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Original Article

A Critical Analysis of the Literature Regarding Surgical Approach and Outcome for Adult Low-Grade Isthmic Spondylolisthesis

Kwon, Brian K MD, FRCSC*; Hilibrand, Alan S MD; Malloy, Kelly MD; Savas, Paul E MD§; Silva, Marco T MD; Albert, Todd J MD; Vaccaro, Alexander R MD

Author Information
Journal of Spinal Disorders & Techniques: February 2005 - Volume 18 - Issue - p S30-S40
doi: 10.1097/01.bsd.0000133064.20466.88
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Abstract

A variety of surgical approaches have been described to achieve spinal stabilization, neural decompression, and deformity correction in patients with a low-grade isthmic spondylolisthesis. The posterior approach in which the direct decompression of the neural elements can be achieved and posterolateral fusion performed has been the most popular approach in both adolescents and adults.1,2 Advances in spinal internal fixation have led to the widespread use of pedicle screw fixation to stabilize posterolateral fusions, although an improvement in patient outcomes with such fixation has not been well established.3 Whereas an isolated posterior decompression and fusion can achieve direct decompression of the neural elements and motion segment stability, it does not reconstruct the anterior column, may exacerbate kyphosis, and requires considerable stripping of paraspinal soft tissues.

Alternatively, anterior lumbar interbody fusion (ALIF) reconstructs the anterior column, may correct lumbosacral kyphosis, places the bone graft construct under compression, and avoids the stripping of paraspinal muscles. A direct decompression of the exiting nerve roots, however, is not possible, and only by restoring disk height is an indirect decompression achieved. Also, anterior approaches to the disk space endanger major vascular structures and place the hypogastric nerve plexus at risk, which, if injured in males, may cause retrograde ejaculation.4

The acknowledged limitations of either an isolated posterior or anterior procedure have led to combined approaches that potentially exploit the benefits of each. Combined anterior and posterior procedures could include an ALIF with supplemental posterior decompression and fusion or alternatively a posterior (PLIF) or transforaminal lumbar interbody fusion, which reconstructs the anterior column from a posterior approach. Although combined procedures can theoretically accomplish all of the surgical goals in the management of isthmic spondylolisthesis (stabilization, neurologic decompression, deformity correction), they require more operative time, increase perioperative morbidity, and may be more technically difficult than an anterior or posterior procedure alone.

The literature contains numerous reports on the surgical management of adults with low-grade isthmic spondylolisthesis that have described the outcomes of posterior, anterior, or combined procedures. However, no large-scale prospective randomized comparisons of these techniques have been published to establish the optimal approach. Indeed, an extensive review of the existing literature describing radiographic and clinical outcomes of adult patients undergoing surgery for isthmic spondylolisthesis revealed predominantly retrospective nonrandomized case series reports with a variety of unvalidated radiographic or clinical outcome measures, thus precluding any meaningful meta-analysis. We therefore performed a critical review of these studies with the objective of determining whether the radiographic or clinical outcomes were influenced by the surgical approach used (ie, posterior, anterior, or combined). We also attempted to identify the impact of surgical and patient factors such the use of posterior spinal fixation, the performance of a laminectomy, a history of smoking, and the presence of secondary gain issues (workers’ compensation or litigation status) upon these outcomes.

