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Minimally Invasive Surgery Versus Open Surgery Spinal Fusion for Spondylolisthesis

A Systematic Review and Meta-analysis

Lu, Victor M., MD∗,†,‡; Kerezoudis, Panagiotis, MD∗,†; Gilder, Hannah E., BS∗,†; McCutcheon, Brandon A., MD, MPP∗,†; Phan, Kevin, BS; Bydon, Mohamad, MD∗,†

doi: 10.1097/BRS.0000000000001731
LITERATURE REVIEW
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Study Design. Systematic review and meta-analysis.

Objective. Compare minimally invasive surgery (MIS) and open surgery (OS) spinal fusion outcomes for the treatment of spondylolisthesis.

Summary of Background Data. OS spinal fusion is an interventional option for patients with spinal disease who have failed conservative therapy. During the past decade, MIS approaches have increasingly been used, with potential benefits of reduced surgical trauma, postoperative pain, and length of hospital stay. However, current literature consists of single-center, low-quality studies with no review of approaches specific to spondylolisthesis only.

Methods. This first systematic review of the literature regarding MIS and OS spinal fusion for spondylolisthesis treatment was performed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for article identification, screening, eligibility, and inclusion. Electronic literature search of Medline/PubMed, Cochrane, EMBASE, and Scopus databases yielded 2489 articles. These articles were screened against established criteria for inclusion into this study.

Results. A total of five retrospective and five prospective articles with a total of 602 patients were found. Reported spondylolisthesis grades were I and II only. Overall, MIS was associated with less intraoperative blood loss (mean difference [MD], −331.04 mL; 95% confidence interval [CI], −490.48 to −171.59; P < 0.0001) and shorter length of hospital stay (MD, −1.74 days; 95% CI, −3.04 to −0.45; P = 0.008). There was no significant difference overall between MIS and OS in terms of functional or pain outcomes. Subgroup analysis of prospective studies revealed MIS had greater operative time (MD, 19.00 minutes; 95% CI, 0.90 to 37.10; P = 0.04) and lower final functional scores (weighted MD, −1.84; 95% CI, −3.61 to −0.07; P = 0.04) compared with OS.

Conclusion. Current data suggests spinal fusion by MIS is a safe and effective approach to treat grade I and grade II spondylolisthesis. Moreover, although prospective trials associate MIS with better functional outcomes, longer-term and randomized trials are warranted to validate any association found in this study.

Level of Evidence: 2

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN

Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN

Sydney Medical School, University of Sydney, Australia.

Address correspondence and reprint requests to Mohamad Bydon, MD, Department of Neurologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, USA; E-mail: bydon.mohamad@mayo.edu

Received 5 March, 2016

Revised 13 May, 2016

Accepted 23 May, 2016

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

No relevant financial activities outside the submitted work.

Spondylolisthesis is the displacement of a vertebral body that can present as mechanical low back pain, radiculopathy, or neurogenic claudication. Etiologies include spondylolysis (isthmic spondylolisthesis) and degeneration (degenerative spondylolisthesis). For patients with spondylolisthesis refractory to conservative therapy, surgical intervention represent an alternative option with studies1–4 demonstrating the potential benefit of surgery in improving quality of life.

Traditionally, surgical approaches for degenerative and isthmic spondylolisthesis involve open surgery (OS) with direct decompression and instrumented fusion to address the instability associated with vertebral slip. Fusion techniques vary and include transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), lateral interbody fusion, anterior lumbar interbody fusion, and posterior lumbar fusion (PLF).

Within the last decade, minimally invasive surgery (MIS) techniques have emerged. MIS proponents emphasize the benefits of minimizing postoperative pain and function, shortening recovery, reducing blood loss, minimizing soft tissue damage, and maintaining paraspinal structural integrity while minimizing scar tissue.5 These benefits are particularly relevant for spondylolisthesis, where an open approach may further destabilize support structures such as the facet joints, ligamentous structures, and musculature.

Many studies have focused on comparing perioperative, functional, and pain outcomes between MIS and OS in treating general lumbar degenerative diseases (including spondylolisthesis, disc disease, and spinal stenosis). Systematic evidence has investigated MIS versus OS in this group of conditions for spinal fusion,6–9 laminectomy,10,11 discectomy,12 and pedicle screw fixation.13 However, to the best of our knowledge, no review of spondylolisthesis has analyzed perioperative, functional, and pain outcomes between MIS and OS. Thus, the aim of this study was to compare outcomes of spondylolisthesis treated either by MIS or by OS and contextualize the results with respect to general lumbar degenerative diseases.

