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胫骨中间段切除治疗原发性骨肿瘤:带血管腓骨自体骨移植联合或不联合异体骨移植是否能实现持久重建?

Intercalary Resection of the Tibia for Primary Bone Tumors: Are Vascularized Fibula Autografts With or Without Allografts a Durable Reconstruction?

作者信息

Campanacci Domenico Andrea, Scanferla Roberto, Marsico Mariagrazia, Scolari Federico, Scoccianti Guido, Beltrami Giovanni, Delcroix Luca, Innocenti Marco, Capanna Rodolfo

机构信息

Department of Orthopaedic Oncology and Reconstructive Surgery, Careggi University Hospital, Florence, Italy.

Department of Paediatric Orthopaedics, Meyer University Hospital, Florence, Italy.

出版信息

Clin Orthop Relat Res. 2024 Mar 21;482(6):960-75. doi: 10.1097/CORR.0000000000003007.

DOI:10.1097/CORR.0000000000003007
PMID:38513152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11124688/
Abstract

BACKGROUND

Reconstruction with vascularized fibula grafts (VFG) after intercalary resection of sarcoma may offer longevity by providing early graft-host union and fracture healing. The ability of the fibula to hypertrophy under mechanical stress, as well as vascularized bone in the area, may also be advantageous, given that soft tissues may be compromised because of resection, chemotherapy, or radiation therapy. VFG with a massive allograft combines the primary mechanical stability of the graft with the biological potential of the vascularized fibula; however, complications and the durability of this combined reconstruction are not well described.

QUESTIONS/PURPOSES: (1) What was the proportion of complications after reconstruction with VFG, with or without allografts? (2) What was the functional result after surgical treatment as assessed by the Musculoskeletal Tumor Society (MSTS) score? (3) What was the survivorship of these grafts free from revision and graft removal?

METHODS

Between 1988 and 2021, 219 patients were treated at our institution for a primary malignant or aggressive benign bone tumor of the tibia with en bloc resection. Of those, 54% (119 of 219) had proximal tibial tumors with epiphyseal involvement and were treated with either intra-articular resection and reconstruction with an osteoarticular allograft, allograft-prosthesis composite (APC), or modular prosthesis according to age, diagnosis, and preoperative or postoperative radiotherapy. Nine percent (20) of patients had distal tibial tumors that were treated with intra-articular resection and reconstruction with ankle arthrodesis using allogenic or autologous grafts, and 0.5% (1 patient) underwent total tibial resection for extensive tumoral involvement of the tibia and reconstruction with an APC. Thirty-six percent (79) of patients had a metadiaphyseal bone tumor of the tibia and were treated with intercalary joint-sparing resection. We routinely use reconstruction with VFG after intercalary tibial resection for primary malignant or aggressive benign bone tumors in patients with long life expectancy and high functional demands and in whom at least 1 cm of residual bone stock of the proximal or distal epiphysis can be preserved. By contrast, we routinely use intercalary massive allograft reconstruction in short resections or in patients with metastatic disease who do not have long life expectancy. We avoid VFG in patients with tibial bone metastasis, patients older than 70 years, or primary bone tumors in patients who may undergo postoperative radiotherapy; in these patients, we use alternative reconstructive methods such as intercalary prostheses, plate and cement, or intramedullary nailing with cement augmentation. According to the above-mentioned indications, 6% (5 of 79) of patients underwent massive allograft reconstruction because they were young and had intercalary resections shorter than 7 cm or had metastatic disease at diagnosis without long life expectancy, whereas 94% (74) of patients underwent VFG reconstruction. The median age at operation was 16 years (range 5 to 68 years). The diagnosis was high-grade osteosarcoma in 22 patients, Ewing sarcoma in 19, adamantinoma in 16, low-grade osteosarcoma in five, fibrosarcoma in three, malignant fibrous histiocytoma and Grade 2 chondrosarcoma in two, and malignant myoepitelioma, angiosarcoma of bone, malignant peripheral nerve sheath tumor of bone, squamous cell carcinoma secondary to chronic osteomyelitis, and desmoplastic fibroma in one patient each. Median follow-up was 12.3 years (range 2 to 35 years). The median tibial resection length was 15 cm (range 7 to 27 cm), and the median fibular resection length was 18 cm (range 10 to 29 cm). VFG was used with a massive allograft in 55 patients, alone in 12 patients, and combined with allogenic cortical bone struts in seven patients. We used VFG combined with a massive allograft in patients undergoing juxta-articular, joint-sparing resections that left less than 3 cm of residual epiphyseal bone, for intra-epiphyseal resections, or for long intercalary resections wherein the allograft can provide better mechanical stability. In these clinical situations, the combination of a VFG and massive allograft allows more stable fixation and better tendinous reattachment of the patellar tendon. VFG was used with cortical bone struts in distal tibia intercalary resections where the narrow diameter of the allograft did not allow concentric assembling with the fibula. Finally, VFG alone was often used after mid- or distal tibia intercalary resection in patients with critical soft tissue conditions because of previous surgery, in whom the combination with massive allograft would result in a bulkier reconstruction. We ascertained complications and MSTS scores by chart review, and survivorship free from revision and graft removal was calculated using the Kaplan-Meier estimator. In our study, however, the occurrence of death as a competing event was observed in a relatively low proportion of patients, and only occurred after the primary event of interest had already occurred. Considering the nature of our data, we did not consider death after the primary event of interest as a competing event.

