Introduction

• Massive bone allografts used as a functional alternative to bone loss following massive tumor resections or trauma.

• Infection is a major cause of failure.• Though many papers have analyzed the

frequency of infection following allograft based surgeries, few have described their management and fewer still have described the reinfection rates.

Aim

• Analyze the frequency of infection in a group of patients treated with massive bone allografts.

• Analyze risk factors such as age, sex, affected bone, type of reconstruction, operative room used, primary or revision procedure, length of postoperative antibiotic administration, and use of chemotherapy.

• Determine the likelihood that treatment of an infected allograft will result in a successful reconstruction.

Patients and Methods

• Retrospective study• Patients treated with massive bone allografts

between 1985 and 2011.• Minimum follow-up was 2 years unless death

occurred earlier (mean, 106 months; range, 6–360 months)

• No patient was lost to follow-up.

• The infection percentage of 673 patients reconstructed with massive bone allografts in long bones was analyzed.– Osteoarticular – 272– Intercalary- 246– Allograft- prosthetic reconsructions- 155

• Mean patient age at the time of diagnosis was 30 years (range, 1–80 years)

• M:F=359:314• Upper limb: Lower limb= 79(12%):594(88%)• Femur-408; Tibia-186• 280 patients received chemotherapy at the

time of procedure, 393 did not.

Diagnosis

• Osteosarcoma(n = 218)• Giant cell tumors (n = 126)• Chondrosarcoma(n = 95)• Ewing’s sarcoma (n = 48) • Bone metastasis (n = 20)• Fibrosarcoma (n = 15) • Malignant fibrohistiocytoma (n = 12)• Chondroblastoma (n = 12)

• Aneurysmal bone cyst (n = 10)

• Fibrous dysplasia (n = 7)• Chondromyxoid fibroma

(n = 8)• Leiomyosarcoma (n = 5)• Osteoblastoma (n = 6)

• Epithelioid hemangioendothelioma (n = 4)

• Adamantinoma (n = 2)• Liposarcoma (n = 1)• Osteofibrous dysplasia (n

= 1)• Revision of another

failed but not infected reconstruction (n =83)

Indications of using allograft

• Patients with benign or low-grade sarcomas. • Those patients with high-grade sarcomas of

bone or eroding into bone with clinical and imaging response to neoadjuvant chemotherapy.

• Another indication was for patients with failure of another reconstruction to augment bone stock.

• In patients receiving radiotherapy, patients with high-grade sarcomas without clinical and imaging response to neoadjuvant chemotherapy or with neurovascular tumor involvement, other approaches such as endoprostheses were used.

Procedure

• Resection of the lesion, including biopsy scars with appropriate bone and soft tissue margins.

• After being thawed in a warm solution, a fresh deep-frozen nonirradiated allograft segment, sized to fit the bone defect, was cut to the proper length.

• 1985-1996- conventional operating room• 1997-2011- clean air enclosure with vertical

airflow.• IV cephalosporin– 1985 -2001: administered for a period of 3 months

(first month 4 g per day, second and third months 2 g per day)

– 2002 and further- administered for a minimum of 24 hours or until the deep drains were discontinued (3 g per day)

• Restricted weightbearing for 3 to 6 months after reconstruction based on radiographic evidence of allograft healing.

• Followup was performed 2 weeks, 6 weeks, and 3 months after surgery

• Then every 3 months until 2 years.• Then every 6 months.• Plain radiographs and physical examination were

performed at each followup

• The frequency of infection, complications, and reoperations after the treatment of infected massive bone allografts was assesed after chart review.

• Survival free of infection was estimated using the Kaplan–Meier method.

• The statistical analysis was performed using the R programming language.

• The variables were analyzed as associated with infection using multivariate logistic regression and included: – Age– Sex– Affected bone– Type of reconstruction– Operative room used– Primary or revision procedure– Length of postoperative antibiotic administration– Use of chemotherapy.

• Those variables with p<0.05 were entered in a logistic regression analysis to assess their association with infection.

Results

• Survivorship free from infection was 92% at 5 years and 91% at 10 years.

