n Feature Article
oncology
S P OT L I G H T O N
Clinical and Functional Outcomes of Tibial
Intercalary Allografts After Tumor Resection
Germán L. Farfalli, MD; Luis Aponte-Tinao, MD; Lucas Lopez-Millán, MD; Miguel A. Ayerza, MD;
D. Luis Muscolo, MD
abstract
Full article available online at ORTHOSuperSite.com. Search: 20120222-25
Reconstruction after intercalary resection of the tibia is demanding due to subcutaneous location, poor vascularity of the tibia, and high infection rate. The purpose of
this study was to evaluate the survivorship, complications, and functional outcome of
intercalary tibial allograft reconstructions following tumor resections.
Intercalary tibia segmental allografts were implanted in 26 consecutive patients after
segmental resections. Patients were followed for an average of 6 years. Allograft survival was determined with the Kaplan-Meier method. Patient function was evaluated
with the Musculoskeletal Tumor Society (MSTS) scoring system. Survivorship was 84%
(95% confidence interval [CI], 98%-70%) at 5 years and 79% (95% CI, 63%-95%)
at 10 years. Allografts were removed in 5 patients due to 3 infections and 2 local
recurrences. Two patients showed diaphyseal nonunion, and 3 patients underwent
an incomplete fracture; no allografts were removed in these patients. Average MSTS
functional score was 29 points (range, 27-30 points).
A
B
Figure: Anteroposterior (left) and lateral (right)
radiographs of the tibia showing an intercalary
custom-made prosthesis with clinical instability
due to aseptic loosening (A). Anteroposterior (left)
and lateral (right) radiographs of the diaphyseal
intercalary allograft 4 years postoperatively with
healed osteotomies and covered by the internal
fixation (B).
Despite the incidence of complications, this analysis showed an acceptable survivorship with excellent functional scores. The use of intercalary allograft has a place in
the reconstruction of a segmental defect created by the resection of a tumor in the
diaphyseal or metaphyseal portion of the tibia.
Drs Farfalli, Aponte-Tinao, Lopez-Millán, Ayerza, and Muscolo are from Carlos E. Ottolenghi
Institute of Orthopedics, Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
Drs Farfalli, Aponte-Tinao, Lopez-Millán, Ayerza, and Muscolo have no relevant financial relationships to disclose.
Correspondence should be addressed to: Germán L. Farfalli, MD, Carlos E. Ottolenghi Institute of
Orthopedics, Italian Hospital of Buenos Aires, Potosí 4247 (1199), Buenos Aires, Argentina (german.
[email protected]).
doi: 10.3928/01477447-20120222-25
MARCH 2012 | Volume 35 • Number 3
e391
n Feature Article
T
he survival rate of patients with
malignant bone tumors improves
over time.1 With this improvement, indications for limb preservation
have become the main treatment for local
control of the disease.1 Because of more
accurate imaging techniques, many tumors compromising the metadiaphyseal
region of the tibia may be treated with
epiphyseal preservation. These tumor resections create segmental bone defects
that can be reconstructed using different
biological2-9 and nonbiological alternatives.10,11 Intercalary segmental allografts
provide a biological spacer with initial
biomechanical stability of the limb, allowing immediate adjacent joint function.
Different allograft sizes and lengths are
available, and after healing of host–donor junctions, they may be incorporated
progressively by the host. However, an
adverse effect of chemotherapy in bone
healing has been reported,12 and clinical
studies have shown a variable incidence of
infection fracture and nonunion.4,7,9
This article reports a group of patients
treated with tibial intercalary allografts
after a tumor resection and analyzes the
mid- and long-term survival of this reconstruction and the complications and functional results that can be expected in this
group of patients.
Materials and Methods
Between May 1990 and July 2008,
twenty-six tibial intercalary allografts
were performed at our institution. The
study group included all consecutive patients (13 women and 13 men) who had
a whole cylindrical intercalary tibial segmental allograft reconstruction after tumor excision, and who were followed up
for >2 years or when the reconstruction
failed. No patients were lost to follow-up.
Mean follow-up was 73 months (range,
9-176 months). Mean patient age was 25
years (range, 4-57 years). The original diagnoses included osteosarcoma in 14 patients, Ewing’s sarcoma in 1, chondrosarcoma in 2, bone metastasis in 1, giant cell
e392
1A
1B
2A
2B
Figure 1: Anteroposterior (left) and lateral (right)
radiographs of the tibia showing an intercalary
custom-made prosthesis with clinical instability
due to aseptic loosening (A). Anteroposterior (left)
and lateral (right) radiographs of the diaphyseal
intercalary allograft 4 years postoperatively with
healed osteotomies and covered by the internal
fixation (B).
