VOL. 88-B, No. 11, NOVEMBER 2006 1487

Intercalary endoprosthetic reconstruction for diaphyseal bone tumours

E. R. Ahlmann, L. R. Menendez

From Keck School of Medicine, University of Southern California, Los Angeles, USA

E. R. Ahlmann, MD, Orthopaedic Oncology FellowLos Angeles County-University of Southern California Medical Center, 1200 N. State Street, GNH 3900, Los Angeles, California 90033, USA.

L. R. Menendez, MD, FACS, Professor, Orthopaedic SurgeonUniversity of Southern California University Hospital, 1510 San Pablo Street, Suite 634, Los Angeles, California 90033, USA.

Correspondence should be sent to Dr E. R. Ahlmann; e-mail: ahlmann2002@yahoo.com

©2006 British Editorial Society of Bone and Joint Surgerydoi:10.1302/0301-620X.88B11. 18038 $2.00

J Bone Joint Surg [Br]

2006;88-B:1487-91.

Received 20 April 2006; Accepted 27 June 2006

Custom-made intercalary endoprostheses may be used for the reconstruction of diaphyseal

defects following the resection of bone tumours. The aim of this study was to determine

the survival of intercalary endoprostheses with a lap joint design, and to evaluate the

clinical results, complications and functional outcome. We retrospectively reviewed six

consecutive patients, three of whom underwent limb salvage with intercalary

endoprostheses of the tibia, two of the femur, and one of the humerus. Their mean age was

42 years (28 to 64). The mean follow-up was 21.6 months (9 to 58). The humeral prosthesis

required revision at 14 months owing to aseptic loosening. There were no implant-related

failures. Musculoskeletal Tumour Society functional outcome scores indicated that patients

achieved 90% of premorbid function.

Custom intercalary endoprostheses result in reconstructions comparable with, if not

better than, those of allografts. Using this design of implant reduces the incidence of early

complications and difficulties experienced with previous versions.

Segmental resection of the diaphysis for pri-mary malignant tumours of bone and for meta-static disease has many advantages, includingpreservation of the juxta-articular bone andthe joint, fewer long-term mechanical prob-lems, and preservation of the epiphysis in chil-dren. Advances in MRI, chemotherapy andreconstructive techniques have made morelimb salvage procedures possible. Althoughthere appears to be a higher incidence of localrecurrence following limb salvage, the overallpatient survival is similar for both amputationand limb salvage.

1

Reconstruction of segmental skeletal defectsfrom intercalary resection of malignanttumours may be performed using large seg-mental allografts,

2-13

autologous grafts,

14-16

bone transport

17

and endoprostheses.

18,19

Reconstruction with allograft is currently themost frequent type of intercalary reconstruc-tion performed, with a survival rate of 75% to89% at ten years.

2,3,5,6,8,11-13

It allows the res-toration of bone stock and soft-tissue recon-struction of ligaments, but the complicationssignificantly outweigh the benefits, especiallywhen used in a systemically compromisedhost.

3,5,7,10

Chemotherapy has an adverseeffect on bone healing

7,10

and is associated withhigh rates of fracture (14.7% to 50.7%),

5,7,11,12

nonunion (17.7% to 63.7%),

5,6,12,13,20,21

delayedunion

5

and infection (6% to 30%).

7,12,13

There

is also the potential for disease transfer fromthe donor to the patient. Reconstruction withautografts may be achieved using extracorpor-eal irradiation,

15

fibular centralisation,

22

freefibular transport,

14,16

and hemicortical autografts.

23

These reconstructions are plagued with similarcomplications to allografts, with high rates ofnonunion and fracture.

14-16

Custom-made intercalary endoprostheseshave the advantage of allowing early mobilisa-tion and return to function, and they eliminatecomplications such as host-donor nonunionand fracture of an allograft.

18,19

However, highrates of loosening, wear and breakage havebeen reported.

15

Few studies have been pub-lished detailing the results of custom-madeintercalary endoprostheses for primary bonetumours.

18,19

The purpose of this study was todetermine the survival of intercalary endopros-theses, and compare the clinical results, com-plications and functional outcome with theresults of intercalary allografts.

