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. 2021 May 7;19:1–10. doi: 10.1016/j.jcot.2021.04.033

Intercalary reconstruction following resection of diaphyseal bone tumors: A systematic review

Costantino Errani a,∗, Shinji Tsukamoto b, Nusaibah Almunhaisen a, Andreas Mavrogenis c, Davide Donati a
PMCID: PMC8138587  PMID: 34040979

Abstract

Introduction

The options for the reconstruction of diaphyseal defects following the resection of bone tumors include biological or prosthetic implants. The purpose of our study was to evaluate different types of intercalary reconstruction techniques, including massive bone allograft, extracorporeal devitalized autograft, vascularized free fibula, and modular prosthesis.

Methods

We performed a systematic review of articles using the terms diaphyseal bone tumor and intercalary reconstruction. All the studies reporting the non-oncological complications such as infection, nonunion and fracture of the intercalary reconstructions were included. We excluded articles published before 2000 or did not involve humans in the study. Case reports, reviews, technique notes and opinion articles were also excluded based on the abstracts. Thirty-three articles included in this review were then studied to evaluate failure rates, complications and functional outcome of different surgical intercalary reconstruction techniques.

Results

Nonunion rates of allograft ranged 6%–43%, while aseptic loosening rates of modular prosthesis ranged 0%–33%. Nonunion rates of allograft alone and allograft with a vascularized fibula graft ranged 6%–43% and 0%–33%, respectively. Fracture rates of allograft alone and allograft with a vascularized fibula graft ranged 7%–45% and 0%–44%, respectively. Infection rates of allograft alone and allograft with a vascularized fibula graft ranged 0%–28% and 0%–17%, respectively. All of the allograft (range: 67%–92%), extracorporeal devitalized autograft including irradiation (87%), autoclaving (70%), pasteurization (88%), low-heat (90%) or freezing with liquid nitrogen (90%), and modular prosthesis (range: 77%–93%) had similar Musculoskeletal Tumor Society functional scores. Addition of a vascularized fibula graft to allograft did not affect functional outcome [allograft with a vascularized fibula graft (range: 86%–94%) vs. allograft alone (range: 67%–92%)].

Conclusion

Aseptic loosening rates of modular prosthesis seem to be less than nonunion rates of allograft. Adding a vascularized fibula graft to allograft seems to increase bone union rate and reduce the risk of fractures and infections, though a vascularized fibula graft needs longer surgical time and has the disadvantage of donor site morbidity. These various intercalary reconstruction techniques with or without a vascularized fibula autograft had similar functional outcome.

Keywords: Bone tumor, Intercalary reconstruction, Massive bone allograft, Extracorporeal devitalized autografts, Vascularized fibula graft, Modular prostheses

1. Introduction

Limb salvage surgery is currently the treatment of choice in patients with bone tumors.1,2 If a tumor extension allows for the preservation of adjacent joints, an intercalary resection can be performed.3 Intercalary resection can be performed for primary as well as metastatic bone tumors.2 However, reconstructions of the diaphysis after the resection of bone tumors are surgically demanding.1,2,4,5 Intercalary reconstructions following a tumor resection include either biological or prosthetic options.1,4,6, 7, 8, 9, 10 The surgical indication needs to be individualized for each type of patient and disease.2,11 Traditionally, the biological intercalary reconstruction after the resection of bone tumors includes a massive bone allograft, extracorporeal devitalized autograft, vascularized free fibula and distraction osteogenesis.1,5,7,12 Prosthetic reconstructions include modular prostheses or three-dimensional printed prostheses.13,14 Each of these surgical techniques has its advantages and disadvantages.2,13 Distraction osteogenesis may be an alternative limb salvage technique but it is time-consuming, unsuitable for large defects, and needs surgery many times.9 Complication rates are high, including delayed ossification and maturation, nonunion at the docking site, pin infection, skin invagination, bone resorption, club foot, and rotational and axis deviations.15, 16, 17, 18 Because these complications are different from those of the other reconstructions, we excluded the distraction osteogenesis from this systematic review. The purpose of this study was to evaluate failure rates, complications and functional outcome of these different surgical intercalary reconstruction techniques except for distraction osteogenesis.