RESULTS

In all, 49% (36 of 74) of patients experienced complications and underwent operative treatment. There were 45 complications in 36 patients. There was one instance of footdrop secondary to common peroneal nerve palsy, four wound problems, one acute vein thrombosis of the VFG pedicle and one necrosis of the skin island, two episodes of implant-related pain, 10 nonunions, six fractures, six deep infections, nine local recurrences, one Achilles tendon retraction, one varus deformity of the proximal tibia with postoperative tibial apophysis detachment, one knee osteoarthritis, and one hypometria. The median MSTS score was 30 (range 23 to 30); the MSTS score was assessed only in patients in whom the VFG was retained at the final clinical visit, although if we had considered those who had an amputation, the overall score would be lower. Revision-free survival of the reconstructions was 58% (95% confidence interval 47% to 70%) at 5 years, 52% (95% CI 41% to 65%) at 10 and 15 years, and 49% (95% CI 38% to 63%) at 20 and 30 years. Eight patients underwent VFG removal because of complications, with an overall reconstruction survival of 91% (95% CI 84% to 98%) at 5 years and 89% (95% CI 82% to 97%) at 10 to 30 years.

CONCLUSION

VFG, alone or combined with an allograft, could be considered in reconstructing a lower extremity after intercalary resections of the tibia for primary bone tumors, and it avoids the use of a large endoprosthesis. However, this procedure was associated with frequent, often severe complications during the first postoperative years and complication-free survival of 58% at 5 years. Nearly 10% of patients ultimately had an amputation. For patients whose reconstruction succeeded, the technique provides a durable reconstruction with good MSTS scores, and we believe it is useful for active patients with long life expectancy. Fractures, frequently observed in the first 5 years postoperatively, might be reduced using long-spanning plate fixation, and that appeared to be the case in our study. Nonbridging fixation can be an option in intraepiphyseal resection when a spanning plate cannot be used or in pediatric patients to enhance fibula hypertrophy and remodeling. We did not directly compare VFG with or without allografts to other reconstruction options, so the decision to use this approach should be made thoughtfully and only after considering the potential serious risks.

LEVEL OF EVIDENCE

Level IV, therapeutic study.

摘要

背景

肉瘤节段性切除术后采用带血管腓骨移植(VFG)重建,可通过促进早期移植骨与宿主骨愈合及骨折愈合来延长使用寿命。鉴于切除、化疗或放疗可能导致软组织受损,腓骨在机械应力下肥大的能力以及该区域带血管的骨组织可能具有优势。VFG与大块同种异体骨移植相结合,兼具了移植骨的主要机械稳定性和带血管腓骨的生物学潜能;然而,这种联合重建的并发症及耐久性尚未得到充分描述。

问题/目的:(1)采用或未采用同种异体骨的VFG重建术后并发症的发生率是多少?(2)根据肌肉骨骼肿瘤学会(MSTS)评分评估,手术治疗后的功能结果如何?(3)这些移植骨无需翻修及移除的生存率如何?

