上肢周围神经综合征概述Author:Seward B Rutkove, MDSection Editor:Jeremy M Shefner, MD, PhDDeputy Editor:April F Eichler, MD, MPH译审:蒋超, 副主任医师Contributor Disclosures我们的所有专题都会依据新发表的证据和同行评议过程而更新。文献评审有效期至:2020-08.|专题最后更新日期:2019-12-18.There is a newer version of this topic available in English.该主题有一个新的英文版本。引言—上肢周围神经损伤的原因和程度差异很大。患者出现肩、臂或手疼痛、感觉缺失或无力时,需考虑到多种疾病:从轻度腕管综合征(carpal tunnel syndrome, CTS)到重度臂丛神经病。下肢周围神经综合征详见其他专题。(参见“下肢周围神经综合征概述”)解剖学—从脊髓C2及以下水平发出的神经根从各自的椎间孔穿出。C2-C4神经根在脊柱附近合并聚集,称为颈丛。颈丛发出的神经包括膈神经和耳大神经。虽然神经系统疾病一般不累及此区域,但是偶有病变会累及此区域,导致头部伸肌无力或膈肌麻痹。C5-T1神经根也从脊柱发出,并在近端发出小分支,参与形成支配前锯肌的胸长神经。然后这些神经根合并成复杂的结构,称为臂丛。解剖学家已界定了臂丛内的数个区域,包括干、股、束、支和近端神经,但是实际上了解各干、束和神经就足以对影响此区域的问题进行正确分类(图 1):●C5和C6神经根合成臂丛上干;C7神经根独自形成中干;C8和T1神经根合成下干。●上干的部分分支参与形成后束,剩余分支则形成外侧束;下干的部分分支也参与形成后束,剩余分支则形成内侧束;中干的部分分支参与形成外侧束,剩余部分参与形成后束。●臂丛外侧区会发出一些神经,从近端到远端包括肩胛背神经、肩胛上神经、肌皮神经以及(部分参与形成)正中神经。尺神经是臂丛内侧区的主要神经,而后束发出多条重要神经,包括腋神经、肩胛下神经、胸背神经以及最重要的桡神经。●在主要神经沿手臂下行的过程中,桡神经和正中神经又发出2条重要分支,分别为骨间后神经和骨间前神经。所有神经均向更远端发出多条分支,除了非常特殊的情况外,这些分支大多不具有临床意义。这些小分支将在临床独特综合征中讨论。发病机制—多种不同病程可能会局部影响正常神经功能,而多发性神经病等疾病会出现更广泛的神经元功能障碍。(参见“多发性神经病概述”)压迫—神经节段受压(包括神经失用和轴突中断)是最常影响上肢神经元结构的问题。神经受压可影响远端神经节段(如CTS中),但也可见于神经根水平极近端区域(例如,颈椎间盘突出压迫脊神经根)。任何卡压部位的病理过程都基本类似。一定程度的神经直接压迫及相关神经缺血在其中起到作用。●最轻微的表现可能是特定体位引发的间歇性症状,一种常见情况是CTS患者腕部弯曲时手部出现感觉异常,这最可能继发于暂时性神经缺血。●随着神经受到更一致、长期的压迫,可出现脱髓鞘。此时症状通常会持续存在,但常因某些运动或体位而恶化。疼痛和无力在早期一般极不明显,但此时越来越突出。●随着神经受压进展,出现Wallerian变性,远端神经节段将丧失功能。重度病例整个远端神经节段都会变性,类似于神经横断(参见下文‘横断’)。从生理学角度看,只要所有神经冲动能通过受压区进行传递,患者就会保持无症状。随着缺血或脱髓鞘的出现,神经传导首先会变慢并最终完全阻滞。神经传导变慢对生理学产生的影响极小;只有在神经元冲动传导完全阻滞时,才会出现功能性感觉缺失或肌无力。随着神经受压加重,越来越多的神经纤维传导会被阻滞。最终,几乎没有神经冲动能通过受压区,同时也开始发生远端神经元变性。横断—急性神经横断(神经断裂)比慢性神经受压要少见得多,可发生于手臂严重创伤时(例如刀伤),此时远端神经与近端神经完全分离。与重度神经受压不同的是,神经横断后每个神经细胞的基底膜不再保持完好,若不进行干预(即,再接手术),神经不可能再生。感觉和运动反应会完全丧失。神经缺血/梗死—神经梗死通常仅发生于血管炎和动脉粥样硬化性疾病。血管炎患者的神经梗死会导致轴突损伤,通常于特定区域发生。上肢某些神经往往最易受累:上臂正中神经和肘段近端的尺神经。(参见“血管炎性神经病的临床表现和诊断”)与压迫性神经病不同的是,神经传导速度并不会减慢。在出现局部神经梗死的数日内,整个远端神经节段都发生变性。但是由于基底膜保持完好,在控制基础疾病后神经可能再生。严重动脉粥样硬化性疾病偶尔也会产生类似表现。放射诱发性损伤—治疗区域包括臂丛的放疗可导致一过性、急性、自限性臂丛神经病。症状包括患侧拇指和食指麻木,以及肩部和肱二头肌无力。臂丛放疗也可引起更严重的迟发性臂丛神经病,表现为感觉异常、感觉减退、无力和反射受损,并可进展为慢性疼痛和进行性手臂瘫痪。该病发生之前的潜伏期不定,潜伏期可持续多年,且病变通常不可逆。主要的诊断困难在于区分放射诱发的迟发性臂丛神经病与肿瘤复发。(参见“臂丛神经综合征”,关于‘肿瘤性和放射诱发性臂丛神经病’一节)炎症—神经或神经根炎性过程也可导致显著的手臂问题。感染性疾病,如单纯疱疹病毒、EB病毒和最常见的带状疱疹病毒感染,均可引发感觉缺失和运动功能障碍综合征。特发性炎性反应也会造成臂丛神经炎综合征(神经痛性肌萎缩)。变性—某些疾病中可能发生神经元局灶变性。最引人关注的平山病(Hirayama disease)是一种局灶性运动神经元丢失,表现为数月期间单侧或双侧上肢进行性无力。这也可能是肌萎缩侧索硬化症的早期表现。(参见“肌萎缩侧索硬化症和其他类型运动神经元病的诊断”,关于‘单肢肌萎缩’一节)代谢性疾病—除了糖尿病或甲状腺功能减退间接性导致局灶神经病变外,代谢疾病通常不会造成局灶性神经病变。压迫性神经病(如CTS)在这类疾病中常见得多,其原因不明。糖尿病偶尔也会表现出血管炎样临床特征(糖尿病多数性单神经病)。(参见“糖尿病性神经病的流行病学和分类”)流行病学—CTS是最常见的单神经病,但不同研究人群的患病率有差异。一项荷兰的人群研究显示,临床CTS患者约占总人数的3.4%,而另外有5.8%的人虽未诊断但很可能存在该病[1]。该病更常见于女性,男性的总患病率仅为0.6%。另一项来自美国Mayo诊所的研究显示,该病的年发病率仅为99/100,000(0.1%),而男女患者比例为1:3[2]。颈神经根病也很常见。Mayo诊所的研究显示,1976-1990年间颈神经根病的平均发病率为83/100,000,男性发病率高于女性[3]。50-54岁人群的发病率最高,C6和C7神经根病变占病例总数的64%。根据Mayo诊所的病历记录,研究者也调查了臂丛神经炎的发病率。该病在12年间的年发病率仅为1.6/100,000[4]。以上数据可能低估了实际发病率,因为轻微的神经根病或臂丛神经炎患者可能从未就医或被误诊为肌肉骨骼损伤。临床表现—提示周围神经疾病的体征和症状详见其他专题。(参见“周围神经和肌肉疾病的鉴别诊断”)极轻度的上肢神经局灶异常可能在因其他原因(例如,检查是否有多发性神经病)进行电生理检查时发现。例如,尺神经跨肘部节段运动传导速度减慢可能符合极轻度的尺神经病。同样,年龄较大的无症状者可在电生理检查或MRI检查时发现颈神经根病或多发性神经根病的证据。然而,仅凭电生理检查和影像学检查结果通常不足以诊断特定的综合征。因此,若检测出正中神经跨腕段传导速度轻度减慢且无相关症状,可做出腕部轻度正中神经病的诊断,而非CTS的临床诊断。诊断性检查电生理检查—肌电图检查(electromyography, EMG)和神经传导检查(nerve conduction studies, NCS)仍是识别上肢神经疾病并对其进行分类的最有效方法。(参见“肌电图概述”和“神经传导检查概述”)EMG/NCS通常易发现正中神经、桡神经或尺神经的局部卡压。肌电图检查者对可能受累的神经节段进行检测(例如CTS患者腕部正中神经),以寻找脱髓鞘的证据(神经传导速度减慢和传导阻滞)。在尺神经病患者的肘段以及桡神经病患者的桡神经沟可能发现类似结果。EMG多为确诊性检查,能提示病变严重程度。对于神经丛病患者,通常在神经丛某一区域(例如上干)发出的数条神经中发现异常。出于技术原因,一般不对神经丛进行传导检查,因此无法寻找脱髓鞘的常见表现。相反,检查仅限于远端神经节段,并寻找有无轴突缺失。例如,在上干病变患者中,正中神经、桡神经和肌皮神经感觉反应波幅通常会降低。由于正中神经和尺神经标准运动检查均局限于下干支配的肌肉,所以检查结果往往是正常的。然而,针极EMG可以检测上干神经纤维支配的肌肉,检查可发现纤颤电位、正尖波以及慢性神经再支配。若下干出现问题,尺神经和前臂内侧皮神经的感觉反应会减弱,并且尺神经和正中神经运动检查会表现出异常。在C8-T1支配的肌肉中,EMG可发现去神经支配和慢性神经再支配的证据。在神经根病中,由于病灶位于后根神经节的近端,所以感觉反应不受影响。除非累及C8-T1神经根,否则运动检查往往也正常。通常只有针极EMG才能发现异常,受累神经根支配的肌肉存在异常。影像学检查—影像学检查是某些患者的首选初始检查。比如,有放射性颈部疼痛、第2-4指感觉缺失以及C7支配肌肉肌无力的患者可能最好先接受颈椎MRI检查。不过,在某些情况下,患者的主诉难以归类。疼痛可能是非局灶性的,肌无力极轻微,并且未发现固定的感觉缺失。在这种情况下,可能首先进行EMG,然后根据其结果,必要时对恰当区域进行影像学检查。一项研究发现,60%的病例中MRI与EMG结果保持一致,但是有40%的患者这两种检查结果不一致,表明这两种检查常可提供互补性信息[5]。X线平片检查效用一般有限,但有少数例外情况。●颈椎屈伸位X线平片有助于发现颈椎不稳,并且能推测退行性变的程度。某平面的椎间盘间隙消失可能提示椎间盘髓核突出。正常颈椎前凸变直可能提示椎旁肌痉挛。还可发现溶骨性病变。●当肺尖病变引发下干神经丛病时,胸部X线检查可能有助于确定病因。胸部X线片还可确定是否存在颈肋。(参见“臂丛神经综合征”)●很少需要行手臂远端平片检查,除非发生创伤或发现可触及的肿块病变。MRI已成为大多数神经系统成像的主要方法。对于颈椎疾病,MRI能确定椎间盘突出、退行性变以及某一神经根受压程度,因此该检查非常重要,尤其是考虑手术选择时。对于特发性神经丛病患者,可能有必要进行一次影像学检查,以排除该区域肿块病变的可能,尤其是对于症状恶化或具有肿瘤病史的患者。当EMG/NCS提示病灶具体定位后,偶尔也进行神经MRI检查。例如,某些急性发作的CTS患者通过腕部MRI发现肿瘤。超声已逐渐成为许多上肢神经系统疾病评估时的重要辅助工具。高分辨率超声尤其能提供神经压迫综合征(如CTS)方面的信息,局部神经增大似乎强烈提示局部病变。超声可能对炎症性和创伤性神经病检查有帮助,并且也可识别出神经的肿瘤性改变。(参见“神经肌肉病的超声诊断”,关于‘神经性病变的超声检查’一节)对于有起搏器或其他植入装置而不能接受MRI检查的患者,CT(尤其是联合脊髓造影)会有帮助。CT也可提供骨结构方面的有用信息。血清学检查—对于出现手臂局部症状的患者,血清学检查往往价值有限,不过,某些检查也值得考虑:●检查CTS患者的甲状腺功能●检查CTS患者的空腹血糖,尤其是可能伴有轻度多发性神经病的患者●对多发性神经根病患者进行莱姆抗体滴度试验,尤其是流行地区的患者●对多发单神经病(至少累及2个肢体)患者进行遗传性压迫易感性神经病基因检测对于多数性单神经病患者,还需进行多种其他实验室检查,以识别潜在疾病。(参见“非系统性血管炎性神经病的治疗和预后”)腰椎穿刺—有不寻常临床表现的神经根病患者需接受腰椎穿刺。应检查脑脊液(cerebrospinal fluid, CSF)是否有炎症证据(包括脑脊液蛋白水平和单个核细胞水平上升),还需进行针对莱姆病和梅毒的血清学检查。正中神经综合征腕管综合征—腕管是由上方的腕横韧带(屈肌支持带)和下方的腕骨构成(图 2)。正中神经及9根前臂屈肌腱一定会穿过该解剖管道(图 3)。CTS具有多种病理生理学因素,认为腕管内压力升高在CTS临床发病中起重要作用。(参见“腕管综合征的病因和流行病学”)CTS是最常见的上肢单神经病。症状通常包括正中神经支配区的疼痛性感觉异常,累及第1-3指以及第4指桡侧半(图 4)。这些症状通常会在夜间加剧,常使患者从睡眠中醒来。然而,该病具有广泛变异性。疼痛和感觉异常可能局限于腕部或累及整个手部。感觉症状常向近端放射至前臂,少数情况下放射至肘部以上至肩部。随着正中神经卡压加剧,患者可出现固定的感觉缺失和无力。(参见“腕管综合征的临床表现和诊断”)CTS的治疗包括采用腕部夹板固定的保守治疗,尤其是在夜间或进行可加剧症状的活动时。当保守治疗无效时,向腕部注射类固醇往往有助于缓解症状(大多数病例至少可获得暂时缓解)。手术松解屈肌支持带适用于保守治疗无效且持续存在症状的患者,手术效果通常极佳。(参见“腕管综合征的治疗和预后”)旋前圆肌综合征—正中神经卡压偶尔发生于前臂近端神经穿过旋前圆肌的部位。此综合征罕见,一般见于体能活跃者,如专业自行车骑手。患者可能出现前臂疼痛和整个外侧手掌感觉缺失。鱼际感觉缺失也很典型,据此可与CTS相区分,CTS中鱼际区域感觉正常。电生理检查能够发现前臂传导速度减慢,病情严重者可出现传导阻滞。针极检查可发现正中神经支配的前臂肌肉(包括桡侧腕屈肌)存在异常。旋前圆肌综合征的治疗通常需要减少促发症状的活动。非甾体类抗炎药可一定程度缓解疼痛;若疼痛持续,向旋前圆肌压痛部位注射皮质类固醇和局部麻醉剂(10-20mg醋酸甲泼尼龙加1mL的1%盐酸利多卡因,采用23G或25G针头)有所帮助。若采取以上治疗措施后仍持续存在失能数月,可考虑旋前圆肌内神经减压术。骨间前神经病变—正中神经在肘部发出分支形成骨间前神经。骨间前神经然后沿前臂前部下行,负责支配以下肌肉:拇长屈肌、第2和第3指深屈肌以及旋前方肌。骨间前神经并不参与皮肤感觉,因此该神经功能障碍仅以这组肌肉无力为特征。体格检查时,患者无法用拇指和食指做出标准的“O”形(“okay”手势)。单纯骨间前神经损伤非常罕见,但可见于严重的前臂创伤。骨间前神经病更常见于神经痛性肌萎缩(臂丛神经炎)患者。(参见下文‘臂丛神经病’)其他疾病—一些成人的肱骨远端附着有一条小韧带(Struthers韧带),罕见情况下,更近端的正中神经受压可发生在这些人的肘部稍上方区域。血管炎性病变患者在类似的肘部近端区域最易出现正中神经梗死。临床检查若发现正中神经和骨间前神经支配的多个肌肉出现肌无力,则有助于这两种疾病的诊断。电生理检查也会发现这些肌肉存在纤颤电位和正波。感觉缺失仍局限于手外侧面。尺神经综合征肘部和腕部尺神经病—肘部和腕部尺神经病将简要总结在此,详细内容见其他专题。(参见“肘部与腕部尺神经病变”)肘部尺神经病(图 5)是影响上肢的第二常见压迫性神经病。轻度病例的症状包括第4指和第5指感觉缺失和感觉异常(图 6)。更严重的患者会出现明显的手部骨间肌无力,患者或许会诉握力减弱和动作笨拙。肘部疼痛也较常见,不过并非普遍现象。尺神经支配的前臂肌肉受累会导致手指和腕屈曲无力。(参见“肘部与腕部尺神经病变”,关于‘临床特征’一节和“肘部与腕部尺神经病变”,关于‘肘部尺神经病变’一节)腕部偶尔会出现尺神经受压(图 7)。与正中神经一样,尺神经也穿过腕部,其穿行管道称为腕尺管(Guyon's canal)。神经受压可发生于腕尺管内或其远端(手的近端区域)。腕部尺神经受压的临床表现可能与肘部受压类似:骨间肌无力以及第4指和第5指感觉缺失和感觉异常。不过,该综合征患者受尺神经支配的手指屈肌不受影响,某些患者小鱼际肌的受累程度要轻于其他手部肌肉,如第一骨间背侧肌。(参见“肘部与腕部尺神经病变”,关于‘腕部尺神经病变’一节)多数情况下,若根据临床症状或体征怀疑有尺神经病变,可通过电生理检查或影像学检查确诊。有一些激发手法可用于检测尺神经病,但是这些手法的敏感性和特异性似乎欠佳。(参见“肘部与腕部尺神经病变”,关于‘诊断’一节)对于通常表现为间歇性感觉症状并且电生理检查发现跨肘传导速度减慢的轻度尺神经病患者,保守治疗常能改善病情,或者病情可维持稳定数年。有持续性感觉缺失和肌无力但无萎缩的患者通常发病较急(有时具有较轻微的间歇性症状既往史),而且电生理检查常会发现兼有传导阻滞和传导速度减慢。这类患者通常在3-6个月内出现临床及电生理指标改善。肌无力和麻木症状持续超过6个月的患者应考虑手术干预。(参见“肘部与腕部尺神经病变”,关于‘治疗’一节和“肘部与腕部尺神经病变”,关于‘保守治疗’一节)应根据临床情况和影像学检查结果来治疗腕部尺神经病。对于有创伤性病因或外在/内在神经受压证据的患者,应考虑手术治疗。肘部或腕部尺神经病引起重度肌无力、萎缩和持续性感觉缺失的患者,其电生理检查会发现轴突损伤的证据。对于较年轻患者或急性发病(<6个月)患者,应考虑转至外科。然而,对于年龄较大或医学状况欠佳的患者以及慢性(2年或以上)重度受累的患者,手术干预的益处不太确定。(参见“肘部与腕部尺神经病变”,关于‘手术治疗’一节)其他综合征—尺神经穿出肘管的位置偶尔会发生尺神经病。糖尿病患者中,尺神经病可发生于前臂。在血管炎性病变中,尺神经梗死通常发生于肘部近端。桡神经综合征桡神经沟的桡神经病变—桡神经沿上臂内侧下行,之后绕过肱骨中段,靠后方走行。桡神经靠近肱骨走行的区域称为桡神经沟,桡神经极易在此处受压。长时间施压常会使该区域的神经受压。“周末晚麻痹(Saturday night palsy)”指的就是这种疾病,因为醉酒的人常出现此问题。体格检查时可见肱三头肌肌力正常,但腕伸肌无力(即“腕下垂”)、手指伸肌无力且肱桡肌无力。患者还可能出现手背感觉缺失,并可能向上延伸至前臂后侧。确定细微肱桡肌无力的最佳方法是让患者前臂保持在介于旋前与旋后中间的姿势(“锤桌”姿势),接着要求患者对抗阻力屈曲前臂,然后通过触诊来评估患侧肌肉体积,并与健侧相对比。患者也常伴有尺神经支配的手部肌肉无力和拇指外展无力,前者很可能与手指伸肌维稳作用缺失情况下动作执行困难相关。因为拇长展肌属于桡神经支配的肌肉,所以拇指外展受累。有时难以区分桡神经沟急性桡神经病与导致手臂无力的中枢神经系统病变。大多数导致手臂无力的中枢神经系统疾病对伸肌的影响往往大于对屈肌的影响。因此,腕部伸展无力(即腕下垂)和手指伸展无力的病因不太明确,可能是急性桡神经病,也可能是中枢神经系统病变。肱三头肌肌力相对保留以及局限于手背的感觉缺失是有助于提示桡神经沟桡神经病的表现。最重要的是,桡神经病也会导致肱桡肌无力,而中枢神经系统疾病对肱桡肌的影响往往较小。骨间后神经病变—桡神经在肘部近端发出分支形成骨间后神经,支配前臂伸肌。桡神经沿前臂下行形成不含运动成分的桡神经浅支,为手背提供皮肤感觉。大多数情况下,骨间后神经病仅表现为明显疼痛。伸展中指诱发疼痛,通过神经阻滞能缓解疼痛,这两点有助于识别轻微病变[6]。重度外上髁炎(网球肘)患者的持续性疼痛是由于该区域神经受压。(参见“肱骨上髁炎(网球肘和高尔夫球肘)”)与骨间前神经病变类似,骨间后神经病变也可以是臂丛神经炎的一部分。(参见下文‘臂丛神经病’)若手指伸肌无力患者的更近端肌肉(包括肱桡肌和桡侧腕伸肌)肌力保留,也应考虑骨间后神经病变。对于严重病例,详细检查可能发现患者腕伸展时腕部向桡侧偏斜,其原因是尺侧腕伸肌受累而桡侧腕伸肌肌力得以保留。前臂旋后也无力。治疗—对于单次压迫性桡神经损伤(例如,桡神经周末晚麻痹)患者,通常采用保守治疗。物理治疗、腕部夹板固定(以保持腕部功能)以及疼痛管理最为重要。预后通常较好,可完全康复。一项纳入51例压迫性桡神经病变患者的回顾性研究中,23例可获得随访数据,在平均3.4个月期间(范围0.5-6个月),这23例患者均达到完全临床恢复[7]。创伤所致严重神经损伤的患者可能需后续检查和EMG。重度进行性神经受压或神经横断可能难以与受创时神经损伤的单次发作相区分。若临床上或电生理学均未见任何改善,则需要进一步影像学检查或手术探查。对于确诊的前臂骨间后神经病变患者,神经减压术外科干预有所帮助[6]。不过,也应考虑神经痛性肌萎缩的可能。(参见“臂丛神经综合征”,关于‘神经痛性肌萎缩’一节)近端神经病变—其他多种单纯性局部神经病变可能影响上肢,包括肩胛上神经病变、胸长神经病变以及腋神经病变,这些疾病少见。肩胛上神经病变和腋神经病变可能表现为手臂外展和外旋无力;胸长神经病变通常会导致翼状肩胛(图片 1)。感觉缺失和感觉异常仅见于腋神经病变。这些疾病通常都会出现疼痛。EMG和NCS会发现异常局限于受累神经支配的肌肉。肩胛上神经病变—肩胛上神经起自臂丛上干(图 1),发出感觉支到盂肱关节和肩锁关节,并发出运动支支配冈上肌和冈下肌。肩胛上神经损伤最常见的病因是肩胛上切迹处神经卡压,其次是冈盂切迹处神经卡压[8]。大多数肩胛上切迹神经卡压患者都会出现明显的肩部疼痛,并伴有冈上肌(肩外展)无力和冈下肌(肩外旋)无力。肌萎缩也可能较明显。相比之下,冈盂切迹水平发生的肩胛上神经损伤会导致无痛性肩外旋无力以及冈下肌萎缩。直接创伤是肩胛上神经病变的常见病因,例如橄榄球比赛中擒抱并摔倒(对方抱球球员)、跌倒或肩袖撕裂引起的[8,9]。拉伸、牵引或重复动作的活动也可损伤神经,正如报道显示,举重、排球、棒球和体操运动员发生过肩胛上神经损伤[10-12]。少数情况下,肩胛上神经可因肿块(如腱鞘囊肿或肿瘤)压迫而损伤。一项研究纳入了27例MRI显示有神经周肿块的肩胛上神经卡压患者,其中腱鞘囊肿21例,恶性肿瘤5例[13]。根据疼痛、肌无力、肌萎缩以及肩胛胸运动受限等临床表现可怀疑为肩胛上神经卡压。虽然电生理检查和影像学检查可能有助于确诊临床疾病,但是许多疑似肩胛上神经卡压病例的检查结果均呈阴性。因此,有必要继续进行临床观察。治疗和预后因神经损伤类型不同而异[8]。对于重复创伤患者,避免诱发性运动常常足以使患者恢复,配合物理治疗和锻炼维持关节活动度并强化肩部和肩袖肌力。对于保守治疗无法缓解病情的患者,可考虑肩胛横韧带松解手术和关节镜肩胛上神经减压术[14-16]。手术切除适用于有囊肿或肿瘤的患者。胸长神经病变—胸长神经是一条单纯运动神经,起自第5、第6和第7颈神经根(图 1)。胸长神经功能障碍会导致前锯肌麻痹,从而形成翼状肩胛。检查翼状肩胛时,患者伸展双臂并按压墙面,从后方看,受累的肩胛骨会从胸部突出(图片 1)。胸长神经损伤的主要原因如下[8,17]:●神经痛性肌萎缩●创伤或受压●重复性运动拉伸或牵引神经典型神经痛性肌萎缩的特征为:臂丛干、束或多条神经支配区剧烈疼痛发作,然后出现斑片状无力,通常伴有翼状肩胛。某些神经痛性肌萎缩病例是单纯的胸长神经病变。(参见“臂丛神经综合征”,关于‘神经痛性肌萎缩’一节)肩部或侧胸壁遭受直接打击(例如,橄榄球运动)或侵入性操作(例如,第1肋骨切除术、乳房切除联合腋窝淋巴结清扫术、斜角肌切除术、放置胸管、锁骨下神经丛麻醉以及心胸外科手术)可导致胸长神经创伤[8,18,19]。某些术后发病的病例可能因麻醉中固定上臂位置导致神经血管受压或牵引所致。据推测,神经受压是搬运重物(例如,用肩背背包)引发神经损伤的机制。体育运动或体力劳动相关的重复性动作可能导致神经拉伸或牵引,尤其是手臂处于高于头、伸展的姿势,而整脊手法偶尔也会导致神经拉伸或牵引[20]。治疗和预后随神经损伤机制不同而有差异[8]。神经痛性肌萎缩恢复缓慢,需要1-3年时间(参见“臂丛神经综合征”,关于‘神经痛性肌萎缩’一节)。搬运或重复性活动引起的胸长神经损伤大多为不完全损伤,可在6-24个月内自行消退。患者应避免诱发性运动以及避免用肩搬运重物[8]。物理治疗和锻炼对保持关节活动度以及强化斜方肌和菱形肌而言很重要。创伤引起的胸长神经损伤通常较严重,且恢复程度有限或根本不会恢复。对于功能无法恢复的患者,可以选择手术治疗[8,21,22]。这些手术包括肌肉转移和筋膜移植的各种联合术(例如,胸大肌胸骨头转移)。也有一些病例报告称,使用胸背神经或胸内侧神经进行神经移位获得了成功[23,24]。然而,单纯前锯肌无力引发的功能受限大多相对轻微,无需手术干预。腋神经病变—腋神经源自臂丛后束(图 1),发出皮肤感觉纤维至肩外侧的椭圆区域,并支配三角肌(肩外展)和小圆肌(肩外旋)。腋神经病变最常见的病因是创伤,通常由肩关节脱位或肱骨骨折引起[8]。全身麻醉或手臂高于头部的俯卧睡姿也可引发腋神经病变。此外,四边孔内偶尔会发生神经卡压,四边孔的上界为小圆肌,外侧界为肱骨,内侧界为肱三头肌长头,下界为大圆肌[25,26]。腋神经受累也可以是神经痛性肌萎缩综合征的一部分,但很少单独发病。腋神经病变的临床特征包括肩外侧出现边界清楚的感觉缺失区域[8]。由于其他肌肉可协助肩外展和外旋,所以肌无力的程度各异,但重度肌无力较少见。保守治疗包括旨在保持关节活动度的物理治疗和锻炼。不完全神经损伤患者通常需要3-4个月恢复。重度病变患者、保守治疗的最初数月未见缓解的患者[27,28]以及复发性肩关节脱位的患者,可选择包括神经移植术在内的手术干预。脊髓副神经病变—脊髓副神经是从上颈神经根发出的颅神经,负责支配胸锁乳突肌和斜方肌,斜方肌的主要功能在于维持肩关节稳定。单纯性脊髓副神经病变最常见的原因包括颈后三角颈淋巴结活检以及颈全清扫术等局部手术[29]。钝性神经损伤也很常见(例如由体育运动或搏斗所致)。一份报告显示,大力按摩引起过脊髓副神经病变[30]。副神经病变的临床表现包括患侧肩部下垂或肩胛带压低以及外展无力[29,31]。更近端的脊髓副神经病变会出现胸锁乳突肌萎缩和无力,而更远端的病变会导致斜方肌萎缩和无力。临床特征不包括感觉缺失,这是因为脊髓副神经是单纯运动神经。然而,患者常会出现疼痛,这可能是臂丛受牵引造成的[29]。通常会观察到明显的翼状肩胛[17]。检查肩部无力最简单的方法是让患者手臂外展至180°,副神经病变患者无法完成后90°的手臂外展动作。重要的是,由于肩部不稳定,所以无法准确评估三角肌、菱形肌和前锯肌等其他肩部肌肉的肌力。预后随病因不同而异。对于较严重的病变,肌肉转移有助于稳定肩胛骨和改善功能。肌皮神经病变—肌皮神经起自臂丛外侧束,包含C5、C6和C7神经根发出的神经纤维。肌皮神经穿过喙肱肌后,沿手臂前侧在肱二头肌与肱肌之间下行,继续前行进入前臂成为前臂外侧皮神经。肌皮神经支配喙肱肌、肱二头肌和肱肌,并为前臂外侧提供皮肤感觉。因此,肌皮神经病变的临床特征包括屈肘无力,并伴前臂外侧感觉缺失。单纯性肌皮神经病变较罕见,但直接创伤、肩关节脱位、剧烈运动或麻醉过程中手臂位置不正均可损伤此神经[32-35]。该病通常适合保守治疗[35]。若保守治疗无效,外科减压术可能有帮助[35,36]。臂丛神经病—臂丛(图 1)是周围神经系统中最复杂的结构[37],易受创伤,或可能因相邻结构病变而继发受损。大多数臂丛疾病呈区域性受累,而非整个臂丛受累。(参见“臂丛神经综合征”)将疾病定位于臂丛的具体区域通常是诊治臂丛神经病患者最重要的第一步。一旦成功定位,确定具体病因往往变得相对简单。一些简单的规律能有助于准确定位臂丛病灶。●肌无力一般呈“肌节”模式分布:C8-T1肌肉无力表明臂丛下干/内侧束可能出现问题;C5和C6肌肉无力可能是臂丛上干/外侧束出现问题;局限于单一神经的肌无力不太可能由臂丛神经病变引起,但臂丛神经炎除外。●桡神经或腋神经支配的肌肉(例如三角肌、肱三头肌、肱桡肌、腕伸肌及腕屈肌)受累与臂丛后束受累相符。●几乎没有单纯的臂丛中干病变,通常会同时出现臂丛下干或上干一定程度受累。C7神经根病的可能性明显更高。●延伸至前臂内侧的固定感觉缺失符合臂丛下干/内侧束病变;延伸至前臂外侧的感觉缺失符合臂丛上干/外侧束病变。这些区域的皮肤受臂丛直接发出的神经分支支配。●前锯肌无力(导致翼状肩胛)、棘肌无力(导致手臂外旋无力和手臂外展初始无力)或菱形肌无力(肩胛回缩和上抬)更有可能是神经根病或是神经根病的一部分,因为这些肌肉均受臂丛极近端分支或脊神经本身的分支所支配。一个重要例外是臂丛神经炎,因为前锯肌往往会受累。臂丛的具体疾病详见其他专题。(参见“臂丛神经综合征”)颈神经根病—神经根病是一种累及神经根的病理过程。颈神经根病是急性和慢性颈痛的常见原因。该病将简要总结在此,详细内容参见其他专题。(参见“颈神经根病的临床特点和诊断”)大多数神经根病由神经根受压引起。压迫性颈神经根病的发病机制主要有两种,分别是颈椎病和颈椎间盘突出症。低位颈神经根(尤其是C7神经根)比高位颈神经根更常受压。非压迫性神经根病的一些病因包括感染(尤其是带状疱疹和莱姆病)、神经根梗死、肿瘤浸润、肉芽肿组织浸润、根性撕脱伤和脱髓鞘。几乎所有颈神经根病患者都会出现颈部、肩部或手臂疼痛,但疼痛通常不能协助准确定位病变神经根水平。疼痛可能是非典型的,可表现为胸痛(假心绞痛)、乳房疼痛或面部疼痛。头部转动、咳嗽或打喷嚏可能会加重症状。对于疑似颈神经根病患者,神经系统评估的主要目的在于发现肌节和皮区分布模式的肌无力和感觉障碍。单纯性神经根病变的典型临床表现总结在表中(表 1)。若出现提示神经根损伤的局部体征和症状,或出现保守治疗无法缓解的持续性症状,则需进行神经影像学检查和电生理检查。治疗—颈神经根病患者的治疗详见其他专题。(参见“颈神经根病的治疗和预后”)其他局灶性肌萎缩—局灶性或单肢肌萎缩(包括平山病)是一种以单个肢体单纯运动无力为特征的罕见疾病(一些平山病病例出现双侧肢体症状),是一种局限性运动神经元病。(参见“肌萎缩侧索硬化症和其他类型运动神经元病的诊断”,关于‘单肢肌萎缩’一节)多数性单神经病—累及多条神经的缺血性病变可能会引起令人混淆的临床表现。尽管如此,大多数患者存在分布更广(包括双腿)的神经受累。治疗基础疾病仍是多数性单神经病的治疗原则。尽管最初的神经损伤很严重,但只要患者的疾病类型对免疫抑制疗法有反应,那么患者的恢复情况会很好。不同病因(包括Churg-Strauss病、类风湿关节炎、Wegener肉芽肿病等)的血管炎患者均可通过免疫抑制治疗显著改善神经系统失能。血管炎(系统性受累或仅限于神经受累)引起的多数性单神经病详见其他专题。(参见“血管炎性神经病的临床表现和诊断”)多灶性运动神经病—多灶性运动神经病(multifocal motor neuropath, MMN)也称多灶性运动神经病伴传导阻滞,是一种罕见的免疫介导性脱髓鞘神经病变,其特征为进行性不对称性肌无力和肌萎缩但不伴感觉异常,该表现与运动神经元病表现相似。(参见“多灶性运动神经病”)MMN最常为亚急性发病,症状为非对称性肌无力,同时出现手臂和手部肌无力的下运动神经元体征,但不伴感觉缺失。MMN中的神经元受累通常为斑片状,一些神经不受累而另一些神经严重受累。运动神经传导检查通常会发现传导阻滞的证据。同一神经节段的感觉神经传导正常。30%-80%的患者会出现抗GM1抗体滴度升高。(参见“多灶性运动神经病”,关于‘临床特征’一节)静脉用免疫球蛋白和其他形式的免疫抑制疗法可治疗MMN。(参见“多灶性运动神经病”,关于‘治疗’一节)带状疱疹性神经根神经节炎—除疼痛性皮疹外,带状疱疹患者还可能出现与皮疹分布接近的神经分布区的肌无力和感觉缺失。炎症可累及神经根和后根神经节,可能导致明显的神经源性损伤。偶尔还会出现相关的脊髓病。总结●上肢周围神经损伤的主要机制是压迫、横断、缺血、炎症、神经元变性以及辐射暴露。(参见上文‘发病机制’)●腕管综合征(CTS)是最常见的影响上肢的单神经病,其次是肘部尺神经病。颈神经根病也很常见。(参见上文‘流行病学’)●肌电图(EMG)和神经传导检查(NCS)有助于识别上肢周围神经疾病并对其进行分类。(参见上文‘诊断性检查’)●典型CTS的特点是正中神经支配区域疼痛或感觉异常,并累及手部外侧(图 4)。这些症状通常会在夜间加剧,常会使患者从睡眠中醒来。保守治疗包括腕部夹板固定,而保守治疗无效的中至重度CTS患者可选择接受糖皮质激素注射和手术松解。(参见上文‘腕管综合征’)●罕见的正中神经综合征包括正中神经穿过旋前圆肌处被卡压,以及正中神经在肘部发出的骨间前神经的单纯性损伤。(参见上文‘旋前圆肌综合征’和‘骨间前神经病变’)●肘部尺神经病(图 5)是影响上肢的第二常见压迫性神经病。轻度病例的症状包括第4指和第5指感觉缺失和感觉异常(图 6)。较严重的病例会出现手部骨间肌无力。偶见腕部尺神经受压(图 7),其临床表现类似于肘部尺神经受压。然而,该综合征患者尺神经支配的手指屈肌不受累。通常,轻度肘部尺神经病经保守治疗可获得改善,或保持稳定。肌无力和麻木症状持续超过6个月的患者应考虑手术干预。(参见上文‘尺神经综合征’)●桡神经容易在其靠近肱骨走行的区域(即桡神经沟)受压。肱三头肌肌力正常,但是会出现腕伸肌无力(即腕下垂)、指伸肌无力和肱桡肌无力。患者也可出现手背感觉缺失,并可能向上延伸至前臂后侧。骨间后神经病患者通常会出现前臂疼痛和手指背屈无力。对于桡神经单次压迫性损伤患者,一般采用保守治疗。对于确诊的前臂骨间后神经病患者,在排除神经痛性肌萎缩后,行神经减压术外科干预有所帮助。(参见上文‘桡神经综合征’)●上肢近端局灶性神经病变包括肩胛上神经病变、胸长神经病变和腋神经病变。(参见上文‘近端神经病变’)●臂丛(图 1)易受创伤,并可能因邻近结构病变而继发性受损。大多数臂丛神经病呈区域性受累,而非整个臂丛受累。(参见上文‘臂丛神经病’)●颈神经根病是急性和慢性颈部疼痛的常见病因。大多数神经根病的病因是颈椎病和/或颈椎间盘突出症导致的神经根受压。低位颈神经根(尤其是C7神经根)更常受压。非压迫性神经根病的一些病因包括感染(尤其是带状疱疹和莱姆病)、神经根梗死、肿瘤浸润、肉芽肿组织浸润、根性撕脱伤和脱髓鞘。单纯性神经根病变的典型临床表现总结在表中(表 1)。(参见上文‘颈神经根病’)●其他影响上肢的少见周围神经综合征包括局灶性肌萎缩、多数性单神经病、多灶性运动神经病(MMN)以及带状疱疹性神经根神经节炎。(参见上文‘其他’)使用UpToDate临床顾问须遵循用户协议.参考文献de Krom MC, Knipschild PG, Kester AD, et al. 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引言—脊髓损伤(spinal cord injury, SCI)是常见事件;在美国,创伤性脊髓损伤的发病率约为每年54例/100万人,2017年,创伤性脊髓损伤的幸存者约有280,000例[1]。尚不