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MATERIALS AND METHODS

Search Strategy

This study was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses.14 Electronic searches were performed independently by two reviewers (V.M.L. and H.E.G.) using Ovid Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), EMBASE, and Scopus in January 2016 without time frame limitations. Unpublished literature was searched from dissertations, conference proceedings, trial registries from ACP Journal Club, and Database of Abstracts of Review of Effectiveness (DARE). Only English-language citations were considered. The following were used as either keywords or Medical Subject Headings (MeSH) in all combinations in the search strategy: “minimally invasive”/“minimal access” and “lumbar spine”/“lumbar vertebra” and “spinal fusion”/“surgical procedure” and “spondylolisthesis”. Generated reference lists were compared and reviewed for potential relevance and assessed using the inclusion and exclusion criteria.

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Selection Criteria

Studies eligible for this systematic review and meta-analysis compared completely MIS and completely OS spinal fusion procedures for spondylolisthesis. For the purpose of this review, MIS procedures included percutaneous, mini-open, and muscle-splitting approaches to the spine whilst OS procedures involved complete spinal exposure. Inclusion criteria included (1) confirmed diagnosis of either degenerative or isthmic lumbar spondylolisthesis only; (2) at least one of the following outcomes: operative time, blood loss, hospital stay, fusion rates, complications, and pre- and postoperative functional and pain scores by Oswestry Disability Index (ODI) and visual analog scale (VAS), respectively; and (3) direct comparative study design. Exclusion criteria included (1) less than 10 patients per study arm; (2) cohorts involving other diagnosed lumbar degenerative disorders without spondylolisthesis; (3) case reports and series without comparator group; and (4) editorials, reviews, opinion, and commentary articles. Manual search of reference lists was performed to ensure relevant studies were not missed. Authors of studies were contacted directly for clarification if there were concerns about overlapping cohorts and the study with the most complete reporting was selected.

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Data Extraction

The extracted data included methodology data, study design, patient demographics, operation features (i.e., Meyerding classification of olisthesis grade, procedure type approach, and number of vertebral levels fused) operative outcomes (i.e., operative time, intraoperative blood loss, and length of stay in hospital after surgery). Functional outcomes were also at the end of study follow-up were also reported and included ODI on a scale between 0% and 100%. With this scoring system, minimal disability is considered between 0% and 20% and bed-bound status expected between 80% and 100%. Back pain outcome at the end of study follow-up as measured by the VAS was also reported. VAS is reported on a scale of 1 to 10, where 1 is no pain experienced and 10 is the worst possible pain imaginable. Other reported outcomes included intraoperative durotomy, wound infection, and revision surgery. When mean and standard deviation of values were not reported, estimations were made if possible based on available graphs and published methodologies.15,16 Data extraction from articles, tables, and figures was performed by one reviewer (V.M.L.) with accuracy of data entry confirmed by second reviewer (H.E.G.).

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Cohort Comparison

From the studies reporting patient demographics, pooled means for age, sex (% male) and number of surgical levels were calculated using a weighted distribution. Continuous variables were compared using two-sample t test and the number of surgical levels were compared using two-proportion z test with statistical significance established for two-tailed value <0.05.

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Meta-analysis of Clinical Outcomes

The odds ratio (OR), mean difference (MD), or weighted MD were used as summary statistics. In the present study, both fixed- and random-effects models were tested. I2 statistic was used to estimate the percentage of total variation across studies, owing to heterogeneity rather than chance, with values greater than 50% considered as substantial heterogeneity. In the present meta-analysis, the results using the random-effects model were presented to take into account the possible clinical diversity and methodological variation between studies. Specific analyses considering confounding factors were not possible because raw data were not available. All P values were two-sided. All statistical analysis was conducted with Review Manager Version 5.3.2 (Cochrane Collaboration, Software Update, Oxford, UK).

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Evidence Quality and Publication Bias Assessment

The quality of evidence for each study was assessed independently by two reviewers (V.M.L. and H.E.G) using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. Each study was rated overall as either high, moderate, low, or very low based on the study design, limitations, results, precision, and evidence used. Cases of discrepancy were resolved through discussion. Funnel plot methodology was used to assess the interstudy risk of publication bias, plotting proportion of an event against its precision and analyzing for asymmetry.

