerus (2) Distal tibia (2)
15 (14–17) 13 (12–14) 49
Distal tibia (3) Distal radius (2) Distal ulna (1)
11
6
IM nail, intramedullary nail.
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Location
Type of fixation
Percentage of initial defect
Percentage of defect after allograft
Average overlapping length (cm)
Non‐cemented stem (9)
53 (34–65)
24 (12–34)
3.7 (1.9–5.6)
4.5 (3–7)
47 (36–65)
12 (5–18)
3.5 (2.3–6)
5.6 (4–7)
54 (46–62) 64 (56–74)
24 (16–33) 36 (20–58)
4.9 (4.6–5.2) 3.3 (1.4–6.5)
3.5 (3–4) 6.1 (3–7)
75 (74–76) 75 (74–77)
5 55
2.4 (1.5–3.3) 4.7 (4.1–5.4)
3.5 (3–4) 13 (12–14)
28 (27–30) 46 (42–50) 20
0 0 0
2.4 (1.4–3.2) 4.2 (3.7–4.7) 1.8
7.6 (5–9) 5.5 (3–8) 8
IM nail (2) Screw (3) Cemented stem (2) IM nail (2) Non‐cemented stem (5) Cemented stem (2) Screw (2) Cemented stem (1) Non–cemented stem (1) IM nail (3) Plate (2) IM nail (1)
Time to Union (months)
Overlapping Allograft Reconstruction
369
(range, 1.4–6.5 cm). Patient age 12 cm (P ¼ 0.014) shortened the average time to union (Table III). The percentage of initial defect, location of defect (upper vs. lower extremity), use of chemotherapy, fixation method, length of overlapped bone, and type of host–allograft junction (diaphyseal– diaphyseal vs. diaphyseal–metaphyseal) did not affect the time to union.
DISCUSSION
Fig. 3. A: Plain radiograph of a 7‐year‐old girl showing osteosarcoma of the humerus with long intramedullary extension of the tumor. B: Post‐ operative radiograph showing reconstruction with an adult femur and fixation with a screw. C: Radiograph taken 5 years post‐operatively, showing complete union, and remodeling of the graft.
knee amputation with local recurrence 19 months post‐operatively. This patient showed union at 9 months post‐operatively and was in excellent functional state before the development of local recurrence. The other patients showed union at 7 months post‐operatively, but displayed progressive resorption of the graft. This patient underwent onlay allograft 3‐years after the initial operation. The average Musculoskeletal Tumor Society functional score was 26.6 (88.7%) of 30 points in 34 patients. All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3–14 months). The average length of overlapping was 3.5 cm
Fig. 4. A: Plain radiograph of a 19‐year‐old lady showing low‐grade osteosarcoma of the proximal humerus. B: Post‐operative radiograph showing reverse shoulder‐overlapping allograft composite reconstruction. C: Radiograph taken 2 years post‐operatively, showing solid union at the allograft–host junction. Journal of Surgical Oncology
Currently, the three most popular methods for reconstruction of large bone defects after tumor resection are tumor prosthesis, biologic, and biologic–composite reconstruction. To improve the outcome of these three methods, understanding the underlying cause of failure is a prerequisite. Amount of bone resection is one of the main causes of prosthesis failure [1,3–4]. In pediatric patient, bone stock loss or osteoporosis may imperil subsequent lengthening procedure or switching to adult type modular prosthesis. Therefore, restoration of bone stock at time of primary reconstruction may decrease the rate of mechanical complication. Biologic reconstruction is limited by relatively high rate of junction non‐union and allograft fracture [14– 16]. Therefore, to improve the outcome of these three reconstructive options, novel use of allograft, which shows lower rates of non‐union and fracture than traditional size‐matched end‐to‐end allograft is essential. In this regard, overlapping allograft reconstruction is an excellent method in terms of primary union rate and time to union [10– 11,17]. Although, our cohort was not large in number, no case showed non‐union. Moreover, the time to union of overlapping allograft was comparable to that of long‐bone fracture [18]. Finally, use of an
TABLE III. Associations Between Time to Union and Clinical Variables
Variables Age 50% Length of allograft 12 cm >12 cm Fixation method IM nail or prosthesis stem Others Overlapping length 3 cm >3 cm Overlapping method Circumferential Partial Types of host–allograft junction Diaphysis–diaphysis Others IM nail, intramedullary nail.