Fibrodysplasia ossificans progressiva进行性骨化性纤维发育不良 (Fibrodysplasia ossificans progressiva)Author:John E Tis, MDSection Editor:William A Phillips, MDDeputy Editor:Mary M Torchia, MDContributor DisclosuresLiterature review current through:Jul 2020.|This topic last updated:Aug 14, 2019.Topic Outline·SUMMARY AND RECOMMENDATIONS·INTRODUCTION·EPIDEMIOLOGY·PATHOGENESIS·CLINICAL FEATURES·LABORATORY FEATURES·RADIOGRAPHIC FINDINGS·DIAGNOSIS·DIFFERENTIAL DIAGNOSIS·MANAGEMENT·Prevention of flare-ups·Avoid biopsies, surgery, and trauma·Prevention of falls·Prevention of viral illnesses·Immunizations·Glucocorticoid prophylaxis·Symptomatic management of early lesions·Preventive dental care·Hearing evaluation·Respiratory health·PROGNOSIS·SUMMARY AND RECOMMENDATIONS·REFERENCEINTRODUCTION—Fibrodysplasia ossificans progressiva (FOP; MIM #135100; also called myositis ossificans progressiva or "stone man disease") is a rare connective tissue disorder characterized by severe, progressive heterotopic ossification of soft tissues that spans joints and results in an ectopic skeleton [1]. It severely decreases mobility and causes significant disability with no effective treatment.The clinical features and treatment of FOP will be reviewed here. Heterotopic ossification as a complication of surgery or trauma is discussed separately. (See "Complications of total hip arthroplasty", section on 'Heterotopic ossification'and "Surgical management of severe lower extremity injury", section on 'Heterotopic ossification'and "Surgical management of severe lower extremity injury".)EPIDEMIOLOGY—The prevalence is approximately 1 in 2 million with no sex, racial, ethnic, or geographic predisposition [1]. There are no known risk factors.PATHOGENESIS—FOP is caused by mutations in the ACVR1/ALK2gene on chromosome 2q24, which encodes activin A receptor type I/activin-like kinase 2, a bone morphogenetic protein type I receptor [2]. Most cases are sporadic, but autosomal dominant germline transmission has been reported in a small number of cases.CLINICAL FEATURES—Patients with FOP generally appear normal at birth except for bilateral malformation of the great toes, which are characteristically short and laterally deviated (hallux valgus); the first metatarsals are malformed and the first toes have an absent or fused interphalangeal joint [1] (picture 1).Variable clinical features of FOP include short, malformed thumbs (in approximately 50 percent), clinodactyly, neck stiffness, and hearing loss (in approximately 50 percent) [3,4].Sporadic, painful episodes of rapidly progressive soft tissue swelling ("flare-ups") typically begin during the first decade of life [4-7]. These usually present as nodules on the head or back and occur at a median age of 1.5 years, although 10 percent of patients present with nodules in the neonatal period [8]. The soft tissue swellings may resolve but more often transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into ribbons, sheets, or plates of heterotopic bone [9]. Flare-ups may be precipitated by soft tissue injury, intramuscular injection, surgical incisions, falls, muscular stretching, or viral illness [10]. They typically begin in the head, neck, and shoulders and progress from cranial to caudal, dorsal to ventral, axial to appendicular, and proximal to distal [4]. The diaphragm, tongue, extraocular muscles, cardiac muscles, and smooth muscles are spared.FOP lesions go through predictable stages. Pain, erythema, tenderness, swelling, and warmth are present in the first few weeks. During the intermediate stage, induration increases but pain and erythema improve. During the late stage (after 12 weeks), the nodule hardens with radiographic ossification, but the swelling resolves [11]. In a survey of 44 patients with FOP, the average age of onset of heterotopic ossification was 5 years, restrictive ossification was present in 80 percent of patients by age 7, and 95 percent of patients had severely restricted motion in the upper extremity by age 15 [12].The heterotopic bone eventually extends across joints, resulting in progressive and irreversible immobility, weight loss (secondary to ankylosis of the jaw), and thoracic insufficiency syndrome (image 1). Patients are dependent upon diaphragmatic breathing because the diaphragm is spared. Most patients die of respiratory depression or pneumonia. Starvation (related to ankylosis of the jaw) used to be a common cause of death, but modern feeding tubes have made starvation a less common cause of death. (See 'Prognosis'below.)LABORATORY FEATURES—Biochemical studies (eg, serum alkaline phosphatase, parathyroid hormone level, renal function, urinary calcium, and phosphate) are usually normal [13]. Alkaline phosphatase is elevated in some patients during new episodes of heterotopic ossification formation [14].RADIOGRAPHIC FINDINGS—Characteristic radiographic features of FOP include joint malformations, particularly of the great toe (eg, bilateral hallux valgus deformity, malformed first metatarsal, absent or fused interphalangeal joint), and soft tissue ossification [3]. Preosseous lesions and early heterotopic ossification are visible on bone scan, computed tomography, or magnetic resonance imaging before radiographs [13,15].Variable radiographic features of FOP include proximal medial tibial osteochondromas (approximately 90 percent); orthotopic fusions of the posterior elements of the cervical spine (approximately 80 percent); broad, short femoral necks (approximately 50 percent); and malformations of the thumbs (approximately 50 percent) [1,3].DIAGNOSIS—FOP is a clinical diagnosis that is confirmed with molecular genetics. FOP should be suspected in children with hallux valgus, progressive soft tissue swelling, and nodules on the head or back. Biopsy of the soft tissue lesions may precipitate a flare-up and should be avoided [10,16].Definitive diagnosis requires genetic confirmation with specific molecular genetic studies that detect missense mutations or "in frame" deletions in the protein-encoding region of the ACVR1gene [3,8,17]. Consultation with a clinical geneticist is recommended before genetic testing [16].DIFFERENTIAL DIAGNOSIS—The differential diagnosis of FOP includes other conditions associated with malformed great toes, soft tissue swelling, or heterotopic ossification. The combination of these three findings generally distinguishes FOP from these conditions.●Other conditions with malformed great toes– Other conditions associated with malformed great toes include isolated congenital malformations, brachydactyly, synostosis and symphalangism syndromes (ie, fusion of bones and joints of the fingers or toes), and juvenile bunions [3,18]. In contrast to these conditions, children with FOP often have other skeletal malformations (eg, malformations of the thumb, cervical spine abnormalities, osteochondromas of the proximal medial tibia), rapidly progressive soft tissue swelling, and heterotopic ossification [3]. Juvenile bunions are not present in the neonatal period, whereas the hallux valgus deformity in FOP is present at birth.●Other conditions with femoral or tibial osteochondromas– Distal femoral and proximal tibial osteochondromas also may occur in patients with hereditary multiple osteochondromas [19]. However, patients with hereditary multiple osteochondromas do not typically have malformed great toes or episodic flare-ups. (See "Nonmalignant bone lesions in children and adolescents", section on 'Osteochondroma and hereditary multiple osteochondromas'.)●Other conditions with heterotopic ossification– Heterotopic ossification also may occur in children with progressive osseous heteroplasia (POH; MIM #166350), a rare genetic condition characterized by cutaneous ossification that progresses to involve subcutaneous and deep connective tissues [1]. POH is distinguished from FOP by the sites of ossification and lack of great toe malformation and "flare-ups." Although acquired heterotopic ossification also occurs at sites of trauma, it is rare in young children and not usually associated with great toe malformation or flare-ups.●Other conditions with rapidly progressive soft tissue lesions– Rapidly progressive soft tissue lesions may raise concern for neoplasms and other tumors (eg, soft tissue sarcoma, osteosarcoma, aggressive juvenile fibromatosis [extra-abdominal desmoid tumors]) or lymphedema [3,19]. However, the sudden onset and rapid change in size and shape (often within hours) of soft tissue lesions associated with FOP is not characteristic of these conditions. Evaluation of the great toes and consideration of FOP should be considered before biopsy is performed. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Clinical presentation'and "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation, diagnosis, and histology", section on 'Clinical presentation'and "Desmoid tumors: Epidemiology, risk factors, molecular pathogenesis, clinical presentation, diagnosis, and local therapy", section on 'Clinical presentation and diagnosis'.)MANAGEMENT—There is no medical or surgical treatment to prevent or reverse the ossification associated with FOP. Instead, management of FOP is supportive and focuses on prevention of flare-ups, patient and family education and counseling, and improved quality of life.Children with FOP should be managed in consultation with an expert in FOP. Consensus guidelines from the International Clinical Council on FOP (ICC) and consultants for the medical management of FOP are available on the International Fibrodysplasia Ossificans Progressiva Association website[16].Prevention of flare-upsAvoid biopsies, surgery, and trauma—Biopsies and removal of lesions are contraindicated because they precipitate aggressive ossific reaction in the soft tissues. Similarly, correction of fixed deformities often leads to further ossification and loss of motion [4].Attempts at resecting the ankylosis across the jaw have been unsuccessful and are not recommended [20,21]. Scoliosis is usually not addressed surgically because spinal fusion, especially posterior fusion, in younger patients generally results in worsening of the curve [22]. However, rapidly progressive lumbar curves in children younger than five years of age may warrant anterior, with or without posterior, surgical treatment to prevent progression [23].FOP patients have increased anesthetic risks due to restrictive lung disease, fused cervical vertebrae, restricted oral access, and abnormal cardiac conduction. Considerations for general anesthesia in patients with FOP are provided in the ICC guidelines[16].Prevention of falls—Falls may lead to injury and painful flare-ups. In a survey of 135 patients with FOP, 81 percent reported an injury related to a fall; two-thirds of falls led to painful flare-ups and one-half of falls led to permanent disability [24]. Strategies to prevent falls include limiting high-risk activities, installing handholds and other safety measures in living spaces, and the use of headgear [16].Prevention of viral illnesses—Viral illnesses can cause flare-ups of FOP [25]. Strategies to prevent viral illness include frequent washing of the hands with soap and water or an alcohol-based hand sanitizer; not touching the eyes, nose, or mouth with hands unless the hands are washed; and limiting contact with people who are sick [16,26]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Hand hygiene'.)Immunizations●Influenza vaccine– Influenza infections may trigger flare-ups of FOP [25]. The ICC suggests annual influenza vaccination for patients with FOP, with specific caveats [16]:The live attenuated influenza vaccine(LAIV) is not recommended because it may precipitate a flare-up.The inactivated influenza vaccine(IIV) should be administered according to a modified protocol in which it is administered subcutaneously rather than intramuscularly.Influenza vaccine should notbe administered during a flare-up or within six to eight weeks of a flare-up.Influenza vaccine should notbe administered near a joint or muscle group that has been affected by FOP.Close contacts of patients with FOP also should receive annual influenza immunization. The ICC recommends that close contacts of patients with FOP receive IIV rather than LAIV [16].●Other vaccines– Recommendations for other vaccines are individualized according to the potential benefits and harms for the particular vaccine in a particular patient. Factors to be considered include the risk of precipitating a flare-up, the risk of exposure to a vaccine-preventable disease, and the number of doses of vaccines received before the child was diagnosed with FOP. Detailed recommendations are provided in the ICC guidelines[16]. In general:Vaccines should notbe administered during a flare-up or within six to eight weeks of a flare-up.Vaccines should notbe administered near a joint or muscle group that has been affected by FOP.Diphtheria- or tetanus-toxoid containing vaccines (eg, the combination diphtheria, tetanus, and acellular pertussis vaccine) may cause flare-ups, heterotopic ossification, and permanent loss of joint motion [16,27]. They should be avoided in children with FOP unless indicated to prevent life-threatening illness [16].Flare-ups also may be caused by vaccines that contain components of diphtheria and tetanus as protein conjugates (eg, Haemophilus influenzaetype b [Hib] vaccine; meningococcal serogroups A, C, W, and Y vaccine; pneumococcal conjugate vaccine; combination Hib and meningococcal serogroup C vaccine). The safety of these vaccines for patients with FOP is uncertain.Intramuscular (IM) injections are contraindicatedbecause they precipitate flare-ups.Whether vaccines that are typically administered IM are effective when administered subcutaneously is uncertain. There is some evidence to effectiveness for hepatitis A and B vaccines when administered subcutaneously [28,29], but evidence for other vaccines that are typically administered IM (eg, human papillomavirus vaccine, meningococcal serogroup B vaccine) is lacking.Subcutaneous administration is routinely recommended for the following vaccines, which are generally considered safe for patients with FOP: measles, mumps, and rubella (MMR) vaccine; the varicella vaccine; the combination MMR and varicella vaccine; and inactivated poliovirus vaccine[16,30].Glucocorticoid prophylaxis—A short course of glucocorticoids may be warranted to prevent flare-ups within 24 hours of severe soft tissue trauma or emergency, elective, major, or minor surgery (eg, appendectomy, dental surgery) [16]. The ICC suggests prednisone1 to 2 mg/kg orally once or twice per day (maximum daily dose 100 mg) for three to four days [16]. Equivalent doses of other oral glucocorticoids may be administered. Although glucocorticoid prophylaxis has not been studied systematically in patients with FOP, inflammation plays in important role in the development of FOP flare-ups [31,32].Symptomatic management of early lesions—A short course of glucocorticoids may be warranted for the early symptomatic management of flare-ups affecting the jaw, submandibular area, or major joints (eg, hip); consultation with an expert in FOP is recommended for patients with submandibular flare-ups. The ICC suggests prednisone1 to 2 mg/kg orally once or twice per day (maximum daily dose 100 mg) for three to four days [16]. Equivalent doses of other oral glucocorticoids may be administered.When administered within the first 24 hours of a flare-up, a short course of glucocorticoids may reduce inflammation and tissue edema and prevent flare-ups. Glucocorticoids usually are not used in the symptomatic management of the neck or trunk because these flare-ups are typically prolonged