MATERIALS AND METHODS

A MEDLINE search of the English literature was performed for spondylolisthesis, limiting the query to humans and all adults (over age 18) between January 1955 and December 2003. Abstracts were reviewed, and studies that described the surgical management of adult patients with isthmic spondylolisthesis were selected. These were further screened to determine whether the study included a description of the fusion rate (radiographic outcome), the clinical outcomes, or both in at least five adult patients with low-grade isthmic spondylolisthesis (Meyerding grade 0, 1, or 2). Studies that described surgical outcomes in patients with isthmic and degenerative spondylolisthesis were included only if the results were stratified in a way that made it possible to identify the results in those patients with an isthmic pathology. Similarly, studies that described surgical outcomes in patients with both low- and high-grade isthmic spondylolisthesis were included only if the results within the low-grade patients could be delineated. Studies in which a laminectomy alone or a pars defect repair alone was performed were not included. A “posterior” procedure was one in which a posterior or posterolateral fusion was performed, with or without spinal fixation or a laminectomy. An anterior procedure was one in which an interbody fusion was performed. These included both stand-alone ALIFs and PLIFs in which no posterior or posterolateral fusion was attempted. A combined procedure included an interbody fusion with some form of posterior or posterolateral fusion. Three spine surgeons reviewed the abstracts of the search results and read all articles that potentially satisfied the inclusion criteria.

The primary objective of this systematic review was to summarize the existing English literature concerning the surgical management of adult patients with low-grade isthmic spondylolisthesis to determine whether the radiographic fusion and clinical outcomes of adult patients with low-grade isthmic spondylolisthesis were superior with one of three possible surgical approaches: posterior alone, anterior alone, or a combined anterior-posterior procedure. Recognizing the wide variability by which authors determine and report successful fusion (ie, sometimes with and sometimes without independent observers, advanced imaging, or grading schemes), we were forced to simply score radiographic outcome as either “solid fusion” or “pseudarthrosis” based on the description by the authors. In most cases, this distinction was made clear by the authors; in studies that used a grading scale such as that of Lenke et al5 to assess fusion, only those cases in which the fusion was “definitely solid” were considered fused. The means by which clinical outcomes were determined and reported was similarly quite variable in the literature (ie, patient reported or surgeon reported, with or without independent observers, using a 4-point scale, 3-point scale, or some other outcome measure), and so, again, we were forced to simplify the clinical outcome as either “successful” or “unsuccessful.” In most of the studies, clinical outcomes were described on a 4-point scale (eg, excellent, good, fair, and poor). In such studies, the patients who achieved either an excellent or a good result were deemed to have had a “successful” outcome. In studies that rated clinical outcome on a 3-point scale (eg, excellent, satisfactory, and poor), patients with the middle rating were assigned a “successful” outcome if the authors described them as having returned to work (or age-appropriate activities) or requiring nonnarcotic analgesics.

The influence of patient covariates on radiographic and clinical outcomes was also evaluated. Where defined, the number of patients within each study who smoked or were on worker’s compensation or engaged in litigation was documented. Surgical covariates for posterior procedures were also studied, including the use of spinal internal fixation and the performance of a laminectomy. These covariates were then studied with regard to radiographic fusion rate and clinical outcomes. Statistical analysis was performed with Fisher exact test χ2 analysis for independence between pairs of groups based on surgical approach (ie, anterior, posterior, and combined) and among each covariate (ie, smokers versus nonsmokers).

RESULTS

Inclusion of Studies

The MEDLINE literature search and review of bibliographies of relevant studies yielded 34 suitable studies in which the clinical and/or radiographic outcomes of over 1000 patients with low-grade isthmic spondylolisthesis could be distinguished according to whether they had undergone a posterior, anterior, or combined surgical procedure.3,5-37 Twenty-six studies described the radiographic or clinical outcomes of adult patients undergoing an isolated posterior fusion procedure (posterolateral fusion with or without decompression or spinal fixation). Five studies described the results of patients undergoing an isolated ALIF. Nine studies evaluated patients undergoing a combined anterior and posterior stabilization procedure. The sum of the aforementioned number of studies (26, 5, and 9) exceeds 34 because some studies included a mixture of patients undergoing two surgical approaches (eg, posterior and combined anterior-posterior). The fusion radiographic and clinical outcomes of these studies are summarized in Tables 1-3.

