位于颈3的上颈椎脊索瘤

1、 Author：Liang Jiang作 者：姜亮 Orthopaedic Department, Peking University Third Hospital, 单 位：北医三院第一页，共二十八页。Chordoma is a rare low-grade malignant neoplasm derived from the remnants of the embryonic notochord. This locally invasive neoplasm is subject to recurrence after treatment. The median survival tim

2、e is estimated to be 6.3 years. 定义：脊索瘤是一种少见的起源于胚胎脊索残留组织的低分化恶性肿瘤。 特点：容易复发。统计学：中位生存期是6.3年。 Abstract第二页，共二十八页。Various treatment approaches have been attempted, including radical excision, radiotherapy and chemotherapy. Treatment outcome is significantly influencedby the size and site of the chordoma. R

3、ecently, Imatinib, a molecular-targeted agent, has been shown to have antitumor activity in chordoma. Proton radiotherapy,stereotactic radiotherapy and intensity-modulatedradiotherapy have also been used. Surgical treatment is still the primary choice for chordoma. It has become more aggressive in r

4、ecent years, evolving from intralesional or partial excision to en bloc resection. However, upper cervicallocalizations make such en bloc resection in most cases not possible.治疗进展：传统治疗包括根治性切除、放疗和化疗等。“Imatinib”的分子靶向治疗药物显示对于脊索瘤有治疗效果。光子放疗，stereotactic 放疗以及调强放疗亦应用于脊索瘤的治疗。外科治疗仍旧是脊索瘤的首选治疗方法。近一些年脊索瘤的外科治疗从瘤

5、内刮除发展至部分切除直至全脊椎大块切除。然而，上颈椎独特的解剖位置使大块全脊椎切除治疗脊索瘤很难实现。 Abstract第三页，共二十八页。 We present and discuss the therapeuticchallenges of a young female with large retropharyngeal chordoma who presented to our institution after conventional photon beam radiotherapy. This C2/3 tumor was classified IB according to t

6、he Enneking classification. It distributed to layers AD and sectors 16 according to the Weinstein Boriani Biagini Classification. The left vertebral artery (VA) was encapsulated and displaced. One stageintralesional extracapsular tumor excision and reconstruction was achieved by combined bilateral h

7、igh anterior cervical approaches and posterior approach. No recurrence or metastasis was observed 3 years after the operation. She returned to her previous occupation as office worker.本文内容：我们在这里报道一位经过放疗的年轻的咽后脊索瘤女性患者。根据Enneking分期为IB期，根据WBB分期则为1-6区A-D层，左侧椎动脉被包绕并且移位。一期采用上颈椎联合双前外侧切口以及后侧入路对该例患者成功实施了囊外切除术

8、。术后3年随访患者无局部复发以及转移。 Abstract第四页，共二十八页。 Keywords Keywords Chordoma Atlantoaxial spine Surgery关键词 脊索瘤 寰枢椎 外科手术第五页，共二十八页。A 26-year-old female presented to our institution after a transoral biopsy of a large retropharyngeal tumor, which was diagnosed as a chordoma. She had dysphagia and neck pain 9 mont

9、hs ago. The retropharyngeal mass was noticed by otolaryngologist. After transoral biopsy, she had conventionalphoton beam radiotherapy with 40 Gy and then her symptoms totally disappeared. Since there was noreduction of tumor volume 6 months after radiotherapy, she was referred to our department. Sh

10、e had no other significant medical history and she did not exhibit any neurological deficit.年龄：26岁性别：女性病史：患者9月前出现颈痛并吞咽困难，首先是由耳鼻喉科医生发现咽后肿物。在经口活检确诊后患者接受了40个Gy的放疗，症状完全消失。由于放疗后6月瘤体未见缩小，患者遂来就诊。患者既往体健，无神经损伤症状。 临 床 资 料第六页，共二十八页。 Fig. 1 张口位像可以看到颈2椎体左侧边界不清的溶骨性改变。CT平扫可以看到颈2-3虫蚀样骨质破坏。矢状位MRI可以看到肿瘤从齿状突基底延伸至颈3椎体。

11、在轴位像上肿瘤压迫硬膜囊以及左侧颈内动脉。左椎动脉被包绕并移位。脊髓被挤向右侧。根据WBB分区病变位于A-D层和1-6区，根据Enneking分期为IB期。第七页，共二十八页。Fig. 2 Layers (AD) and Quadrants involvement according to Weinstein Boriani Classification (normal cervical vertebra represented)第八页，共二十八页。Chordoma is a relatively rare low-grade malignant neoplasm deriving from