2. Methods

We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Metaanalyses statement.19

2.1. Eligibility criteria

All the studies reporting the non-oncological complications such as infection, nonunion and fracture of the intercalary reconstruction except for distraction osteogenesis following tumor resection, were included. Articles published before 2000 or articles that did not involve humans in the study were excluded. Case reports, opinion articles, reviews or technique notes were excluded.

2.2. Literature search and study selection

We searched for the terms diaphyseal bone tumor and intercalary reconstruction in the Medline, EMBASE and Scopus electronic database. References in the selected research papers were further checked for relevant additional publications.

2.3. Data collection and presentation

The two authors (CE and NA) individually screened the titles and summaries of specific studies and evaluated the quality of the studies. If there was a disagreement, a consensus was reached between the two or by consulting with a third author. We used a data collection sheet to collate the following data: authors, year of publication, name of publishing journal, type of study, number of patients, age, histology of the resected tumor, type of reconstruction, adjuvant chemotherapy and radiotherapy, complications such as nonunion, aseptic loosening, implant failure, fracture (graft fracture or periprosthetic fracture), infection, oncological outcome, the Musculoskeletal Tumor Society (MSTS) functional score,20 and length of follow-up.

2.4. Data summary

We summarized the data of the selected studies. All studies included in this review were not randomized, therefore data pooling (meta-analysis) was not appropriate and not performed.

2.5. Assessment of methodological quality

Two authors (CE and NA) individually evaluated the quality of the included studies. If they did not agree, they reached an agreement either by discussion or by consulting with a third author. We independently graded the articles selected for the final analysis according to the Risk of Bias Assessment tool for Nonrandomized Studies (RoBANS tool) for assessing the quality of nonrandomized studies in meta-analyses.21

2.6. Search results

Of the 70 relevant studies found by the search strategy, 33 studies were finally selected for this review (Fig. 1). The characteristics of the 33 studies were summarized (Table 1).1,3, 4, 5, 6, 7, 8,10,12,14,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 There was no randomized study among these 33 studies.

Fig. 1.

Fig. 1

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This flow chart shows the search for relevant articles.

Table 1.

Overall study characteristics.