Table 1
Table 1:
Studies Describing Patients Undergoing a Posterior Procedure Alone
Table 1
Table 1:
(continued) Studies Describing Patients Undergoing a Posterior Procedure Alone
Table 2
Table 2:
Studies Describing Patients Undergoing an Anterior Procedure Alone
Table 3
Table 3:
Studies Describing Patients Undergoing a Combined Anterior-Posterior Procedure

Limitations of Included Studies

Of all 34 studies included, only 4 (Bjarke et al,3 Carragee,21 McGuire and Admundson,14 and Moller and Hedlund32) were prospective randomized controlled studies with minimum 24-month follow-up that compared one form of treatment against another. Of the 30 retrospective studies included, only 6 performed comparisons of two different forms of treatment,15,20,24,28,30,35 whereas the remaining 24 described the authors’ experience with one technique. In only 10 of 34 studies did the authors indicate that the assessment of radiographic fusion and functional outcome was performed by an independent reviewer.1,17,24,26,27,32,33,37 The radiographic and clinical follow-up was performed at a minimum of 24 months postoperatively in 19 of 34 studies, although the average length of follow-up was >24 months in all but 4 studies.9,13,19,31 Considering these variables in combination for the 30 retrospective studies in this review, only 5 studies included patients with both a minimum of 24 months of follow-up and an independent assessment of radiographic and clinical outcomes: 4 of the 26 studies describing posterior procedures10,16,24,27 and 2 of the 6 studies describing combined anterior-posterior procedures.24,37 Two retrospective studies describing combined anterior-posterior procedures had an independent review of radiographic fusion but did not indicate that the review of clinical outcome was performed independently.17,33

Radiographic Outcomes

Patients undergoing combined anterior and posterior procedures had a 98.2% fusion rate (167/170). Those undergoing a posterior procedure alone had an 83.3% fusion rate (741/890), whereas those undergoing anterior stabilization alone had a 74.0% fusion rate (57/77). The fusion rate for those with a combined procedure was significantly higher than that of the posterior or anterior procedures alone (P < 0.0001 for both). The difference in fusion rates between posterior or anterior procedures (83.3% vs 74.0%) approached but did not achieve statistical significance (P = 0.059), although the trend certainly exists for a higher fusion rate with posterior procedures alone.

Clinical Outcomes

Patients undergoing a combined anterior and posterior fusion had a successful clinical result in 86.4% of cases (108/125), whereas only 74.8% of patients (609/814) who had a posterior procedure alone had a successful result, a statistically significant difference (P = 0.0045). Patients with an anterior procedure alone had an 89.6% rate of successful clinical results (60/67), which was not significantly different from that of the combined procedures (P = 0.65) but was significantly better than that of posterior procedures alone (P = 0.0047). Within the group of studies describing combined procedures, a subanalysis of those patients with an ALIF-posterior-posterolateral fusion compared against those with a PLIF-posterolateral fusion revealed no significant difference in radiographic or clinical outcomes (P = 0.068 and P = 0.43, respectively). The results of the comparisons between surgical approaches (posterior versus anterior versus combined) are summarized in Table 4.

Table 4
Table 4:
Analysis of Radiographic Fusion and Clinical Results Based on Surgical Approach

Covariate Analysis

The use of spinal internal fixation, performance of a laminectomy, nicotine usage, and presence of secondary gain in the form of a workers’ compensation claim or litigation were covariates analyzed as potential factors influencing the surgical outcomes. In the studies describing patients with an anterior procedure alone or combined procedures (6 and 7 studies, respectively), these covariates were either (a) uniform throughout the patients (eg, all patients with combined surgery had some form of posterior fixation, whereas no patients with anterior surgery had fixation), (b) not assessed (eg, secondary gain issues were not described in any of these 12 studies), or (c) described but the results could not be distinguished (eg, eight smokers were identified in the study by Wang et al,17 but their outcomes could not be distinguished from those of the nonsmokers within the study). Therefore, although not originally intended, the covariate analysis was limited to studies of posterior surgery alone, and hence, this analysis describes the influence of these factors on the outcome of posterolateral fusion (Table 5).