12、remnants of the notochord, constituting between 1 and 4% of malignant bone tumors. It predominantly arises from the axial skeleton, while extra-axial chordoma has also been reported. Its incidence has been estimated to be one per one million inhabitants per year. It can affect patients from all ages

13、 with a predilection for men with a ratio of 1.61 (10). The frequently reported anatomic distribution of chordoma, sacral *50%, spheno-occipital *35%, spinal *15%, was based primarily on 262 patients from the Mayo Clinic experience.Based on more recent 400 cases from the United States 10, 32% of cas

14、es were presented at cranial sites, 33% spinal and 29% sacral. Median age is around 60 years, but skull-base presentations affect a younger age, and mayeven occur in children and adolescents. 脊索瘤是少见的起源于胚胎残留脊索组织的低分化恶性肿瘤，占恶性骨肿瘤的1-4%，主要起源于中轴骨骼系统，其他部位也见报道。统计学显示其每年发病率为百万分之一。各个年龄段均可发病，男性多于女性，男女比率为1.6：1。美国

15、纽约的Mayo医学中心统计262例脊索瘤按照解剖部位分类，蝶枕部为35%，骶骨50%。其他脊柱阶段15%。美国最近的400例病例统计，32%位于颅部，33%脊柱，29%位于骶骨。平均发病年龄为60岁，颅底部脊索瘤发病年龄较轻，甚至见于儿童和青少年。 诊断和流行病学第九页，共二十八页。Chordoma is characteristically slow-growing, locally invasive neoplasm. In most cases, the Enneking stage is IBlow grade malignant, extracompartmental. Additi

16、onally, they can be difficult to distinguish radiographicallyand pathologically from chondrosarcoma. Sometimes, chordoma has dumbbell shape which could be diagnosed as neuromas. Spine chordomas have also been diagnosed as tuberculosis and hemangioma. The mainstay to achieve appropriate diagnosis is

17、a biopsy performed by trocar under CT scan control with the biopsy track that can be excised during the surgical excision. 脊索瘤具有缓慢生长、局部侵袭的特点。大部分病例为IB期-低度恶性、间室外。依靠影像学和病理学资料仍旧难以将其与软骨肉瘤鉴别。有时具有扇贝样表现被误诊为神经瘤。脊柱脊索瘤也有误诊为结核和血管瘤的报道。获得正确诊断的主要依据是在CT引导下用套管针行穿刺活检，穿刺路径可以在之后的外科手术中切除。 诊断和流行病学第十页，共二十八页。 Metastases ar

18、e rare and occur to the lung or to the spine, exceptionally they can occur in other sites of the musculoskeletal system or even in the skin, brain, and other organs. The survival rate appears to be affected more by local tumor progression than by metastasis. The life expectancy from diagnosis is 6 m

19、onths to 2 years in the untreated skull base chordoma patient. Median survival was 6.3 years in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, looking at a 22 years database record. In the United States the 5- and 10-year relative survival rates were

20、 67.6 and 39.9%, respectively. There were no significant differences in survival although median survival was slightly lower inspinal chordomas (5.9 years) compared to cranial (6.9 years) and sacral (6.5 years) presentations. 脊索瘤少见转移，一般转移至肺脏或者脊柱，偶尔也可转移至肌骨系统其它部位或者皮肤、颅内等脏器。生存率多与原发灶关系密切而与转移灶则关系甚微。未经治疗的

21、颅底脊索瘤从诊断开始预计生存期为6月至2年。美国国家肿瘤研究中心22年数据统计显示其脊索瘤中位生存期为6.3年。在美国其5年和10年生存率分别是67.6%和39.9%。尽管脊柱脊索瘤的中位生存率稍低，但是与颅底和骶骨相比并无明显统计学差异。 诊断和流行病学第十一页，共二十八页。Because of their location, behavior, and the confusing diagnostic picture, chordomas can be difficult to manage. Treatment outcome is significantly influenced by

22、 the size and site of the chordoma. In general, cervical chordomasare so uncommon that articles have reported long-term follow-up evaluation of such tumors on a case-by-casebasis only.Atlantoaxial chordoma is extremely difficult to treatmainly because of its location close to vital structures.Since