and recurrent.After discontinuation of the glucocorticoid, or if glucocorticoids are not used, topical or systemic nonsteroidal anti-inflammatory medication (eg, ibuprofen) may be used for symptomatic management during the remainder of the flare-up. Local application of cool packs also may be helpful.The use of glucocorticoids in the symptomatic management of FOP flare-ups is based upon the importance of inflammation in FOP flare-ups [31,32]. In a survey, 75 percent of 500 patients used short-term glucocorticoids for flare-ups of the limbs; among these, 31 percent reported that glucocorticoids always improved symptoms, and 55 percent reported that they occasionally did; 12 percent reported that they had complete resolution of a flare-up with glucocorticoids [9].Use of ibuprofen(or other prostaglandin inhibitors) may prevent heterotopic ossification because inflammatory prostaglandins are thought to stimulate induction of heterotopic bone [33-35].Preventive dental care—Preventive dental care is a crucial component of the management of FOP and should begin as soon as possible. Preventive dental care is discussed separately. (See "Preventive dental care and counseling for infants and young children".)Consultation with a dental professional with expertise in FOP is recommended before any dental procedure [16]. Injections of local anesthetic for dental procedures should be avoided [36].Hearing evaluation—Children with FOP are at increased risk for conductive hearing loss. They should undergo evaluation for hearing impairment with audiometry at least every other year [16]. (See "Hearing loss in children: Screening and evaluation", section on 'Formal audiology'.)Respiratory health—Chest deformity and scoliosis in patients with FOP may decrease respiratory capacity. Respiratory health can be maintained in patients with FOP through active respiratory activity (eg, singing, incentive spirometry, peak flow whistles) [16].PROGNOSIS—Most patients require a wheelchair by age 20 years [1]. Alternative feeding methods (eg, feeding tubes, gastrostomy tubes) have prolonged the life span of patients with ankylosis of the jaw. In a review of information from two large registries, the median lifespan was approximately 40 years; the most common causes of death were thoracic insufficiency (54 percent) and pneumonia (15 percent) [37].SUMMARY AND RECOMMENDATIONS●Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a rare connective tissue disorder caused by mutations in the ACVR1/ALK2gene, which encodes a bone morphogenetic protein receptor. Most cases are sporadic. (See 'Epidemiology'above and 'Pathogenesis'above.)●Characteristic clinical features include bilateral malformation of the great toes at birth (they are short and laterally deviated [ie, hallux valgus]) (picture 1);sporadic, painful episodes of rapidly progressive soft-tissue swelling ("flare-ups"); and heterotopic ossification that eventually spans joints, resulting in progressive and irreversible immobility, weight loss, and thoracic insufficiency syndrome. (See 'Clinical features'above.)●Flare-ups usually begin in the first decade of life, presenting as nodules on the head or back. They can be precipitated by soft tissue injury, intramuscular (IM) injection, surgical incision, falls, muscular stretching, or viral illness. (See 'Clinical features'above.)●FOP should be suspected in children with hallux valgus, progressive soft tissue swelling, and nodules on the head or back. Definitive diagnosis requires molecular genetic studies that detect missense mutations or "in frame" deletions in the protein-encoding region of the ACVR1gene. Biopsy of soft tissue lesions may precipitate a flare-up and should be avoided. (See 'Diagnosis'above.)●The differential diagnosis of FOP includes other conditions associated with malformed great toes, soft tissue swelling, or heterotopic ossification. The combination of these three findings generally distinguishes FOP from these conditions. (See 'Differential diagnosis'above.)●There is no medical or surgical treatment to prevent or reverse the ossification associated with FOP. Management is supportive and focuses on prevention of flare-ups, patient and family education and counseling, and improved quality of life (see 'Management'above):Biopsies, surgery, and trauma should be avoided if possible. (See 'Avoid biopsies, surgery, and trauma'above.)Limiting activities with a high-risk of falls, installing handholds and other safety measures, and use of headgear may prevent falls or severe trauma from falls. (See 'Prevention of falls'above.) IM injection of vaccines is contraindicated. Additional immunization precautions are discussed above. (See 'Immunizations'above.) Preventive dental care is discussed separately. (See "Preventive dental care and counseling for infants and young children".)Children with FOP should undergo evaluation for hearing impairment with audiometry at least every other year. (See 'Hearing evaluation'above.)Respiratory health can be maintained through active respiratory activity (eg, singing, incentive spirometry, peak flow whistles). (See 'Respiratory health'above.)REFERENCES1.Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: clinical and genetic aspects. Orphanet J Rare Dis 2011; 6:80.2.Kaplan FS, Xu M, Seemann P, et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat 2009; 30:379.3.Kaplan FS, Xu M, Glaser DL, et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics 2008; 121:e1295.4.Rogers JG, Geho WB. Fibrodysplasia ossificans progressiva. A survey of forty-two cases. J Bone Joint Surg Am 1979; 61:909.5.Kartal-Kaess M, Shore EM, Xu M, et al. Fibrodysplasia ossificans progressiva (FOP): watch the great toes! Eur J Pediatr 2010; 169:1417.6.Mantick N, Bachman E, Baujat G, et al. The FOP Connection Registry: Design of an international patient-sponsored registry for Fibrodysplasia Ossificans Progressiva. Bone 2018; 109:285.7.Baujat G, Choquet R, Bouée S, et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis 2017; 12:123.8.Piram M, Le Merrer M, Bughin V, et al. Scalp nodules as a presenting sign of fibrodysplasia ossificans progressiva: a register-based study. J Am Acad Dermatol 2011; 64:97.9.Pignolo RJ, Bedford-Gay C, Liljesthrm M, et al. The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. J Bone Miner Res 2016; 31:650.10.Kitterman JA, Kantanie S, Rocke DM, Kaplan FS. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics 2005; 116:e654.11.Orthopaedic-related syndromes. 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腕骨骨折概述Author:Kevin deWeber, MD, FAAFP, FACSMSection Editors:Patrice Eiff, MDChad A Asplund, MD, MPH, FAMSSMDeputy Editor:Jonathan Grayzel, MD, FAAEM翻译:刘浩, 主任医师,教授Contributor Disclosures我们的所有专题都会依据新发表的证据和同行评议过程而更新。文献评审有效期至:2020-06.|专题最后更新日期:2019-02-08.There is a newer version of this topic available inEnglish.该主题有一个新的英文版本。引言腕骨为手腕部的一组骨,其近端与桡骨和尺骨相接,远端与掌骨相接。该组骨一共有8块,合称为腕骨,通常分为近侧列(手舟骨、月骨、三角骨和豌豆骨)和远侧列(大多角骨、小多角骨、头状骨和钩骨)。一般情况下,腕骨骨折由直接或间接创伤引起。本专题将概述基本的腕骨解剖、损伤机制、体格检查和影像学检查的一般原则,以及成人腕骨骨折的初始诊疗。常见且重要腕部损伤详见其他专题。(参见“成人亚急性或慢性腕部疼痛的评估”和“成人急性腕部疼痛的评估”和“成人桡骨远端骨折”和“手舟骨骨折”和“三角骨骨折”和“月骨骨折及月骨周围损伤”和“头状骨骨折”和“钩骨骨折”)流行病学—手部骨折是最常见的肢体损伤,约占所有骨折的18%。腕骨骨折则占手部骨折的8%以上[1-3]。手舟骨骨折是目前最常见的腕骨骨折,占所有手部骨折的10%,并占所有腕骨骨折的60%-70%[4,5]。其次为三角骨骨折,占腕骨骨折的13%-28%。随后是大多角骨、钩骨、头状骨和小多角骨骨折,占腕骨骨折的2%-4%。豌豆骨骨折最罕见,占0.5%-1%[1,6-8]。分类和临床表现腕骨骨折分类的主要依据是骨折所在的解剖位置(参见下文‘临床解剖学’),其次是损伤的特点,包括伴随的移位、脱位,以及骨折(粉碎性骨折与非粉碎性骨折)产生的骨碎块的数目。需要注意的是,很大一部分腕骨骨折涉及多块腕骨,因此若有一块腕骨发生骨折,临床医生应当寻找有无其他腕骨损伤。累及桡骨或尺骨远端的孤立性骨折虽然被归为“腕部骨折”,但并不累及腕骨。(参见“骨折处理的一般原则:骨折愈合和骨折描述”)骨折的简要介绍—与8块腕骨(影像 1)骨折相关的问题将在相应的专题单独讨论,列举如下:●手舟骨骨折(影像 2)手舟骨骨折是最常见的腕骨骨折,约占所有腕骨骨折的2/3。最常见的发生机制为跌倒时用手掌撑地,且手腕呈伸展、桡侧偏移的姿势。患者通常表现为手腕桡侧疼痛、肿胀、腕部活动受限、鼻烟窝压痛(图 1),以及受到沿拇指的轴向载荷时出现疼痛。手舟骨骨折的诊断和处理详见其他专题。(参见“手舟骨骨折”)●月骨骨折(影像 3)急性月骨骨折最常见于跌倒时以手掌撑地且手腕呈伸展姿势,或见于其他一些腕部过度背伸性损伤。患者通常表现为腕部疼痛,活动腕关节或抓握动作可加重疼痛。由于月骨位于关节囊内,肿胀可能并不明显。若就诊较晚,则患者可能仅主诉腕关节僵硬或活动度降低。月骨骨折的诊断和处理详见其他专题。(参见“月骨骨折及月骨周围损伤”)●三角骨骨折(影像 4)三角骨骨折是第二常见的腕骨骨折,多为韧带撕脱性骨折。患者通常有创伤史以及腕部尺侧疼痛。体格检查一般能发现腕部背侧(图片 1)或沿尺骨远端边缘的压痛点。三角骨骨折的诊断和处理详见其他专题。(参见“三角骨骨折”)●豌豆骨骨折(影像 5)豌豆骨骨折最常见的发生机制是跌倒时以手掌撑地且腕部呈伸展姿势,或者是用掌根敲击硬物。患者通常表现为腕部掌面尺侧的疼痛和肿胀。豌豆骨处(图片 2)及小鱼际区域有压痛。豌豆骨骨折的诊断和处理详见其他专题。(参见“豌豆骨骨折”)●大多角骨骨折(影像 6)大多角骨骨折通常发生在跌倒时以手掌撑地时。患者通常没有明显肿胀,但有显著不适,比其他腕骨骨折更严重。捏拢指尖时有疼痛和无力表现,如比“OK”手势,或用拇指去接触小指指尖。大多角骨骨折的诊断和处理详见其他专题。(参见“Trapezium fractures”)●小多角骨骨折(影像 7)小多角骨骨折一般发生在第二(食指)掌骨受到轴向载荷时,罕见情况下也可见于腕部背侧的直接创伤。患者通常表现为手背肿胀,手背侧紧邻第二掌骨底近端处有压痛点(图片 3)。小多角骨骨折的诊断和处理详见其他专题。(参见“小多角骨骨折”)●头状骨骨折(影像 8)头状骨是最大的腕骨。单纯头状骨骨折通常是由跌倒时手握拳撑地导致。患者表现为手背侧疼痛和肿胀。背侧面头状骨区域(紧邻第三掌骨近端)通常有压痛。头状骨骨折的诊断和处理详见其他专题。(参见“头状骨骨折”)●钩骨骨折(影像 9)钩骨骨折可涉及钩骨钩或钩骨体。钩骨钩骨折更常见,发生于跌倒时以手掌撑地,或是做挥鞭动作时(如网球、高尔夫或棒球),该过程中球拍或球棒握持部分的底端可造成骨损伤。患者表现为掌侧面钩骨钩处有深部压痛(图片 4)。钩骨骨折的诊断和处理详见其他专题。(参见“钩骨骨折”)临床解剖学腕部解剖结构详见其他专题。(参见“腕关节的解剖学和基础生物力学”)手部近端约3cm由8块腕骨构成(影像 1)。腕骨细分为近侧列和远侧列。腕骨近侧列包括(从桡侧向尺侧):●手舟骨●月骨●三角骨(背侧)●豌豆骨(掌侧)腕骨远侧列包括(从桡侧到尺侧):●大多角骨●小多角骨●头状骨●钩骨损伤机制如果患者能够描述腕部受伤时的情况,这一信息可能提示哪个或哪些腕骨发生了损伤,并可影响初始影像学检查[2,3,9]。需注意的是,下面的描述仅涉及腕骨骨折,而这些机制可能导致其他损伤(如,跌倒时腕伸展着地造成的桡骨远端骨折)。轴向载荷—腕部的轴向载荷可能造成手舟骨骨折,还可能引起舟月韧带断裂,导致舟月骨分离(影像 10)。第一掌骨(拇指)的轴向载荷可导致大多角骨发生垂直于大多角骨-第一掌骨关节面的关节内骨折;而食指掌骨的轴向载荷可能导致与之相关节的小多角骨骨折。(参见“成人急性腕部疼痛的评估”,关于‘舟月不稳定’一节和“Trapezium fractures”和“小多角骨骨折”)腕部过度背伸—涉及腕部过度背伸的损伤,如跌倒时手部伸展着地,可迫使舟骨向桡骨背侧移位而造成骨折(影像 2)。伸展过度性损伤也可造成月骨和三角骨骨折。(参见“手舟骨骨折”和“月骨骨折及月骨周围损伤”和“三角骨骨折”)跌倒时手掌着地可能导致豌豆骨的线性骨折,但此类骨折更可能是由对豌豆骨本身的直接冲击造成,而非由腕部过度伸展造成。偶尔,腕部过度背伸可能导致豌豆骨的撕脱性骨折,这通常发生在尺侧腕屈肌肌腱的远端附着点。(参见“豌豆骨骨折”)腕部过度屈曲—腕部过度屈曲可能导致累及三角骨韧带附着处的撕脱性骨折。(参见“三角骨骨折”)偏移、牵拉或旋转—由腕部(或第一掌骨)强力偏移、牵拉或旋转导致的损伤,可能引起韧带或关节囊应力,进而引起任何一个腕骨的撕脱性骨折。对掌面的直接冲击—由直接冲击导致的豌豆骨与三角骨挤压(如,用掌根敲击硬物)可能导致豌豆骨骨折,或造成豌豆骨背侧关节面的软骨损伤。(参见“豌豆骨骨折”)钩骨钩也容易因作用于腕横韧带的直接压力而受到损伤,导致钩骨钩从钩骨体撕脱。跌倒时以手掌撑地或经作用在钩骨钩部的棍棒、球拍或球棒末端传递的力,也可导致钩骨骨折。(参见“钩骨骨折”)多种力的组合—轴向载荷和过度屈曲或过度背伸联合作用时,比如跌倒时手握拳撑地,可能导致头状骨骨折,常伴有相关的脱位。(参见“头状骨骨折”)症状和检查发现评估急性腕痛患者时需了解的重要问题包括疼痛部位、患者的优势手、从事的职业或运动以及什么活动会加重疼痛。腕痛患者的表现及病史采集详见其他专题。(参见“成人急性腕部疼痛的评估”和“成人亚急性或慢性腕部疼痛的评估”)疼痛和压痛的位置有助于确定损伤最可能发生于哪块骨或哪些骨,还能指导影像学检查的需求(影像 1和图 2和图 3)。鼻烟窝压痛(图片 5和图 1)提示手舟骨损伤,但也可能是大多角骨损伤。触诊手背桡侧的Lister结节(图 2和图片 6)有助于明确舟月关节的位置,该关节紧邻Lister结节远端。疼痛主要在掌面时损伤较可能发生在豌豆骨(位于小鱼际近端根部(图片 2))或钩骨钩(位于小鱼际区域内(图片 4)),或者是鱼际近端根部的舟骨掌侧(远端)(图片 7)。腕骨骨折后出现的疼痛通常造成腕部活动减少以及腕部屈伸和手部抓握的肌力减弱。应评估患者的神经血管功能,因为骨折和脱位可损伤邻近神经或血管。任何可能伴有神经血管损伤的骨折都需要紧急治疗并请手外科会诊。其他特异性检查将在具体骨折的相关专题中详细讨论。影像学检查怀疑为腕骨骨折时,要获取的标准X线平片包括后前位片(posteroanterior, PA)、斜位片和正侧位片。其他位X线平片的选择取决于骨折的可疑部位;这些额外摄片将在针对特定损伤的专题中进行更详细的讨论。特定情况下,某些视图的X线平片可能提供有用信息,简要总结如下:●手舟骨位片(最大尺侧移时腕部的后前位片)有助于发现可疑的手舟骨骨折(影像 11)。(参见“手舟骨骨折”)●腕管位片有助于发现钩骨钩骨折(影像 9)。(参见“钩骨骨折”)●握拳姿势下的后前位片有助于显示舟月韧带断裂造成的舟月关节不稳。腕骨间的间距一般为2-3mm,超过3mm时提示韧带断裂(影像 12)[10]。(参见“成人急性腕部疼痛的评估”,关于‘舟月不稳定’一节)●Bett位片(手腕旋前约20°时的前后位)有助于识别临床怀疑的大多角骨骨折。临床医生应谨记,常规X线平片对识别腕骨骨折的敏感性较低[6,7]。因此,如果X线检查未发现明显异常,但临床上仍怀疑有骨折(如,有骨性压痛以及损伤机制符合条件),应进行CT或MRI检查。CT能非常准确地识别腕骨骨折或脱位,也可在怀疑关节内移位时评估关节面[11]。而MRI在此基础上还能发现急性和慢性骨/软组织损伤[12]。如果怀疑有严重软组织损伤(如韧带断裂或脱位),则应进行MRI检查。如果超声技能娴熟,也是诊断包括腕骨骨折在内的多种腕部损伤的有效辅助手段。实施腕部超声检查详见其他专题。(参见“Musculoskeletal ultrasound of the wrist”)鉴别诊断除了骨折,腕部可发生其他的创伤性损伤,包括:●腕部关节囊的扭伤●多个腕骨间韧带中任何韧带扭伤,这可能导致腕骨的半脱位或脱位●多条横跨腕部的肌腱的任何肌腱损伤●浅表软组织挫伤●不伴骨折的骨挫伤●神经损伤(桡神经,尺神经,正中神经)●三角纤维软骨复合体(triangular fibro-cartilage complex, TFCC)的挫伤和撕裂●既存腱鞘囊肿的破裂●既存炎性关节病(如,类风湿性关节炎)的加重如何评估腕部疼痛患者的更全面讨论参见其他专题(参见“成人急性腕部疼痛的评估”和“成人亚急性或慢性腕部疼痛的评估”)。手术转诊的指征手术转诊的指征因受累骨及损伤机制而不同。这些内容将在针对特定腕骨损伤的各个专题进行讨论。立即转诊的基本指征相同,包括:任何持续的血管损伤或神经功能障碍、开放性骨折、移位性骨折、伴有脱位或骨性不稳定的骨折,以及发生任何严重并发症。(参见“骨折治疗的一般原则:早期和晚期并发症”)处理骨折处理的一般原则适用于腕骨骨折。以下是推荐的处理措施:●固定骨折,最小化进一步的组织损伤,尤其是神经和血管结构的损伤。由于骨折可能导致软组织严重肿胀,初始固定通常采用可拆卸石膏或玻璃纤维夹板或热塑形夹板。随后可拆除夹板,以便进行骨折复位、固定和石膏塑形。(参见“肌肉骨骼损伤的夹板固定基本技术”)●冰敷受伤部位,尽可能减轻肿胀(参见“急性骨折的一般处理原则”)●通过骨折固定、冰敷和服用非处方镇痛药(如对乙酰氨基酚),可充分缓解大多数患者的疼痛。在最初3-5日,有时需要阿片类镇痛药来控制疼痛。若之后患者还要求使用阿片类药物,则应重新评估是否存在夹板或石膏固定不佳、漏诊损伤或出现骨折并发症而引起的疼痛不适。(参见“急性骨折的一般处理原则”,关于‘疼痛管理’一节和“骨折治疗的一般原则:早期和晚期并发症”)非甾体类抗炎药对骨折愈合是否有效还有争议,但如果有明确的或者可疑的急性骨折,最好避免使用此类药物,以降低骨折不愈合的风险。相关问题详见其他专题。(参见“非选择性非甾体类抗炎药的不良反应概述”,关于‘肌肉骨骼损伤的愈合’一节)腕骨骨折固定以后,腕部的康复非常重要。如果没有高质量的康复,腕部功能完全恢复可能很慢,甚至可能恢复不完全,从而导致慢性残疾。只要有可能,我们推荐将患者转诊至有处理腕部损伤经验的职业治疗师或物理治疗师。腕骨骨折的治疗和康复一般由以下几个阶段构成:●炎症和修复阶段–发生在骨折固定期间,如上文所述。●过渡至成熟阶段–固定后,腕部出现僵硬和疼痛。在进行轻柔、被动的关节活动度锻炼之前,热疗(在热水或固体石蜡中浸泡数分钟)等治疗可能有帮助。关节活动度锻炼可在腕部活动的三个平面进行:屈-伸、尺-桡侧偏和旋前-旋后。如果需要的话,应注意恢复手指活动度。完全恢复腕部活动度可能需要数周时间,但在1-2周后通常可获得显著改善。●成熟阶段–一旦骨折愈合且腕部活动能力恢复,患者需2-8周恢复腕部和手部肌肉的力量。这些肌肉包括:腕屈肌和腕伸肌、尺侧倾肌群和桡侧倾肌群、旋前肌和旋后肌,以及指屈肌和指伸肌。相关训练可通过使用弹性阻力带(由健侧手提供手动阻力)或专门设计的器械(见于物理治疗诊所)完成。治疗师也可使患者逐渐过渡到特殊训练,这些训练是对需要重新掌握的职业相关或体育相关任务进行重复。额外信息资源腕骨骨折的额外信息可从其他文献获得,这些文献分别从骨科手术的角度[9,13]、初始处理的角度[14]及运动医学的角度[3,10,15]对腕骨骨折进行讨论。患者教育UpToDate提供两种类型的患者教育资料:“基础篇”和“高级篇”。基础篇通俗易懂,相当于5-6年级阅读水平(美国),可以解答关于某种疾病患者可能想了解的4-5个关键问题;基础篇更适合想了解疾病概况且喜欢阅读简短易读资料的患者。高级篇篇幅较长,内容更深入详尽;相当于10-12年级阅读水平(美国),适合想深入了解并且能接受一些医学术语的患者。以下是与此专题相关的患者教育资料。我们建议您以打印或电子邮件的方式给予患者。(您也可以通过检索“患者教育”和关键词找到更多相关专题内容。)●基础篇(参见“患者教育:石膏和夹板护理(基础篇)”和“患者教育:骨折(基础篇)”和“患者教育:常见腕部损伤(基础篇)”)●高级篇(参见“Patient education: Cast and splint care (Beyond the Basics)”)总结●腕骨骨折分类的主要依据是骨折所在的解剖位置和骨折特征。八块腕骨可被细分为近侧列和远侧列(影像 1)。具体每块腕骨骨折参见相应专题。(参见上文‘分类和临床表现’和‘临床解剖学’)●疼痛的位置和受伤机制为损伤的部位提供了线索。本文阐述了不同腕骨骨折的特定损伤机制和检查发现。(参见上文‘损伤机制’和‘症状和检查发现’)●怀疑腕骨骨折时,要获取的标准X线平片包括腕部的后前位(PA)片和标准侧位片。还可针对疑似骨折部位进行其他视图的X线检查,但X线平片的总体敏感性较低。如果初始X线检查无明显异常,但临床上仍怀疑骨折,可使用夹板固定腕部并在7-10日内再次进行X线检查,或者是进行高级影像学检查(如CT或MRI)。(参见上文‘影像学检查’)●腕骨骨折的初始处理包括固定、冰敷和镇痛。骨折愈合后,适当的物理治疗对恢复腕部的活动和肌力至关重要。(参见上文‘处理’)使用UpToDate临床顾问须遵循用户协议.参考文献van Onselen EB, Karim RB, Hage JJ, Ritt MJ. Prevalence and distribution of hand fractures. J Hand Surg Br 2003; 28:491.Suh N, Ek ET, Wolfe SW. Carpal fractures. J Hand Surg Am 2014; 39:785.Urch EY, Lee SK. Carpal fractures other than scaphoid. Clin Sports Med 2015; 34:51.Alshryda S, Shah A, Odak S, et al. Acute fractures of the scaphoid bone: Systematic review and meta-analysis. Surgeon 2012; 10:218.Duckworth AD, Jenkins PJ, Aitken SA, et al. Scaphoid fracture epidemiology. J Trauma Acute Care Surg 2012; 72:E41.Welling RD, Jacobson JA, Jamadar DA, et al. MDCT and radiography of wrist fractures: radiographic sensitivity and fracture patterns. AJR Am J Roentgenol 2008; 190:10.Balci A, Basara I, ekdemir EY, et al. Wrist fractures: sensitivity of radiography, prevalence, and patterns in MDCT. Emerg Radiol 2015; 22:251.Hey HW, Chong AK, Murphy D. Prevalence of carpal fracture in Singapore. J Hand Surg Am 2011; 36:278.Geissler WB, Slade JF. Fractures of the carpal bones. In: Green's Operative Hand Surgery, 6th ed, Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH (Eds), Churchill Livingstone, 2011.Ingari JV. Wrist and hand. In: DeLee and Drez's Orthopedic Sports Medicine Principles and Practice, 3rd ed, DeLee JC, Drez D, Miller MD (Eds), Saunders Elsevier, Philadelphia 2010.Kaewlai R, Avery LL, Asrani AV, et al. Multidetector CT of carpal injuries: anatomy, fractures, and fracture-dislocations. Radiographics 2008; 28:1771.Murthy NS, Ringler MD. MR Imaging of Carpal Fractures. Magn Reson Imaging Clin N Am 2015; 23:405.Gaebler C, McQueen MM. Carpus fractures and dislocations. In: Rockwood and Green's Fractures in Adults, 7th ed, Bucholz RW, Heckman JD, Court-Brown CM, Tornetta P (Eds), Lippincott, Williams, & Wilkins, Philadelphia 2010.Eiff MP, Petering RC. Carpal fractures. In: Fracture Management for Primary Care, 3rd ed, Eiff MP, Hatch RL (Eds), Saunders, Philadelphia 2013.Marchessault J, Conti M, Baratz ME. Carpal fractures in athletes excluding the scaphoid. Hand Clin 2009; 25:371.
