腰椎间盘突出症治疗的循证医学综述(中英对照版)3/4

Spine Patient Outcomes Research Trial
The largest study comparing surgical and nonoperative treatment for lumbar disc herniation is the Spine Patient Outcomes Research Trial (SPORT) (Table 3).14-17 This study was unique in that it included both randomized and observational arms, which allowed patients to be included even if they did not agree to randomization. Patients were enrolled at 13 multidisciplinary spine practices in 11 states. All patients had radicular pain, neurological findings, and an MRI-confirmed disc herniation that coincided with their symptoms, which were at least 6 weeks in duration. The surgical intervention was a standard open diskectomy, and nonoperative treatment consisted of “usual care” that was suggested to include at least education and counseling, physical therapy, and nonsteroidal anti-inflammatory medications if tolerated. Many nonoperative patients also received narcotics and epidural injections. The study was powered to detect a 10 point change from baseline on its primary outcome measures; the Short Form-36 bodily pain and physical function scales18 and the ODI.19 Secondary outcome measures included patient self-reported improvement, satisfaction with symptoms and care, work status, and the Sciatica Bothersome Index. The initial reports detailed the first 2 years of follow-up,15,17 while the 4-year follow-up data were recently reported.16 Addi-tional subgroup analyses evaluated the effect of herniation location, morphology, and intervertebral level on outcomes.20,21
脊柱患者治疗结果研究试验
对腰椎间盘突出症手术与非手术治疗进行比较的最大的研究便是脊柱患者治疗结果研究试验（SPORT）（表3）[14-17]。该研究的独特之处便是其包括随机性和观察性两种方式，这样即使患者不同意进行随机化研究也可以将其纳入进来。纳入的患者来自美国11各州的13个多学科脊柱外科临床中心，这些患者都具有根性疼痛，神经病学改变，MRI上有与症状相符的明确的椎间盘突出，并且症状持续至少6周。手术干预采用标准的开放椎间盘切除术，非手术治疗主要为“常规处理”，通常至少包括健康宣教与建议、理疗、如果能耐受的话给予非甾体类抗炎药。很多非手术患者还接受了麻醉药和硬膜外注射等治疗。该研究认定治疗结果的主要评价指标在其初始值基础上改变10个点视为有变化，这些指标包括SF-36躯体疼痛和运动功能等级评分[18]和ODI[19]。评价结果的次要指标包括患者自我报告的改善程度、对症状和治疗的满意度，工作状况和坐骨神经痛焦虑指数。其初步报告详细介绍了前两年的随访结果[15,17]，最近则发表了4年随访的数据[16]。另外的亚组分析则评价了椎间盘突出的部位、形态和椎间隙水平对治疗结果的影响[20, 21]。

The most surprising result of the SPORT RCT was the high rate of protocol nonadherence (ie, crossover from the assigned treatment group to the other group). In the first 2 years, 40% of patients assigned to surgery never underwent surgery, whereas 45% of patients assigned to nonoperative treatment underwent surgical intervention. While the crossover from nonoperative treatment to surgery was expected, the high rate of crossover in the other direction (ie, surgery to nonoperative treatment) was not. This high rate of crossover precluded meaningful analysis of the data on an ITT basis because the 2 groups were very similar in treatment received at 2 years. Nonetheless, the ITT analysis was presented as the primary analysis. As would be expected, there were no significant differences on any of the primary outcome measures. Despite the homogeneity of treatment across the 2 groups, the surgery group did improve significantly more on the sciatica bothersome index over the first 2 years (-10.1 vs -8.5 at 2 years, P = 0.003). A secondary as-treated analysis was performed with adjustment for potential confounders. This demonstrated large and statistically significant treatment effects of surgery on the 3 primary outcome measures (ie, the surgery group improved 15 points more on the ODI than the nonoperative group at 1 year).
SPORT RCT最为意外的结果便是无法坚持既定方案（即从被分配的治疗组变换到另一治疗组）的比率很高。在最初2年，分配进行手术的患者40%没有进行手术，而分配进行非手术治疗的患者45%进行了手术治疗。虽然从非手术治疗变换为手术治疗是意料之中的，但另一个方向的变换（即手术变换为非手术治疗）则并非如此。如此高的变换率使得无法应用ITT分析方法对数据有效的分析，因为2年时，两组接受治疗的情况非常相似。尽管如此，ITT分析还是被当作主要的分析方法。同预期的结果相似，无论主要的还是次要的评价指标，两组间的差异没有统计学意义。虽然两组间治疗方式的变换存在均一性，在最初2年，手术治疗组坐骨神经痛焦虑指数的改善还是更为明显（两年时分别为-10.1和-8.5，P= 0.003）。同时还进行了次要的接受治疗分析，以调整可能的混杂。结果显示，在3项主要的评价指标上，手术治疗具有很大的有统计学意义的优势（手术组1年时ODI的改善比非手术组多15点）。