23、there is a large dural space at the C1C2 location, thetumor usually gets quite large before the patient has some clinical manifestation. Compression of neural tissues and invasion of the brainstem or spinal canal may result in serious neurologic complications. It often encapsulates and/or displaces

24、the vertebral artery and nerve roots. 由于脊索瘤发病部位、生物学行为以及难以诊断，治疗较难。疗效明显与肿瘤的大小、部位相关。一般而言，颈椎的脊索瘤非常少见，长期随访结果都是建立在个案报道基础之上。 由于寰枢椎临近较多重要的解剖结构，治疗尤为困难。由于C1-2椎管宽阔，患者往往在肿瘤相当大时方出现临床症状。压迫神经组织以及侵袭脑干或者椎管可以导致严重的神经系统并发症。肿瘤经常侵袭椎动脉和神经根并使其移位。 诊断和流行病学第十二页，共二十八页。Various treatment approaches have been attempted, including

25、 isolated radiotherapy, combined radiation and surgical excision, and surgical excision alone. Surgery remains the treatment mainstay of chordoma. Excellent team work is needed for aggressive and successful surgical treatment in most cases. These factors plead for early referral to a tertiary care c

26、enter with advanced surgical capabilities and availability of newer modalities of radiation therapy. 对脊索瘤已经采取包括适形放疗、外科手术治疗和二者结合的治疗法方法。外科治疗仍旧是脊索瘤的首选方法。成功的外科手术需要优秀的医生团队，并且需要早期在具有专业外科技术和放疗设备的中心进行治疗。治疗方法和文献依据第十三页，共二十八页。Chemotherapy has long been known to be inactive in chordoma. It alone might be an opt

27、ion for supportive care once the disease extends and progresses. Cisplatin could be used locally after tumor resection, if marginal tumor contamination is suspected. Recently, Imatinib, a proteintyrosine kinase inhibitor and a molecular-targeted agent, has been shown to have antitumor activity in ch

28、ordoma 9. The mechanism is poorly understood, although blockade of platelet-derived growth factor (PDGF) signaling has beenproposed as the cause of tumor control. 脊索瘤对化疗不敏感。但是当疾病进展时化疗又成为唯一的选择。在肿瘤切除后如果怀疑边界被肿瘤污染，可以在局部应用顺铂。最近有一种称作Imatinib的分子靶向治疗药物显示对于脊索瘤有治疗效果。尽管血小板源性生长因子信号传递阻止被怀疑为抑制肿瘤的机制，但其机理仍不清楚。 治疗方法

29、第十四页，共二十八页。Chordomas were traditionally recognized as radioresistant.The tolerance dose of the spinal cord is lower than thecurative dose, which should at least be in the 70 Gy range 3. But radiation is valuable, especially for incomplete excision. In conventional photon radiotherapy a dose of less

30、than 4550 Gy is well within the radiation tolerance, given less than a 5% probability of myelopathy within 5 years. However, with the advent of new radiation modalities (i.e. the proton beam, charged carbon ions, stereotactic radiotherapy and intensity-modulated radiotherapy), it is possible to deli

31、ver high doses of radiation while protecting vital structures. Adjuvant radiation is now warranted and has offered improved clinical outcomes. There is extensive experience in the management of chordomas with proton beam therapy, and favorable results have been demonstrated 6. For the radiation onco

32、logist it is easier to identify the tumor margin before the surgery, but such preoperative radiotherapy might lead to higher operative and post operative complication rates. Postoperativeradiation is more common in clinical practice, but the tumor margin is more difficult to identify and the metal i

33、mplants might disturb the radiation efficacy. Radiationports also need to be configured to treat the surgical route and the tumor bed in order to reduce the risk of surgical seeding. The cost-effectiveness ratio for carbon radiotherapy is 2,539 per 1% increase in survival, or 7,692 peradditional lif

34、e year 7. Most authors suggest that maximal tumor excision surgery followed by high-dose radiotherapy should be the standard of care for these patients, while Boriani have demonstrated that margin-free en-bloc resection alone is enough. 放 疗第十五页，共二十八页。 既往认为脊索瘤对放疗不敏感。放疗治疗剂量至少需要70Gy，但是脊髓的承受剂量低于此水平。但是放疗