Table 5
Table 5:
Covariate Analysis of Radiographic Fusion and Clinical Outcomes

The patients who had a posterolateral fusion with internal fixation had a significantly higher rate of fusion (90.2%; 333/369) than those who did not receive spinal fixation (77.4%; 254/328) (P < 0.0001). Similarly, patients who had a posterolateral fusion with internal fixation had a significantly higher rate of successful clinical outcomes (84.9%; 304/358) than those with uninstrumented fusions (64.4%; 192/298) (P < 0.0001). The performance of a laminectomy did not influence fusion rates (83.0% [284/342] fused with laminectomy vs 88.7% [157/177] fused without; P = 0.0.093), nor did it significantly alter clinical outcomes (74.0% [267/361] successful results with laminectomy vs 79.8% [186/233] without laminectomy; P = 0.11). Patients who smoked, however, had significantly worse rates of fusion (74.7% [74 of 99] of smokers vs 91.4% [85/93]) of nonsmokers; P = 0.0023) and successful clinical outcomes (59.6% [59/99] of smokers vs 80.6% [75/93] of nonsmokers; P = 0.0017). Patients who were identified as having secondary gain issues had similar fusion rates as those not involved in a compensation or litigation claim (57.9% [11/19] vs 50.0% [10/ 20]; P = 0.75). The clinical outcomes, however, of those with secondary gain issues were significantly worse than those without, with only 35.6% (16/45) of workers’ compensation or litigation patients achieving a successful result compared with 81.8% (36/44) of patients without such secondary gain issues (P < 0.0001).

DISCUSSION

The purpose of this study was to summarize and critically assess the existing literature on the surgical management of adult low-grade isthmic spondylolisthesis with the objective of determining whether the rates of radiographic fusion and of clinical success were influenced by the surgical approach taken (posterior alone, anterior alone, or combined anterior-posterior). A review of the various surgical reports included here demonstrates the substantial weaknesses in the literature on this topic. Of the 34 studies included in this review, only 4 were prospective randomized controlled studies. Generally speaking, these four studies compared the use of spinal instrumentation3,14,32 or the performance of a laminectomy21 in patients undergoing posterolateral fusions and thus did not provide a true comparison between the “posterior alone” surgical approach and either an anterior alone or combined approach. In essence, no prospective randomized controlled trials have been performed that compare the three surgical approaches (eg, a posterolateral instrumented fusion versus a PLIF). Furthermore, of the remaining 30 retrospective studies in the review, only 6 performed comparisons between two different surgical techniques, and only 5 included a minimum of 2-year follow-up with radiographic and clinical outcomes measured by an independent reviewer. Recognizing that such limitations exist within the available surgical literature on this topic, a meta-analysis of the literature is clearly not possible. We therefore pooled the results of the patients within these studies in an attempt to delineate whether some generalizations could be made from the larger compilation of patients. Although no individual study reported on any more than 74 patients, and on average the number of patients in each study was approximately 33, the pooling of these studies allowed for the evaluation of over 1100 patients. From these pooled data, it would appear that patients with combined anterior and posterior procedures had the highest rate of radiographic fusion and clinical success. Analysis of various covariates indicated that the use of spinal fixation was associated with higher rates of fusion and clinical success, whereas smoking portended a poor radiographic and clinical outcome.