Patients and Methods

We retrospectively reviewed six consecutivepatients who had undergone limb salvage for aprimary malignant bone tumour or metastaticdisease, using intercalary prosthetic recon-struction between July 1988 and July 2005.Patients who had revision of a pre-existingimplant performed elsewhere or reconstruc-

1488 E. R. AHLMANN, L. R. MENENDEZ

THE JOURNAL OF BONE AND JOINT SURGERY

tion for non-neoplastic disease were excluded. All thepatients had been referred to the senior author (LRM) forfurther management. There were four men and two womenwith a mean age of 42 years (28 to 64). The diagnosisincluded osteogenic sarcoma in two patients, metastaticrenal cell carcinoma in two, adamantinoma in one andmalignant fibrous histiocytoma of bone in one (Table I).The primary site of the tumour was the tibia in threepatients, the femur in two and the humerus in one. Themean length of bone resected was 12.3 cm (8 to 16). Thestudy design and protocol were approved by the institu-tional review board.

Before the operation all patients underwent a thoroughoncological assessment to determine the extent of local dis-ease and the presence of distant metastases. Staging studies,including plain radiographs and MRI of the limb, CT scansof the chest and total body scintigraphy, were performedprior to biopsy. MRI was performed to define the extent ofthe lesion, the involvement of the soft tissues, especially theneurovascular bundle, and the level of transection of thebone. Patients with malignant primary bone tumours werestaged according to the system adopted by the Musculo-skeletal Tumour Society.

24

All four patients were stage IIBat the time of diagnosis. When indicated, patients receivedthe standard pre-operative chemotherapy regimen in use atthe time of treatment. The one patient with malignantfibrous histiocytoma also had neoadjuvant radiation to thetibia. The mean length of follow-up was 21.6 months (9 to58).

Once the decision had been made to perform intercalaryresection and endoprosthetic reconstruction, anteroposte-rior and lateral radiographs were taken with a size markerplaced at the level of the bone to determine magnification,and the level of bone transection marked at between 2 cmand 5 cm from the most proximal and distal extents of thetumour as seen on MRI, with the aim of ideally obtaining a5 cm margin. If it appeared that less than 5 cm of bonewould remain proximally and distally after resection, inter-calary resection could not be performed. The shortestlength of bone required for fixation of the implant stem is 5cm; fixation in a shorter segment is hazardous owing to thepossibility of early loosening. The marked radiographs

were then sent to Stryker (Rutherford, New Jersey) formanufacture of the implant. The titanium intercalary pros-thesis used to replace the segmental defect is a four-compo-nent bi-stemmed coupled device with a lap joint, a side-to-side mating junction with hemicylindrical cross-sections ofequal lengths. With the current design, the two stemmedcomponents are mated to one-half of a lap joint each usinga Morse taper design. The lap joint is then reduced

in situ

and locked with two set screws (Fig. 1).All the operations were performed by the senior author

(LRM). The biopsy tract was excised as an ellipse and left incontinuity with the resected specimen, which was removed

enbloc

with a wide margin in all cases. After negative marginshad been confirmed by intramedullary frozen section, recon-struction was undertaken. The proximal and distal intramed-ullary canals were reamed to the appropriate size, 2 mmlarger than the implant stems. Stems were then secured with a2 mm mantle of polymethylmethacrylate. Once the cementhad fully hardened, each half of the lap joint was placed on toeach stem, taking care to achieve the appropriate rotationalalignment. The lap joint was then assembled and reduced

in

Table I.

Details of six patients with diaphyseal tumours treated with intercalary endoprostheses

CaseAge (yrs)

Gen-der Diagnosis Stage

*

Chemotherapy LocationBone resected (cm) Complications MSTS

†

Follow-up (mths)

1 58 M Metastatic renal cell cancer

N/A Yes Tibia 12 None 26 16

2 28 F Adamantinoma IIB No Tibia 9 None 28 263 39 M Malignant fibrous his-

tiocytomaIIB Yes Tibia 13 None 28 9

4 32 F Osteogenic sarcoma IIB Yes Femur 16 None 27 125 29 M Osteogenic sarcoma IIB Yes Femur 16 None 28 96 64 M Metastatic renal cell

cancerN/A Yes Humerus 8 Aseptic loosening of

distal stem at 14 months

25 58

* according to the Musculoskeletal grading system

24

† MSTS, Musculoskeletal Tumour Society score

25

Fig. 1

Intra-operative photograph of custom-made intercalary segmentaldefect replacement system with two-stemmed components that havebeen mated to one-half of a lap joint each by a Morse taper design. Thelap joint has been reduced in situ and locked with two set screws.