Author Year Reference Number of patients Age Histology Type of reconstruction (number of patients) Adjuvant chemotherapy Adjuvant radiotherapy Nonunion (Allograft/Autograft), Aseptic Loosening (Modular prosthesis) Implant failure Fracture Infection Oncological outcome MSTS score Follow-up (months)
Agarwal et al. 2010 22 25 2 to 43 Osteosarcoma (13), Ewing sarcoma (11), Chondrosarcoma (1) Allograft,extracorporeally radiated autograft, or vascularized fibula graft (19), Modular prosthesis (6) Done for Osteosarcoma and Ewing sarcoma NR Nonunion (26%), Aseptic loosening (0%) 16% 4% 8% CDF (16) Local recurrence (2) 90%–100% Median 34
Albergo et al. 2020 4 107 Median16, 19 Osteosarcoma (47), Ewing sarcoma (33), Chondrosarcoma (9), the other tumors (8) Allograft (71), Modular prosthesis (36) 63, 32 NR Nonunion (6%), Aseptic loosening (33%) 0%, 11% 24%, 0% 6%, 3% Local recurrence (3) Mean 92%, 91% Mean 129, 114
Aldlyami et al. 2005 6 35 Median 29 Osteosarcoma (12), Ewing sarcoma (12), Chondrosarcoma (2), and the other tumors (9) Modular prosthesis (35) Done for Osteosarcoma and Ewing sarcoma NR Aseptic loosening (20%) 6% 3% 3% CDF (21) Local recurrence (5) NR Mean 107
Aponte-Tinao 2012 5 83 Mean 26 Osteosarcoma (41), Ewing sarcoma (15), Chondrosarcoma (7), the other tumors (20) Allograft (83) 15 3 Nonunion (27%) 0% 17% 1% Local recurrence (3) Mean 90% Median 61
Benevenia et al. 2016 23 41 Mean 63 Bone metastasis (26), the other tumors (15) Modular prosthesis (41) NR NR Aseptic loosening (12%) 15% 0% 2% CDF (7) Local recurrence (7) Mean 77% Mean 14
Bus et al. 2014 24 87 Median 17 Osteosarcoma (34), Ewing sarcoma (17), Adamantinoma (15), Chondrosarcoma (11), the other tumors (10) Allograft (87) 52 9 Nonunion (40%) 26% 29% 14% Local recurrence (2) NR Median 84
Campanacci et al. 2014 25 12 Mean 23 Osteosarcoma (10), Ewing sarcoma (2) Allograft with a vasularized fibula graft (12) 12 0 Nonunion (0%) 8% 8% 8% CDF (9) Local recurrence (0) Mean 90% Mean 147
Campanacci et al. 2018 26 23 Mean 16 Osteosarcoma (11), Ewing sarcoma (8), Chondrosarcoma (2), the other tumors (2) Allograft with a vasularized fibula graft (23) 19 0 Nonunion (13%) 0% 22% 0% CDF 18 Local recurrence (0) Mean 94% Mean 141
Chen et al. 2005 27 29 9 to 74 Osteosarcoma (23), Chondrosarcoma (2), and the other tumors (4) Allograft (14), Extracorporeally radiated autograft (15) 28 NR Nonunion (43%, 7%) 0% 14%, 20% 0% CDF (20) Local recurrence (2) Mean 87% Mean 71
Davidson et al. 2005 28 16 Mean 19 Osteosarcoma (7), Ewing sarcoma (6), Chondrosarcoma (3) Extracorporeally radiated autograft with a vasularized fibula graft (16) Done for Osteosarcoma and Ewing sarcoma 1 Nonunion (31%) 25% 6% 6% Local recurrence (0) Mean 93% Mean 45
Deijkers et al. 2005 29 35 Median 24 Osteosarcoma (15), Ewing sarcoma (4), Chondrosarcoma (8), the other tumors (8) Allograft (35) Done for Osteosarcoma and Ewing sarcoma NR Nonunion (9%) 0% 34% 9% Local recurrence (4) 77%–80% Median 86
Errani et al. 2019 1 81 Mean 13 Osteosarcoma (46), Ewing sarcoma (31), Adamantinoma (4) Allograft with a vasularized fibula graft (81) Done for Osteosarcoma and Ewing sarcoma NR NR 16% 23% 6% CDF (66) Local recurrence (7) Good to excellent in 91% of patients Mean 96
Errani et al. 2020 30 46 Mean 11 Osteosarcoma (31), Ewing sarcoma (15) Allograft (21), Allograft with a vasularized fibula graft (25) 46 0 Nonunion (23%, 16%) 2% 24%, 28% 5%, 16% Local recurrence (1, 2) Mean 89%, 86% Median 123
Frisoni et al. 2012 31 101 Mean 20 Osteosarcoma (62), Ewing sarcoma (19), Chondrosarcoma (3), the other tumors (17) Allograft (71), Allograft with a vasularized fibula graft (30) 80 0 Nonunion (27%) 25% 31% NR NR NR Median 112
Han et al. 2014 32 30 Mean 25 Osteosarcoma (17), Ewing sarcoma (2), Adamantinoma (4), the other tumors (7) Low-heat treated autograft (13), Allograft (17) 22 0 Nonunion (42%, 15%) NR 23%, 12% 15%, 6% CDF (28) Local recurrence (0) Mean 90%, 87% Mean 79
