Skeletal Radiol (2000) 29:335–339 © International Skeletal Society 2000

Shigeru Ehara Jun Nishida Hideo Shiraishi Yoshiharu Tamakawa

Received: 21 December 1999 Revision requested: 16 February 2000 Revision received: 9 March 2000 Accepted: 14 March 2000

S. Ehara, M.D. (✉) · Y. Tamakawa, M.D. Department of Radiology, Iwate Medical University School of Medicine, Morioka 020-8505, Japan J. Nishida, M.D. · H. Shiraishi, M.D. Department of Orthopedic Surgery, Iwate Medical University School of Medicine, Morioka 020-8505, Japan

A RT I C L E

Pasteurized intercalary autogenous bone graft: radiographic and scintigraphic features

Abstract Objective. Pasteurized autogenous bone graft sterilized at a low temperature (60°C) is one option for reconstruction after resection of bone and soft tissue tumors. The purpose of this investigation was to assess the normal and abnormal radiographic and scintigraphic findings of pasteurized intercalary autogenous bone graft after resection of bone and soft tissue sarcomas. Design. This was a retrospective evaluation of the radiography and bone scintigraphy findings in patients after treatment of bone and soft tissue sarcomas using an intercalary pasteurized autogenous bone graft. Patients. Among 10 consecutive patients, eight had intercalary grafts,

Introduction Pasteurization, heating at a low temperature (60°C), is a method of sterilization commonly used for cows' milk. A pasteurized autogenous bone graft, as well as an autoclaved bone graft (using a high temperature, 120°C), can be used for reconstruction after the resection of bone and soft tissue tumors when bone banks for allograft are not readily available [1]. Such pasteurization is reported to eliminate viable tumor cells while relatively preserving osteoinductive activity and mechanical strength, particularly for bending and torsion. Evaluation of such bone grafts is based on radiography, because CT and MR imaging have limited roles due to the frequent presence of metallic implants. Although bone scintigraphy is advocated by some for evaluation [2, 3], the findings are still controversial. The purpose of this investigation was to assess the normal and abnormal

and they constitute the subjects of this study. All available radiography and bone scintigraphy findings were reviewed for the healing process and the possibility of complications. Results and conclusions. Healing and incorporation of the graft were observed in five patients during the follow-up, but the other three did not heal satisfactorily. Rapid incorporation of pasteurized autogenous bone graft can be demonstrated by means of radiography and bone scintigraphy. Key words Bone graft · Postsurgical changes · Bone scintigraphy · Radiography · Bone tumors

radiographic and scintigraphic findings of pasteurized autogenous bone grafts after resection of bone and soft tissue sarcomas.

Patients and methods This was a retrospective evaluation of the radiography and bone scintigraphy findings in patients following treatment of bone and soft tissue sarcomas using intercalary pasteurized autogenous bone grafts performed between May 1994 and July 1997. Eight patients with intercalary grafts (2 were hemigrafts without a complete bone circumference) among ten consecutive patients constitute the subjects of this study (Table 1). The resected bone segments containing sarcoma were sterilized in normal saline at a low temperature (60°C for 30 min) after curettage of the tumor tissue, and the osseous portion was placed back into the bone defects. Informed consent was obtained from all patients. Radiographs were reviewed for the healing process and the possibility of complications. The normal process of healing was assessed in terms of periosteal and endosteal callus formation. Be-

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Table 1 Summary of results Case no.

Age, Gender

Histology

Location

Scintigraphy (months)

Last follow-up (months)

Outcome

1

17F

Parosteal osteosarcoma

Distal femur

6, 14, 26, 46

64

2

48F

Leiomyosarcoma, soft tissue

2, 6

48

3 4

36F 41F

Chondrosarcoma Alveolar soft part sarcoma

2, 4, 8, 13 3, 6

33 37

Uneventful Uneventful

5

18M

Osteosarcoma

Thigh (proximal femoral hemigraft) Mid-femur Calf (mid-tibial hemigraft) Proximal humerus