Figure 2: Intraoperative photograph taken after the
adamantinoma of the diaphyseal tibia was resected
and the bone defect was reconstructed with an intercalary allograft (A). Anteroposterior radiograph
showing a 14-year follow-up control with an intercalary allograft stabilized with 3-plate fixation in the
proximal and distal osteotomies. The entire length
of the allograft is protected with plate fixation (B).
tumor in 1, malignant fibrohistiocytoma
in 1, chondromyxoid fibroma in 1, fibrosarcoma in 2, adamantinoma in 1, osteoblastoma in 1, and revision of another intercalary reconstruction (prosthesis) in 1
(Figure 1). No adjuvant radiation therapy
was used in this group of patients.
The surgical procedure began with
resection of the lesion, including biopsy
scars with appropriate bone and soft tissue
margins, and insertion of a fresh deep-frozen allograft segment sized to fit the bone
defect. These nonirradiated allografts
were harvested and stored according to
a technique that has been described previously.7 Allografts were selected on the
basis of a comparison of radiographs and
computed tomography scans of the patient
with those of the donor to achieve the closest anatomic match. After being thawed in
a warm solution, the donor bone was cut
to the proper length. All allograft–host
junctions were made with a transverse osteotomy. Plates and screws were used for
internal fixation in 21 patients (Figure 2),
and intramedullary locked nails were used
in 5 patients. In 7 patients, the host patellar tendon was sectioned during tumor
removal. The remaining tendon was reat-
tached to the corresponding tissue of the
allograft. Antibiotics were given intravenously according to a usual prophylactic
protocol, and no routine anticoagulation
therapy was used. An external immobilizer was used until the wound had healed.
Progressive passive range of motion exercises were started during the first week
postoperatively. Most patients were seen
postoperatively at 1 and 2 weeks; 1, 2,
and 3 months; every 3 months thereafter
until 2 years; and then annually. Sixteen
patients received adjuvant chemotherapy
and 10 did not.
Plain radiographs were taken at every visit, beginning 1 month postoperatively. Clinical records, postoperative
radiographs, and all follow-up radiographs were reviewed for each patient.
Comparable anteroposterior (AP) and
lateral radiographs were chosen for analysis. The radiographic appearance of the
junction, fixation method, use of adjuvant
chemotherapy, and complications were
recorded. The allograft–host junction was
considered to be radiographically healed
when the junction line no longer was visible or the junction was bridged with periosteal bone on AP and lateral radiographs.
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Tibial Intercalary Allografts After Tumor Resection | Farfalli et al
The functional evaluation was performed in both groups using the revised
30-point functional classification system
established by the Musculoskeletal Tumor
Society (MSTS),13 which assesses pain,
functional limitation, walking distance,
use of a support, emotional acceptance,
and gait. Each variable was assessed on a
5-point scale.
The allograft survival rate was estimated using the method of Kaplan-Meier.
The procedure was considered a failure
when the allograft was removed as a revision procedure or amputation. We used
Cox regression to analyze which factors
negatively influenced the results. Factors
analyzed were the use of chemotherapy
and the type of fixation. We used SPSS
17.0 for Windows (SPSS Inc, Chicago,
Illinois) for statistical analyses.
Results
The overall survival rate of the 26 intercalary allografts, as calculated with the
Kaplan-Meier method, was 84% (95%
confidence interval [CI], 90%-70%) at 5
years and 79% at 10 years (95% CI, 95%63%) (Figure 3). Complications that required a second surgical procedure were
recorded for 10 patients, including 2 local
recurrences, 3 deep infections, 3 nondisplaced fractures, and 2 nonunions. In 5
of these 10 patients, the allograft was removed, and the patients were considered
to have failed results (Table).
Both patients with local recurrences
were treated with amputation. In all patients who had an acute deep infection,
the allograft was removed and a temporary cement spacer with antibiotics was
implanted. After 6 weeks of intravenous
antibiotics and another 6 weeks of oral
antibiotics, an intercalary allograft was reimplanted in 2 patients, and the remaining
patient still has the cement spacer.
All patients with nondisplaced fractures and the 2 patients who underwent
nonunion were treated with autologous
bone graft and a new plate, without removing the original allograft (Figure 4).
MARCH 2012 | Volume 35 • Number 3
3
Figure 3: Kaplan-Meier curve for survival of the tibial intercalary allografts. Abbreviation: Cum, cumulative.
We observed a statistical tendency in
patients treated with chemotherapy to
have a higher number of general complications (P5.07). No statistical relationship was found between different types
of internal fixation and general complications.