The high fusion rate of combined procedures in low-grade isthmic spondylolisthesis is consistent with the experience of other authors in the treatment of other lumbar degenerative disorders.38 What is perhaps less expected is the significantly higher rate of successful clinical outcomes with the combined procedures as compared with the posterior procedures. Although a strong correlation between radiographic fusion and positive clinical outcome has not been clearly established for many conditions within the lumbar spine, in this review of isthmic spondylolisthesis, a number of authors did report a strong association between the achievement of solid fusion and a successful clinical outcome.12,14,19,23,27 This association is certainly borne out in the patients with combined procedures who had both high fusion rates and successful clinical outcomes. It is worth noting, however, that whereas the pooling of patients across the literature produced a higher rate of fusion and successful clinical outcome in combined procedures compared with posterior procedures, only two studies actually performed direct comparisons between the two.20,24 Although both of these studies described higher rates of fusion with PLIF compared with posterolateral fusion alone, they arrived at contradictory conclusions regarding successful clinical outcomes. Suk et al20 describe higher rates of “excellent” outcomes in patients undergoing PLIFs than in those undergoing posterolateral fusions, whereas Madan and Boeree24 describe significantly lower rates of satisfactory outcomes in those having PLIFs. Neither study, however, was prospective or randomized. Unfortunately, the inconsistent reporting of complications made it impossible to determine among the pooled studies if the complication rate was substantially higher for the combined procedures as compared with anterior or posterior procedures alone, although a lower clinical success rate would be expected if the complication rate was exceedingly high for the combined procedures.

The covariate analysis demonstrated not only a significantly higher fusion rate with spinal internal fixation but also more successful clinical outcomes. The higher fusion rate is consistent with previous literature that has demonstrated that pedicle screw fixation facilitates bony fusion and reduces the pseudarthrosis rate of posterolateral fusions.39-42 The more successful clinical outcome, however, conflicts with four independent prospective randomized studies that have evaluated posterolateral fusions with or without pedicle screw supplementation fixation, all of which have failed to identify any significant improvement in self-reported clinical outcomes with the addition of pedicle screw fixation.3,43-45 Two of these studies, those of Moller and Hedlund44 and Bjarke et al,3 were included in this systematic literature review of isthmic spondylolisthesis. Although Moller and Hedlund32 report similar clinical results between instrumented and noninstrumented patients, Bjarke et al3 specifically report worse clinical outcomes in patients undergoing instrumented fusion as compared with noninstrumented patients with internal fixation.

The performance of a laminectomy did not appear to significantly influence the reported radiographic fusion or clinical outcomes, although there was a trend toward a higher pseudarthrosis rate (P = 0.093) and unsuccessful clinical outcome (P = 0.11) in patients undergoing a laminectomy. Although not achieving statistical significance, this trend among the pooled data is consistent with the findings of the only study to have actually randomized patients to a fusion with or without laminectomy.21 This prospective randomized controlled trial found that patients who underwent laminectomies actually fared significantly worse in terms of both fusion and clinical outcome than those who did not. The lack of a substantial improvement in clinical outcomes for those patients undergoing a laminectomy is interesting insofar as the decompression of neural elements is often thought to be an important aspect of the surgical management of this condition. This suggests that decompression may be less important than achieving spinal stabilization in the surgical management of adult isthmic spondylolisthesis and supports the association between successful fusion and clinical outcomes. However, as the indications for laminectomy varied widely among the studies, caution should be exercised in making strong conclusions about the value of laminectomy in these patients, particularly if a severe neurologic deficit is present.

As expected, smoking status had a strong correlation with the development of a pseudarthrosis and with unsuccessful clinical outcomes. Similarly, patients who were on workers’ compensation or pursuing litigation had significantly worse clinical outcomes than those patients with no secondary gain issues, despite having no significant differences in radiographic fusion. It should be noted, however, that this result was heavily influenced by the findings of Vaccaro et al,22 who contributed 24 of the 89 patients for this covariate analysis. In this study, none of the 13 workers’ compensation patients had a successful clinical result compared with 9 of 11 noncompensation patients, despite equivalent fusion rates.

There are a number of limitations to the performance of such a systematic review. Our analysis pooled the results of patients who had a procedure done posteriorly, anteriorly, or in a combined fashion. Clearly, the indications for surgery and the actual type of surgical procedure varied among and within these three groups. For example, combined procedures included an ALIF with posterolateral fusion or a PLIF with posterolateral fusion. Although these conceptually achieve both anterior column support and posterior stabilization, there are well recognized differences in terms of morbidity and cost associated with these procedures.46,47 Similarly, posterior procedures alone differed in terms of fixation and decompression, although these covariates were analyzed separately. The variations in surgical indications and techniques between these studies must be considered when attempting to interpret both the primary analysis of this study (between surgical approaches) and the secondary analysis of covariates. The difficulty in knowing how comparable the patients were across the studies should discourage the reader from making strong conclusions in the absence of results from a prospective randomized trial.