Infection, pseudoarthrosis Uneventful

1

31

6

68F

Plasmacytoma

Mid-femur

4, 5, 7

Pseudoarthrosis, metastasis Pseudoarthrosis

7 8

60F 53M

Chondrosarcoma Chondrosarcoma

Proximal humerus Mid-femur

2 1, 3

8 (lost to follow-up) 28 Uneventful 26 Uneventful

cause it was difficult to evaluate endosteal callus in the early phase, we did not attempt to grade callus formation. Instead, we used radiography to confirm the outcome of bone grafting, since radiographic changes were delayed in our initial experience. Bone scintigraphy was performed between 2 and 3 h after the intravenous injection of 555 MBq of 99mTc-hydroxymethylene diphosphonate (HMDP), and whole body scanning and images of the region with an abnormal uptake on the whole body images were obtained, including postoperative sites. The uptake at the host-graft junction and the cortical rim were graded as: – (less than the normal side or the normal portion of the same bone), 0 (same as the normal side or the normal portion of the same bone) or + (more than the normal side or the normal portion of the same bone). The time period after surgical treatment was not controlled because of the retrospective nature of this study. The routine radiographic follow-up protocol after surgery for patients with no signs of complications was every 3 months for a half-year and every 6–12 months until complete bone incorporation was evident. The follow-up periods with bone scintigraphy were 1–46 months after surgery, and the clinical follow-up periods were 24–64 months, except for one patient who was unavailable for follow-up 8 months after surgery.

Results Healing and incorporation of the graft were observed in five cases during the follow-up (Table 1). In one patient (case 1), after an infection in the operated region, pseudoarthrosis developed and revision of the grafting was performed twice. Resorption of the host bone and pseudoarthrosis occurred in one patient (case 5), and one patient with radiological evidence of pseudoarthrosis was unavailable for follow-up 8 months after surgery (case 6). Radiographic changes were delayed compared with the bone scintigraphic changes. Two types of healing processes were noted (Table 2). One type occurred without evident periosteal callus and the healing was completed in a relatively early phase (7–18 months after surgery; cases 2, 3, and 7) (Fig. 1). The other type was char-

Table 2 Summary of radiographic findings Case no.

Radiographic findings

Period (months)

1 2 3 4

Pseudoarthrosis Solid bridging, no periosteal callus Solid bridging, no periosteal callus Calcified periosteal callus Bone bridging (partially open) Complete fusion Resorption of host bone, pseudoarthrosis Pseudoarthrosis Solid bridging, no periosteal callus Periosteal callus Bone bridging, progression of callus formation

7 18 15 4 21 37 20 6 7 12 24

5 6 7 8

acterized by periosteal callus formation in an early phase and a slow progression of the callus formation into the opposed host and graft bones (cases 4 and 8) (Fig. 2). In all patients an increased uptake (grade +) at the host side of the host-graft junction was seen at the first bone scintigraphy after surgery (1–2 months). In one patient with an uneventful recovery (case 3), a gradually decreased uptake (grade + to 0) on the host side and an increased uptake (grade +) on the graft side were evident. The uptake at the host-graft junction (grade +) was persistent in one patient with infection and pseudoarthrosis (case 1). The shaft of the graft (grade –) was photondeficient at 1–2 months after surgery in all cases. In the patients without complications, increased activity on the surface of the cortex (grade 0 or +), less prominent than at the host-graft junction, was seen after 3 months. In one patient with infection and pseudoarthrosis (case 1), the uptake increased (grade +), but in two patients with pseudoarthrosis (cases 5, 6), the graft remained with poor activity (grade -) after 4 months (Fig. 3). These findings indicate that the uptake at the host-graft junc-

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Fig. 1A–D A 36-year-old woman after resection of chondrosarcoma of the femur and reconstruction with pasteurized autogenous graft. No evidence of complications is noted at 33 months after surgery. A Bone scintigraphy at 2 months after surgery. The uptake at the host-graft junction is increased and the shaft of the graft is photon-deficient. B Bone scintigraphy at 4 months after surgery. The uptake in the shaft of the graft is now evident. C Bone scintigraphy at 12 months after surgery. The uptake at the host-graft junction is relatively decreased. D Anteroposterior view of the femur at 14 months after surgery. Osseous fusion at the host-graft junctions (arrows) is evident with no periosteal callus

tion did not contribute to prediction of the prognosis, and that the activity at the cortical rim was probably more important in this regard.

Discussion The radiographic findings of graft incorporation are similar to those of osteotomy. As seen in the healing of osteotomy, endosteal callus between the opposed bones and periosteal callus are the two main components of healing. Endosteal callus is often not evident on radiography until solid bone bridging occurs. Periosteal callus may be evident radiographically at an early stage. The time required for the healing process and incorporation of the graft varies according to the type of graft (e.g., allograft, autoclaved bone, pasteurized bone), but host factors such

as blood supply and weight-bearing are also important after the extensive resection of a sarcoma. Kattapuram et al. have investigated the radiographic changes in intercalary allografts [4]. They saw the peak of periosteal reaction and callus formation at 10 months after surgery. Our results may be similar, but the comparison cannot be made because of the small number of cases in our series. Bone scintigraphy using 99mTc- biphosphonate compounds has been used for the evaluation of vascularization of bone grafts [2], since the radionuclide distributes in the skeleton through the arterial flow, and stays there presumably due to chemiabsorption, reflecting the activity of bone metabolism. The uptake of radiotracer in allografts after the resection of bone and soft tissue sarcomas has been studied, but it is still controversial. Smith and colleagues used bone scintigraphy for the evaluation of the allograft after removal of bone neoplasm, and ob-