Hanna et al. 2010 8 23 Mean 41 Osteosarcoma (9), Ewing sarcoma (3), Chondrosarcoma (7), and the other tumors (4) Modular prosthesis (23) 12 4 Aseptic loosening (4%) 8% 4% 4% CDF (16) Local recurrence (1) Mean 87% Mean 97
Higuchi et al. 2017 33 18 Mean 12 Osteosarcoma (18) Frozen autograft (18) Yes NR Nonunion (11%) 0% 17% 11% CDF (13) Local recurrence (3) Mean 90% Mean 46
Houdek et al. 2018 12 29 Mean 12 Osteosarcoma (18), Ewing sarcoma (8), and the other tumors (3) Allograft (11), Allograft with a vasularized fibula graft (18) NR NR Nonunion (34%) 17% 45%, 44% 18%, 0% CDF (22) Local recurrence (2) Mean 90% Mean 156
Houdek et al. 2016 7 18 Mean 11 Osteosarcoma (9), Ewing sarcoma (5), the other tumors (4) Allograft with a vasularized fibula graft (18) NR NR Nonunion (33%) 0% 39% 0% CDF (15) Local recurrence (1) Mean 93% Mean 96
Jeon et al. 2006 34 21 Mean 35 Osteosarcoma (7), Ewing sarcoma (2), Chondrosarcoma (2), MFH of bone (5), and STS (5) Pasteurized autograft (21) 18 NR Nonunion (24%) 0% 10% 14% CDF (16) Local recurrence (2) Mean 88% Mean 74
Khattak et al. 2006 35 19 Mean 21 Osteosarcoma (12), Ewing sarcoma (3), the other tumors (4) Autoclaved autograft (19) Done for Osteosarcoma and Ewing sarcoma NR Nonunion (5%) 5% 0% 11% Local recurrence (2) Mean 70% Mean 49
Krieg et al. 2007 36 16 Mean 17 Primary bone sarcoma (16) Extracorporeally radiated autograft (3), Extracorporeally radiated autograft with a vascularized fibula graft (13) Done for Osteosarcoma and Ewing sarcoma NR Nonunion (31%) 0% 6% 0% CDF16 local recurrence0 Median 85% Mean 50
Li et al. 2010 37 11 Mean 19 Osteosarcoma (6), Ewing sarcoma (3), the other tumors (2) Allograft with a vasularized fibula graft (11) 8 1 Nonunion (9%) 9% 0% 0% CDF (7) Local recurrence (2) Mean 92% Mean 34
Liu et al. 2020 14 12 Mean 37 Osteosarcoma (11), the other tumor (1) Modular prosthesis (3D-printed prosthesis) (12) 11 NR Aseptic loosening (0%) 0% 0% 0% CDF (10) Local recurrence (1) Mean 93% Mean 23
Lu et al. 2020 38 23 Mean 14 Osteosarcoma (23) Frozen autograft with a vascularized fibula graft (8), Allograft with a vasularized fibula graft (15) 23 NR Nonunion (0%, 13%) 0% 0% 0%, 7% CDF (6, 9) Local recurrence (1, 1) Mean 90%, 88% Mean 43, 47
Lun et al. 2018 10 34 Mean 65 Bone metastasis (34) from lung (27%), breast (18%) and liver cancers (15%) Allograft (18), Modular prosthesis (16) NR NR Nonunion (39%), Aseptic loosening (6%) NR 17%, 6% 28%, 6% Local recurrence (2) Mean 67%, 90% Mean 7
Muscolo et al. 2004 39 59 Mean 35 Osteosarcoma (26), Ewing sarcoma (7), Chondrosarcoma (7), the other tumors (12) Allograft (59) 35 4 Nonunion (19%) 0% 7% 5% CDF 41 Local recurrence (6) NR Mean 60
Nakamura et al. 2013 40 6 Mean 10 Ewing sarcoma (6) Extracorporeally radiated autograft (6) 6 NR Nonunion (17%) 0% 0% 0% Local recurrence (1) 40%–100% Mean 41
Puri et al. 2012 41 32 Mean 15 Osteosarcoma (16), Ewing sarcoma (16) Extracorporeally radiated autograft (32) Yes NR Nonunion (16%) 16% 0% 13% CDF (19) Local recurrence (3) Mean 87% Mean 34
Rabitsch et al. 2013 3 12 Mean 18 Osteosarcoma (4), Ewing sarcoma (6), and the other tumors (2) Allograft with a vasularized fibula graft (12) 7 2 Nonunion (33%) 0% 33% 17% CDF (9) Local recurrence (0) NR Mean 39
Sewell et al. 2011 42 18 Mean 43 Osteosarcoma (5), Ewing sarcoma (2), Adamantinoma (2), the other tumors (9) Modular prosthesis (18) 10 7 Aseptic loosening (22%) 0% 11% 6% Local recurrence (1) Mean 77% Mean 59
Weichman et al. 2015 43 12 Mean 16 Osteosarcoma (7), Ewing sarcoma (3), Adamantinoma (2) Allograft with a vasularized fibula graft (12) Done for Osteosarcoma and Ewing sarcoma 5 Nonunion (25%) NR 8% 17% CDF (11) Local recurrence (1) NR Mean 41
Zekry et al. 2017 44 34 Mean 35 Osteosarcoma (21), Bone metastasis (7), and the other tumors (6) Frozen autograft (34) NR NR Nonunion (15%) 0% 18% 6% CDF (20) Local recurrence (4) Mean 90% Mean 62
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MSTS, Musculoskeletal Tumor Society; NR, not reported; CDF, continuous disease free.