引言—骨肉瘤是骨的原发恶性肿瘤,其特征是恶性肿瘤细胞产生类骨质或不成熟骨[1-3]。骨肉瘤比较少见。美国每年诊断的新发病例有750-900例,其中约400例发生于20岁以下的儿童和青少年[4,5]。骨肉瘤虽然少见,但却是儿童和青少年最常见的原发性恶性骨肿瘤(图 1),在15-19岁青少年和年轻成人的最常见恶性肿瘤中居第5位[6,7]。通过有效的化疗,恶性骨组织肉瘤患者的生存情况已显著改善。在采用化疗前,80%-90%的骨肉瘤患者虽然局部肿瘤得到了控制,但仍发生了转移性疾病,并死于该病。据推测(后来得以证实),大多数患者在诊断时已存在亚临床的转移性疾病,甚至在没有明显临床转移灶的情况下[8,9]。如果在疾病负担较低时开始化疗,则可成功根除这些沉积病灶。因此,除低级别骨旁骨肉瘤患者和某些骨膜骨肉瘤患者以外(化疗的价值存在疑问),所有其他骨肉瘤患者均应行辅助化疗,且大多数在术前阶段进行。采取多学科治疗,则至少2/3的非转移性肢体骨肉瘤患者会长期存活,多达50%的局限性肺转移患者可治愈,约25%表现为更广泛转移性疾病的患者预计可获得长期无复发生存。本专题将概述骨肉瘤患者的流行病学、临床表现、诊断、分期和组织病理学。原发性骨肿瘤的诊断性评估和活检技术,治疗和结局概述,骨组织肉瘤的外科手术治疗指导原则,以及骨肉瘤治疗中的化疗将会单独详细讨论。 (参见“骨肿瘤的诊断与活检技术”和“骨源性肉瘤的术前评估、组织学分型和外科治疗原则”和“骨肉瘤治疗中的化疗和放疗”)流行病学—如上文所述,骨肉瘤是一种少见的肿瘤;仅占美国每年所有癌症诊断的1%。与尤文肉瘤不同(在年龄较大的成人中极为罕见),骨肉瘤的发病年龄呈双峰分布,分别出现于青春期早期和65岁以上(图 2)[10]。肿瘤部位和患者生存情况视就诊时的年龄而异。儿童—骨组织肉瘤约占儿童期所有癌症的6%,而骨肉瘤约占儿童期所有癌症的3%[11]。然而,骨肉瘤是儿童和年轻成人最常见的原发性恶性骨肿瘤。在20岁以下的个体中,骨肉瘤占所有骨癌的56%,而尤文肉瘤占34%-36%,软骨肉瘤不到10%[10]。 (参见“尤文肉瘤家族肿瘤的流行病学、病理学和分子遗传学”)对于儿童,骨肉瘤的发病高峰是13-16岁(图 1),与青少年生长突增期一致。骨肉瘤在男孩中更常见,黑人和其他人种多于白种人,但原因不明[4,10,12]。儿童骨肉瘤的最常见部位是长骨干骺端,尤其是股骨远端(在一项大型人群病例系列研究中占75%[10])、胫骨近端和肱骨近端[13,14]。成人—通常认为成人的骨肉瘤是由Paget骨病经肉瘤性转化而成的继发性肿瘤,或者是受照射骨、骨梗死或某些其他良性骨病变的继发性肉瘤[10]。 (参见“放疗相关肉瘤”)在美国,所有发生于60岁以上患者中的骨肉瘤,半数以上为继发性[15]。而在亚洲,Paget病相对少见,且40岁以上患者中的骨肉瘤大多为原发性[16,17]。Paget病情况下的骨肉瘤(Paget病性肉瘤)的预后总体较差。 (参见下文‘危险因素’)相比于诊断的儿童病例,成人骨肉瘤更常出现在中轴部位(虽然同儿童一样,但下肢骨是单一的最常见部位[10]),以及既往接受过放射或有基础骨异常的区域。诊断时年龄超过60岁的患者在就诊时发生转移性疾病的风险也更高[18]。对于年龄较大的成人骨肉瘤患者,与儿童一样,男性更多见[10]。但与儿童不同的是,白种人比黑人或其他人种更常见[10]。危险因素和发病机制—在儿童中,大多数骨肉瘤是散发性的,而少数病例具有遗传易感性。在年龄较大的成人中,约1/3的骨肉瘤病例出现于Paget骨病中,或者作为第二癌症或较迟发生的癌症出现[10]。危险因素—已经确定了几种易感因素[19]。先前放疗或化疗—儿童期实体肿瘤放疗后20年期间,骨肉瘤是最常见的第二原发性肿瘤。早期评价表明约3%的骨肉瘤可归因于先前的放疗。然而,可能会显示更高的发病率,因为更多患者在最初放疗后能活到发生这一并发症。放疗到出现继发性骨肉瘤的时间平均为12-16年;儿童期癌症存活者间隔时间更短。 (参见“放疗相关肉瘤”,关于‘流行病学与组织学分布’一节和“放疗相关肉瘤”,关于‘放疗剂量与暴露年龄’一节)对于儿童期癌症存活者,先前接受过化疗(尤其是烷化剂)也与继发性骨肉瘤相关,且可能会增强既往放疗的影响。 (参见“放疗相关肉瘤”,关于‘化疗药物’一节)Paget病和其他良性骨病变—40岁以上的骨肉瘤患者病例常与Paget病有关,Paget病是一种以骨转换加速为特征的局灶性骨骼病[20]。尽管Paget病患者的骨肿瘤发病率明显增加,但仅0.7%-1%[21]。肉瘤性转化最常见于长期Paget病中,但并不一定与骨受累程度有关。尽管这种情况在组织学上与其他骨肉瘤无法鉴别,但常见多处骨受累,且预后总体较差。 (参见“Paget骨病的临床表现与诊断”)Paget病的病因尚不明确,但现认为遗传因素起了致病作用。Paget病和Paget病性骨肉瘤均与18号染色体杂合性缺失有关,可能涉及了相同位点的某个假定抑癌基因[22-24]。在散发性Paget骨病和Paget病性骨肉瘤中,已发现染色体5q35上SQSTM1基因的体细胞突变[25]。除Paget病以外,其他良性骨病变据报道也会导致恶变为原发性骨肿瘤的风险增加。这些病变包括慢性骨髓炎、骨梗死灶,以及良性骨肿瘤(如骨纤维异常增殖症等)[26,27]。(参见“儿童及青少年良性骨肿瘤”,关于‘纤维异常增殖症’一节)也有报道称,骨肉瘤发生在金属植入物附近,但尚未确定具有明确的因果关系,可能仅仅是巧合。遗传性疾病—许多骨肉瘤患者存在遗传易感性,尤其是儿童。一项研究纳入了1120例癌症患儿,采用新一代测序技术来确定种系易感突变对骨肉瘤的促发作用,发现39例骨肉瘤患者中7例(18%)存在被认为致病或可能致病的突变[28]。大多数突变位于RB1基因(遗传性视网膜母细胞瘤相关基因)和TP53基因(Li-Fraumeni综合征相关基因)。●与遗传性视网膜母细胞瘤相关的基因异常(即视网膜母细胞瘤基因的种系突变)会导致发生第二原发性肿瘤的风险增加,其中60%的第二原发性肿瘤为软组织肉瘤和骨肉瘤[29-31]。较迟发生成骨性肉瘤的风险不仅存在于放疗照射野中,也存在于远离放疗照射野的长骨中。与遗传性视网膜母细胞瘤患者相比,散发型视网膜母细胞瘤患者中该风险低得多。例如,在一项纳入了1604例视网膜母细胞瘤患者的研究中,在诊断后第50年,遗传性病例的第二癌症累积发病率为51%,而对于非遗传性(散发性)病例仅为5%[29]。 (参见“视网膜母细胞瘤的临床表现、评估和诊断”,关于‘流行病学’一节和“放疗相关肉瘤”,关于‘遗传易感性’一节)●Li-Fraumeni综合征是一种家族性癌症综合征,受累的家族成员呈现出一系列肿瘤,包括乳房肿瘤、软组织肿瘤、肾上腺皮质肿瘤、脑肿瘤、白血病和骨肉瘤[32]。这些患者中很多都携带p53抑癌基因的生殖系失活突变,该抑癌基因参与了细胞周期调节和维持基因组完整性[33-35]。 (参见“Li-Fraumeni综合征”)尽管存在这种重要关联,但仅少数骨肉瘤归因于Li-Fraumeni综合征[36,37]。一项病例系列研究纳入了235例未经选择的骨肉瘤儿童,仅3%的儿童携带有p53组成性生殖系突变[36]。除了遗传性视网膜母细胞瘤和Li-Fraumeni综合征外,已知会使患者容易发生骨肉瘤的其他遗传性疾病包括:Rothmund-Thomson综合征(Rothmund-Thomson syndrome, RTS),以及相关的Bloom综合征与Werner综合征。●RTS(也称为先天性皮肤异色症)是一种常染色体隐性遗传病,具有独特的皮肤表现(萎缩、毛细血管扩张、色素沉着)、毛发稀疏、白内障、身材矮小、骨骼异常,以及骨肉瘤风险显著增高[38,39]。一项队列研究纳入了41例RTS患者,其中有13例(32%)发生了骨肉瘤[38]。临床上,RTS患者发生这些肿瘤的年龄往往比一般人群小。●已发现约2/3的RTS患者存在RECQL4基因的一种特定功能缺失性突变,与骨肉瘤风险密切相关。一项病例系列研究纳入了33例RTS患者,结果表明在10例无该基因截短突变的患者中,无一例发生骨肉瘤,而23例有截短突变的患者在230人年的观察期内,骨肉瘤的发病率为每年5例[40]。Bloom综合征和Werner综合征存在RecQ基因家族的其他基因突变,且这两种疾病有重叠的临床特征,包括易发生骨肉瘤[40]。由于这些遗传性疾病与骨肉瘤有关,尤其是在有多处原发恶性肿瘤的情况下[41],所以对于新诊断为骨肉瘤的患者,仔细详细询问家族史很重要。然而,上述新一代测序研究中,对于包括骨肉瘤患儿在内的大多数癌症患儿,无法根据其家族史预测是否有潜在的易感综合征[28]。分子发病机制—尽管骨肉瘤的病因学不明,但以下几点显示了骨肉瘤的发生与骨快速生长之间的关联:●骨肉瘤的发病高峰出现于青春期生长突增期●肿瘤似乎最常发生于骨长度和骨大小增长最多的部位(股骨远端、胫骨近端和肱骨近端的干骺区)(图 3)。●女孩发生骨肉瘤的年龄较小,这与其骨龄更大和青春期生长突增更早的情况相一致。人们据此推测,骨肿瘤的发生是因为在某一时间,即快速增殖细胞对致癌物、有丝分裂错误或其他导致肿瘤性转化的事件尤为易感时,正常的骨生长和重塑过程出现了异常[42]。然而,研究生长和发育相关因素与骨组织肉瘤风险间的关联性,未发现一致的关联模式[43,44]。这种异常或致肿瘤发生异常的具体特性仍不明,是要深入研究的主题[19,45,46]。与其他肉瘤不同,骨肉瘤不存在特征性的易位和其他分子遗传学异常。 (参见“软组织与骨肉瘤的致病因素”,关于‘遗传学和分子发病机制’一节)大多数骨肉瘤的核型复杂且不平衡。据报道,骨肉瘤中最常发生杂合性缺失(意味着某个推定的抑癌基因缺失)的是染色体3q、13q(视网膜母细胞瘤基因的位点)、17p(p53基因的位点)和18q(该染色体区域与Paget病中的骨肉瘤有关)(参见上文‘Paget病和其他良性骨病变’)[22,23,47-49]。骨肉瘤中常有视网膜母细胞瘤蛋白肿瘤抑制因子通路和p53肿瘤抑制因子通路的共同失活[19,50,51]。鉴于Li-Fraumeni综合征(一种p53突变性失活的遗传性疾病)家族中的骨肉瘤发病率增加,令人特别容易想到p53通路异常可能对肿瘤发生起到促进作用。 (参见上文‘遗传性疾病’)正常或“野生型”p53似乎对于骨的正常发育和生理功能起一定作用[52],因为p53无效的小鼠在子宫内表现出颅骨不能生长和骨纵向生长延迟[53]。此外,p53无效小鼠的骨细胞裂解物也不能激活正常的细胞凋亡通路[50]。p53和其他分子通路(如,Wnt、Notch、IGF和mTOR信号通路)对骨肉瘤发病机制的促进作用不属于本专题的讨论范畴;参见其他优秀的综述[45,54]。正如下文要讨论的那样,推测大多数患者在就诊时有转移性疾病,且大多是亚临床的。基因表达谱分析(通过采用DNA微阵列分析)以及全基因组测序工作正开始揭示掌控转移可能性的分子学事件,这些发现可能为以后的分子靶向治疗创造了条件[45]。临床表现—大多数骨肉瘤患者表现为局限性疼痛,通常持续数月。疼痛通常开始于损伤之后,可能随时间时轻时重。通常没有诸如发热、体重减轻和不适等全身性症状。体格检查中最重要的发现是软组织肿块,通常较大且触诊有压痛。骨肉瘤好发于长骨干骺端区域(图 4)。最常受累部位的递减次序为:股骨远端、胫骨近端、肱骨近端、股骨中段和近端,以及其他骨[55]。除了碱性磷酸酶(约40%患者)[56]、乳酸脱氢酶(lactate dehydrogenase, LDH)(约30%患者)[57]和红细胞沉降率升高以外,实验室评估通常正常。实验室评估异常与疾病严重程度无关,但LDH水平极高患者的临床结局较差[58]。就诊时,10%-20%的患者有明确的大型转移性疾病,根据美国肌肉骨骼肿瘤协会(Musculoskeletal Tumor Society, MSTS)所用的分期系统,归为Ⅲ期(参见下文‘分期系统’)。远处转移瘤最常累及肺部,但也可累及骨[59]。据推测,隐匿性微转移瘤存在于大多数似乎有临床上局限性疾病的患者中,因为在辅助化疗时代之前,80%以上的骨肉瘤患者发生了转移性疾病,尽管其局部肿瘤得到了控制。据推测这些患者在诊断时已存在亚临床转移瘤[60]。常规使用全身性辅助化疗后,至少2/3的非转移性骨肉瘤儿童和青少年会长期存活,表明化疗可成功根除微转移瘤。骨肉瘤成人患者的预后较差,尤其是65岁以上的患者[61]。诊断与分期评估—首先引起医生怀疑是原发性骨肿瘤的诊断性检查通常是受累部位的普通X线摄影[62]。普通型骨肉瘤(占骨肉瘤病例的大多数,见下文)的特征包括:正常骨小梁受到破坏、肿瘤边界模糊,以及无骨内膜骨反应。受累骨的特征是射线不透区与射线可透区混合存在、皮质破坏和骨膜新生骨形成,伴有Codman三角形成(宿主骨膜骨不完全反应)(影像 1)。软组织肿块不同程度骨化,呈放射样或“日光四射”样。 (参见“骨肿瘤的诊断与活检技术”)鉴别诊断—在多达2/3具有特征性的放射影像学表现、临床特征和肿瘤部位的患者中,可预测骨肉瘤的正确组织学诊断[63]。然而,放射影像学表现不具有诊断意义,因此确诊需行活检。骨肉瘤的主要鉴别诊断包括:其他恶性骨肿瘤(即尤文肉瘤、淋巴瘤和转移瘤),有时包括良性骨肿瘤(如软骨母细胞瘤、成骨细胞瘤(影像 2和影像 3)),以及非肿瘤性疾病(如骨髓炎、朗格汉斯细胞组织细胞增生症和动脉瘤样骨囊肿)。 (参见“儿童及青少年良性骨肿瘤”和“儿童及青少年骨朗格汉斯细胞组织细胞增生症(嗜酸性肉芽肿)”和“成人骨髓炎概述”和“疑似骨髓炎时的影像学检查方法总结”)偶尔,普通X线摄影上异常不明显。对于这类病例,如果临床上高度怀疑骨肿瘤(即长骨疼痛进行性加重或疼痛持续时间超过受伤后预计疼痛时间,如6周或以上),则应行MRI检查。甚至对于普通X线摄影有特征性表现的患者,也需要行MRI来制定手术计划(参见下文‘分期系统’)。分期诊断性检查—相比于那些有局限性病变的患者,就诊时已有明显转移性疾病的患者,其结局显著更差。由于很大比例的转移瘤患者(包括多达半数的局限性肺累及患者)可治愈,所以有必要进行全面的分期诊断性检查帮助制定手术计划。影像学检查—骨肉瘤的分期诊断性检查应包含以下内容(表 1)[64]:●受累长骨全段需行MRI检查。一项多机构研究纳入了387例儿童和成人患者,其结论表明CT与MRI对于骨和软组织肿瘤局部分期的准确性相等[65]。然而,在大多数情况下优选MRI,因为其能更好地界定软组织受累范围(尤其是对于神经血管束、关节和骨髓受累)和是否存在跳跃性病灶(即,同一骨中的髓质病变,但未与原发灶直接相连)(影像 4)[66]。MRI检查方案应包括冠状位T1序列。●CT扫描最适合用于评估胸部的转移性疾病,这是至关重要的,因为约80%的骨肉瘤转移灶会累及肺部[60,67]。由于可能存在假阳性结果,如果病变不确定但被视为代表“可能的”转移灶,则或许需要进行组织学检查来证实。然而,CT可能会低估转移瘤累及肺部的范围[68,69]。在一项研究中,除开胸手术期间用手触诊肺部以外,任何其他检查方法均会导致超过1/3病例的转移瘤被漏诊[68]。由此人们开始怀疑,当目标是切除肺部的所有转移瘤时,使用微创手术(如,胸腔镜转移瘤切除术)是否可取[70-72]。 (参见“肺转移瘤手术切除的效果、指征、术前评估及手术技术”)区别转移灶与良性结节可能比较困难,尤其是对于肉芽肿性疾病患病率较高的成人,以及生活在真菌病(尤其是组织胞浆菌病)流行地区的儿童。 (参见“肺组织胞浆菌病的诊断和治疗”,关于‘何时怀疑组织胞浆菌病’一节)虽然钙化可以是良性病变的一种征象,但也可见于骨肉瘤转移瘤中[73]。欧洲和美国骨肉瘤研究小组制定了评估疑似肺转移瘤的指导标准,EURAMOS 1(AOST0331)试验正在使用该标准(表 2)[74]。●锝放射性核素骨扫描是评估全身骨是否存在多发性病灶的优选方法。尽管PET对评估术前化疗疗效的效用可能更大,但至少1项研究表明,该检查对于发现骨肉瘤骨组织转移的作用不及放射性核素骨扫描[75],发现肺转移瘤的作用不及螺旋CT[76]。PET和PET/CT联合影像学检查对于骨肉瘤患者的作用尚未完全了解,其应用也未达成共识[76,77]。美国国家综合癌症网络(National Comprehensive Cancer Network, NCCN)的指南建议使用PET扫描和/或骨扫描作为疑似骨肉瘤的诊断性检查[78]。来自美国儿童肿瘤专家组骨肿瘤委员会的影像学检查指南推荐,采用放射性核素骨扫描和/或PET扫描进行全身分期评估(表 1)[64]。不论选用哪一种检查,在整个治疗过程中和治疗后监测期间,均应使用同一种影像学检查方法。活检—一旦疑诊为原发骨肿瘤,就应将患者转诊至在治疗此类肿瘤方面具有专业技能的医疗机构做进一步处理,包括诊断性活检。若选择开放性活检,应由骨肉瘤处理方面经验丰富的骨外科医生进行,理想情况下还应由这名医生进行根治手术。如果介入放射科医生计划进行针芯穿刺活检,则放射科医生应与骨外科医生商讨活检穿刺路径。在仔细考虑日后根治性手术后合理制定活检计划很重要,以免危及到后续治疗,尤其是保肢手术[79]。这一专题将会单独详细讨论。 (参见“骨肿瘤的诊断与活检技术”)分期系统—MSTS分期系统最常用于骨组织肉瘤分期,由弗罗里达大学的Enneking制定[80,81]。这是一个手术分期系统,不用于决定骨肉瘤患者的内科治疗(化疗)。MSTS分期系统通过分级[低级别[(Ⅰ期) vs 高级别(Ⅱ期)]来描述非转移性恶性骨肿瘤的特征,并根据病灶的局部解剖学范围[间室内(A型) vs 间室外(B型)]进一步细分。对于骨肿瘤,通过肿瘤是否延伸穿过受累骨的皮质来判定间室状态;大多数高级别骨肉瘤属于间室外型。有远处转移的患者归为Ⅲ期。组织学分类—骨肉瘤的组织学诊断依据是,存在恶性肉瘤性间质,并产生肿瘤性类骨质和骨。目前认为骨肉瘤起源于间充质干细胞,该干细胞可分化为纤维组织、软骨或骨。因此,骨肉瘤与软骨肉瘤和纤维肉瘤具有很多共同的特征(表 3)[14],后两者属于同一骨组织肉瘤家族,骨肉瘤很容易与它们混淆。然而,软骨肉瘤和纤维肉瘤没有诊断骨肉瘤所必需的编织骨基质,据此可以与骨肉瘤鉴别。由于一些骨肉瘤仅生成有限程度的类骨质,且组织形态学多样,可能需要免疫组织化学来证实诊断。与尤文肉瘤和许多软组织肉瘤不同,骨肉瘤与任何特征性的染色体易位无关[82]。 (参见“尤文肉瘤家族肿瘤的流行病学、病理学和分子遗传学”和“软组织与骨肉瘤的致病因素”)普通型骨肉瘤—最大的一组骨肉瘤是普通型(髓内高级别)骨肉瘤,约占所有骨肉瘤的90%[14,83]。这类肿瘤通常累及长骨干骺端(图 3),最常见于青少年和年轻成人。根据主要的细胞成分,可将普通型骨肉瘤再细分为:成骨细胞型(约占普通型骨肉瘤的50%)、软骨母细胞型(25%)或成纤维细胞型(25%)骨肉瘤(表 3)[62]。尽管组织学表现不同,但这些肿瘤的临床行为和处理相似。●成骨细胞型骨肉瘤的特征是恶性肿瘤细胞产生大量骨样基质,在其周围形成精细或粗糙的花边;大量的骨样基质可能会导致恶性间质细胞变形(图片 1)。一些肿瘤含有较厚的骨样基质小梁,形成不规则的吻合网。其矿化程度不一。●成纤维细胞型骨肉瘤主要由高级别的梭形细胞间质构成,此间质中仅有局灶区域产生骨(图片 2)。更具多形性的肿瘤可能与以前称为骨恶性纤维组织细胞瘤(malignant fibrous histiocytoma, MFH)的未分化型高级别多形性骨组织肉瘤相似,但前者有肿瘤产生的骨样基质,后者有骨膜反应性宿主编织骨(可能存在于肿瘤周围),可通过这些特点进行鉴别。●在软骨母细胞型骨肉瘤中,大部分肿瘤中均有明显的软骨基质产生。虽然大多数肿瘤往往级别较低,但软骨样区域可能含有在细胞学上非典型的细胞,是高级别肿瘤的特征。这些软骨母细胞型病灶混合产生骨性小梁的恶性梭形细胞(图片 3)。组织学变异型—除这3种普通型骨肉瘤的亚分类以外,还有几种变异型:●小细胞型●血管扩张型●多病灶型●MFH亚型最初认为这些变异型的预后较差。然而,采用现代的积极治疗,这些变异型的生物学行为似乎相似。其他亚型(近皮质骨旁骨肉瘤和骨膜骨肉瘤)的生物学行为更具惰性。骨旁骨肉瘤更常见于年龄较大的患者,骨膜骨肉瘤与典型骨肉瘤的年龄分布相似。小细胞型骨肉瘤—小细胞型骨肉瘤值得注意的地方在于,在常规光学显微镜下观察苏木精和伊红(hematoxylin and eosin, H&E)染色的切片时,可能与其他“小圆蓝色细胞肿瘤”(如,尤文肉瘤)混淆[84,85]。确诊可能需要进行免疫组织化学染色、细胞遗传学和分子遗传学检测[86,87]。 (参见“尤文肉瘤家族肿瘤的治疗”)血管扩张型骨肉瘤—血管扩张型骨肉瘤是一种高级别的血管性肿瘤,含极少量的类骨质[88]。因为其在普通X线摄影上仅有溶骨表现,因此可能与动脉瘤样骨囊肿或骨巨细胞瘤(giant cell tumor of bone, GCTB)相混淆。其肉眼看似“多囊性血袋”,通常无实性肿瘤肿块[83]。因此,在活检时可能难以获得诊断性组织。在组织学上,极少量的类骨质形成和大量的多核巨细胞(图片 4),使人联想到良性GCTB。然而,这些细胞具有高度多形性。 (参见“骨巨细胞瘤”)该型骨肉瘤的年龄分布及治疗与典型高级别骨肉瘤相同。对化疗的反应及生存情况与普通型骨肉瘤相似[89,90]。多病灶型骨肉瘤—罕见情况下,患者在诊断时表现为同步发生多处病灶,且均像是原发性肿瘤。很难确定这些病变是同步发生的多处原发灶,还是转移瘤。无论是哪一种判定结果,预后通常较差。多中心性骨肉瘤也可能具有异时性,治疗首个病灶后数年才出现其他骨性病灶。未分化型高级别多形性骨组织肉瘤—未分化型高级别多形性骨组织肉瘤(以前称为骨MFH)与骨肉瘤相似,但无类骨质产生[91]。尽管这类肿瘤在诱导化疗后的肿瘤坏死率较低,但长期生存率与普通型骨肉瘤相近[92]。表面(近皮质)骨肉瘤—表面骨肉瘤与这些髓内变异型骨肉瘤相比,在预后和治疗方面不同。这类骨肉瘤包括低级别骨旁骨肉瘤、中等级别骨膜骨肉瘤和高级别表面骨肉瘤[92-94]。对于低级别和中级别变异型,只要未侵入骨髓腔且无去分化成分,单纯手术就可能治愈[95,96]。●骨旁骨肉瘤–这类肿瘤中最常见的通常为骨旁骨肉瘤,是低级别成纤维细胞(可产生编织骨或板层骨)形成的一种表面病变。与普通型髓内骨肉瘤相比,该型发生于年龄较大(通常是20-40岁)的人群。股骨远端后侧是最常受累的部位,但也可能累及其他长骨。肿瘤起源于皮质,形成基底较宽的病变。然而,随着时间推移,病变可能侵入皮质进入骨内膜腔。常规骨旁骨肉瘤的治疗方法为单纯性手术切除,预期生存率约为90%[97,98];然而,对于有去分化成分的骨旁骨肉瘤患者,可能采用辅助化疗。●骨膜骨肉瘤–骨膜骨肉瘤是一种中等级别的软骨母细胞性表面骨肉瘤,常位于胫骨近端,与普通型髓内骨肉瘤的年龄分布相同(影像 4)。其转移的可能性高于低级别的骨旁肿瘤,但低于典型的髓内骨肉瘤。辅助化疗对骨膜骨肉瘤的作用尚有争议。由于该型骨肉瘤的转移率估计为20%,很多中心推荐行辅助化疗。然而,回顾性报告表明,该型骨肉瘤比典型骨肉瘤的结局更好(一项研究中的10年生存率为84%[99]),接受辅助化疗的患者与接受单纯手术的患者相比无获益[99,100],以及接受辅助化疗的患者中出现了数量令人担忧的第二恶性肿瘤[99]。部分由于骨膜骨肉瘤罕见,目前尚未针对这类问题进行随机试验,从而限制了可从现有文献中得出的结论。●高级别表面骨肉瘤–普通型高级别骨肉瘤也可能发生于骨表面,可能与骨旁骨肉瘤或骨膜骨肉瘤相混淆。其治疗方法与普通型髓内骨肉瘤相似。颌部骨肉瘤—另一种独特的变异型是颌部骨肉瘤,其往往发生于年龄较大的患者、呈惰性病程,相比远处转移更容易局部复发。骨外骨肉瘤—骨外骨肉瘤是一种发生于软组织的恶性肿瘤,不累及骨和骨膜,可产生类骨质、骨或软骨样物质(影像 5和影像 6)[101-106]。大多数发生于既往接受过放疗的情况下。与骨组织骨肉瘤不同,骨外骨肉瘤发生于年龄较大的患者人群,其好发的解剖学部位不同(最常见的部位为股部),且对基于多柔比星的化疗显示出相对化学抵抗[102-104,107]。通常按照具有侵袭性行为的软组织肉瘤进行治疗。 (参见“肢体和胸壁原发性软组织肉瘤的局部治疗”和“局部复发和不能切除的局部晚期四肢软组织肉瘤的治疗”和“软组织肉瘤的临床表现、组织病理学、诊断性评估及分期”和“四肢软组织肉瘤的辅助化疗与新辅助化疗”和“转移性软组织肉瘤的全身性治疗”)患者教育—UpToDate提供两种类型的患者教育资料:“基础篇”和“高级篇”。基础篇通俗易懂,相当于5-6年级阅读水平(美国),可以解答关于某种疾病患者可能想了解的4-5个关键问题;基础篇更适合想了解疾病概况且喜欢阅读简短易读资料的患者。高级篇篇幅较长,内容更深入详尽;相当于10-12年级阅读水平(美国),适合想深入了解并且能接受一些医学术语的患者。以下是与此专题相关的患者教育资料。我们建议您以打印或电子邮件的方式给予患者。(您也可以通过检索“患者教育”和关键词找到更多相关专题内容。)●基础篇(参见“患者教育:骨癌(基础篇)”)总结●骨肉瘤是一种少见的原发性恶性骨肿瘤,特征是恶性肿瘤细胞产生类骨质或不成熟的骨。 (参见上文‘引言’)●骨肉瘤的发病年龄呈双峰分布,分别出现于青春期早期和65岁以上。骨肉瘤是儿童和年轻成人最常见的原发性骨肿瘤;发病高峰年龄为13-16岁。 (参见上文‘儿童’)●大多数儿童骨肉瘤是散发性的。少数病例与遗传性易感综合征有关,例如遗传性视网膜母细胞瘤、Li-Fraumeni综合征、Rothmund-Thomson综合征(RTS),以及相关的Bloom综合征和Werner综合征。 (参见上文‘危险因素’)●通常认为成人骨肉瘤是继发性肿瘤,来自Paget骨病或一些其他良性骨病变的肉瘤性转化。美国60岁以上患者的所有骨肉瘤中半数以上为继发性,而在亚洲,Paget病相对少见,原发性骨肉瘤比例较高。 (参见上文‘成人’和‘Paget病和其他良性骨病变’)●大多数骨肉瘤患者表现为局限性疼痛,通常持续数月。体格检查中最重要的发现是软组织肿块,通常较大且触诊有压痛。就诊时,10%-20%的患者有明确的转移性疾病,最常累及肺部。 (参见上文‘临床表现’)●需要活检确诊。在仔细考虑日后根治性手术的前提下合理制定活检计划很重要,以免危及到后续治疗,尤其是保肢的机会。 (参见上文‘活检’)●骨肉瘤的组织学诊断依据是存在恶性肉瘤性间质并伴有肿瘤性类骨质和骨的产生。普通型(高级别髓内)骨肉瘤约占所有骨肉瘤的90%。其他较少见的组织学变异型包括:小细胞型、血管扩张型、多病灶型、表面(近皮质)型和骨外骨肉瘤,未分化型高级别多形性骨组织肉瘤[以前称为骨恶性纤维组织细胞瘤(MFH)],以及颌部骨肉瘤。颌部骨肉瘤较常见于年龄较大的患者中。 (参见上文‘组织学分类’)●一旦确立骨肉瘤的诊断,则分期评估应包括受累骨全段的MRI、胸部CT、锝放射性核素骨扫描和/或PET。 (参见上文‘分期诊断性检查’)致谢—UpToDate公司的编辑人员感谢对这一专题的早期版本做出贡献的Murali Chintagumpala, MD。
引言—20世纪早期,尤文肉瘤(Ewing sarcoma, ES)和外周原始神经外胚叶肿瘤(primitive neuroectodermal tumor, PNET)(以前被称为外周神经上皮瘤)最初
引言自引入前列腺特异性抗原(prostate specific antigen, PSA)筛查以来,前列腺癌诊断时的临床表现已明显改变。虽然就诊时大部分患者为局限于前列腺的病变,但仍有相当一部分患者就诊时已出现转移,转移会影响患者的生活质量,同时也是患者死亡的原因,因此转移性前列腺癌仍是重要的临床问题。最常见的转移为成骨性骨转移。这些转移通常有症状,可引起疼痛、体弱和功能障碍。前列腺癌骨转移的治疗为姑息性治疗。治疗的目标为改善生存、缓解疼痛、改善患者的活动能力以及防止并发症(如,病理性骨折、硬膜外脊髓压迫症)。本专题将总结晚期前列腺癌骨转移的治疗。治疗方法包括特异针对骨骼转移的治疗,破骨细胞抑制以防止骨受累并发症,以及针对癌症的全身性治疗。骨转移的临床表现和评估以及晚期前列腺癌患者的总体治疗策略详见其他专题。(参见“成人肿瘤患者骨转移的流行病学、临床表现及诊断”和“晚期前列腺癌骨转移:临床表现及诊断”和“播散性去势敏感性前列腺癌治疗概述”)有症状骨转移患者的治疗外照射 — 对于骨痛局限于1个部位或数量有限部位的去势抵抗性前列腺癌患者,首选治疗方法为外照射。外照射的内容详见其他专题。(参见“骨转移痛的放射治疗”)骨靶向放射性同位素 — 骨扫描发现骨转移部位存在异常核素吸收,且与骨痛密切相关,这是采取骨靶向放射性同位素治疗的先决条件。这些放射性同位素具有不同的物理特性(表 1),主要用于有症状的成骨性骨转移晚期前列腺癌患者。镭-223是一种发射α粒子的放射性物质,是唯一在经恰当选择的患者中可延长OS和减少症状性骨骼事件(symptomatic skeletal event, SSE)的放射性药物(参见下文‘镭-223’)。虽然发射β粒子的放射性同位素可缓解疼痛,但不会显著延长OS。(参见下文‘发射β粒子的放射性同位素’)镭-223 — 镭-223(223Ra)是一种发射α粒子的亲骨性元素,其衰减产生的高能量辐射距离比发射β粒子的放射性同位素短得多,因此可在治疗肿瘤时最大程度减少对正常骨髓的毒性。在多灶性症状性骨转移前列腺癌患者中,镭-223可以延长OS,并降低骨病导致的SSE。镭-223适用于治疗去势抵抗性前列腺癌、有症状骨转移和无内脏转移的患者。但是,尚未确定适合镭-223治疗患者的最佳选择标准[1]。关于在临床试验之外镭-223联合其他系统性疗法治疗去势抵抗性前列腺癌的作用,目前尚未进行系统研究,故不推荐将其与任何其他药物联合使用。(参见下文‘基于镭-223的联合治疗’)ALSYMPCA试验 — 在Ⅲ期ALSYMPCA试验中,镭-223使总体生存期和初次发生SSE的时间都有所延长[2,3]。SSE的定义是需要进行外照射来减轻骨骼症状、新发症状性病理性骨折、出现脊髓压迫或肿瘤相关的骨科手术干预。在ALSYMPCA试验中,所有患者都存在去势抵抗性前列腺癌伴多发性骨转移,且在接受多西他赛化疗后疾病仍进展或不适合接受多西他赛化疗。纳入条件还包括存在2处或更多处骨转移且没有已知内脏转移。该试验将921例患者按2:1的比例随机分配至接受最佳支持治疗加镭-223(每4周1剂,持续6个周期)或最佳支持治疗加安慰剂。可选择的最佳支持治疗包括各种二线激素疗法和双膦酸盐。骨扫描发现,大约80%的患者存在至少6个转移灶,40%存在至少20个转移灶。近60%的患者既往接受过多西他赛化疗。关键的研究结果包括[2-5]:●镭-223组的总体生存期(该试验的主要终点)显著长于安慰剂组(中位14.9个月 vs 11.3个月,HR 0.70,95%CI 0.58-0.83)[2]。所有患者亚组在生存获益方面一致,包括曾接受过和没有接受过多西他赛化疗的患者。●两组对比,首次出现SSE的时间延长且具有统计学意义(中位数为15.6个月 vs 9.8个月,HR 0.66,95%CI 0.52-0.83),SSE包括第一次需要使用外照射缓解症状、新发病理性骨折、脊髓压迫或肿瘤相关骨科手术干预[3]。如果单独分析SSE,在使用外照射缓解症状(HR 0.67)和脊髓压迫(HR 0.52)方面,两组的差异都具有统计学意义。而在新发病理性骨折(0.62)或骨科手术干预(0.72)方面,两组的差异没有统计学意义,但此类事件的数量有限。该试验进行过程中未进行常规X线摄影,因此所有SSE都为临床检查发现。●一项预先设定的亚组分析显示,对于有多西他赛用药史的患者和没有多西他赛用药史的患者,镭-223的效果相似[4]。无论既往是否使用过多西他赛,治疗的耐受性都较好,但在既往用过多西他赛的患者中,3-4级血小板减少症的发生率较高(9% vs 3%)。●与安慰剂相比,镭-223治疗的安全性良好,所有不良事件的发生率均较低;3-4级不良事件的发生率差异没有临床意义。一项最终分析考察了患者接受最后一剂镭-223后3年的长期安全性数据,证实该疗法的耐受性良好且没有出现新的安全性问题。在405例接受长期随访的患者中,1例患者发生了再生障碍性贫血,没有患者出现急性髓系白血病、骨髓增生异常综合征或新发原发性骨肿瘤[5]。在研究药物给药期间,接受镭-223治疗的患者的生活质量较好[2]。该临床试验使用了6剂镭-223(每4周1剂),这也是获得批准的镭-223给药方案。一项随机试验表明,使用更大剂量的镭-223或使用多达12个周期的延长方案并无任何益处[6]。来自有限数量患者的数据表明,给予第二个周期的镭-223(注射6剂),血液系统毒性不大且对限制疾病进展具有一些早期效果[7]。还需进行其他试验以进一步评估再治疗的作用。目前尚无随机试验比较了镭-223与其他已知可延长去势抵抗转移前列腺癌患者总生存期的药物(表 2)。目前尚未确定适合镭-223治疗的患者的最佳选择标准[1]。影响不同治疗方法的先后顺序和组合的因素见其他专题。(参见“播散性去势敏感性前列腺癌治疗概述”)基于镭-223的联合治疗 — 有学者研究了镭-223联合其他药物治疗去势抵抗性前列腺癌的作用。然而,尚未确定这种联合治疗的益处,且至少有部分数据表明,镭-223+阿比特龙会导致有害结局。鉴于这些资料,对于大部分患者,我们建议不要同时启用镭-223和阿比特龙。对于已使用阿比特龙的患者,加用镭-223是否安全以及是否有临床获益,目前还不清楚。若采取这种方案,则最好确保患者还接受骨改良药物,如唑来膦酸或地诺单抗。●两项非随机研究中,共有299例患者接受了镭-223+阿比特龙或恩杂鲁胺[8,9]。有部分患者同时接受了地诺单抗治疗,两项研究均未发现其有任何新的安全性问题,且结果提示患者的生存期有所改善。●但后来一项关于阿比特龙+镭-223或安慰剂的Ⅲ期安慰剂对照试验未能确认联合治疗的益处;而且联合治疗增加了骨折率[10]。该试验中,806例骨转移为主的去势抵抗性前列腺癌患者基本没有症状且未接受过化疗,他们接受了阿比特龙+泼尼松/泼尼松龙治疗,然后被随机分配至接受镭-223或安慰剂。中位随访22个月时,与安慰剂组相比,镭-223组中有更多的患者发生了至少1种SSE或死亡(49% vs 47%)。该研究未达到主要终点,镭-223+阿比特龙组中无SSE中位生存期为22.3个月,而单纯阿比特龙组为26个月,即使用镭-223使骨骼事件风险升高了22%。联合治疗组中的骨折发生率为29%,而对照组为11%。有一点值得注意,两组中都只有大约40%的患者接受了破骨细胞抑制剂。镭-223组中的总体生存期缩短并不具有统计学意义(30.7个月 vs 33.3个月,HR 1.195,95%CI 0.950-1.505),但可能具有临床意义。基于这些发现,加拿大卫生部(Health Canada)推荐不要将镭-223与醋酸阿比特龙+泼尼松/泼尼松龙联合应用,而欧洲药品管理局(European Medicines Agency)规定只对以下患者使用镭-223:之前接受了至少2次治疗的骨转移前列腺癌患者或不能接受任何其他治疗的患者。基于已发布的资料,我们认同这些限制,不推荐镭-223+阿比特龙的联合治疗。●值得注意的是,在后续一项随机试验中发现破骨细胞抑制剂具有降低骨折率的作用,这项PEACE Ⅲ期试验比较了恩杂鲁胺+镭-223与单用恩杂鲁胺治疗无症状或轻度症状的转移性去势抵抗性前列腺癌患者。在公布ERA 223结果后,修订了临床试验方案,强制要求所有患者使用破骨细胞抑制剂。有关其中一部分治疗患者(n=146)的初步报告显示,联合治疗与单用恩杂鲁胺(无破骨细胞抑制剂)的骨折风险分别为33%和13%,而通过强制要求持续使用破骨细胞抑制剂,上述骨折升高风险几乎全部消除,联合治疗组骨折风险变为3%,单用恩杂鲁胺组风险变为0[11]。●一项Ⅱ期试验纳入了53例存在2处或更多骨转移且未接受过化疗的去势抵抗性前列腺癌患者,将其随机分配至多西他赛+镭-223组或单独用多西他赛组[12]。联合治疗组的血清肿瘤标志物(PSA和骨碱性磷酸酶)下降更持久。