Similar to the as-treated analysis of the RCT, the observational trial demonstrated a large, significant benefit of surgery on all primary and secondary outcome measures over the first 2 years after controlling for potential confounders. For example, the surgery patients improved 13 points more on the ODI at 2 years compared with the nonoperative patients. Work status was the 1 outcome measure on which the sur-gery patients did not improve significantly more than the nonoperative patients at 2 years. Given the aforementioned problems with the ITT analysis, the 4-year data from the RCT and observational cohorts were combined, and an adjusted as-treated analysis was performed. The differences observed at the 2-year follow-up persisted at 4 years, with the surgery group improving significantly more than the nonoperative group on all primary and secondary outcomes other than work status. Unlike the MLSS, the differences between the 2 groups did not appear to decrease over time.
与RCT的接受治疗分析结果类似，对潜在的混杂进行控制后，观察性试验中，2年时所有主要和次要的评价指标都显示手术治疗具有很大的明显的优势。例如，2年时手术治疗的患者比非手术者ODI的改善多13点。2年时工作状况是唯一一个手术组患者没有明显改善的评价指标。考虑到ITT分析存在上述的问题，将RCT研究中4年时的数据与观察性队列研究结合，校准后进行了接受治疗分析。2年随访时显示出的差异，至4年时仍然存在，除了工作状态以外的其他主要和次要评价指标，手术组的改善程度比非手术组更明显。与MLSS不同，两组间的差异并没有随着时间的延长而减小。

As-treated subgroup analyses were performed to evaluate the effect of herniation location, morphology, and intervertebral level on outcomes. These demonstrated that although patients with central disc herniations had worse back pain than patients with lateral herniations, and patients with protrusions had less severe symptoms at baseline than those with extrusions or sequestrations, the change from baseline in back pain scores was similar across location and morphology subgroups.21 Another subgroup analysis reported that patients with upper (L2-3 or L3-4) lumbar disc herniations had a greater treatment effect of surgery than patients with L5-S1 herniations.20 Patients with L4-5 herniations had intermediate treatment effects.
对亚组进行的接受治疗分析，评价了椎间盘突出的部位、形态和椎间隙水平对治疗结果的影响。结果显示，虽然中央型椎间盘突出的患者背痛程度比侧方突出的患者更显著，椎间盘突出的患者初始症状相比脱出或游离的患者要轻一些，而相对初始状况而言，背痛评分的改变与突出部位、和形态学等亚组无关[21]。另一项亚组分析显示高位腰椎间盘突出（L2-3或L3-4）的患者手术治疗的结果比L5S1突出的患者更好[20]，而L4-5突出的患者其疗效居中。