Long-term functional results were evaluated at last follow-up in the 21 patients
who retained the allograft, with a mean
follow-up of 39 months. Mean MSTS
functional score was 29 of 30 (96.6%)
(range, 27-30). For patients in whom the
extension mechanism was reconstructed,
physical examination revealed that the
arc of active motion of the knee averaged
96.4° (range, 88°-120°). Mean extensor
lag was 2.5° (range, 0°-5°).
Discussion
Segmental tibial bone losses caused by
tumor resection can be reconstructed with
different techniques, including insertion
of metal implants,10,11 autogenous bone
grafts,2 distraction osteogenesis,8 or massive bone allografts.7,9 Intercalary segmental allografts can be fixed to small epiphy-
seal host fragments, obtaining immediate
limb stability and allowing active adjacent
joint motion. After healing of both osteotomies, allografts may be incorporated
progressively by the host. However, an
adverse effect of chemotherapy on bone
healing has been reported,12 and clinical
studies have shown a variable incidence
of infection, fracture, and nonunion.7,9 We
analyzed the survivorship of intercalary
segmental tibia allograft in patients after
tumor resection and the incidence of deep
infections, fractures, and nonunions that
occurred. To evaluate a more homogenous
population, we only included segmental
allografts located at the tibia, excluding
joint intercalary allograft arthrodesis.
Our study had limitations. First, we
had no control group with alternate approaches. Second, some potential uncontrolled variables existed, such as the
amount of soft tissue resection, extension
of internal fixation, amount of compression at the host–donor junction, and anatomic allograft fitting. Although this is a
large series for the type of reconstruction,
the subcohorts are too small and hetero-
e393
n Feature Article
Table
Allograft Outcomes
Patient No./
Sex/Age, y
Local
Recurrence
Infection
Fracture
Nonunion
Plate
No
No
No
No
Plate
Yes
No
No
No
CS
Plate
No
No
No
No
Ewing
Plate
No
No
No
Yes
MFH
Plate
No
No
No
No
6/F/4
CF
Nail
No
No
No
No
7/F/25
FS
Nail
No
No
No
No
8/M/57
REV
Plate
No
No
No
No
9/M/30
FS
Plate
Yes
No
No
No
10/M/19
OS
Plate
No
No
No
No
11/F/57
MTS
Nail
No
No
No
No
12/F/28
OS
Plate
No
Yes
No
No
13/M/16
OS
Plate
No
No
No
No
14/F/14
OS
Plate
No
No
Yes
No
15/F/18
OS
Nail
No
No
No
No
16/M/21
OS
Plate
No
No
No
No
17/F/12
OS
Plate
No
No
Yes
No
18/M/18
OS
Plate
No
No
No
No
19/M/10
OS
Plate
No
No
No
No
20/M/17
OS
Plate
No
Yes
No
No
21/M/16
OS
Plate
No
No
No
Yes
22/F/13
OS
Plate
No
No
Yes
No
23/M/24
OS
Nail
No
Yes
No
No
24/M/34
OS
Plate
No
No
No
No
25/F/16
OB
Plate
No
No
No
No
26/M/27
GCT
Plate
No
No
No
No
Diagnosis
Fixation
1/F/33
ADT
2/M/55
CS
3/F/42
4/F/11
5/F/48
Abbreviations: ADT, adamantinoma; CF, chondromyxoid fibroma; CS, chondrosarcoma;
Ewing, Ewing’s sarcoma; FS, fibrosarcoma; GCT, giant cell tumor; MFH, malignant
fibrohistiocitoma; MTS, metastasis; OB, osteoblastoma; OS, osteosarcoma; REV, revision.
geneous (with various confounding and
uncontrolled variables) to have adequate
power to identify whether and how these
influence graft survival.
Previous clinical studies have shown
that allografts can survive for decades.
Mankin et al4 reported a survival rate of
76% among 718 patients who had allograft
reconstruction; the study included 163 intercalary allografts that had better results
(84%) than osteoarticular allografts (73%)
e394
or allograft prostheses (77%). Another
study had a 5-year survival rate of 79% in
59 intercalary allografts reconstruction of
the lower extremity.11 The current study’s
results are consistent with others, showing
an overall survival rate of 84% at 5 years
and 79% at 10 years.
Some studies report that allograft
failures are mostly related to local recurrences, allograft infections, fractures, and
nonunions. The frequency of infection in
4A
4B
4C
4D
Figure 4: Anteroposterior radiograph showing a
patient with a tibial diaphyseal osteosarcoma (B).
Magnetic resonance image of a 13-year-old girl
showing a diaphyseal osteosarcoma without compromise of both epiphyses (B). Anteroposterior
radiograph showing a 12-month follow-up control
with an intercalary allograft stabilized with 2 plates.