单用多西他赛组的发热性中性粒细胞减少发生率更高(15% vs 0)。然而,目前尚无这种联合方案的长期安全数据,其应用仍处于试验阶段。该试验仍在进行中,更多信息可查询DORA 试验(DORA trial) (多西他赛每3周1次vs镭-223+多西他赛每6周1次)。发射β粒子的放射性同位素 — 在开发镭-223之前,临床上已对多种发射β粒子的放射性同位素评估和应用(表 1)。研究最广泛的药物为锶-89和钐-153。其他研究过的同位素包括磷-32、铼-186和铼-188[13]。●有多项临床试验评估了锶-89治疗前列腺癌骨转移的疗效[14-17]。其中最大的一项试验(757例患者)将锶-89与多西他赛化疗相联合[17]。意向治疗分析发现,各组的总体生存期和临床无进展生存期的差异均无统计学意义。●两项小型Ⅲ期随机试验比较了钐-153与安慰剂。这两项试验均发现,钐-153缓解疼痛的作用比安慰剂有效[18,19]。发射β粒子的放射性同位素的主要毒性为骨髓抑制,锶的骨髓抑制作用比钐更显著。这种毒性限制了此类物质的使用,没有证据表明使用发射β粒子的放射性同位素可延长患者生存期。双膦酸盐 — 对于尚未使用破骨细胞抑制剂的前列腺癌患者,静脉用伊班膦酸或其他双膦酸盐可能替代外照射来治疗骨转移所致疼痛。然而,美国并未批准将这些药物用于该适应证。(参见“破骨细胞抑制剂治疗乳腺、前列腺及其他部位实体瘤的骨转移”,关于‘双膦酸盐’一节)一项多中心试验纳入了470例骨转移所致疼痛的前列腺癌患者,将其随机分配至接受单次静脉用伊班膦酸(6mg)或放疗(8Gy,一次给予)[20]。4周时疼痛未缓解的患者可转为接受另一种治疗。4周和12周时,两个治疗组中疼痛缓解的差异并无统计学意义。两个治疗组的治疗转变率差异没有统计学意义(初始接受伊班膦酸的患者中为31%,初始接受放疗的患者中为24%);总体生存期的差异也没有统计学意义(中位值12.9个月 vs 12.2个月)。虽然放疗仍是大多数骨转移所致局限性骨痛患者的标准治疗方法,但对于放疗无效的患者以及特殊临床状况(如患者存在放疗禁忌证),静脉用伊班膦酸是一种有效的治疗方法。聚焦超声 — 对于标准放疗无效或不适合接受放疗的患者,采用磁共振引导聚焦超声可缓解疼痛性骨转移[21]。聚焦超声波可提高成像焦点的温度,从而引起热组织消融。一项国际多中心试验证实该方法有效且安全,因此监管机构批准了这种设备的使用[22]。(参见“骨转移瘤的影像引导下消融”,关于‘结局’一节)手术 — 一般仅对发生病理性骨折或硬膜外脊髓压迫症的转移性前列腺癌患者进行手术或椎体后凸成形术,以治疗其骨病变。(参见“肿瘤性硬膜外脊髓压迫症(包括马尾综合征)的治疗和预后”和“骨转移、多发性骨髓瘤和淋巴瘤患者中完全性病理性骨折和病理性骨折倾向的评估和处理”)镇痛药 — 若专门针对转移性疾病的措施不能充分控制癌症相关骨痛,现有多种药物可用于治疗。癌症患者中的疼痛治疗详见其他专题。(参见“阿片类药物治疗癌症疼痛:镇痛最优化”和“癌症疼痛治疗:对乙酰氨基酚和非甾体类抗炎药的使用”和“癌症疼痛治疗:辅助镇痛药(协同镇痛药)”和“癌症疼痛的心理、康复和整合治疗”)全身性抗癌治疗 — 对于转移性前列腺癌引起骨转移的患者,全身性抗癌治疗为其治疗的重要组成部分。雄激素剥夺治疗(androgen deprivation therapy, ADT)作为初始治疗以及去势抵抗性前列腺癌的多种其他治疗方式参见其他专题(参见“播散性去势敏感性前列腺癌治疗概述”)。全身性治疗还会影响SSE或SRE(skeletal-related events, SRE)的发生频率。SSE是临床上可检测到的事件,并不依赖于常规影像学检查获得的结果。SSE为临床上明显的事件,而不是临床上不明显但放射学检查可检测到的事件。已证实可降低骨骼事件发生频率的药物包括镭-223、恩杂鲁胺和阿比特龙,以及破骨细胞抑制剂地诺单抗和唑来膦酸(表 3)。(参见“去势抵抗性前列腺癌的雄激素通路靶向治疗”和‘破骨细胞抑制’)骨转移并发症的预防镭-223 — 镭-223除了可治疗骨转移引起的症状外,研究证实其还可显著降低症状性骨转移患者中的SSE发生率。SSE包括首次使用外照射缓解症状、新发病理性骨折、脊髓压迫或肿瘤相关骨科手术干预。(参见上文‘镭-223’)针对镭-223的确定性临床试验仅限于有症状骨转移患者,尚未评估其治疗无症状性骨转移患者的作用。破骨细胞抑制 — 前列腺癌患者的骨转移主要为成骨性骨转移,但也有由破骨细胞介导的显著溶骨性成分。此类患者确实会发生病理性骨折,但发生频率通常低于以溶骨性转移为主的其他癌症。此外,ADT可引起骨吸收和骨丢失增加,这会增加发生骨质疏松性骨折的风险。(参见“雄激素剥夺治疗的副作用”,关于‘骨质疏松和骨折’一节和“破骨细胞抑制剂治疗乳腺、前列腺及其他部位实体瘤的骨转移”和“骨转移的机制”,关于‘溶骨性骨转移vs成骨性骨转移’一节)骨转移所致SRE的预防 — 对于去势抵抗性前列腺癌骨转移患者,破骨细胞抑制(双膦酸盐或地诺单抗)可降低骨相关并发症的发生率,可推荐使用这些药物。然而,在激素敏感性转移性前列腺癌患者中进行的试验表明,破骨细胞抑制并不会显著降低SRE的发生率;因此,这种情况下不适合使用此类药物。去势抵抗性前列腺癌双膦酸盐 — 对于去势抵抗性前列腺癌骨转移患者,双膦酸盐可延迟SRE的发生;SRE是一个复合终点,包括病理性骨折、骨骼放疗、骨骼手术以及脊髓压迫症。对于去势抵抗性前列腺癌患者,现有充分数据支持将大多数患者的唑来膦酸剂量定为每12周1次,而非每4周1次。然而,对于存在广泛或高度症状性骨转移的患者(包括所有正在接受镭-223的患者),我们仍然倾向于采用每4周1次的剂量方案,至少最初采用该方案。(参见“破骨细胞抑制剂治疗乳腺、前列腺及其他部位实体瘤的骨转移”,关于‘给药间隔’一节)一项试验纳入了643例在接受ADT时疾病进展的患者,并证实了唑来膦酸对发生骨转移的去势抵抗性前列腺癌患者有益[23]。该试验将这些患者随机分配至接受两种唑来膦酸剂量之一(4mg或8mg)或安慰剂,各组都是每3周给药1次。由于肾毒性风险升高,研究者在试验早期将8mg剂量的唑来膦酸减至4mg。随访24个月时,唑来膦酸组的SRE发生率显著低于安慰剂组(38% vs 49%),且发生SRE的中位时间显著更长(488日 vs 321日)[24]。唑来膦酸组患者的疼痛和镇痛评分显著低于安慰剂组,但在病情进展、体能状态和生活质量评分方面,各组均无差异。其他双膦酸盐并非同样有效[25]。针对氯膦酸二钠的临床研究并未得出确定结果[26-28],两项针对帕米膦酸二钠的试验并未发现其在SRE或疼痛控制方面的益处具有统计学意义[29]。美国批准将唑来膦酸用于存在骨转移的去势抵抗性前列腺癌患者。欧洲专利药品委员会已批准将唑来膦酸用于所有发生骨转移的前列腺癌患者。地诺单抗 — 地诺单抗是一种完全人源化的单克隆抗体,该抗体可与RANK配体结合,该配体是破骨细胞形成和活化途径的关键因素。(参见“地诺单抗治疗骨质疏松”和“骨转移的机制”)研究者已在一系列的临床情况中评估了地诺单抗。地诺单抗被批准用于预防前列腺癌骨转移患者SRE的发生,以及用于治疗接受ADT前列腺癌患者的骨丢失。对于已确定存在骨转移的去势抵抗性前列腺癌患者,地诺单抗预防发生SRE的作用比唑来膦酸有效,但并不能延长总体生存期或延迟疾病进展。一项双盲Ⅲ期试验纳入了1901例至少存在一处骨转移灶的去势抵抗性前列腺癌患者,将其随机分配至接受地诺单抗(120mg)或唑来膦酸(4mg),各组都为每4周给药1次[30]。两个治疗组的患者都被建议使用钙和维生素D补充剂。该研究的主要目的是确定首次发生SRE(病理性骨折、需要进行放疗或手术或脊髓压迫症)的时间。中位随访约12个月时,得到了以下结果:●与唑来膦酸组相比,地诺单抗组首次发生SRE的时间显著更迟(中位时间20.7个月 vs 17.1个月,HR 0.82,95%CI 0.71-0.95)。●两组总体生存期(19.4个月 vs 19.8月,HR 1.03)或疾病进展时间(两组均为8.4个月,HR 1.06)的差异并无统计学意义。●两种治疗的耐受性都较好。与唑来膦酸组相比,地诺单抗组有颌部骨质坏死(osteonecrosis of the jaw, ONJ)更频繁(2.3% vs 1.3%)的趋势,但这些差异并无统计学意义。地诺单抗组中低钙血症的发生率也显著更高(13% vs 6%)。此外,地诺单抗组患者中低磷血症的发生率超过25%[31]。去势敏感性前列腺癌 — 与去势抵抗性前列腺癌患者中的结果相比,对于存在骨转移的去势敏感性前列腺癌患者,在ADT初始治疗期间开始使用唑来膦酸并无任何益处。CALGB 90202试验将645例患者随机分配至接受唑来膦酸或安慰剂[32]。该试验由于企业赞助商撤回资金支持而过早终止。中位随访24个月时,就首次发生SRE的时间而言,两组的差异并无统计学意义(中位值为31.9个月 vs 29.8个月,HR 0.97)。总体生存期差异也无统计学意义(中位数38个月 vs 36个月,HR 0.88,95%CI 0.70-1.12)。关于地诺单抗预防去势敏感性前列腺癌患者发生SRE的作用,目前尚无相关数据。预防ADT相关骨丢失 — 在接受ADT治疗前列腺癌的患者中,双膦酸盐和地诺单抗都可显著降低骨转化率以及增加骨密度。这种情况下的随机试验结果参见其他专题。(参见“雄激素剥夺治疗的副作用”,关于‘地诺单抗’一节和“雄激素剥夺治疗的副作用”)预防或延迟骨转移 — 对于未转移的去势抵抗性前列腺癌患者,随机试验并未证实双膦酸盐和地诺单抗有较好的风险/收益比。双膦酸盐 — 虽然临床前资料表明双膦酸盐对前列腺癌具有抗肿瘤作用,但对于没有骨转移的去势抵抗性前列腺癌患者,没有研究证实辅助使用双膦酸盐可显著降低骨转移的发生率。Ⅲ期ZEUS试验纳入了1433例高危前列腺癌患者(PSA≥20ng/mL、Gleason评分为8-10或存在淋巴结转移),并将其随机分配至接受唑来膦酸(每3个月4mg)或安慰剂,持续4年[33]。中位随访4.8年后,两组的骨转移(4年发病率,唑来膦酸组14.7% vs 对照组13.2%)发生率差异并无统计学意义。一项规模较小的试验采用了氯膦酸二钠,也未证实可降低骨转移的发生率[34]。地诺单抗 — 虽然地诺单抗可延迟未转移的去势抵抗性前列腺癌患者首次出现骨转移的时间,但其并不能延长总生体存期或总体无进展生存期,且会引起相当多的病例出现ONJ。地诺单抗尚未被批准用于此适应证。但对于没有骨转移但PSA升高且PSA倍增时间不到6个月的患者,可考虑使用地诺单抗。一项Ⅲ期临床试验纳入了1432例未转移的去势抵抗性前列腺癌患者,将其随机分配至接受地诺单抗或安慰剂组[35]。所有患者都接受了双侧睾丸切除术或至少持续6个月的促性腺激素释放激素激动剂或拮抗剂的连续治疗。如果连续3次测定都显示PSA升高,则确定患者为去势抵抗性。如果血清PSA≥8.0μg/L或PSA倍增时间<10个月,则将患者归类为骨转移高风险。与安慰剂相比,地诺单抗显著延长了患者的无骨转移生存期(29.5个月 vs 25.2个月,HR 0.85,95%CI 0.73-0.98)。首次发生骨转移的时间也显著推迟了4个月。然而,总体生存期的差异并无统计学意义(中位44个月 vs 45个月,HR 1.01)。该试验的一项后续探索性分析发现,PSA快速倍增的患者较短时间内出现了骨转移[36]。此外,地诺单抗对延迟骨转移发生的作用比安慰剂更明显。对于PSA倍增时间≤6个月的患者,地诺单抗组中骨转移的中位时间为25.9个月,安慰剂组为18.7个月(HR 0.77,95%CI 0.64-0.93)。地诺单抗治疗组中有5%的患者出现ONJ,而安慰剂组中没有患者出现。地诺单抗组中低钙血症的发生率更高(1.7% vs 0.3%)。钙和维生素D — 开始破骨细胞抑制剂治疗前,应评估钙和维生素D的水平,如果较低应在用药前予以纠正。如果没有禁忌证(如,之前存在高血钙症、复发性肾结石),所有接受破骨细胞抑制剂的患者都应接受钙和维生素D补充治疗,以防止发生继发性甲状旁腺功能亢进症和低钙血症,以及确保有足够的钙用于骨修复/愈合。副作用 — 虽然一些大型随机临床试验已明确使用破骨细胞抑制有益,但这些药物可引起极少数病例出现严重毒性。重要的潜在副作用包括:●ONJ●低钙血症●肾功能受损(双膦酸盐有该副作用但地诺单抗没有)并发症的潜在风险不应妨碍破骨细胞抑制剂的应用。仔细选择患者、避免对高风险患者使用这些药物以及在治疗期间持续警惕并发症,这对最大程度降低严重并发症的风险很重要[37,38]。破骨细胞抑制剂(双膦酸盐和地诺单抗)相关并发症的预防和治疗参见其他专题。(参见“抗骨吸收药物在晚期恶性肿瘤患者中的治疗风险”)学会指南链接部分国家及地区的学会指南和政府指南的链接参见其他专题。(参见“Society guideline links: Diagnosis and management of prostate cancer”和“Society guideline links: Cancer pain”)总结与推荐●中轴骨的成骨性转移是晚期前列腺癌最常见的转移部位。优选姑息治疗,目标是缓解疼痛、改善患者活动能力以及预防并发症(如,病理性骨折或硬膜外脊髓压迫)。●全身性治疗是患者综合治疗的重要部分,以控制症状并延缓骨转移进展。(参见“播散性去势敏感性前列腺癌治疗概述”)●对于全身性治疗不能控制疼痛且只有1个或数量有限的局灶性症状性骨转移的患者,我们建议行外照射而非给予静脉用伊班膦酸(Grade 2B)。(参见上文‘外照射’和‘双膦酸盐’)对于接受外照射的患者,我们建议对受累区域给予单次照射,剂量为8Gy(Grade 2A)。(参见“骨转移痛的放射治疗”,关于‘外照射’一节)●对于去势抵抗性前列腺癌患者,如果存在全身性治疗或外照射无法控制的多灶性症状性成骨性骨转移,则发射α粒子的骨靶向放射性同位素(如,镭-223)可能提供显著的姑息性治疗益处。(参见上文‘骨靶向放射性同位素’)镭-223应仅用于特定的去势抵抗性前列腺癌患者:有症状性骨转移且无内脏转移。(参见上文‘ALSYMPCA试验’)尚未证实镭-223联合全身性治疗的益处,至少有部分数据表明,同时启用镭-223+阿比特龙会导致有害结局。对于大部分患者,我们建议不要同时启用镭-223和阿比特龙(Grade 2B)。对于已使用阿比特龙的患者,加用镭-223是否安全以及是否临床有效目前还不清楚。若选用这种方案,患者还应接受骨改良药物,如唑来膦酸或地诺单抗。(参见上文‘基于镭-223的联合治疗’)●对于存在骨转移的去势抵抗性前列腺癌患者,我们推荐使用破骨细胞抑制剂(地诺单抗或唑来膦酸)来降低骨转移患者发生骨骼并发症的风险(Grade 1A)。一项大型随机试验显示地诺单抗的疗效更好,因此我们建议大多数患者使用地诺单抗而非唑来膦酸(Grade 2A)。对于费用和/或报销为重要考虑因素的患者,唑来膦酸是一种合适的替代选择。(参见上文‘去势抵抗性前列腺癌’)如果选择唑来膦酸,现有充分证据支持将大多数去势抵抗性前列腺癌患者的剂量定为每12周1次,而非每4周1次。然而,对于存在广泛或高度症状性骨转移的患者(包括所有正在接受镭-223的患者),我们仍然倾向于采用每4周1次的剂量方案,至少最初采用该方案。(参见上文‘双膦酸盐’)●控制癌症相关骨痛是患者整体治疗的一项重要内容,尤其对于已经实施了特异针对骨转移的各项措施仍无法有效控制的情况。(参见“阿片类药物治疗癌症疼痛:镇痛最优化”和“癌症疼痛治疗:对乙酰氨基酚和非甾体类抗炎药的使用”和“癌症疼痛治疗:辅助镇痛药(协同镇痛药)”和“癌症疼痛的心理、康复和整合治疗”)
Tibial Plateau FractureRelated SummariesShin painGeneral InformationDescriptionany fracture of the proximal tibia, ranging from simple lateral split to complex comminuted fracture with severe soft tissue injury1,2,3,4TypesSchatzker classification1,2,4type I - pure cleavage (split) of lateral tibial plateau type II - cleavage (split) with depression of lateral tibial plateau type III - pure central depression of lateral tibial plateau type IV - fracture of medial plateau type V - bicondylar fractures type VI - fracture with dissociation of tibia metaphysis and diaphysis Muller AO classification (also adopted by Orthopedic Trauma Association [OTA])1,2type A - extra-articular fractures A1 - avulsion A2 - metaphyseal simple A3 - metaphyseal multifragmentary type B - partial articular fractures B1 - pure split B2 - pure depression B3 - split-depression type C - complete articular fractures (with detachment of fragments from diaphysis) C1 - articular simple, metaphyseal simple C2 - articular simple, metaphyseal multifragmentary C3 - articular multifragmentary each subtype further divided into 3 additional subtypes denoting lateral (.1), medial (.2), or bilateral (.3) type often preceded by 41, with 4 denoting tibial fracture, and 1 denoting proximal location Moore classification1type I - coronal split fracture of medial tibia plateau which displaces distally type II - fracture of entire condyle type III - rim avulsion fracture type IV - rim fracture displaced distally or impacted and crushed type V - 4-part fracture where tibial eminence separates from diaphysis and condyles Definitionsknee-specific patient-reported outcome measuresInternational Knee Documentation Committee (IKDC) subjective knee evaluation formassesses improvement or deterioration in symptoms, function, and sports activities due to knee impairmentappropriate for use in patients with a variety of knee conditions, including ligament injuriesmeniscal injuriesarticular cartilage lesionspatellofemoral pain18-item scale with 3 domains assessingsymptoms, including pain, stiffness, swelling, locking/catching, and giving way (7 items)sport activities (1 item) and daily activities (9 items)current knee function (1 item) and knee function prior to knee injury (not included in the total score) responses vary for individual items, including yes/no responses, 5-point Likert scales, and 11-point numerical rating scalespossible score range is 0-100, where 100 indicates no limitation with daily or sporting activities and absence of symptoms References 22588746Arthritis Care Res (Hoboken) 2011 Nov;63 Suppl 11:S208full-textoriginal scale can be found in 11573919Am J Sports Med 2001 Sep-Oct;29(5):600, commentary can be found in 11799013Am J Sports Med 2002 JanWestern Ontario and McMaster Universities Osteoarthritis (WOMAC) Indexself-administered or interview-administered questionnaire assessing disease course or response to therapeutic intervention in patients with hip and/or knee OAconsists of 24 items divided into 3 subscales, includingpain (severity during various positions or movements; 5 items)function (difficulty performing daily functional activities; 17 items)stiffness (severity after periods of inactivity; 2 items)available in 5-point Likert scale, 11-box numerical rating scale, and 100-mm visual analog scale (VAS) formatsLikert scale - scale ranges from 0 indicating "none" to 4 indicating "extreme"11-box numerical rating scale - horizontal scale, with left end box indicating "none" and right end box indicating "extreme"100-mm VAS - scale ranges from 0 indicating "none" to 100 indicating "extreme"Reference - 22588746Arthritis Care Res (Hoboken) 2011 Nov;63 Suppl 11:S208full-textKnee injury and Osteoarthritis Outcome Score (KOOS) questionnairedeveloped as an extension of the WOMAC Index (questions from the WOMAC Index version 3.0 are included in the KOOS questionnaire)42-item questionnaire evaluating short- and long-term symptoms, and function in patients with knee injury and osteoarthritis5 KOOS subscales includepain frequency and severity during functional activities (9 items)other symptoms (7 items), such asseverity of knee stiffnesspresence of swelling, grinding or clicking, catching, and/or range of motion restrictionactivities of (function in) daily living (equivalent to function subscale in WOMAC; 17 items)function in sport and recreation (5 items)knee-related quality of life (4 items)Likert scale-based scoring system, each item has 5 possible answer options with scores ranging from 0 (no problems) to 4 (extreme problems)scores are transformed to a 0-100 scale, with higher scores indicating fewer knee problemsno aggregate score is calculated; each subscale is analyzed separatelyvalidated for anterior cruciate ligament reconstruction, meniscectomy, and total knee replacementReference - 14613558Health Qual Life Outcomes 2003 Nov 3;1:64full-textLysholm knee scoreevaluation of function in patients with knee ligament injury and anteromedial, anterolateral, combined anteromedial/anterolateral, posterolateral rotatory, or straight posterior instability8 domains of revised scale includelimpsupport (using cane or crutches)locking (locking sensation of knee)painstair climbinginstability (giving way sensation of knee)swellingsquattingscores range from 0 to 100excellent outcome 95-100 pointsgood outcome 84-94 pointsfair outcome 65-83 pointspoor outcome < 65 pointsReferences22588746Arthritis Care Res (Hoboken) 2011 Nov;63 Suppl 11:S208full-textoriginal scale can be found in 4028566Clin Orthop Relat Res 1985 Sep;(198):43Tegner activity scoreassesses ability of patients with knee ligament injuries to perform various functions related to work and sporting activitiesdeveloped to complement the Lysholm knee scale1 activity level is selected from a range of 11 levels that best represents the patient's activity levellevels range from 0 to 10, with higher levels representing participation in higher-level activitiesactivity level 0 indicates the patient is on sick leave and receiving disability due to knee problemactivity level 10 indicates the patient participates in national elite competitive sportsReferences22588746Arthritis Care Res (Hoboken) 2011 Nov;63 Suppl 11:S208full-textoriginal scale can be found in 4028566Clin Orthop Relat Res 1985 Sep;(198):43Western Ontario Meniscal Evaluation Tool (WOMET)health-related quality of life tool for patients with meniscal tears, or meniscal repair or resection16-item scale with 3 domains assessingphysical symptoms (9 items)sports/recreation/work/lifestyle (4 items)emotions (3 items)each item is scored using a VAS (100-mm lines anchored at ends by extremes of dimension being measured)total possible score ranges from 0 to 1,6000 is best or least symptomatic score1,600 is highest and most symptomatic scoremay be reported as a total overall score, score for each domain, or as a percentage of normal (to calculate percentage of normal the total score is subtracted from 1,600, divided by 1,600, then multiplied by 100)Reference - 17873546Clin J Sport Med 2007 Sep;17(5):349Oxford knee scoreassesses symptoms directly related to kneeconsists of 12 questions that are rated on a Likert scale, with values from 0 to 4a summative score is calculated, with 48 as best possible score (least symptomatic) and 0 as worst possible score (most symptomatic)Reference - 24253376Knee Surg Sports Traumatol Arthrosc 2014 Aug;22(8):1933Hospital for Special Surgery (HSS) knee scoreassessment for suspected injury to ≥ 1 knee ligamentmaximum score is 50 points, indicating normal knee functionif all subjective questions are answered as normal, 18 points are awarded; questions focus on presence of pain or swelling, difficulty with stair-climbing or cutting maneuvers, other functional impairment, and loss of confidence in kneeif all objective questions are answered as normal, 32 points are awarded; questions focus on presence of tenderness, effusion, soft tissue swelling, muscle weakness, loss of motion, or ligament laxityoutcome grading scale41-50 points considered good to excellent outcome30-40 points considered fair outcome< 30 points considered poor outcomeReferences6826594J Bone Joint Surg Am 1983 Mar;65(3):323original scale can be found in 856512Clin Orthop Relat Res 1977 Mar-Apr;(123):115EpidemiologyWho is most affectedpatients > 50 years old reported to account for > 50% of tibial plateau fractures (9531914Am Fam Physician 1998 Mar 15;57(6):1314) low-energy injury with unilateral depression fractures most common