Predictive factors for delayed union in liquid nitrogen-treated autografts following tumor resection: a retrospective study

Limb salvage surgery is the standard treatment for malignant bone and soft tissue tumors of the lower extremities. Frozen autografts treated with liquid nitrogen are widely used due to their potential for biological incorporation, immune tolerance, and the elimination of disease transmission risks. However, delayed union and non-union are common complications that present significant challenges in bone healing. This study aimed to identify the risk factors associated with delayed union to optimize treatment strategies and improve patient outcomes. Patients who underwent lower-extremity reconstruction with frozen autografts between January 2011 and December 2023 were included in this retrospective study. The patients were divided into two groups: those who achieved bone union within 12 months and those who did not. Univariate analysis was performed to evaluate whether significant differences existed in 15 factors between the two groups. Categorical variables were recorded as numbers and analyzed using Fisher’s exact test. Continuous variables were recorded as medians (ranges) and analyzed using the Mann–Whitney U test. The cut-off values and area under the curve were calculated based on the significance of the continuous variable factors. Of the 19 cases enrolled, 11 achieved bone union within 1 year after surgery. The overall complication rate was 26.3%, and the non-union rate was 15.8%. Univariate analysis identified three significant risk factors for delayed union: a longer length of bone treated with liquid nitrogen (cut-off: 15 cm), a larger osteotomy gap (cut-off: 1.3 mm), and higher preoperative alkaline phosphatase (ALP) levels (cut-off: 100 U/L). The findings of this study emphasize the importance of careful preoperative planning, including minimizing the length of the bone treated with liquid nitrogen and reducing the osteotomy gap during surgery. Additionally, vascularized fibular grafts may be considered in high-risk cases, particularly when the treated bone segment exceeds 15 cm or preoperative ALP levels are elevated. This study underscores the critical role of surgical techniques and preoperative assessments in optimizing bone healing outcomes.

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Journal
BMC Cancer
Published
2025-11-28
DOI
https://doi.org/10.1186/s12885-025-15349-5
Primary Topic
Sarcoma Diagnosis and Treatment
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article
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article

Predictive factors for delayed union in liquid nitrogen-treated autografts following tumor resection: a retrospective study

Yusei Katsuyama, Daichi Hayashi, Ryosuke Nishi, Naoki Mizoshiri et al.
BMC Cancer
Sarcoma Diagnosis and Treatment
article

Predictive factors for delayed union in liquid nitrogen-treated autografts following tumor resection: a retrospective study

Yusei Katsuyama, Daichi Hayashi, Ryosuke Nishi, Naoki Mizoshiri, Toshiharu Shirai, Ryu Terauchi, Kenji Takahashi, Yuki Mori, Seiji Shimomura
article en

Abstract

Limb salvage surgery is the standard treatment for malignant bone and soft tissue tumors of the lower extremities. Frozen autografts treated with liquid nitrogen are widely used due to their potential for biological incorporation, immune tolerance, and the elimination of disease transmission risks. However, delayed union and non-union are common complications that present significant challenges in bone healing. This study aimed to identify the risk factors associated with delayed union to optimize treatment strategies and improve patient outcomes. Patients who underwent lower-extremity reconstruction with frozen autografts between January 2011 and December 2023 were included in this retrospective study. The patients were divided into two groups: those who achieved bone union within 12 months and those who did not. Univariate analysis was performed to evaluate whether significant differences existed in 15 factors between the two groups. Categorical variables were recorded as numbers and analyzed using Fisher’s exact test. Continuous variables were recorded as medians (ranges) and analyzed using the Mann–Whitney U test. The cut-off values and area under the curve were calculated based on the significance of the continuous variable factors. Of the 19 cases enrolled, 11 achieved bone union within 1 year after surgery. The overall complication rate was 26.3%, and the non-union rate was 15.8%. Univariate analysis identified three significant risk factors for delayed union: a longer length of bone treated with liquid nitrogen (cut-off: 15 cm), a larger osteotomy gap (cut-off: 1.3 mm), and higher preoperative alkaline phosphatase (ALP) levels (cut-off: 100 U/L). The findings of this study emphasize the importance of careful preoperative planning, including minimizing the length of the bone treated with liquid nitrogen and reducing the osteotomy gap during surgery. Additionally, vascularized fibular grafts may be considered in high-risk cases, particularly when the treated bone segment exceeds 15 cm or preoperative ALP levels are elevated. This study underscores the critical role of surgical techniques and preoperative assessments in optimizing bone healing outcomes.

BMC CancerVol. 26(1)
Kyoto Prefectural University of Medicine (JP)
Openalex Percentile: Top 45%
Sarcoma Diagnosis and Treatment
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