INTERCALARY ENDOPROSTHETIC RECONSTRUCTION FOR DIAPHYSEAL BONE TUMOURS 1489

VOL. 88-B, No. 11, NOVEMBER 2006

situ

; two set screws were placed through the implant tolock the joint in place. All three patients with intercalarytibial resections required muscle flaps for soft-tissuecover of the implant, including two local rotational flapsand one latissimus free muscle transfer (Fig. 2). All thewounds were then closed in the usual manner and a suc-tion drain inserted. The patients received antibioticsuntil the drain was removed once the output haddecreased to < 50 ml/day, and were discharged from hos-pital when medically stable.

Immediately after operation the patients were allowed tobear full weight and mobilise as tolerated without the use ofa brace or cast. Routine follow-up was undertaken everythree months for the first two years after surgery, every sixmonths between two and five years after treatment, andannually for 10 years thereafter.

Failure was defined as revision of any or all components ofthe implant, removal of the implant, or amputation of thelimb. The patients’ records were reviewed for the onset ofcomplications and causes of failure leading to revision,

Fig. 2e

A 39-year-old man with malignant histiocytoma of bone showing a) anteroposterior and b) lateral radiographs of the tibia showing a large lyticdestructive lesion of the middle third of the shaft. c) MRI axial T1-weighted and d) sagittal fat spin-echo sequences show extensive destruction of theanterior cortex with a large associated soft-tissue mass. A 13 cm segment of bone was resected and replaced with the cemented intercalary implant,shown on e) the anteroposterior and f) lateral radiographs.

Fig. 2b Fig. 2cFig. 2a

Fig. 2d Fig. 2f

1490 E. R. AHLMANN, L. R. MENENDEZ

THE JOURNAL OF BONE AND JOINT SURGERY

including infection, recurrent tumour, aseptic loosening,fatigue failure and peri-prosthetic fracture. The findings werecompared to historical controls from the existing literature.

The functional outcome was assessed for all survivingpatients using the revised Musculoskeletal Tumour Societyfunctional rating system.

25

This uses a 30-point scale toweight equally each of six parameters, comprising pain,functional limitation, walking distance, use of a support,emotional acceptance and gait. Patients completed a ques-tionnaire, either by telephone or at their latest review. Thequestionnaire was administered by an investigator (ERA)who was not involved in the care of the patient.

Statistical analysis was performed using the Kaplan-Meier method to generate survival curves, with cor-responding 95% confidence intervals (CI) for implant andpatient survival using the GraphPad Prism software(GraphPad Software Inc., San Diego, California). The dateof implantation of the initial prosthesis was the start of thecurve and the end-point was defined as the need for revi-sion, removal of the implant or amputation.

Results

The patient with the intercalary implant of the humerusunderwent revision for aseptic loosening of the distal stem14 months after the operation. Revision of the stem wascarried out and the patient has since remained asympto-matic, with no evidence of loosening 44 months after thesecond procedure. The remaining five patients had no clin-ical or radiological evidence of loosening. The overall sur-vival of the intercalary implants based on the Kaplan-Meierestimates was 100%(95% CI 0.239 to 1.571) at one yearand 83% (95%CI 0.348 to 2.125) at two years. The long-est-surviving implant has remained in place for 44 months.There were no infections, local recurrences, wound compli-cations, peri-prosthetic fractures or failures of the implants.

The mean follow-up was 21.6 months (9 to 58) at whichtime all the patients were alive and well. The meanMusculoskeletal Tumour Society functional outcomescore

25

was 27 (25 to 28), indicating 90% normal function.The patient with the lowest score had undergone early revi-sion of the humeral stem. His functional deficits wererelated mainly to weakness as a result of his condition as awhole. The functional outcome for reconstructions of thelower limb was excellent.

25

No patient required assistivedevices for walking. All were satisfied with the outcomeand stated that they would have the same procedure againunder similar circumstances.

Discussion

The improved life expectancy of patients with malignanttumours of bone has led to an increased emphasis on limbsalvage and maximisation of function. The optimal methodof reconstruction after resection of diaphyseal tumoursremains a subject of debate. Important considerations totake into account when performing reconstruction afterintercalary resection of a tumour include the morbidity of

the procedure, the incidence of complications, the func-tional demands of the patient and the durability of thereconstruction. The large size of the skeletal defects thatrequire reconstruction limits the options available. Vascu-larised and non-vascularised autogenous grafts are associ-ated with morbidity at the donor site and are notappropriate for large defects.