Number
Time to union (month)
23 12
4.6 (3–9) 7.4 (4–14)
0.001
15 20
5.9 (3–14) 5.3 (3–9)
0.519
25 10
5.4 (3–14) 5.9 (3–12)
0.568
16 19
5.3 (3–9) 5.8 (3–14)
0.587
13 22
5.7 (3–9) 5.5 (3–14)
0.832
10 25
7.2 (4–14) 4.9 (3–9)
0.014
28 7
5.9 (3–14) 5.2 (3–9)
0.378
11 24
5.2 (3–9) 5.8 (3–14)
0.546
28 7
4.7 (3–8) 9.0 (5–14)
0.011
17 18
6.2 (3–14) 5.0 (3–8)
0.187
P value
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oversized allograft frees us from finding a size‐matched allograft and is generally stronger. Our study is limited by the small number of patients and short follow‐ up. We also did not include concurrent controls, therefore, we can compare our results only with observations or data in the literature. However, the number of patients allowed us to assess graft survival and union of those who underwent this reconstructive procedure. Additionally, this study group had some inherent heterogeneity in terms of patient age, diagnosis, use of chemotherapy, amount of overlapping, type of internal fixation, and types of overlapping, all of which could affect union. In terms of graft survival and graft‐related complications, our surgical goals were met. Except for one case with local recurrence, no allograft had to be removed due to infection, fracture, or non‐union. Compared with the reported infection rate of 5–29% in end‐to‐end method, 0% infection rate in our study may be explained by the low proportion of revision cases (16/35, 45.7%), the small percentage of patients undergoing chemotherapy at the time of reconstruction (17/35, 48.6%), low proportion of proximal tibial location (7/35, 20%), the use of cortical shell type allograft, and relatively short follow‐up period [9,19–20]. Furthermore, because average age in our cohort was 15 years (median, 12.5 years), there is a possibility that small patient size can be one reason for the low complication rates compared with historical control. Allograft fracture is another cause of failure. The reported incidence of allograft fracture has ranged from 6% to 50% [6,21,22]. Type of fixation, non‐union, and resorption of bone can contribute to graft fracture. Plate constructions show higher incidence of fracture due to residual screw holes in the allograft [23]. Use of irradiated allograft also is a factor for increased rate of allograft fracture or resorption [9,24]. Although, the 0% fracture rate in our study remains to be verified due to the short follow‐up period, use of strong, oversized fresh‐frozen allograft, fixation of weight‐bearing bone with an IM nail or prosthesis stem, and, above all, early solid union by using an overlapping method may have contributed to the excellent outcome in our study. How to increase the primary union rate and decrease the risk of resorption or fracture are issues in biologic or composite biologic reconstruction. The reported risk of allograft non‐union and resorption range from 13% to 70% and 7% to 46%, respectively [9,19,20,25,26]. When junctional union is not obtained, the load‐sharing properties of the allograft are minimal, and eventually, the longevity of the allograft– prosthesis composite is threatened. To enhance junctional union in end‐ to‐end allograft procedures, such strategies as autogenous bone grafting, step‐cut osteotomy, and compressible IM nailing have been attempted,
with reported benefits and limitations [27–29]. Meanwhile, the overlapping allograft method improves the intrinsic stability of the construct and markedly increases the apposed bone surface area. In terms of primary union rate and time to union, overlapping allograft shows superior results compared with traditional end‐to‐end coaptation (Table IV). Moreover, this method frees us from finding a size‐matched allograft, which may expand the use of allograft (especially in pediatric cases). However, there are several practical points to discuss. First, regarding the length of overlapping, Healey et al. [10] stressed at least 5 cm of overlapping to optimize stability and promote healing. However, average overlapping length in our study was 3.5 cm and this variable did not affect the time to union. We believe the quality of contact (stout cortex‐to‐cortex coaptation) is more important than mere length of overlapping. In our study, a 9‐year‐old girl who had cortical‐cancellous contact (incomplete removal of allograft cancellous bone) showed delayed union followed by progressive graft resorption; eventually, onlay allograft was inevitable. Second, Healey et al. recommended use of a temporary circumferential wire or bone‐holding clamp to prevent cracking of the thin allograft cortical shell at the overlapping junction. However, we did not experience any allograft cracking without such protective procedures. Instead, in cases without over‐reaming of the allograft medullary canal, we noted cracking of the allograft cortex at prosthesis–allograft interface during the impaction process. Third, regarding factors related to time to union, it is reasonable that age 12 cm also showed shorter time to union should be interpreted carefully. Because the average age of patients with an allograft >12 cm (12 years) was younger than that of patients with an allograft
