L. A. Aponte-Tinao, M. A. Ayerza, J. I. Albergo, G. L. Farfalli, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Clin Orthop Relat Res. 2020 Mar;478(3):517-524. doi: 10.1097/CORR.0000000000000806.
Massive bone allografts have been used for limb salvage in patients undergoing bone tumor resections as an alternative to endoprostheses. Although several studies on massive allograft reconstructions for bone tumors reported that most complications occur in the first 3 years after surgery, there are no long-term reports on complications to substantiate this contention. We believe such information is important so that surgeons and patients can make more informed decisions when choosing a reconstructive method after tumor resection.
QUESTIONS/PURPOSES: (1) What is the survival of allografts free from removal, amputation, or joint replacement in patients treated for bone tumors in the lower limb with a minimum of 10 years of followup? (2) What complications occur after 10 or more years of followup? (3) Are there factors associated with allograft survival, such as age, sex, the affected bone, reconstruction type (intercalary or osteoarticular allograft), tumor type (malignant or benign), failure type, and chemotherapy use?
We retrospectively analyzed the records of 398 patients treated in one center with benign or malignant bone tumors in the femur or tibia between 1986 and 2007. During the period in question, our general indications for using allografts (354 patients) included patients with benign or low-grade sarcomas and patients with high-grade sarcomas with clinical and imaging response to neoadjuvant chemotherapy. Other approaches such as endoprostheses (44 patients) 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. We excluded from the analysis 53 patients treated with allograft-prosthetic composites, 46 with hemicondylar osteoarticular allografts, and 57 with intercalary hemicylindrical allografts. The study was thus performed in 198 patients treated with segmental massive allografts in the long bones of the lower extremity (132 femurs and 66 tibias) after resection of a primary bone tumor, including 120 patients treated with osteoarticular and 78 with segmental intercalary allografts. A total of 32 (16%) of the 198 patients died before 10 years, and graft status was known in all of those patients; these patients were included (mean followup, 192 months; range, 1-370 months). All remaining 166 patients who were not known to have died before 10 years were accounted for at least 10 years after the allograft procedure (mean, 222 months; range, 120-370 months). No patient was lost to followup. The mean age was 22 years (range, 2-55 years); 105 patients were male (53%) and 93 were female. The predominant diagnoses were osteosarcoma (n = 125, 63%), giant cell tumor of bone (n = 27, 14%), and Ewing's sarcoma (n = 19, 10%). In all, 146 patients (74%) underwent chemotherapy. Selected variables were analyzed using multivariate logistic regression analyses to identify risk factors of allograft removal, joint replacement, or amputation. We performed competitive risk analysis with allograft removal, joint replacement, or amputation as the endpoint at 5, 10, and 20 years. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system.
The risk of allograft removal, joint replacement, or amputation was 36% at 5 years (95% CI, 30-43), 40% at 10 years (95% CI, 33-47), and 44% at 20 years (95% CI, 37-51). Fractures occurred in 15% (29 patients), infection in 14% (27 patients), nonunion in 12% (23 patients) and tumor recurrence in 7% (13 patients). Thirty-two patients died of disease before 10 years; nine of these patients had a second surgery before death, eight had an amputation, and one underwent graft removal. Of the 166 patients who were still alive 10 years after the allograft procedure, 36 underwent allograft removal, six patients underwent joint replacement, and four had an amputation; however, after 10 years, six more allografts were removed (four due to fractures, one due to infection, and one due to instability), and another patient was amputated due to a second malignancy. After controlling for potentially confounding variables including death, we found that the risk of allograft removal, joint replacement, or amputation in osteoarticular tibial grafts (58% [95% CI, 43-73] at 5, 10, and 20 years) was higher than that of osteoarticular femur allografts (29% [95% CI, 18-39] at 5 years, 30% [95% CI, 19-40] at 10 years, 37% [95% CI, 25-48] at 20 years; p = 0.010) and tibia intercalary allografts (26% [95% CI, 7-45] at 5, 10 and 20 years; p = 0.020). Fractures occurred more frequently in the femur (18% [95% CI, 11-25]) than in the tibia (5% [95% CI, 0-10]; p < 0.010), and infections occurred more frequently in the tibia (24% [95% CI, 14-35]) than in the femur (4% [95% CI, 0-8]; p < 0.001). With the number of patients we had, we found no difference in the proportion of local recurrence in the tibia (12% [95% CI, 4-20]) compared with the femur (5% [95% CI, 1-9]; p < 0.053).
Infections were the most common complications associated with allograft removal in the first 2 to 3 years after reconstruction and were more frequently associated with tibial allograft removal. Fractures were more commonly associated with graft removal with longer term followup and were more frequently associated with femoral allograft removal. Although we cannot directly compare our results with other types of reconstructions, we believe that allografts still have a role in the reconstruction of patients with a benign or low-grade bone tumor. Future studies in femoral allograft with longer followup should be performed to analyze factors that may explain why some grafts fail, such as the percent of the length of the bone resected, type and number of plates and screws used and type of fixation (rods versus plates). There was a higher incidence of graft removal in patients with proximal tibia osteoarticular allografts, which has led us to use this type of reconstruction only in pediatric patients over the last 15 years.
Level III, therapeutic study.