14,16

Autoclaved or irradiatedautografts are often used as an alternative to allografts butare associated with a high rate of nonunion, fracture andinfection.

15

Distraction osteogenesis has proved useful inthe treatment of post-traumatic defects in bone, but its usein patients undergoing treatment for malignant bonetumours is limited by the adjuvant treatments being givenand the long period of treatment.

17

The most commonlyused technique is allograft reconstruction, but custom-made endoprostheses are now being used more frequently.

2-

13

Intercalary reconstruction with large-segment allograftshas the advantage of allowing for reconstruction of liga-ments to the implant and accurate matching of the graft tothe defect.

5,7,8

The disadvantages include the potential fordisease transfer, the long period of immobilisation requiredfor bony union, and a high incidence of nonunion, infectionand fracture.

2-13

Custom-made endoprostheses allow anearly return to function and immediate weight-bearing,without the complications seen with allografts.

The frequency of nonunion after massive allograft recon-struction has been recorded as between 17.7% and63.7%.

5,6,12,13,20,21

An association between the immuno-suppressive effects of adjuvant chemotherapy and non-union of the allograft-host junction has been suggested.

7,10

A reduction in bone remodelling and vascular invasion ofthe graft, resulting in delayed osteointegration, may resultfrom chemotherapy.

7

Fracture of the graft has beenreported to occur in 14.7% to 50.7% of cases,

5,7,11,12

andhas been suggested to result from the use of dead bone,which remains structurally weak and never incorporatesfully into the host.

26-28

Reconstruction with endoprosthesesavoids these problems and avoids the long period of immo-bilisation and partial weight-bearing after allograft recon-struction,

2-13

with immediate return to function for patientswho may have a limited life expectancy.

A previous study

18

evaluating 18 intercalary endo-prostheses performed for malignant tumours of thehumerus, femur and tibia found that four patients (22%)required revision for loosening. Both patients who had ahumeral reconstruction experienced early loosening by18 months, but none developed wear or breakage of theimplant at a mean follow-up of 65 months. Anotherstudy,

19

of 34 patients evaluating the use of a modularintercalary humeral replacement system of a differentdesign from that used in the current study reported fail-ure of the implant in six (17.6%), usually due to disen-gagement or instability of the components of the male-female junction. The only failure in our series was in theone patient who had a humeral reconstruction, who suc-cessfully underwent revision and remains asymptomatic.

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VOL. 88-B, No. 11, NOVEMBER 2006

It may be that the increased rotational stresses in theupper extremity lead to a higher rate of failure with humeralreconstructions.

We have experienced no failures attributable to the designof the implant. Prior to the development of the lap jointdesign, the initial implant consisted of a two-component bi-stemmed conically-coupled joint locked with two set screws.Only a limited range of diameters and lengths of stem wasavailable, resulting in implants that were often undersized.

19

In these implants, the most common reason for failure was dis-engagement or instability of the conically-coupled joint whichoccurred as early as one month after initial implantation.

19

Wedid not encounter these problems with our custom-madeimplants.

Many patients develop a bone bridge linking the proximaland distal bone fragments, essentially encasing the implantwith heterotopic bone. This was previously noted along themedial aspect of femoral intercalary reconstructions.

18

It isunclear why this develops, but it may be of benefit in prevent-ing or limiting aseptic loosening. It is possible that the bonebridge shields the prosthesis from stress and thereby prolongsits survival. The current intercalary implant is smooth, with-out coating, but in future it may be beneficial to coat it with aporous coat or hydroxyapatite to further stimulate bone pro-duction.

The functional outcome in this series was excellent, withpatients regaining a mean of 90% of their premorbid function.This is in contrast to outcomes noted after allograft recon-struction, ranging between 80% and 90% of normal func-tion,

15

but with many studies finding only 40% to 50% oftheir patients having excellent results.

2,4,5,7,8

Intercalary resection and reconstruction is of benefit topatients with diaphyseal tumours as adjacent joint function ispreserved. The results of endoprosthetic replacement are com-parable with, if not better than, those of large-segmental allo-grafts. In the lower limb the clinical and functional outcomesappear excellent, while in the upper limb the high rotationalstresses may lead to early loosening. Using this design ofimplant reduces the incidence of early complications and thedifficulties experienced with previous versions.

No benefits in any form have been received or will be received from a commercialparty related directly or indirectly to the subject of this article.

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