方法

1988年至2021年间,我院共治疗219例因原发性恶性或侵袭性良性胫骨骨肿瘤而接受整块切除的患者。其中,54%(219例中的119例)为近端胫骨肿瘤累及骨骺,根据年龄、诊断及术前或术后放疗情况,接受了关节内切除并用骨关节同种异体骨、同种异体骨 - 假体复合物(APC)或模块化假体进行重建。9%(20例)患者为远端胫骨肿瘤,接受了关节内切除并用同种异体或自体移植骨进行踝关节融合重建,0.5%(1例患者)因胫骨广泛肿瘤累及接受了全胫骨切除并用APC进行重建。36%(79例)患者为胫骨骨干中段骨肿瘤,接受了节段性关节保留切除。对于预期寿命长、功能需求高且近端或远端骨骺至少保留1 cm残余骨量的原发性恶性或侵袭性良性骨肿瘤患者,我们常规在胫骨节段性切除后采用VFG重建。相比之下,对于短节段切除患者或预期寿命不长的转移性疾病患者,我们常规采用节段性大块同种异体骨重建。对于胫骨骨转移患者、70岁以上患者或可能接受术后放疗的原发性骨肿瘤患者,我们避免使用VFG;在这些患者中,我们采用其他重建方法,如节段性假体、钢板加骨水泥或带骨水泥强化的髓内钉固定。根据上述指征,6%(79例中的5例)患者因年轻且节段性切除长度小于7 cm或诊断时患有转移性疾病且预期寿命不长而接受了大块同种异体骨重建,而94%(74例)患者接受了VFG重建。手术时的中位年龄为16岁(范围5至68岁)。诊断为高级别骨肉瘤的患者有22例,尤文肉瘤19例,造釉细胞瘤16例,低级别骨肉瘤5例,纤维肉瘤3例,恶性纤维组织细胞瘤和2级软骨肉瘤各2例,恶性肌上皮瘤、骨血管肉瘤、骨恶性周围神经鞘瘤、慢性骨髓炎继发鳞状细胞癌和促纤维组织增生性纤维瘤各1例。中位随访时间为12.3年(范围2至35年)。胫骨切除的中位长度为15 cm(范围7至27 cm),腓骨切除长度的中位值为18 cm(范围10至29 cm)。55例患者采用VFG联合大块同种异体骨,12例单独使用VFG,7例联合同种异体皮质骨支撑物使用VFG。对于近关节、保留关节的切除术后残留骨骺骨小于3 cm的患者、骨骺内切除患者或长节段性切除患者(此时同种异体骨可提供更好的机械稳定性),我们采用VFG联合大块同种异体骨。在这些临床情况下, VFG与大块同种异体骨的组合可实现更稳定的固定以及髌腱更好的腱性重新附着。在远端胫骨节段性切除中,当同种异体骨直径狭窄无法与腓骨同心组装时,采用VFG联合皮质骨支撑物。最后,由于既往手术导致软组织条件较差的患者,在胫骨中段或远端节段性切除后常单独使用VFG,因为与大块同种异体骨联合使用会导致重建体积更大。我们通过查阅病历确定并发症及MSTS评分,并使用Kaplan - Meier估计器计算无翻修及移植骨移除的生存率。然而,在我们的研究中,死亡作为竞争事件的发生率相对较低,且仅在感兴趣的主要事件已经发生后才出现。考虑到我们数据的性质,我们未将感兴趣的主要事件发生后的死亡视为竞争事件。

结果

总共有49%(74例中的36例)患者出现并发症并接受了手术治疗。36例患者共出现45种并发症。包括1例因腓总神经麻痹导致的足下垂、4例伤口问题、1例VFG蒂急性静脉血栓形成和1例皮岛坏死、2例植入物相关疼痛、10例骨不连、6例骨折、6例深部感染、9例局部复发、1例跟腱挛缩、1例近端胫骨内翻畸形伴术后胫骨骨骺分离、1例膝关节骨关节炎和1例子宫发育不全。MSTS评分的中位值为30(范围23至30);MSTS评分仅在最后一次临床随访时保留VFG的患者中进行评估,不过如果我们将接受截肢的患者纳入考虑,总体评分会更低。重建的无翻修生存率在5年时为58%(95%置信区间47%至70%),10年和15年时为52%(95%CI 41%至65%),20年和30年时为49%(95%CI 38%至63%)。8例患者因并发症接受了VFG移除,总体重建生存率在5年时为91%(95%CI 84%至98%),10至30年时为89%(95%CI 82%至97%)。

结论

对于原发性骨肿瘤胫骨节段性切除后的下肢重建,可考虑单独或联合同种异体骨使用VFG,并且避免使用大型内置假体。然而,该手术在术后最初几年常伴有频繁且往往较为严重的并发症,5年时无并发症生存率为58%。近10%的患者最终接受了截肢。对于重建成功的患者,该技术可提供持久的重建效果且MSTS评分良好,我们认为它对预期寿命长的活跃患者有用。术后前5年经常观察到的骨折,可通过使用长跨度钢板固定来减少,在我们的研究中似乎也是如此。当无法使用跨度钢板时,非桥接固定可作为骨骺内切除的一种选择,或者在儿科患者中用于促进腓骨肥大和重塑。我们未将使用或未使用同种异体骨的VFG与其他重建选择进行直接比较,因此在决定采用这种方法时应谨慎考虑,且需充分考虑潜在的严重风险。