在进行骨肿瘤切除的患者中，大块同种异体骨移植已被用于保肢治疗，可作为内置假体的替代物。尽管有几项关于骨肿瘤大块同种异体重建的研究报告称，大多数并发症发生在手术后的前 3 年内，但尚无长期报告证实这一观点。我们认为，此类信息非常重要，以便外科医生和患者在肿瘤切除后选择重建方法时能够做出更明智的决策。
问题/目的：（1）在至少随访 10 年的下肢骨肿瘤患者中，同种异体骨无移除、截肢或关节置换的存活率是多少？（2）10 年以上随访时会发生哪些并发症？（3）同种异体骨存活率是否与年龄、性别、受累骨、重建类型（骨-关节同种异体或节段性同种异体）、肿瘤类型（恶性或良性）、失败类型和化疗使用等因素有关？
我们回顾性分析了 1986 年至 2007 年间在一家中心接受治疗的股骨或胫骨良性或恶性骨肿瘤的 398 例患者的记录。在研究期间，我们使用同种异体骨（354 例患者）的一般适应证包括良性或低度肉瘤患者和对新辅助化疗有临床和影像学反应的高级别肉瘤患者。如果患者接受放疗、高级别肉瘤患者对新辅助化疗无临床和影像学反应或存在神经血管肿瘤侵犯，则采用内置假体复合材料（44 例）等其他方法。我们排除了 53 例接受同种异体-假体复合材料治疗的患者、46 例接受半髁状骨-关节同种异体骨治疗的患者和 57 例接受节段性半圆柱形同种异体骨治疗的患者。因此，在 132 例股骨和 66 例胫骨原发性骨肿瘤切除后接受节段性同种异体大块移植的 198 例患者中进行了分析，包括 120 例接受骨-关节同种异体和 78 例接受节段性同种异体骨移植的患者。198 例患者中有 120 例（16%）在 10 年之前死亡，这些患者的同种异体骨状态均已知；这些患者包括在分析中（平均随访时间，192 个月；范围，1-370 个月）。所有其余 166 例在 10 年之前未被报告死亡的患者，在同种异体手术后至少随访 10 年（平均，222 个月；范围，120-370 个月）。无患者失访。平均年龄为 22 岁（范围，2-55 岁）；105 例为男性（53%），93 例为女性。主要诊断为骨肉瘤（n=125，63%）、骨巨细胞瘤（n=27，14%）和尤文肉瘤（n=19，10%）。共有 146 例（74%）患者接受了化疗。采用多变量逻辑回归分析对选定变量进行分析，以确定同种异体骨移除、关节置换或截肢的危险因素。我们采用竞争风险分析，以同种异体骨移除、关节置换或截肢为终点，在 5 年、10 年和 20 年时进行分析。使用肌肉骨骼肿瘤学会（MSTS）-93 评分系统评估患者功能。
5 年时同种异体骨移除、关节置换或截肢的风险为 36%（95%CI，30-43），10 年时为 40%（95%CI，33-47），20 年时为 44%（95%CI，37-51）。发生骨折 29 例（15%），感染 27 例（14%），骨不连 23 例（12%）和肿瘤复发 13 例（7%）。32 例患者在 10 年前因疾病死亡；其中 9 例患者在死亡前进行了第二次手术，8 例进行了截肢，1 例进行了同种异体骨移除。在同种异体手术后 10 年仍存活的 166 例患者中，36 例进行了同种异体骨移除，6 例进行了关节置换，4 例进行了截肢；然而，在 10 年后，又有 6 例同种异体骨被移除（4 例因骨折，1 例因感染，1 例因不稳定），另有 1 例患者因第二恶性肿瘤被截肢。在控制包括死亡在内的潜在混杂因素后，我们发现胫骨骨-关节同种异体骨（5 年、10 年和 20 年时 58%[95%CI，43-73%]）同种异体骨移除、关节置换或截肢的风险高于股骨骨-关节同种异体骨（5 年时 29%[95%CI，18-39%]，10 年时 30%[95%CI，19-40%]，20 年时 37%[95%CI，25-48%]；p=0.010）和胫骨节段性同种异体骨（5 年时 26%[95%CI，7-45%]；p=0.020）。股骨骨折更常见（18%[95%CI，11-25%]），而胫骨骨折更常见（5%[95%CI，0-10%]；p<0.010），胫骨感染更常见（24%[95%CI，14-35%]），而股骨感染更常见（4%[95%CI，0-8%]；p<0.001）。在我们拥有的患者数量中，我们发现胫骨（12%[95%CI，4-20%]）与股骨（5%[95%CI，1-9%]；p<0.053）的局部复发比例无差异。
在重建后 2 至 3 年内，同种异体骨移除的最常见并发症是感染，并且与胫骨同种异体骨移除更为相关。骨折更常与长期随访时的同种异体骨移除相关，并且与股骨同种异体骨移除更为相关。尽管我们不能直接将我们的结果与其他类型的重建进行比较，但我们认为同种异体骨在良性或低度骨肿瘤患者的重建中仍有作用。未来应在股骨同种异体骨中进行更长时间的随访研究，以分析导致某些移植物失败的因素，例如切除骨的长度百分比、使用的钢板和螺钉的类型和数量以及固定类型（棒材与钢板）。近端胫骨骨-关节同种异体骨重建的移植物移除发生率较高，这导致我们在过去 15 年中仅在儿科患者中使用这种类型的重建。
III 级，治疗性研究。