SPORT represents the largest study to date comparing surgery with nonoperative treatment for lumbar disc herniations. Its strengths include the use of stringent inclusion criteria, validated back-specific and general health outcome measures, powerful statistical modeling to account for baseline differences between the groups, and the inclusion of patients from 13 different spine centers. The major limitation of the SPORT RCT was the high rate of protocol nonadherence that prevented a meaningful ITT analysis of the data. While the as-treated analysis was carefully adjusted to account for the baseline differences between the 2 groups, the benefits of randomization were lost. As a result, there is still no Level I evidence comparing surgery with nonoperative treatment for the treatment of lumbar disc herniations. Given that it is not possible to control for unmeasured confounders, the as-treated analysis may have overstated the treatment effect of surgery. Another limitation of SPORT and all other studies of disc herniation was the lack of blinding of patients to treatment received. Sham surgery is the only way to overcome this threat to validity, and although it has been suggested, it seems unlikely that patients would enroll in such a study or that institutional review boards would approve it.22 Given the lack of blinding, perhaps the placebo effect of surgery may have contributed to the better outcomes for the surgery patients.
SPORT是迄今为止比较腰椎间盘突出症患者手术与非手术治疗样本量最大的研究。该研究的优势主要包括采用了较为严格的纳入标准，应用了有效的脊柱特异性和一般健康结果评价方法，有效的统计模型对组间初始状况的差异进行了处理，纳入的患者来自13个不同的脊柱临床中心。SPORT RCT的局限主要是未能坚持预定方案的比率较高，从而无法对数据进行有效的ITT分析。虽然应用接受治疗分析进行谨慎的调节可解决2组间基础状况差异的问题，但却削弱了随机化的优势。最终仍然无法得到比较腰椎间盘突出症手术与非手术治疗的Ⅰ级证据。考虑到不可能控制那些无法预测的混杂，接受治疗分析则可能会夸大手术的治疗效果。SPORT和所有其他关于椎间盘突出的研究都具有的另一个不足之处，便是无法对患者接受的治疗实施盲法，为了克服对有效性的干扰，假手术是唯一的途径，虽然有这样的观点，但不太可能实施，因为患者可能不愿意加入这样的研究，抑或伦理委员会不会批准[22]。考虑到没有实施盲法，或许手术治疗的安慰剂效应也会使手术治疗的患者获得更好的治疗结果。

Proponents of various nonoperative therapies have criticized studies like SPORT for failing to specify a well-defined nonoperative regimen.23 The advantage of specifying “usual care” as the nonoperative treatment was the increased generalizability this provided as it more closely reflected what was being offered to patients. However, patients may have improved more with a specific nonoperative treatment regimen, especially as they had failed to improve with “usual care” over time leading up to enrollment. Unfortunately, the best type of nonoperative care for disc herniations has not been rigorously defined, so it was not possible to select a more specific regimen based on the available scientific literature.
各种非手术治疗的研究者也批评类似SPORT这样的研究，没有对非手术治疗进行明确的限定[23]。限定非手术治疗为“常规处理”的好处在于，这些措施很多患者正在应用，这样更加容易推广应用。然而，患者可能应用某种特异性的非手术疗法可以获得更大的改善，尤其是某些纳入研究之前应用“常规处理”较长时间仍未能得到改善的患者。遗憾的是，腰椎间盘突出症最好的非手术治疗方式并没有严格的定义，因此参考现有的文献，选择一项更为明确的方法是不太可能的。

Discussion
All the major studies comparing surgery with nonoperative treatment of lumbar disc herniation have reached the following conclusions: (1) surgery tends to improve symptoms faster and to a greater degree than nonoperative treatment, (2) surgery is safe and the complication rates are low, (3) patients who initially meet the indications for surgery but elect nonoperative treatment may eventually improve to an acceptable level of pain and function, (4) surgery does not improve the return to work rate compared with nonoperative treatment, and (5) nonoperative treatment is safe. The surgical outcomes of SPORT and MLSS patients were remarkably similar, though the nonoperative outcomes were not as favorable in the MLSS, which resulted in SPORT having a smaller treatment effect of surgery. While all enrolled patients met the indications for surgery, 55% of patients assigned to nonoperative treatment avoided surgery in the SPORT RCT as did 61% of the patients assigned to nonoperative treatment in the study by Peul et al.9 This suggests that many patients who can tolerate living with their symptoms for a period may be able to improve to an acceptable level of function without surgery if they choose. Despite consistent agreement across studies about the benefit of surgery, the duration of benefit is still unclear. While Weber’s study and the MLSS suggested that the treatment effect of surgery tends to decrease with time, the SPORT data gave no indication that the treatment effect was decreasing between 2 and 4 years. It is anticipated that SPORT will continue to follow patients out to 10 years, however, the MLSS and Weber’s study suggests that there is very little change in outcomes between 5 and 10 years.