2.7. Methodological quality of included studies

The assessment of the quality of the individual studies using the RoBANS tool showed an overall moderate risk of bias. All of the included 33 studies showed that “selection of participants” is high, “confounding variables” is high, “measurement of exposure” is low, “blinding of outcome” is low, “incomplete outcome data” is low, and “selective outcome reporting” is low.

3. Results

Complications and functional outcomes were summarized for each reconstruction method in Table 2.

Table 2.

Summary of complications and functional outcomes for each reconstruction method.

Nonunion (Allograft/Autograft), Aseptic Loosening (Modular prosthesis)(%) Implant failure (%) Fracture (%) Infection (%) MSTS score (%)
Allograft 64, 929, 1532, 1939, 2330, 275, 3910, 4024, 4327 04, 05, 027, 029, 039, 2624 739, 1232, 1427, 175, 1710, 244, 2430, 2924, 3429, 4512 027, 15, 530, 539, 64, 632, 929, 1424, 1812, 2810 6710, 7929, 8732, 8930, 905, 924
Allograft with a vascularized fibula graft 025, 937, 1326, 1338, 1630, 2543, 333, 337 03, 07, 026, 038, 825, 937, 161 037, 038, 825, 843, 2226, 231, 2830, 333, 397, 4412 07, 012, 026, 037, 61, 738, 825, 1630, 173, 1743 8630, 8838, 9025, 9237, 937, 9426
Extracorporeally radiated autograft 727, 1641, 1740 027, 040, 1641 040, 041, 2027 027, 040, 1341 8727
Extracorporeally radiated autograft with a vascularized fibula graft 3128 2528 628 628 9328
Frozen autograft 1133, 1544 033, 044 1733, 1844 644, 1133 9033, 9044
Frozen autograft with a vascularized fibula graft 038 038 038 038 9038
Pasteurized autograft 2434 034 1034 1434 8834
Autoclaved autograft 535 535 035 1135 7035
Low-heat treated autograft 4232 NR 2332 1532 9032
Modular prosthesis 014, 022, 48, 610, 1223, 206, 2242, 334 014, 042, 66, 88, 114, 1523 04, 014, 023, 36, 48, 610, 1142 014, 223, 34, 36, 48, 610, 642 7723, 7742, 878, 9010, 914, 9314
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MSTS, Musculoskeletal Tumor Society; NR, not reported.

3.1. Allograft versus modular prosthesis

Nonunion rates of allograft ranged 6%–43%,4,5,10,24,27,29,30,32,39 while aseptic loosening rates of modular prosthesis ranged 0–33%4,6,8,10,14,22,23,42 (Table 2). This indicates that aseptic loosening rates of modular prosthesis seem to be less than nonunion rates of allograft. Lun et al.10 compared the clinical outcomes and complications for patients who had intercalary reconstruction using allograft (18 patients) or modular prosthesis (16 patients) for femoral shaft metastatic tumors, with a mean age of 64.5 years. Aseptic loosening rate of modular prosthesis was less than nonunion rate of allograft (6% vs. 39%, respectively).10 Fracture and infection rates of modular prosthesis were less than those of allograft (fracture: 6% vs. 17%, infection: 6% vs. 28%, respectively).10 Patients with prosthetic reconstructions had significantly shorter period to full weight bearing and length of hospital stay compared to those who received allograft reconstructions.10 Albergo et al.4 also reported that the time to full weight bearing in patients reconstructed with modular prosthesis (median 3 weeks) was significantly shorter compared to that in patients reconstructed with allograft (median 22 weeks).

3.2. The efficacy of adding a vascularized fibula graft

Nonunion rates of allograft alone and allograft with a vascularized fibula graft ranged 6%–43%4,5,10,24,27,29,30,32,39 and 0%–33%,3,7,25,26,30,37,38,43 respectively (Table 2). Fracture rates of allograft alone and allograft with a vascularized fibula graft ranged 7%–45%,4,5,10,12,24,27,29,30,32,39 and 0%–44%,1,3,7,12,25,26,30,37,38,43 respectively (Table 2). Infection rates of allograft alone and allograft with a vascularized fibula graft ranged 0%–28%4,5,10,12,24,27,29,30,32,39 and 0%–17%,1,3,7,12,25,26,30,37,38,43 respectively (Table 2). Adding a vascularized fibula graft to allograft seems to increase bone union rate and reduce the risk of fractures and infections.