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Fig. 2A–C A 53-year-old man after resection of chondrosarcoma of the femur and reconstruction with pasteurized autogenous graft. No evidence of complications is noted at 26 months after surgery. A Bone scintigraphy done at 3 months after surgery. The uptake at the host-graft junction is prominent, and there is increased uptake in the cortical rim of the graft. B Anteroposterior view of the femur at 12 months after surgery. The distal host-graft junction is fused with no periosteal callus. Periosteal reaction is prominent at the proximal host-graft junction that is still open. (arrows: hostgraft junctions). C Anteroposterior view of the femur at 24 months after surgery. There is periosteal new bone formation on the medial aspect of the proximal host-graft junction with solid osseous union (arrows: host-graft junctions)

Fig. 3A,B A 68-year-old woman after resection of solitary plasmocytoma and reconstruction with pasteurized bone graft and polymethylmethacrylate cement. The graft was clinically loosened 8 months after surgery. A Bone scintigraphy at 5 months after surgery. The uptake in the host bone is intense, and the activity of the cortical rim is relatively poor with photon-deficient segments (arrows). B Anteroposterior radiograph at 8 months after surgery. Bone resorption at the host-graft junctions (arrows) and the lack of calcified callus are evident

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served a persistently increased uptake at the bone-graft junction and a variable uptake in the periphery the graft [5]. Bar-Sever et al. saw an increased uptake at the host graft junction and the photon-deficient allograft, stable over time [6]. On the other hand, Van Laere and colleagues observed a diffusely increased uptake at the host-graft junction within the first few months after surgery, and a rim of increased uptake on the surface of cortex within the first 6 months [7]. They also saw partial tracer uptake in the graft in 72% of cases at an average of 19.6 months and diffuse uptake indicating complete revascularization in 24% of cases at an average of 31.4 months. This pattern of change in uptake is similar to that in our cases, but the uptake in the graft, representing revascularization and incorporation of the graft, occurs earlier in our series using a pasteurized autograft. However, further experience is needed to determine the difference between allografts and pasteurized autografts.

The limitation of this study lies in the small number of cases and the lack of control over the follow-up period. The role of bone scintigraphy is better evaluated in a prospective study. Another limitation is the lack of SPECT in the evaluation. Although SPECT is essential in complex or flat bones such as the vertebrae and the pelvis, its role in the tubular bones seems to be limited. In conclusion, bone scintigraphy using a 99mTc-biphosphonate compound is a suitable method for assessing bone incorporation of the bone graft. A pasteurized autogenous bone graft shows rapid incorporation on radiography and bone scintigraphy. Radiographic and bone scintigraphic findings may be similar to those seen in the other types of grafts, although the difference in the time course of bone incorporation is still not certain.

References 1. Manabe J. Experimental studies on pasteurized autogenous bone graft. J Jpn Orthop Assoc 1993; 67:255–266 [in Japanese]. 2. Stevenson JS, Bright RW, Dunson GL, Nelson FR. Tc-99m phosphate bone imaging: a method for assessing bone graft healing. Radiology 1974; 110:391–394.

3. Palestro CJ. Radionuclide imaging after skeletal interventional procedures. Semin Nucl Med 1995; 25:3–14. 4. Kattapuram SV, Phillips WC, Mankin HJ. Intercalary bone allografts: radiographic evaluation. Radiology 1989; 170:137–141. 5. Smith JT, Smith LM, Rinsky L, Goris ML. Long-term scintigraphic appearance of extremities following bone tumor resection and allograft reconstruction. Clin Nucl Med 1991; 16:907–909.

6. Bar-Sever Z, Connolly LP, Gebhardt M, Treves ST. Skeletal scintigraphy in the evaluation of osteosarcoma patients following allograft reconstruction. J Nucl Med 1996; 37:28P. 7. Van Laere K, Casier K, Uyttendale D, et al. Technetium-99m-MDP scintigraphy and long-term follow-up of treated primary malignant tumors. J Nucl Med 1998; 39:1563–1569.