in elderly patients who have simple fall1,5high-energy injury with comminuted fracture and soft tissue damage most common in young and middle-aged patients involved in motor vehicle accident or fall from height1,5rare in young adults and children before closure of epiphyseal plate1reported to be more common in males than females1Incidence/Prevalencetibial plateau fractures reportedly account for 1.3% of all fractures18% of fractures in the elderly2Possible risk factorsosteoporosis in elderly patients1,4Associated conditionshigh-energy fractures may be associated with damage to other bony structures or solid organs1Etiology and PathogenesisCausesvehicular and vehicular-pedestrian accidents1,2,3falls1,2,3,4sporting or recreational activities (for example, tackle football, rugby)1,2medial tibial plateau fracture after medial Oxford unicompartmental knee arthroplasty in case series (mnh17549863pcxh25311315pmdc17549863pOrthopedics 2007 May;30(5 Suppl):28EBSCOhost Full Text) Pathogenesismechanisms of injury1,2,4sideways bending force (varus or valgus stress) vertical compression of lower limb (axial loading) combination of both shearing or compression from femoral condyles causing split or depression fractures History and PhysicalHistory and PhysicalHistoryChief concern (CC)knee pain or swelling4inability to bear weight on injured leg4History of present illness (HPI)knee pain secondary to trauma (such as fall or traffic accident)1,2,3,4rapid onset (within 2 hours) of large, tense, joint effusion may indicate tibial plateau fracture and hemarthrosis (mnh13678139p t ccxh10786308t c pmdc13678139p t cAm Fam Physician 2003 Sep 1;68(5):907EBSCOhost Full Textfull-text) Past medical history (PMH)ask about comorbidities that increase risk of complications3coronary artery disease emphysema heavy smoking poorly controlled diabetes PhysicalGeneral physicalexamine for associated injuries such as damage to other bony structures or solid organs, especially with high-energy injuries1confirm inability to bear weight on injured leg4Extremitiesgive appropriate analgesia before examining injured limb4assess soft tissue for1,2,3,4swelling (may be secondary to hemarthrosis) and bruising (conditions which may indicate need for staged management) abrasions, lacerations, and blisters relation of open wounds to fracture site assess for tenderness distal to knee4examine for joint effusion (mnh13678139p t ccxh10786308t c pmdc13678139p t cAm Fam Physician 2003 Sep 1;68(5):907EBSCOhost Full Text) assess neurologic and vascular status of limb1,2,4distal pulses peroneal nerve function (sensation over first web space and ankle and toe dorsiflexion) assess joint stability (examine collateral and cruciate ligaments)4assess for compartment syndrome5perform serial leg compartment exams for minimum 24 hours note tenderness on palpation note skin pallor over compartment see also Acute limb compartment syndromeDiagnosisDiagnosisDiagnosisMaking the diagnosissuspect tibial plateau fractures in patients with4knee pain and swelling secondary to trauma rapid onset of large, tense joint effusion (within 2 hours of injury) suggests hemarthrosis secondary to tibial plateau fracture (mnh13678139p t ccxh10786308t c pmdc13678139p t cAm Fam Physician 2003 Sep 1;68(5):907EBSCOhost Full Text) inability to bear weight on injured leg fracture confirmed by x-rayDifferential diagnosiscommon causes of knee pain in children and adolescents patellar subluxation patellar tendinopathy Osgood-Schlatter diseasereferred pain osteochondritis dissecans in adults patellofemoral pain syndrome medial plica syndromeanserine tendinopathy (pes anserine bursitis) ligamentous sprains meniscus tears inflammatory arthropathy septic arthritisin older adults knee osteoarthritisgoutcalcium pyrophosphate dihydrate deposition diseasepopliteal cystReference - mnh13678140p t ccxh10786314t c pmdc13678140p t cAm Fam Physician 2003 Sep 1;68(5):917EBSCOhost Full Textfull-textTesting overviewx-rays of knee (anteroposterior, lateral, and oblique) computed tomography (CT) - used when more detailed examination of bony architecture required, especially to aid surgical planning magnetic resonance imaging (MRI) - used when ligamentous or meniscal injuries are suspected if impaired limb perfusion suspected, perform duplex ultrasound or angiography1Imaging studiesx-ray anteroposterior1,2,3,4angled 10 degrees in craniocaudal direction to approximate posterior slope of plateau allows evaluation of fracture lines extending into joint and inspection of tibial spines lateral - to identify coronal plane split fractures1,2,3,4oblique - may provide more information about fracture pattern1,2,3,4see also Decision rules for x-ray use in knee injuriescomputed tomography (CT) used when more detailed examination of bony architecture required, especially to aid surgical planning1,2axial, sagittal, and coronal reconstructions can provide information about2,3,53-dimensional fracture pattern articular involvement degree of comminution can help diagnosis bony ligament avulsions2less useful with gross tibial displacement, angulation or shortening, and often beneficial to wait until leg length has been restored with external fixator before performing for clearer images of fracture fragments3,5magnetic resonance imaging (MRI) used when ligamentous or meniscal injuries are suspected1,2,5cannot be done after fixation with metal devices5comparative efficacy use of CT scan or MRI in addition to x-rays may change treatment plan in up to a quarter of patientsbased on 2 diagnostic cohort studies 52 tibial plateau fractures evaluated using knee x-rays (anteroposterior, lateral, 2 oblique views), CT scan, and MRI 3 surgeons were randomly assigned to evaluate x-rays alone vs. x-rays with CT vs. x-rays with MRI (including soft tissue injuries documented by experienced MRI radiologist) compared to x-rays alone, fracture classification changed with addition of CT scan in 6% of cases addition of MRI in 21% of cases MRI changed treatment plan in 23% of cases CT scan changed treatment plan in 9% of cases Reference - 12368643J Orthop Trauma 2002 Oct;16(9):63221 tibial plateau fractures evaluated using knee x-rays and CT scans 2 orthopedic traumatologists, 2 orthopedic residents, and 2 skeletal radiologists evaluated fractures using x-rays alone vs. x-rays in combination with CT scan addition of CT scan changed treatment plan in mean 26% of cases Reference - 9334949J Orthop Trauma 1997 Oct;11(7):484American College of Radiology (ACR) Appropriateness Criteria for acute trauma to knee can be found at ACR 2014 PDFdiscussion of radiologic evaluation of the lower extremity can be found in 9531914Am Fam Physician 1998 Mar 15;57(6):1314full-textManagementTreatmentTreatmentManagement overviewstable, minimally displaced fractures may be treated conservatively with splint, long leg cast, or cast brace for 8-12 weeks1,2medical managementopen fractures require antibiotic prophylaxis check tetanus immunization and update as needed consider deep vein thrombosis prophylaxis assess for compartment syndrome5perform serial leg compartment exams for minimum 24 hours note tenderness on palpation note skin pallor over compartment see also Acute limb compartment syndromesurgical managementsurgery indicated for intra-articular fractures with > 2 mm joint depression or separation significantly displaced metaphyseal components or metaphyseal components angulated > 5 degrees open injuries fractures with vascular injury fractures with associated ligamentous injuries requiring stabilization surgical options include external fixation with or without limited internal fixation internal fixationscrew fixationpercutaneous screw fixation - used for Schatzker type I (AO type B1) or low-energy type IV fractures raft screw construct - used for pure depression fractures (Schatzker type III) staged management - external fixation used to allow soft tissue injuries to recover before definitive internal fixation give first-generation cephalosporin within 1 hour prior to surgical incision and continue for 24 hours Activityundisplaced fractures can be treated with immobilization1,2splint, long leg cast, or cast brace for 8-12 weeks brace initially locked in extension progressive range of motion may be increased up to 90 degrees by 4 weeks bed rest appropriate for short period patient may begin knee range of movement exercises after 4-6 weeks 4-8 weeks of nonweight bearing with crutches Medicationsfor open fractures1give antibiotic prophylaxis cephalosporin antibiotic appropriate as first-line treatment aminoglycoside may be added in case of motor vehicle accident with mild contamination add anaerobe cover in case of farm-yard injury make sure tetanus immunization is current or give booster if needed consider deep vein thrombosis prophylaxis1in children with uncomplicated extremity fractures, oral ibuprofen is as effective as oral morphine for pain reduction and has fewer adverse events (level 1 [likely reliable] evidence)Randomized Trialmnh25349008pmdc25349008pCMAJ 2014 Dec 9;186(18):1358studySummary1based on randomized trial Randomized Trial183 children (mean age 11 years) presenting to emergency department with uncomplicated extremity fracture that did not require surgery were randomized to ibuprofen 10 mg/kg vs. morphine 0.5 mg/kg orally up to 4 doses every 6 hours as needed for 24 hours after discharge fracture locations included radius, ulna, clavicle, humerus, elbow, forearm, tibia, and fibula 26.8% did not have severe enough pain to require analgesics and were excluded from modified intention-to-treat analysis pain assessed immediately before and 30 minutes after every dose on Revised Faces Pain Scale (range 0-5, with higher score indicating more severe pain), minimal clinically important difference was ≥ 1-point difference patients in both groups had median pain score of 2 at discharge comparing ibuprofen vs. morphine mean reduction in pain score after first dose 1.3 vs. 1.5 (not significant) adverse events in 30.9% vs. 56.1% (p < 0.01, NNH 4) consistent results for pain reduction after each subsequent dose in subgroups of children taking multiple doses PubMed25349008CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne20141209CMAJ1861813581358 Reference - mnh25349008pmdc25349008pCMAJ 2014 Dec 9;186(18):1358EBSCOhost Full TextSurgery and proceduresPresurgery considerationssurgical indications include1intra-articular fractures with > 2 mm joint depression or separation significantly displaced metaphyseal components or metaphyseal components angulated > 5 degrees open injuries fractures with vascular injury fractures with associated ligamentous injuries requiring stabilization open fractures may require debridement1to prevent infection, begin first-generation cephalosporin within 1 hour prior to surgical incision and continue for 24 hours3optimal surgical results achieved by3providing stable fixation restoring coronal tibial alignment using soft tissue sparing techniques current surgical options focus on indirect reduction techniques and soft tissue preservation methods rather than anatomic reconstruction with rigid fixation5staged management (external fixation followed by internal fixation) may be required for fractures associated with significant soft tissue injuries2,3,5allows resolution of soft tissue injuries before definitive surgery while preventing further cartilaginous or soft tissue damage definitive fracture surgery may be delayed for up to 3 weeks1,2,3reduces risk of wound breakdown, infection, loss of knee function, or loss of limb due to early operation in presence of soft tissue damage1knee-spanning external fixation devices used for maximum 3 weeks3,5staged management reportedly effective with low complication rate in treatment of patients with high-energy tibial plateau fractures (level 3 [lacking direct] evidence)Case Series16056075J Orthop Trauma 2005 Aug;19(7):448studySummary3based on case series Case Series53 patients (mean age 47 years) with 57 high-energy tibial plateau fractures treated with immediate knee-spanning external fixation followed by definitive repair with plates and screw constructs or conversion to ring fixator mean follow-up 15.7 months mean Western Ontario McMaster (WOMAC) functional knee score 91 range of knee motion at final follow-up 1 degree to 106 degrees complications included deep wound infections in 5% nonunions in 4% significant knee stiffness (< 90 degrees) in 4% need for additional surgery in 16% PubMed16056075Journal of orthopaedic trauma20050801J Orthop Trauma197448448 Reference - 16056075J Orthop Trauma 2005 Aug;19(7):448limited evidence for negative wound pressure therapy in patients with grade III B tibial fracturesSystematic Review25595096Clin Orthop Relat Res 2015 May;473(5):1802studySummarylimited evidence for negative wound pressure therapy in patients with grade III B tibial fractures (Clin Orthop Relat Res 2015 May)04/27/2015 07:16:00 AMHospital_MedicineMusculoskeletal_DisordersOrthopedic_DisordersSurgery_and_ProceduresHospital_Medicine Musculoskeletal_Disorders Orthopedic_Disorders Surgery_and_Procedureslimited evidence for negative wound pressure therapy in patients with grade III B tibial fractures (Clin Orthop Relat Res 2015 May)04/27/2015 07:16:00 AM255950964based on systematic review of mostly observational studies Systematic Reviewsystematic review of 13 studies (1 randomized trial and 12 observational studies) evaluating negative wound pressure therapy in patients with grade III B tibial fracturesno study provided information regarding timing of internal fixation or duration of external fixation statistical analysis not performed, statistical analyses of individual studies not reported comparing negative wound pressure therapy to gauze dressings, negative wound pressure therapy associated with decreased infection rates in 2 of 4 studies negative wound pressure therapy associated with longer time (> 72 hours) to wound coverage without increase in infection rates in 8 of 10 studies decreased rates of flap surgery in 6 of 6 studies PubMed25595096Clinical orthopaedics and related research20150501Clin Orthop Relat Res473518021802 Reference - 25595096Clin Orthop Relat Res 2015 May;473(5):1802negative pressure wound therapy may decrease rate of deep infections compared to gauze dressing in patients with severe open fractures (level 2 [mid-level] evidence)based on small randomized trial 59 patients with severe open fractures were randomized to negative pressure wound therapy vs. standard fine mesh gauze dressing prior to wound closure and followed for 9 months all patients had repeat irrigation and debridement every 48-72 hours until wound closure interventions applied to wounds between irrigation and debridement procedures most common fractures included tibial (42%), pilon (13%), and femur (16%) fractures comparing negative pressure wound therapy vs. gauze dressing, deep infections in 5.4% vs. 28% overall (p = 0.024, NNT 5) 8% vs. 36% (no p value reported) in subgroup of patients with tibial fractures in patients with wound infections, negative