35、对于未能完全切除的脊索瘤是很有必要的。普通放疗中患者的承受剂量范围是小于40-50Gy，并且5年内发生放射性脊髓病的几率小于5%。然而新放疗技术的应用，可以在给予大剂量放疗射线的同时保护重要组织。辅助放疗目前已经被认可，取得较好的临床疗效。采用光子射线治疗脊索瘤目前已经取得较好的疗效，并积累了丰富的经验。对肿瘤放疗专家而言，在术前比术后更容易确认肿瘤边界。但是术前放疗增加了手术以及术后并发症的发生率。术后放疗在临床上应用更为普遍，但是肿瘤边界更难确定，并且内植物会影响放疗效果。要调整放疗设备来照射手术径路以及肿瘤边界以降低外科肿瘤种植的风险。费用量效比率为生存率增加1%的代价为2539元，或者

36、每延长生存期1年代价为7692元。 大部分的医生认为最大范围的肿瘤切除和最大量的放疗应该作为治疗的标准。但是Boriani认为沿边界行全椎体切除已经足够。 放 疗第十六页，共二十八页。Chordomas are characterized by frequent recurrences after incomplete surgical resection, usually within 23 years. Boriani, states that Prognosis is heavily affected by the appropriateness of the first surgica

37、l treatment; once recurred, further treatments are always unsuccessful at midterm. Others may prefer incomplete surgical excision to preserve initially the neurologic function, despite the risk of increased recurrence that will lead tofurther palliative surgery.Surgical treatment has become more agg

38、ressive in recent years, evolving from intralesional or partial excision to en bloc resection. In 1997, Weinstein, Boriani et al. described their Classification system for surgical staging for spine tumors. Such system is based on dividing the vertebra in 12 quadrants and different layers of tumor i

39、nvolvement from A to D. Tomita described total en bloc spondyloectomy (TES) using a threadwire T-saw for malignant vertebral tumors in the thoracolumbar spine. To achieve a wide resection margin, Boriani and his colleagues even removed the dura infiltrated by tumor and reconstructed the dura defect

40、withdural patch. 外科治疗第十七页，共二十八页。 脊索瘤的特点是外科不全切除后较高的复发率，一般是在2-3年内。Boriani认为预后受初次手术正确与否影响极大，一旦复发进一步的治疗往往是徒劳的。另外有医生更倾向于采用部分外科切除术以保留神经功能，尽管这增加了复发的几率并且需要进一步的姑息性手术治疗。近年来外科治疗迅速发展，已经从瘤内刮除、部分切除发展至全椎体整块切除。1997年，Weinstein等发表了他们的脊柱肿瘤分类分期方法。将椎体分为12个区域，A-D层。Tomita描述了他的采用线锯对胸椎的恶性肿瘤进行了全椎体大块切除术。为了能够完整切除肿瘤Boriani甚至切除了

41、被肿瘤侵蚀的硬膜，并且采用硬膜材料进行修补。 外科治疗第十八页，共二十八页。In 2006, Boriani and his colleagues 1 published a retrospective study of 52 chordomas cases of the mobile spine in a 50-year period. Twelve of 16 cases having intralesional extracapsular excision with radiation had recurrence at average 30 months, while 12 of 18

42、 patients havingen bloc resection are continuously disease-free (CDF) at average 8 years. They noted that the only treatment protocol associated with CDF at follow-up longer than 5 years is margin-free en bloc resection. Major complications include vertebral artery injury, cerebrospinal fluid (CSF)

43、leak, nerve palsies and paralysis. The mortality rate for skull base tumors is frequently quoted at 5%, and this number is 7.7% in Borianis spine series. In his series nodifferentiation in the type of radiotherapyused was mentioned. They also did not discuss the difference between cervical and thora

44、columbar chordoma. Cervical tumor excision, especially in the atlantoaxial region, might mandate more sophisticated surgical technique. In the cervical spine few cases have been reported of en bloc excision, due to anatomical constraints. Even less radical resection case has ever been reported for a

45、tlantoaxial chordoma 11. The peculiar anatomical complexity of the cervical region includes the dens, the vertebral arteries, the transverse processes around and the nerve roots. Since most chordomas are stage IB at diagnosis, margin free excision means resection of paravertebral muscle, nerve root,

46、 vertebral artery, even dura or retropharyngeal mucosa. These seem impossible for most cases. 外科治疗第十九页，共二十八页。 2006年，Boriani及其同事发表了50年间52例脊索瘤患者的回顾性研究。16例瘤内刮除中的12例患者平均在30个月时复发。18例椎体全切中的12例平均8年完全缓解。他们指明唯一的与无症状生存相关的就是沿边界切除。主要的并发症包括椎动脉损伤、脑脊液漏、神经损伤和瘫痪。颅底脊索瘤的病死率为5%，但是他们统计为7.7%。 在他们的研究中，未提及不同的放疗类型。也没有提及颈椎与胸