In interpreting the radiographic fusion rates and clinical outcomes pooled within this review, it is also worth noting that a wide disparity exists among the studies in the methods by which fusion status was assessed. None of these studies used advanced imaging (eg, computed or plain tomography) to determine fusion, although the study by Johnsson et al13 used roentgen stereophotogrammetry to assess postoperative stability after fusion. Similarly, for the assessment of clinical outcomes, the majority of studies used a clinical scale of excellent, good, fair, and poor, the definitions of which were defined by the surgeons and variable among studies. Very few used validated disease-specific or generic health-related outcome measures. Of particular importance, in many of the studies, both the fusion and the clinical outcomes were not measured independently by an individual uninvolved in the surgery. Clearly, this has the potential to introduce substantial bias into the interpretation of fusion and clinical outcome for each study. Another important problem inherent to such a systematic review is that by pooling all studies and assigning them equal weight, the power of studies that made specific comparisons between surgical approaches or covariates is, to some extent, lost. For example, although the addition of spinal internal fixation was found to be associated with higher fusion rates and successful clinical outcomes when pooling all studies, arguably the most epidemiologically robust study3 to evaluate this question in a prospective randomized manner found exactly the opposite with respect to clinical outcomes. Clearly, there is a need for further such comparisons and those that compare surgical approaches (ie, anterior versus posterior, etc.). Also, the primary analysis of this systematic review compared posterior, anterior, and combined approaches to the spine. However, the preponderance of the literature describes the results of patients undergoing posterior surgery. As a result, the conclusions that may be drawn from the reported results of anterior and combined surgery are based on smaller numbers of patients, with the potential for a greater effect from any surgeon-author bias. These limitations all need to be carefully considered in the interpretation of the findings of this critical review.

One of the major strengths of performing this critical analysis of the literature is that it pools a large body of clinical experience to make generalizations about the effectiveness of surgical approaches for adult low-grade isthmic spondylolisthesis. For example, conclusions about the increased fusion rate and improved clinical outcomes of combined approaches versus posterior approaches were made on the basis of the outcomes of over 900 patients from approximately 30 studies. Similarly, the covariate analysis of laminectomy performance was made on over 500 patients. Notwithstanding the fact that such a pooled analysis obscures the strengths of direct comparisons to some extent, these large numbers make a reasonably compelling statement for surgeons who manage such cases and generate research questions that may be addressed in a prospective randomized fashion.

CONCLUSION

This systematic review illustrates a number of limitations and weaknesses in the surgical literature on adult low-grade isthmic spondylolisthesis, highlighted in particular by the paucity of randomized controlled studies and retrospective studies with both adequate follow-up and independent review. By pooling the results of these studies, we found that the highest rates of radiographic fusion and successful clinical outcomes were associated with combined surgical approaches that address both anterior column support and posterior stability. The addition of internal fixation to posterior procedures was associated with higher fusion rates and better clinical outcomes, whereas the performance of a laminectomy did not appear to significantly influence either, although a trend toward worse results was observed. The poor clinical outcomes observed in smokers and in those on workers’ compensation should be considered carefully by surgeons when discussing expectations of surgical outcomes with these patients. Whereas the pooling of these studies allows for the comparison of large numbers of patients, these findings should be interpreted cautiously, recognizing the limitations of the studies included in the review. Such limitations beg for further prospective randomized controlled trials to more conclusively determine the optimal surgical approach for this common problem.

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Keywords:

isthmic spondylolisthesis; spinal internal fixation; systematic review

© 2005 Lippincott Williams & Wilkins, Inc.