pressure wound therapy associated with significantly improved health-related quality of life Reference - 19704269J Orthop Trauma 2009 Sep;23(8):552, commentary can be found in 20418741J Orthop Trauma 2010 May;24(5):329External fixationbenefits over internal fixation include earlier knee movement and preservation of soft tissues2risks include pin site infection and septic arthritis2may be used as definitive treatment in patients with extensive soft tissue damage requiring flap coverage or with other contraindications to internal fixation1,2,3often used in conjunction with limited internal fixation2,5circular external fixator application with limited internal fixation associated with shorter hospital stay and fewer complications but similar long-term outcomes compared to open reduction and internal fixation in patients with bicondylar tibial plateau fractures (level 2 [mid-level] evidence)Randomized Trial17142411J Bone Joint Surg Am 2006 Dec;88(12):2613studySummary2based on randomized trial with blinding of outcome assessors not stated Randomized Trial82 patients with 83 bicondylar tibial plateau fractures (Schatzker types V and VI; Orthopedic Trauma Association [OTA] types C1, C2, and C3) randomized to circular external fixator application vs. open reduction and internal fixation and followed for 2 years comparing circular fixator vs. open reduction and internal fixation mean hospital stay 9.9 days vs. 23.4 days (p = 0.024) percentage of patients who returned to preinjury activity 20% vs. 2.8% (p = 0.031, NNT 6) at 6 months 27% vs. 5.7% (p = 0.024, NNT 5) at 1 year 30% vs. 12% (p = 0.128) at 2 years total number of complications and reoperations 0.37 per patient vs. 0.93 per patient (p = 0.001) no significant difference in range of motion or knee function as measured by Hospital for Special Surgery (HSS) knee score PubMed17142411The Journal of bone and joint surgery. American volume20061201J Bone Joint Surg Am881226132613 Reference - 17142411J Bone Joint Surg Am 2006 Dec;88(12):2613no further randomized trials identified in systematic review (mnh18175135pcxh34454227pmdc18175135pArch Orthop Trauma Surg 2008 Oct;128(10):1169EBSCOhost Full Text) hybrid fixators hybrid or ring external fixation plus minimal internal fixation reportedly leads to high rate of united fractures in patients with severe tibial plateau fracture (level 3 [lacking direct] evidence)Case Seriesmnh16628996przh106316486pcxh20643996pmdc16628996pOrthopedics 2006 Apr;29(4):355studySummary3based on case series Case Series110 patients with 112 severe intra-articular fractures of the upper tibia (Schatzker type IV, V, and VI) treated with external fixation with wire rings or hybrid frames and minimal internal fixation and followed for mean 5 years fracture united in 99% at mean 13.5 weeks subjective patient assessment excellent or good in 83% functional score excellent or good in 74% no significant difference in clinical results between patients with knee bridging or nonbridging fixation PubMed16628996Orthopedics20060401Orthopedics294355355 Reference - mnh16628996przh106316486pcxh20643996pmdc16628996pOrthopedics 2006 Apr;29(4):355EBSCOhost Full Textexternal circular fixation and limited internal fixation reportedly leads to excellent or good results in patients with complex tibial plateau fractures (level 3 [lacking direct] evidence)Case Series17993949J Trauma 2007 Nov;63(5):1043studySummary3based on case series Case Series59 patients aged 23-63 years with complex tibial plateau fractures (Schatzker types V, VI; OTA types 41-C1.3, C2.3, C3.1, or C3.3) treated with limited internal fixation and circular fixation (hybrid Ilizarov method) used in 1 of 3 ways frame confined to tibia if fixation stable enough to allow knee bending frame extended to distal femur with proximal tibial ring located at level of tibial plateau if joint surface severely unstable frame extended onto distal femur with proximal tibial ring located more distally if skin and soft tissue compromised and no suitable bone for wires or pins placement 30 patients had results evaluated as excellent 27 patients had results evaluated as good PubMed17993949The Journal of trauma20071101J Trauma63510431043 Reference - 17993949J Trauma 2007 Nov;63(5):1043hybrid fixation with or without minimal internal reduction reportedly leads to high rate of union in patients with bicondylar tibial plateau fracture (level 3 [lacking direct] evidence)Case Seriesa9h65278975pmdc21756337pJ Orthop Surg Res 2011 Jul 14;6:35Full TextstudySummary3based on case series Case Series33 patients with 33 bicondylar tibial plateau fractures (Schatzker type V or VI) were treated all patients had hybrid external fixator 19 patients also had open reduction using cannulated screws fracture united in 32 patients (97%) mean time to radiographic evidence of union 3.4 months functional use of knee regained in 26 patients (78.8%) minor complications occurred in 5 patients (15.1%) 1 patient (3%) had major complications including septic nonunion and osteomyelitis requiring revision surgery PubMed21756337Journal of orthopaedic surgery and research20110714J Orthop Surg Res63535 Reference - a9h65278975pmdc21756337pJ Orthop Surg Res 2011 Jul 14;6:35EBSCOhost Full Textfull-textmodified hybrid fixator reported to result in union of high-energy tibial plateau fracture at mean 14 weeks (level 3 [lacking direct] evidence)Case Series21589678Strategies Trauma Limb Reconstr 2011 Apr;6(1):21Full TextstudySummary3based on case series Case Series33 patients with high-energy tibial plateau fractures (Schatzker type V or VI) treated with hybrid fixator combining Ilizarov ring with modified external fixator all fractures united at mean 14 weeks 8 patients developed pin track infection 1 patient developed septic arthritis of the knee PubMed21589678Strategies in trauma and limb reconstruction (Online)20110401Strategies Trauma Limb Reconstr612121 Reference - 21589678Strategies Trauma Limb Reconstr 2011 Apr;6(1):21full-textindirect reduction using traction table and hybrid external fixator reportedly effective for treatment of comminuted tibial plateau fractures (level 3 [lacking direct] evidence)Case Series21846003Acta Orthop Belg 2011 Jun;77(3):349studySummary3based on case series Case Series28 patients (mean age 35 years) with high-energy tibial plateau fractures (Schatzker type V or VI) treated by indirect reduction using traction table and hybrid external fixation mean time to healing 3.2 months mean range of knee movement 110 degrees Rasmussen knee functional score satisfactory in 23 cases unsatisfactory in 5 cases PubMed21846003Acta orthopaedica Belgica20110601Acta Orthop Belg773349349 Reference - 21846003Acta Orthop Belg 2011 Jun;77(3):349small wire external fixation with or without internal fixation reported to result in near full range of motion after high-energy tibial plateau fractures (level 3 [lacking direct] evidence)Case Seriesmnh17709848pmdc17709848pJ Orthop Surg (Hong Kong) 2007 Aug;15(2):137PDFstudySummary3based on case series Case Series38 patients aged 18-60 years with high-energy tibial plateau fracture (Schatzker type V or VI) had small wire external fixation with or without internal fixation at follow-up ≥ 2 years postsurgery mean range of knee movement 132 degrees mean Rasmussen radiological score 14 (on 18 point scale) mean Rasmussen functional score 26 (on 30 point scale) complications included 2 superficial infections, 3 pin site infections, and 4 peroneal nerve palsies PubMed17709848Journal of orthopaedic surgery (Hong Kong)20070801J Orthop Surg (Hong Kong)152137137 Reference - mnh17709848pmdc17709848pJ Orthop Surg (Hong Kong) 2007 Aug;15(2):137EBSCOhost Full TextPDFEBSCOhost Full Textmajority of patients with high-energy tibial plateau fractures treated with fine-wire fixation and limited internal fixation reported to have fair or poor clinical rating scores (level 3 [lacking direct] evidence)Case Series16243333Injury 2005 Dec;36(12):1467studySummary3based on case series Case Series18 patients with complex tibial plateau fractures (14 Schatzker type VI and 4 Schatzker type V) were treated with fine-wire fixation with or without limited internal fixation and followed for mean 28.2 months all fractures united, although 3 cases of delayed union required additional procedures and bone grafting excellent or good Knee Society Clinical Rating scores in 38.9% fair or poor Knee Society Clinical Rating scores in 61.1% PubMed16243333Injury20051201Injury361214671467 Reference - 16243333Injury 2005 Dec;36(12):1467monolateral external fixation with limited internal fixation reported to result in satisfactory knee function and low rate of arthrosis in patients with tibial plateau fracture (level 3 [lacking direct] evidence)Case Series12208910J Bone Joint Surg Am 2002 Sep;84-A(9):1541studySummary3based on case series Case Series30 patients with 31 tibial plateau fractures were treated with monolateral external fixation and limited internal fixation 23 patients with 24 fractures were evaluated at mean 98 months no patient required further reduction surgery 19 patients rated outcome as excellent or good mean knee range of motion 87% compared to contralateral knee mean Iowa knee score 90 points (on 100 point scale) mean articular step off 3.3 mm grade-2 or grade-3 arthrosis in 21% PubMed12208910The Journal of bone and joint surgery. American volume20020901J Bone Joint Surg Am84-A(915411541 Reference - 12208910J Bone Joint Surg Am 2002 Sep;84-A(9):1541knee-spanning (knee-bridging) external fixation (vs. knee-sparing or nonknee-bridging) knee-spanning fixation increases stability in comminuted and osteoporotic bones beneficial for soft tissue healing required if major arterial disruption repaired indications for knee-spanning extension include extensive fracture comminution severe soft tissue damage anterior cruciate ligament deficiency knee extensor damage popliteal artery repair Reference - mnh16628996przh106316486pcxh20643996pmdc16628996pOrthopedics 2006 Apr;29(4):355EBSCOhost Full Texttibiofemoral extension of external fixation associated with similar clinical outcome as nonbridging fixation in patients with tibial plateau fracture (level 2 [mid-level] evidence)based on 2 retrospective cohort studies 112 patients with severe intra-articular fractures of the tibia plateau treated with minimal internal fixation and external fixation with ring or hybrid frames and followed for mean 5 years 82 patients (73.2%) had knee-bridging external fixation no significant difference in clinical or radiological results Reference - mnh16628996przh106316486pcxh20643996pmdc16628996pOrthopedics 2006 Apr;29(4):355EBSCOhost Full Text48 patients with tibial plateau fractures (Schatzker type V or VI) treated with minimally invasive internal and small wire external fixation and followed for mean 38 months 30 patients (62.5%) had extension of external fixation to distal femur (joint spanning fixation) 47 patients (98%) healed at mean 13.5 weeks 36 patients (76%) had excellent or good final clinical result no significant difference between bridging and nonbridging external fixation Reference - 15795572J Orthop Trauma 2005 Apr;19(4):241, correction can be found in J Orthop Trauma. 2006 Jan;20(1):69 pin site care different pin site care regimens may have similar effect on infection rates (level 2 [mid-level] evidence)Cochrane ReviewchhCD004551Cochrane Database Syst Rev 2013 Dec 3;(12):CD004551studySummary2based on Cochrane review of trials with methodological limitations Cochrane Reviewsystematic review of 11 randomized trials evaluating cleansing or dressing regimens for orthopedic percutaneous pin sites in 572 patients with orthopedic fractures all trials lacked blinding of outcome assessors or had unclear allocation concealment no significant differences in infection rates comparing cleansing vs. no cleansing in analysis of 3 trials with 295 patients, results limited by significant heterogeneity sterile antiseptic vs. sterile nonantiseptic solutions in analysis of 3 trials with 920 patients different cleansing methods in analysis of 2 trials with 691 patients different types of dressing in 4 trials CochraneCD004551The Cochrane database of systematic reviews20131203Cochrane Database Syst Rev12CD004551CD004551 Reference - chhCD004551Cochrane Database Syst Rev 2013 Dec 3;(12):CD004551evidence-based guideline on skeletal pin site care from National Association of Orthopaedic Nurses can be found in rzh106623751t pc8h106623751t pOrthop Nurs2005 Mar-Apr;24(2):99Internal fixationscrews, dual plating, or locked plates/fixed-angle devices may be used to stabilize fracture3surgical approaches1anterior-lateral and postero-medial approaches most commonly used, often combined in bicondylar fractures posterior approach with patient in prone position may be used, but may be more challenging for surgeon and has higher risk of neurovascular complications traditional ventral midline incision rarely used due to high risk of wound complications open reduction and internal fixation reportedly allows good alignment and soft tissue injury repair with low complication rates in patients with tibial plateau fracture (level 3 [lacking direct] evidence)Case Seriesmnh15633959pmdc15633959pOrthopedics 2004 Dec;27(12):1281studySummary3based on retrospective case series Case Series114 patients (mean age 43 years) with 117 tibial plateau fractures treated with open reduction and internal fixation and followed for mean 29 months fixation methods included K-wires, screws, buttress plates, compression plates, and combination of multiple methods according to Rasmussen functional score excellent results in 68% good result in 13% fair result in 11% poor result in 9% complications included compartment syndrome in 23% wound infection in 4% deep vein thrombosis in 1.8% PubMed15633959Orthopedics20041201Orthopedics271212811281 Reference - mnh15633959pmdc15633959pOrthopedics 2004 Dec;27(12):1281EBSCOhost Full Textless invasive stabilization system (LISS) fixation allows less disruption of soft tissue compared to traditional plating techniques2LISS fixation associated with similar union rate and knee function as conventional double plating in patients with bicondylar tibial plateau fracture, but may cause higher incidence of postoperative malalignment (level 2 [mid-level] evidence)Randomized Trial18215801Knee 2008 Mar;15(2):139studySummary2based on randomized trial without intention-to-treat analysis Randomized Trial96 patients with bicondylar tibial plateau fractures (AO/OTA type C) randomized to plate fixation by LISS vs. plate fixation by classic double plates and followed for ≥ 24 months 84 patients included in analysis comparing LISS vs. double plates union at 6 months in 100% vs. 97.7% (not significant) postoperative malalignment occurred in 14.6% vs. 2.3% (p = 0.041, NNH 8) mean HSS score (measure of knee function) at 12 months 81.8 vs. 80.3 (not significant) LISS associated with trend toward increased hardware irritation (12.2% vs. 0%, p = 0.057) no significant difference in other complications PubMed18215801The