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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 obtained
Staph 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.

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Massive bone allografts

  • 1.
  • 2. 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.
  • 3. 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.
  • 4. • Determine the likelihood that treatment of an infected allograft will result in a successful reconstruction.
  • 5. 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.
  • 6. • 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)
  • 7. • 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.
  • 8. 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)
  • 9. • 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)
  • 10. 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.
  • 11. • 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.
  • 12. 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.
  • 13. • 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)
  • 14. • 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
  • 15. • 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.
  • 16. • 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.
  • 17. • Those variables with p<0.05 were entered in a logistic regression analysis to assess their association with infection.
  • 18. 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.
  • 19. Factors associated with greater risk of infection
  • 20. • 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.
  • 21. Organisms obtained Staph 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
  • 22. • 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.
  • 23. • Antibiotics administered postoperatively for 6 weeks according to the organism.
  • 24. Complications • Infection not controlled, proceeded to amputation- 4 • Death due to primary diease before secondary reconstruction- 4
  • 25. 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
  • 26. 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.
  • 27. 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.
  • 28. • 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.
  • 29. • 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.
  • 30. 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
  • 31. Infection control • Resection of allograft • Antibiotics • Temporary cement spacer with antibiotics • Repeat reconstruction • However these salvage reconstructions are associated with even higher infection frequency.
  • 32. • Preferable to reconstruct a failed allograft with an endoprosthesis.
  • 33.
  • 34. • Described by bauer in 1910. • Described the outcome and surgical techniques in osteoarticular, intercalary, and allograft-prosthetic composite (APC).
  • 35. • 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.
  • 36. • Complication of articular destruction and joint instability.
  • 37. 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.
  • 38. 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.
  • 40. Hemicylindrical intercalary allografts • After resection of low-grade surface tumors or to reconstruct the cortical window after intralesional curettage of a benign lesion.