3.3. Functional outcome

All of the allograft (range: 67%–92%),4,5,10,29,30,32 extracorporeal devitalized autograft including irradiation (87%),27 autoclaving (70%),35 pasteurization (88%),34 low-heat (90%)32 or freezing with liquid nitrogen (90%),33,34 and modular prosthesis (range: 77%–93%)4,8,10,14,23,42 had similar MSTS functional scores (Table 2). Addition of a vascularized fibula graft to allograft did not affect functional outcome [allograft with a vascularized fibula graft (range: 86%–94%)7,25,26,30,37,38 vs. allograft alone (range: 67%–92%)4,5,10,29,30,32](Table 2). Liu et al.14 reported 12 patients with metaphyseal malignant bone tumors around the knee joint were treated by joint-preserving intercalary resections with the aid of three-dimensional (3D)-printed osteotomy guide plates and reconstructions using 3D-printed intercalary prostheses. At a mean follow-up of 23 months, mean MSTS functional scores was 93% and there was no patients with aseptic loosening, implant failure, fracture or infection.14 Although the follow-up period was short, the results of the 3D-printed intercalary prostheses were excellent.14

4. Discussion

The options for the reconstruction of diaphyseal defects following the resection of bone tumors include biological or prosthetic implants.1,5,8, 9, 10,12,39 Various types of intercalary reconstructions are reported, including allograft, extracorporeal devitalized autograft, vascularized fibula graft, distraction osteogenesis and modular prosthesis.1,5,8,9,12,36

In comparison with prosthetic reconstructions, the benefits of intercalary biological reconstructions include the restoration of bone stock.1,3,9,36 After healing, the allograft may be incorporated by the host and can survive for decades, probably as the outer surface of an allograft becomes populated with living cells and so “revascularized”.5,12,29,39 However, especially during the first two years after surgery and before the incorporation by the host, allograft is reported to have a high incidence of complications such as nonunions, fractures and infections due to its avascular nature.1,5,7 Allografts have been shown to be acellular and have a poor blood supply, so spontaneous healing cannot be expected in the event of complications such as fractures or nonunions.45 Intercalary allografts of the femur appear to have a higher risk of mechanical failure than other long bones.4,24,31

One of the most adverse factors on the outcome seems to be an age of more than 18 years at the time of surgery and length of resection.31 Reconstruction of bone defects larger than 17 cm with allograft alone increases the risk of failure, so it is recommended to reconsider the use of allograft alone.24,29,31 Vascularized fibula graft seems to be a viable option to improve the rate of union in very long resections or to rescue mechanical failure following allograft reconstructions.4,10,25,26,39 The allograft supplies the initial mechanical strength and the vascularized fibula graft provides well-perfused bone and the capability of osteogenesis.3 The union of allograft alone is a very slow osteogenic creeping process, whereas the union of vascularized fibula graft is secondary to the intrinsic blood supply.1 The combination of allograft and vascularized fibula graft is associated with a longer surgical time, a risk of donor site morbidity and a possible stress fracture of the graft.26,46 However, it is possible to add a pedicled vascularized fibula graft if the site to reconstruct is distal femur or tibia, which could reduce the surgical time (Fig. 2).1 Allograft reconstructions need a long time of non-weight bearing to obtain union and graft hypertrophy. Bus et al. analyzed 87 patients who underwent intercalary allograft reconstruction following bone tumor resection, reporting that the median period to full weight bearing was nine months.24 However, when the allograft reconstruction is successful, outcomes are almost always very good and late complications are uncommon.1,4

Fig. 2.

Fig. 2

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Preoperative axial (A) coronal (B) and sagittal (C) CT shows an osteosarcoma of the left tibia in a 18-year old boy; (D) the operating sample after resection; (E) immediate postoperative radiograph shows reconstruction with a massive bone allograft and pedicle vascularized fibula, and (F) a 5-year postoperative radiograph shows graft consolidation.