• 60 patients(9%) were identified with bacterial infection of the bone allograft.

• No viral infection related to hepatitis or HIV found.

Factors associated with greater risk of infection

• After sustaining the infection, in all patients, surgical debridement and antibiotics were performed as a first approach without removal of the allograft and fixation and cultures were obtained.

Organisms obtainedStaph aureus 46

CONS 17

Staph aureus 13

Alpha hemolytic strep 7

Morganella morganii 3

Serratia 2

E.Coli 2

Enterococcus fecalis 2

Multiple organisms 14

• In 11 patient , debridement and antibiotics helped.• In 49 patients(82%) it failed- allograft exit and

cement speacer insertion to control the infection.• Vancomycin (2 g for 40 g of cement) and

aminoglycosides-1 g for 40 g of cement(gentamicin / tobramycin) were mixed empirically to have a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria.

• Antibiotics administered postoperatively for 6 weeks according to the organism.

Complications

• Infection not controlled, proceeded to amputation- 4

• Death due to primary diease before secondary reconstruction- 4

Secondary reconstruction

• 41 patients qith infection control with atleast 6 weeks without antibiotics

• 24 with secondary allograft reconstruction– 11-APC- allograft- prosthesis composite– 10 intercalary– 3 osteoarticular

• 17 endoprosthesis

Complications

• 14 failed( 2 endoprosthesis and 12 allografts) with a new infection.

• All treated with resection of reconstruction and second temporary spacer with antibiotic was implanted.

• 6 cases- endoprosthesis- f/u over 5 yrs• 7 cases- new allograft- (6 intercalary+ 1 APC)• Amputation performed in the remaining case due

to persistent infection.

Limitation

• Infection in all types of allografts in different long bones including intercalary, osteoarticular, and APCs were analysed and whether the graft is a risk factor or not cannot be reliably determined.

• Inherent heterogeneity in terms of diagnosis, chemotherapy, the amount of soft tissue resection, extent of internal fixation, type of prostheses, amount of resection, and anatomic location incidence of infection and complications could be affected.

• Other approaches such as endoprostheses were indicated if the patient received radiotherapy, in patients with high-grade sarcomas without clinical and imaging response to neoadjuvant chemotherapy, or with neurovascular tumor involvement.

• These patients could be at greater risk of infection and were not reconstructed with this method.

• Other reasons for failure of allografts, such as local recurrence and fracture were not excluded.

• The frequency of infection of allografts may be a low estimate.

Conclusions

• Infection rate of 9% was found.• Infections of massive bone allograft treated with

debridement and antibiotics failed in most cases.• Major risk factors for infection – Tibia allografts,– Male patients, – Procedures performed in a conventional operating

room,– Use of longer periods of postoperative antibiotics

Infection control

• Resection of allograft• Antibiotics• Temporary cement spacer with antibiotics• Repeat reconstruction• However these salvage reconstructions are

associated with even higher infection frequency.

• Preferable to reconstruct a failed allograft with an endoprosthesis.

• Described by bauer in 1910.• Described the outcome and surgical

techniques in osteoarticular, intercalary, and allograft-prosthetic composite (APC).

• Osteoarticular allograft-used to replace one side of the joint after major bone loss.

• This alternative does not sacrifice the contralateral side of the joint and allows the surgeon to reattach the host-donor soft tissues.

• Internal fixation to avoid fracture or non union.

• Complication of articular destruction and joint instability.

Unicondylar allografts

• Unicondylar osteoarticular allografts are used after bone tumor resection or trauma bone

• Fracture and nonunion rates are insignificant in this reconstruction due to the metaphyseal location of the reconstruction.

• The major problem with this reconstruction is degenerative joint disease and instability.

Intercalary allografts

• Allograft arthrodesis-reserved in cases when a great loss of soft tissue is present such as after extra-articular tumor resection or failed previous reconstruction with complete loss of muscle function involved in the joint movement.

Intercalary segmental allografts

Hemicylindrical intercalary allografts

• After resection of low-grade surface tumors or to reconstruct the cortical window after intralesional curettage of a benign lesion.