Evidence of union exists in the distal osteotomy,
but nonunion of the proximal osteotomy exists
(C). Anteroposterior radiograph showing a 6-year
control of the intercalary allograft with incorporation of the graft and healing of both osteotomies
after autologous graft was added in the proximal
osteotomy and the lateral plate was exchanged (D).
the overall series of massive allografts
reported in the literature ranged from 6%
to 30%.4 Two extensive series analyzed
infections in intercalary allograft reconstructions. One, from an institution with
extensive experience in massive bone allografts, had a 12% incidence of infection
in 104 allografts.9 The other had a 5%
incidence of infection in 59 patients who
had reconstruction with an allograft of the
lower extremity.7 In the current study, the
incidence of infection for segmental tibia
intercalary allografts was 11.5%.
Evidence exists that 1 of the major complications that causes bone allograft failure
is graft fracture.4,7,9 The reported prevalence of such fractures ranges from 9% to
19%.4,7,9 A higher incidence of allograft
fracture was also reported in relation to
screw holes, suggesting that allografts
are sensitive to stress-concentrating defects.14,15 From 183 allograft–host junctions fixed with plates or nails, Vander
Griend15 reported that plate fixation was
associated with a higher rate of allograft
fracture. It has been suggested that the
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Tibial Intercalary Allografts After Tumor Resection | Farfalli et al
risk of fracture may be diminished by
spanning the entire allograft with a long
plate to provide extracortical support.14,15
In the current study, the incidence of fracture was 11.5%, and all 3 fractures were
treated with new internal fixation and autologous bone graft, without failure of the
original allograft. The fibula offers additional protection to weight bearing in tibia
intercalary allografts.
The incidence of allograft–host junction nonunion was 7.6% in the current
study, but no patient with a nonunion had
an allograft failure. Both patients were
treated with autologous bone grafts and
new internal fixation. Another study that
analyzed the effect of internal fixation on
healing of large allografts showed a significant association between achieving stable
fixation and development of a nonunion,
but no significant differences were found
in this series due to the small number of
patients.7 A recent study that analyzed 8
patients with intercalary reconstruction of
the tibia with a massive allograft with a
vascularized intramedullary fibular graft
showed 2 nonunions, 1 between the allograft and the host and 1 between the
fibula and the allograft.3
The most used surgical options for reconstruction of metadiaphyseal defects of
the tibia after a tumor resection include
biological reconstructions, such as autogenous vascularized fibular grafts,2,16-18
extracorporeally irradiated autogenous
bone,19,20 and distraction osteogenesis.21,22
The remaining nonbiological reconstruction technique includes intercalary endoprostheses.10,23-25
Autogenous fibular graft is a biologic
method that has advantages, such as restoring bone stock, and although high
survival rates have been reported with this
type of reconstruction, it may require a
lengthy period of nonweight bearing to allow for union/graft hypertrophy (average
time to full weight bearing, 21 months).
Some reports show a high incidence of
fractures (up to 50%), no unions (up to
25%), and significant morbidity at the
MARCH 2012 | Volume 35 • Number 3
donor site, and this method may also be
limited for large defects.16-18
Extracorporeally irradiated autogenous
bone grafts are suitable for larger defects,
and survival rates have been reported with
this reconstruction.19,20 Irradiated bone is
brittle and takes a long time to revascularize and incorporate into surrounding
bone. This effect means the patient may
require a lengthy period of nonweight
bearing to allow for union incorporation.
Fractures and nonunions are also common
complications; general complications are
approximately 50%.19,20
Limb-salvage surgery using distraction
osteogenesis with bone transport and application of an external fixator is a biological reconstruction method with acceptable results.21,22 Nevertheless, Tsuchiya et
al22 advised against using this method for
segmental defects .15 cm in length, making the technique inappropriate for larger
femoral defects, commonly seen in sarcomas located at the diaphysis.
Endoprosthetic reconstruction of the
tibial diaphysis results in a reasonable
functional outcome, allowing patients
early weight bearing and function.10,23-25
Some studies report reasonable survival
rates.23,25 Complications with this reconstruction method include aseptic loosening, infection, mechanical failure, fracture
of the prosthesis or adjacent bone, local
recurrence, and metastatic spread. The
problem with this technique is that a large
segment of proximal and distal femoral
bone is needed to fix the stem prosthesis,
and in many situations, only a small segment of epiphysis remains after the tumor
resections. This could limit the diaphyseal
endoprosthesis indications.
Most benign, benign–aggressive, and
malignant tumors located at the metadiaphyseal region of long bones are currently treated with segmental resection.
Reconstruction of these segmental defects
should restore a functional and durable
limb because life expectancy for many of
these patients is several decades. Results
from this series of patients suggest that
segmental tibia allograft reconstruction is
an alternative. However, future advances
to facilitate allograft host bone fixation
and incorporation are needed to obtain
more predictable results.
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