Extracorporeal devitalized resected tumor-bearing bone is a common surgical procedure in some Asian countries with poor bone donations.13 The techniques of devitalizing procedures include irradiation, autoclaving, pasteurization or freezing with liquid nitrogen.13 Major advantage of these procedures are that the dimensions of the devitalized autograft precisely match the host bone.13 Potential complications include nonunion, infection, fracture and bone resorption.13 Graft survival and complications between the extracorporel devitalized autografts and allografts seem to be similar.32,38 However, the major disadvantage of extracorporeal devitalized autograft is related to the absence of material for the histological examination of the effect of chemotherapy and the determination of surgical margins.36 There is a report of basic research showing that liquid nitrogen-frozen bone is superior to other extracorporeal devitalized bones such as autoclaving and pasteurization bones.47 Histological examination of autoclaved bone specimens retrieved 2 years after transplantation revealed that most of the grafts were not incorporated.48 On the other hand, in liquid nitrogen-frozen bone retrieved more than 1 year after transplantation, osteocytes and osteoblasts were found in a wide part of the graft, and the cortical host graft junction showed incorporation along with continuity of bone trabeculae. It indicated that bone formation in the frozen graft had begun.47

By using an intercalary prosthesis, surgical time can be shortened, stability can be obtained immediately, and early weight-bearing is possible.13 Aseptic loosening is a major complication that occurs in up to half of patients.4,10,13,23 Therefore, intercalary prosthetic reconstructions are ideally indicated for elderly patients or patients with limited life expectancy, where early weight-bearing is more important than implant durability.2,13 Several studied reported that complications related to intercalary prosthetic reconstructions range from 14 to 50% and include mechanical failure and aseptic loosening of the proximal or distal stem.4,10,23 Aseptic loosening seems to be the major problem and often occurs as a late complication usually two years after surgery.8,10,42 Benevenia et al. revealed that the highest complication rate occurred in the femur, raising the question if intercalary prosthetic is a viable option in the reconstruction of diaphyseal bone defect in the femur.23 A new emerging surgical technique is the use of 3D-printed intercalary prostheses (Fig. 3). The advantage of this technique is the use of customized surgical osteotomy guide that allow to have an accurate matching between the residual bone and prosthesis.14 In addition, new porous implant designs made possible by additive manufacturing has the potential to improve osteointegration, implant performance and longevity for patients treated with intercalary prosthetic reconstructions.49,50

Fig. 3.

Fig. 3

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Preoperative axial (A) coronal (B) and sagittal (C) CT shows an osteosarcoma of the left tibia in a 17-year old girl; (D) the operating sample after resection; postoperative (E) antero-posterior and (F) lateral radiographs show reconstruction with intercalary 3-D printed prosthesis.

Patients who received intercalary reconstruction often had osteosarcoma or Ewing sarcoma, and almost all received postoperative chemotherapy, which has been shown to increase the risk of infection.51 All of the allograft, extracorporeal devitalized autograft, and modular prosthesis are acellular, lack blood supply, and not resistant to infection. Vascularized fibula grafts have blood supply and can tolerate infection.1 On the other hand, other authors reported that long surgical time because of fibula harvesting and vascular anastomosis may increase the infection risk.3 Puri et al.41 wrapped the extracorporeal devitalized autograft in vancomycin soaked swabs prior to transportation to reduce the risk of infection. In addition to antibiotic prophylaxis, adequate soft tissue covering is considered essential for prevention of infection.29 It is important to collaborate with plastic surgeons to avoid ischemic local skin flaps and dead space.35

5. Conclusions

Currently, there is a little evidence suggesting which is the ideal intercalary reconstruction following bone tumor resection. However, biological reconstructions allow for the opportunity to restore bone stock and despite the high risk of early complications, late complications are rare once graft integration is achieved. Therefore, biological reconstructions seem to be the treatment of choice in young patients with long life expectancy. The literature is controversial whether the allograft or extracorporeal devitalized autograft should be associated with vascularized fibula graft due to the longer surgical time of this procedure and the disadvantage of donor site morbidity. Vascularized fibula graft could be an option to improve the rate of union in very long resections or to rescue mechanical failure following allograft or devitalized autograft reconstructions. Intercalary prostheses provide immediate stability and have low incidence of early complications, but late complications are the main concern. Therefore, intercalary prosthetic reconstructions seem to be the treatment of choice for elderly patients in whom early weight bearing is a priority, as in patients with a metastatic disease or patients with short life expectancy. Recent advances in three dimensional-printing technique for the production of custom materials and porosity of the prosthesis could have the potential to improve incorporation and longevity properties of these new implants in the next future. Multicenter prospective comparative studies would be needed to compare these different types of reconstructions, clarifying which type of reconstruction is suitable for which type of patient and disease.

Declaration of competing interest

All authors have not conflict of interest.

Acknowledgments

The authors thank the patients and their families.

References

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