证据级别

IV级,治疗性研究。

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3
Intercalary frozen autografts for reconstruction of bone defects following meta-/diaphyseal tumor resection at the extremities.
病例报告:个体化3D打印非骨水泥型腓骨远端假体保留外踝用于修复腓骨远端缺损
Front Oncol. 2024 Aug 29;14:1380508. doi: 10.3389/fonc.2024.1380508. eCollection 2024.
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Graft Infections in Biologic Reconstructions in the Oncologic Setting: A Systematic Review of the Literature.肿瘤环境下生物重建中的移植物感染:文献系统综述
J Clin Med. 2024 Aug 8;13(16):4656. doi: 10.3390/jcm13164656.
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Editorial Comment: 35th Annual Meeting of the European Musculo-Skeletal Oncology Society (EMSOS).编辑评论:欧洲肌肉骨骼肿瘤学会(EMSOS)第35届年会
Clin Orthop Relat Res. 2024 Jun 1;482(6):945-946. doi: 10.1097/CORR.0000000000003108. Epub 2024 May 7.
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Joint-Sparing Resection around the Knee for Osteosarcoma: Long-Term Outcomes of Biologic Reconstruction with Vascularized Fibula Graft Combined with Massive Allograft.膝关节周围骨肉瘤的保关节切除术:带血管腓骨移植联合大块同种异体骨生物重建的长期疗效
Cancers (Basel). 2024 Apr 26;16(9):1672. doi: 10.3390/cancers16091672.
节段性冷冻自体骨移植在四肢骨肿瘤切除后骨缺损中的应用
BMC Musculoskelet Disord. 2022 Sep 30;23(1):890. doi: 10.1186/s12891-022-05840-6.
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Highly Cancellous Titanium Alloy (TiAlV) Surfaces on Three-Dimensionally Printed, Custom-Made Intercalary Tibia Prostheses: Promising Short- to Intermediate-Term Results.三维打印定制型胫骨间置假体上的高松质骨钛合金(TiAlV)表面:短期至中期结果令人期待。
J Pers Med. 2021 Apr 28;11(5):351. doi: 10.3390/jpm11050351.
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Reconstruction survival of segmental megaendoprostheses: a retrospective analysis of 28 patients treated for intercalary bone defects after musculoskeletal tumor resections.节段性大块假体重建的存活率:28 例因肌肉骨骼肿瘤切除后骨缺损而接受间插骨缺损治疗的患者的回顾性分析。
Arch Orthop Trauma Surg. 2022 Jan;142(1):41-56. doi: 10.1007/s00402-020-03583-4. Epub 2020 Aug 29.
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Intercalary Allograft Reconstruction of the Proximal Tibia With and Without a Free Fibula Flap in Pediatric Patients.儿童患者中带蒂和不带蒂游离腓骨瓣间插异体骨重建胫骨近端。
J Pediatr Orthop. 2020 Oct;40(9):e833-e838. doi: 10.1097/BPO.0000000000001640.
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Is frozen tumour-bearing autograft with concurrent vascularized fibula an alternative to the Capanna technique for the intercalary reconstruction after resection of osteosarcoma in the lower limb?冷冻肿瘤骨移植联合带血管腓骨移植是否可替代 Capanna 技术用于下肢骨肉瘤切除后节段性骨重建?
Bone Joint J. 2020 May;102-B(5):646-652. doi: 10.1302/0301-620X.102B5.BJJ-2019-1380.R1.
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Long-Term Clinical Outcomes of Intercalary Allograft Reconstruction for Lower-Extremity Bone Tumors.节段性异体骨移植重建治疗下肢骨肿瘤的长期临床疗效。
J Bone Joint Surg Am. 2020 Jun 17;102(12):1042-1049. doi: 10.2106/JBJS.18.00893.
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Do Massive Allograft Reconstructions for Tumors of the Femur and Tibia Survive 10 or More Years after Implantation?异体骨大段重建股骨和胫骨肿瘤,植入后 10 年以上存活率如何?
Clin Orthop Relat Res. 2020 Mar;478(3):517-524. doi: 10.1097/CORR.0000000000000806.
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Combination of Extracorporeally-irradiated Autograft and Vascularized Bone Graft for Reconstruction of Malignant Musculoskeletal Tumor.体外照射自体骨移植与带血管骨移植联合应用于恶性骨肿瘤的重建。
Anticancer Res. 2020 Mar;40(3):1637-1643. doi: 10.21873/anticanres.14113.