47、腰椎脊索瘤的不同。颈椎肿瘤特别是寰枢椎肿瘤要求更复杂的外科技术。由于解剖复杂，关于颈椎肿瘤少见全脊椎切除术的报道。寰枢椎的全脊椎切除术更为少见。复杂的解剖结构包括齿状突、椎动脉、横突和神经根。由于大部分脊索瘤是IB期，边界外切除意味着椎旁肌肉、神经根甚至硬膜和咽后粘膜。对于大部分病例这似乎不可能。 外科治疗第二十页，共二十八页。In 1999, Tomita et al. 5 first described TES for cervical chordoma (IB) through a single anterior approach with T-saw. Unfortunately, a

48、fter the C5 vertebral body had been removed with a T-saw the residual tumor along the C6 root and dura mater had to be removed in a piecemeal fashion. The tumor bed was irrigated by distilled water and cisplatin solution and then underwent adjunctive radiotherapy. Unfortunately, the chordoma recurre

49、d 9 years later in the soft tissue (Tomita personalcommunication). In 2007, Boriani et al. 8 reported en bloc excision for a C4 chordoma (IA) with combined posterior and anterior approach. He concluded that TES is feasible in the midcervical spine by double approaches, provided the tumor involves on

50、ly layers B and C, with a maximum extension to sectors 58. Currier et al. 4 has a similar case with 9 years follow-up.There are three major anterior approaches for atlantoaxial chordoma. The experience and abilities of the surgical team dictates the surgical procedure used. (1) Bilateral high anteri

51、or cervical approach can provideclear visualization of C2 vertebral body and bilateral transverse processes, while the dens is not appropriately exposed 13. (2) The anterior midline transoral with/without transpalatine approach is for spinal lesion located from the midclivus down to the level of C3

52、and laterally within 2 cm to either side of the midline. However, the tumor cannot be radically excised by this approach, if it extends laterally outside the transverse process. Menezes reported transpalatopharyngeal approach for 18 clivuscraniocervicalchordoma cases in 2001. He used piecemeal excis

53、ion with judicious use of curet and a diamond bur for occipital condyles or atlantal lateral mass tumor involvement. The author did not provide radiotherapy and follow-up information in detail; at least one patient had no tumor progression for 10 years. (3) Transmandible approach combined with anter

54、ior cervical approach could provide ideal exposure from clivus to lower cervical spine. This approach is more aggressive and often requires a free flap for the posterior pharyngeal wall reconstruction. Rhines et al. 12 reported the most aggressive TES for C24 chordoma (IB) in 2005. Theyused a right

55、lateral neck dissection and a transmandiblar, circumglossal, retropharyngeal exposure. 外科治疗第二十一页，共二十八页。 在1999年，Tomita等描述了他们采用单纯前路利用线锯对颈椎脊索瘤进行了全脊椎切除术。不幸的是在切除颈5后，颈6神经根周围的肿瘤和硬膜被一片片切除。肿瘤基底被用蒸馏水和顺铂溶液浸泡，术后接受化疗。但是肿瘤9年后复发。2007年，Boriani描述了他们全椎体切除颈4椎体肿瘤采用联合前后入路。他总结到，如果肿瘤位于B和C层并且5-8区采用前后联合入路对于中段颈椎是可行的，并且同样进行了9

56、年的随访。 前路寰枢椎脊索瘤有三种手术方法。1、双侧高位前入路可以清楚暴露颈2椎体和横突，但是齿状突暴露欠佳。2、前正中经口入路经或不经鄂部对于从斜坡向下直至颈3或者中线以内2厘米。但是如果肿瘤超过横突，则不能全切。Menezes2001年报道经咽入路切除了18例颅颈交界脊索瘤，他谨慎使用刮匙钻处理枕骨髁和寰椎侧块。作者未提供详细的放疗以及随后的治疗信息。至少一名患者术后10年无肿瘤进展。3、经下颌入路联合前入路可以提供理想的从斜坡至下颈椎的显露。这个入路暴露更为广泛，需要将咽喉壁翻开以便重建。Rhines等2005报道采用最广泛的暴露方法，采用右侧颈部切开，经下颌骨、舌周、咽后入路。 外科治疗第二十二页，共二