Knee20080301Knee152139139 Reference - 18215801Knee 2008 Mar;15(2):139LISS fixation reportedly effective for treatment of complex tibial plateau fracture (level 3 [lacking direct] evidence)based on 3 case series 38 patients with complex tibial plateau fracture (OTA type 41C) treated with LISS and followed for mean 15 months fracture united in 36 patients (95%) at 4 months postsurgery 2 patients (5%) had prophylactic autogenous bone grafting and fracture united 3 months postgrafting significant loss of knee range of motion (< 90 degrees) occurred in 5 patients (13%) Reference - 15345983J Trauma 2004 Aug;57(2):34033 patients with 34 tibial plateau fractures (OTA type 41C) treated with LISS and followed for ≥ 12 months all fractures healed without further surgery or bone grafting mean time to complete union 15.6 weeks articular step-off average 0.8 mm no cases of deep infection or osteomyelitis Reference - 15475852J Orthop Trauma 2004 Sep;18(8):55225 patients with 26 tibial plateau fractures (AO type A2, A3, C1, C2, or C3) treated with LISS and followed for 3 years varus malalignment occurred in 1 patient with intra-articular fracture severe knee arthrosis and total knee replacement occurred in 2 patients with type AO 41 C3.3 fractures delayed union occurred in 1 patient implants removed from 2 patients Reference - 16456310Clin Orthop Relat Res 2006 Apr;445:222Screw fixationpercutaneous screw fixation1,2fixation of fracture with 2 cancellous screws across fracture2can be used for Schatzker I (AO B1) or low-energy type IV fractures2less suitable for fractures with comminution or significant joint depression2closed reduction and percutaneous screw fixation reported to be effective in patients with displaced tibial plateau fractures (level 3 [lacking direct] evidence)Case Series1428164Injury 1992;23(6):387studySummary3based on case series of 13 patients with displaced tibial plateau fractures Case Series11 of 13 had satisfactory results 1 patient had persistent pain 1 patient had failed fixation PubMed1428164Injury199201Injury236387387 Reference - 1428164Injury 1992;23(6):387raft screw construct may be used for pure depression fractures (Schatzker type III)2depressed fracture elevated, then supported by raft of screws2residual defects may require grafting2four 3.5 mm screws reported to result in statistically significantly stronger repair compared to two 6.5 mm screws in biomechanical study (16647262Knee 2006 Jun;13(3):231) Arthroscopymay be used for assessment of soft tissue injuries and management of articular surface2arthroscopic management associated with similar functional outcome and faster postoperative rehabilitation compared to conventional open reduction in patients with tibial plateau fracture (level 2 [mid-level] evidence)Cohort Studymnh12720016pcxh16922510pmdc12720016pArch Orthop Trauma Surg 2003 Nov;123(9):489studySummary2based on retrospective cohort study Cohort Study28 patients with tibial plateau fracture (Schatzker type II, III or V) treated with arthroscopically-assisted management (19 patients) or conventional open reduction (9 patients) and followed for ≥ 1 year comparing arthroscopic management vs. open reduction mean time to achieve 120 degrees of flexion 4.6 weeks vs. 9.1 weeks (p < 0.05) anatomical reduction (< 2 mm residual displacement postsurgery) in 84% vs. 55% (no p value reported) mean flexion of knee at follow-up 151.3 degrees vs. 148.9 degrees (not significant) PubMed12720016Archives of orthopaedic and trauma surgery20031101Arch Orthop Trauma Surg1239489489 Reference - mnh12720016pcxh16922510pmdc12720016pArch Orthop Trauma Surg 2003 Nov;123(9):489EBSCOhost Full TextBone graft and bone graft substitutesused in cases where depressed fractures have been elevated, leaving bone defect2calcium phosphate cement associated with similar functional outcomes (level 2 [mid-level] evidence), but higher rate of articular subsidence (level 3 [lacking direct] evidence) compared to autogenous bone graft in patients with unstable tibial plateau fracturesRandomized Trial18829901J Bone Joint Surg Am 2008 Oct;90(10):2057studySummarybased on randomized trial with differential loss to follow-up Randomized Trial119 patients aged 16-77 years with acute, closed, unstable tibial plateau fractures (Schatzker types I-VI) undergoing open reduction and internal fixation randomized to subarticular grafting with calcium phosphate cement vs. subarticular grafting with autogenous bone graft follow-up exams at 6 weeks, 3 months, 6 months, and 12 months 13.4% of calcium phosphate cement patients vs. 31.6% of autogenous bone graft patients lost to follow-up before 6-month exam no significant differences in range of motion measurements at 6 or 12 months subsidence of ≥ 2 mm on anteroposterior x-rays occurred in 9% of calcium phosphate cement group vs. 30% of autogenous bone graft group (p = 0.009, NNT 5) PubMed18829901The Journal of bone and joint surgery. American volume20081001J Bone Joint Surg Am901020572057 Reference - 18829901J Bone Joint Surg Am 2008 Oct;90(10):2057bioactive glass granules associated with similar outcomes compared to autogenous bone graft in patients with depressed, comminuted tibial plateau fracture (level 2 [mid-level] evidence)Randomized Trialcxh60278475pmdc21431354pJ Mater Sci Mater Med 2011 Apr;22(4):1073studySummary2based on small randomized trial Randomized Trial25 patients with depressed unilateral comminuted tibial plateau fracture (AO type B2 and B3) randomized to bioglass vs. autogenous bone graft and followed for 1 year no significant difference in redepression of articular surface, functional outcomes, valgus alignment, or patients' subjective evaluation PubMed21431354Journal of materials science. Materials in medicine20110401J Mater Sci Mater Med22410731073 Reference - cxh60278475pmdc21431354pJ Mater Sci Mater Med 2011 Apr;22(4):1073EBSCOhost Full TextPostsurgery carepostsurgical analgesia considerations3morphine or hydromorphone IV (patient-controlled) for 1-2 days after day 2, transition to oral pain control avoid peripheral nerve blocks (may mask signs of compartment syndrome) avoid nonsteroidal anti-inflammatory drugs (NSAIDS) for 6 weeks following surgery (may inhibit bone healing) activity restrictions and weight bearing specific to individual patient and based on3fracture pattern type of stabilization used presence of other injuries patient's ability to mobilize safely physical therapy may be possible at postoperative day 1 with focus on range of motion exercises to regain movement and nourish articular cartilage2,3Consultation and referralorthopedic surgeon Complications and PrognosisComplications and PrognosisComplicationssoft tissue bruising or swelling1,3compartment syndrome1knee stiffness (may be due to initial injury, surgery, scarring, or immobilization)2,3infection2,3osteoarthritis (may be due to initial chondral damage, residual articular discontinuity, or postoperative disrupted mechanical axis)2malunion or nonunion2wound dehiscence3deep vein thrombosis (DVT)2peroneal nerve injury2avascular necrosis of articular fragments2loss of limb3Prognosisneed for total knee arthroplasty at 10 years about 7.3% for patients having fixation surgery for tibial plateau fracture and about 1.8% for general populationCohort Study24430414J Bone Joint Surg Am 2014 Jan 15;96(2):144studySummarybased on retrospective cohort study Cohort Study8,426 patients ≥ 16 years old (median age 49 years) who had fixation surgery for tibial plateau fracture were matched to 33,698 controls (without fracture) matching was by age (same calendar year), sex, income quintile, and urban/rural residence rates of total knee arthroplasty comparing surgery vs. controls (p < 0.0001 for trend, no pairwise comparisons reported) 0.32% vs. 0.29% at 2 years 5.3% vs. 0.82% at 5 years 7.3% vs. 1.8% at 10 years surgery associated with increased risk of total knee arthroplasty after adjustment for comorbidities (hazard ratio 5.3, 95% CI 4.6-6.1) PubMed24430414The Journal of bone and joint surgery. American volume20140115J Bone Joint Surg Am962144144 Reference - 24430414J Bone Joint Surg Am 2014 Jan 15;96(2):144in most patients treated surgically, fractures appear to have uneventful union by 1 year, but approximately one-third have secondary osteoarthritis at mean 14 years (level 2 [mid-level] evidence)Cohort Study17211262J Orthop Trauma 2007 Jan;21(1):5studySummary2based on retrospective cohort study Cohort Study202 patients (mean age at injury 46 years) with surgically treated tibial plateau fracture were followed for 1 year at 1 year uneventful union occurred in 95% mean range of motion 130 degrees in 109 patients with additional follow-up at mean 14 years (range 5-27 years) mean range of motion 135 degrees functional results significantly better for monocondylar fractures compared to bicondylar fractures 31% of patients developed secondary osteoarthritis patients with malalignment > 5 degrees developed moderate-to-severe osteoarthritis more often than patients with anatomic knee axis (27% vs. 9.2%, p = 0.02) no correlation between age and functional results PubMed17211262Journal of orthopaedic trauma20070101J Orthop Trauma21155 Reference - 17211262J Orthop Trauma 2007 Jan;21(1):5, correction can be found in J Orthop Trauma. 2007 Mar;21(3):218 secondary osteoarthritis may be common in patients with tibial plateau fracture, especially after removal of meniscus (level 2 [mid-level] evidence)Cohort Study7562147J Orthop Trauma 1995;9(4):273studySummary2based on cohort study Cohort Study131 patients with tibial plateau fracture evaluated at mean 7.6 years follow-up secondary osteoarthritis occurred in 44% overall 74% of cases with removal of meniscus 37% of cases without removal of meniscus PubMed7562147Journal of orthopaedic trauma199501J Orthop Trauma94273273 Reference - 7562147J Orthop Trauma 1995;9(4):273smoking associated with increased risk of nonunion in tibial and other long-bone fracturesSystematic Review24740664J Bone Joint Surg Am 2014 Apr 16;96(8):674studySummarybased on systematic review of observational studies Systematic Reviewsystematic review of 19 cohort studies evaluating the effect of cigarette smoking on long-bone fracture healing in 6,356 adults with 6,374 fractures compared to no smoking, smoking associated with increased risk of nonunion of tibial fracture (odds ratio [OR] 2.16, 95% CI 1.55-3.01) in analysis of 7 studies with 925 fractures nonunion of any long-bone fracture (OR 2.32, 95% CI 1.76-3.06) in analysis of 10 studies with 1,221 fractures open fracture nonunion (OR 1.95, 95% CI 1.3-2.9) in analysis of 4 studies with 658 fractures no significant differences in healing time or infections PubMed24740664The Journal of bone and joint surgery. American volume20140416J Bone Joint Surg Am968674674 Reference - 24740664J Bone Joint Surg Am 2014 Apr 16;96(8):674Prevention and ScreeningPrevention and Screeningnot applicable Quality ImprovementMedicare Hospital Outpatient Department Quality MeasuresOP-21 Median Time to Pain Management for Long Bone Fracture measured as time (in minutes) from emergency department arrival to time of initial oral, intranasal, or parenteral pain medication administration for emergency department patients with a diagnosis of a long bone fracturesee Medicare Hospital Outpatient Department Quality Measures for additional informationGuidelines and ResourcesGuidelinesGuidelinesGuidelinesAmerican College of Radiology/Society of Pediatric Radiology/Society of Skeletal Radiology (ACR/SPR/SSR) practice parameter on performance and interpretation of magnetic resonance imaging (MRI) of knee can be found at ACR 2015 Oct PDFMusculoskeletal_DisordersACR Appropriateness Criteria for acute trauma to knee (National Guideline Clearinghouse 2015 Jul 27)07/28/2015 02:00:00 PMAmerican College of Radiology (ACR) Appropriateness Criteria for acute trauma to knee can be found at ACR 2014 PDFEast Practice Management Guidelines Work Group practice management guideline on prophylactic antibiotic use in open fractures can be found in 21610369J Trauma 2011 Mar;70(3):751Review articlesreview can be found in 11401171Am J Knee Surg 2001 Spring;14(2):125review can be found in 20345023Zhongguo Gu Shang 2010 Feb;23(2):81[Chinese] Emergency_Medicine Musculoskeletal_Disorders Orthopedic_DisordersCochrane review evaluating surgical fixation methods for tibial plateau fracture (Cochrane Database Syst Rev 2015 Sep 15)12/22/2015 03:40:00 PM263702683Cochrane review evaluating surgical fixation methods for tibial plateau fracture can be found in chhCD009679Cochrane Database Syst Rev 2015 Sep 15;(9):CD009679review of open reduction and internal fixation of fractures of tibial plateau can be found in 19336799J Bone Joint Surg Br 2009 Apr;91(4):426review of osteoporotic tibial plateau fracture can be found in 15913173Am J Orthop (Belle Mead NJ) 2005 Apr;34(4):186review of complications after tibia plateau fracture surgery can be found in 16118010Injury 2006 Jun;37(6):475review of evaluation of patients with knee pain (parts I and II) can be found in mnh13678139p t ccxh10786308t c pmdc13678139p t cAm Fam Physician 2003 Sep 1;68(5):907EBSCOhost Full Textfull-text, mnh13678140p t ccxh10786314t c pmdc13678140p t cAm Fam Physician 2003 Sep 1;68(5):917EBSCOhost Full Textfull-textreview of principles of casting and splinting can be found in mnh19145960pcxh35896095pmdc19145960pAm Fam Physician 2009 Jan 1;79(1):16EBSCOhost Full Textfull-textMEDLINE searchto search MEDLINE for (Tibial plateau fracture) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosisPatient InformationPatient Infohandout on fractures of the proximal tibia from American Academy of Orthopaedic Surgeonstechnical information on tibial and fibular fractures from Patient PlusICD CodesICD CodesICD-10 codesS82.1 fracture of upper end of tibia use optional subclassification codes to indicate 0 closed 1 open ReferencesGeneral references usedThomas Ch, Athanasiov A, Wullschleger M, Schuetz M. Current concepts in tibial plateau fractures. Acta Chir Orthop Traumatol Cech. 2009 Oct;76(5):363-73.Fenton P, Porter K. Tibial plateau fractures: a review. Trauma. 2011 July;13(3):181-87.Dirschl DR, Del Gaizo D. Staged management of tibial plateau fractures. Am J Orthop (Belle Mead NJ). 2007 Apr;36(4 Suppl):12-7.Young CF, Haddad F. Fractures around the knee. Br J Hosp Med (Lond). 2006 May;67(5):M96-8.Berkson EM, Virkus WW. High-energy tibial plateau fractures. J Am Acad Orthop Surg. 2006 Jan;14(1):20-31.DynaMed Editorial ProcessDynaMed topics are created and maintained by the DynaMed Editorial Team and Process.All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.DynaMed provides Practice-Changing DynaMed Updates, with support from our partners, McMaster University and F1000.Special acknowledgementsDynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.Editorial Team role definitionsTopic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. 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Overview and RecommendationsBackground·Osteoporosis (compromised bone strength and bone quality) is