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RESULTS

Literature Search

Our search strategy identified a total of 2489 studies (Figure 1). After removal of 303 duplicative publications, inclusion/exclusion criteria were applied to titles and abstracts of the 2186 articles. This yielded 17 articles that underwent full-text analysis. Ten articles are included in the current review for both qualitative and quantitative analysis. All studies included were single institution observational cohort studies, five of which were retrospective17–21 and five of which were prospective22–26 (Table 1).

Figure 1

Figure 1

TABLE 1

TABLE 1

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Demographics

There were 602 patients analyzed in all studies, with 328 (54%) and 274 (46%) patients undergoing MIS and OS spinal fusion for spondylolisthesis treatment, respectively. Comparative features are included in Table 2. Mean age ranged from 47.9 to 67 years in the MIS group, and 52.6 to 69.1 years in the OS group. Proportion of males ranged from 8.3% to 67.4% in the MIS group, and from 30.0% to 67.6% in the OS group. Mean number of levels fused ranged from 1 to 1.22 levels in the MIS group and from 1 to 1.8 levels in the OS group. Both MIS and OS groups reported fusion rates ranging from 91.7% to 100%. There was no statistically significant difference in the aforementioned features between the MIS and OS cohorts. Two studies considered isthmic and degenerative spondylolisthesis in their cohort, while the remaining studies considered degenerative spondylolisthesis only.

TABLE 2

TABLE 2

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Grade of Spondylolisthesis

Seven studies indicated the grade of spondylolisthesis in their cohorts as per the Meyerding classification (Table 1). Seven included Grade I, while six included Grade II. No higher grades were considered.

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Procedure Type

In terms of spinal fusion type, five studies used TLIF only, two studies used PLIF only, two studies used PLF only, and one study used TLIF in MIS and combination of PLIF and PLF in OS (Table 1).

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Operative Time

Nine studies had sufficient data to extract operative time data (Figure 2A). There was no significant difference overall between the MIS group and the OS group. However, MIS patients in prospective cohort studies underwent significantly longer operations than OS patients (MD, 19.00 minutes; 95% CI, 0.90 to 37.10; P = 0.04), with pooled means of 213 versus 191 minutes, respectively.

Figure 2

Figure 2

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Intraoperative Blood Loss

Eight studies had sufficient data to extract intraoperative blood loss (Figure 2B). There was significantly less intraoperative blood loss overall in the MIS group than the OS group (MD, −331.04 mL; 95% CI, −490.48 to −171.59; P < 0.0001), with pooled means of 199 versus 514 milliliters. This difference was significant in both retrospective and prospective cohort studies.

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Length of Stay

Six studies had sufficient data to extract length of stay in the hospital (Figure 2C). There was significantly shorter length of stay overall in the MIS group compared to the OS group (MD, −1.74 days; 95% CI, −3.04 to −0.45; P = 0.008), with pooled means of 5.3 versus 8.0 days respectively. This difference was significant in both retrospective and prospective cohort studies.

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Oswestry Disability Index

Six studies had sufficient data to extract final ODI scores (≥12 mo) as a measure of disability (Figure 3A). There was no significant difference overall between the MIS group and the OS group. However, MIS patients in prospective cohort studies reported significantly lower final ODI scores than OS patients (weighted MD, −1.84; 95% CI, −3.61 to −0.07; P = 0.04), with pooled means of 13.8 versus 16.1 respectively.

Figure 3

Figure 3

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Visual Analogue Scale

Four studies had sufficient data to extract final VAS scores (≥12 mo) as a measure of back pain (Figure 3B). There was no significant difference between the MIS group and the OS group.

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Complications

All ten studies had sufficient data to extract complication rates (Figure 4). Overall 37 and 44 postoperative complications were observed in the MIS group and OS group respectively. Of complications reported in more than one study, the most common were unintentional durotomy (MIS vs OS: 10 vs 11 cases), malpositioned instrumentation (MIS vs OS: 7 vs 3 cases), and revision surgery (MIS vs OS: 7 vs 6 cases). There was no significant difference between the MIS group and the OS group with respect to overall complications and individual complications reported by more than one study.

Figure 4

Figure 4

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Assessment of Evidence Quality

Based on the GRADE assessment of all studies, the quality of evidence was low in five studies and very low in the remaining five (Table 1).

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Publication Bias

Funnel plots were generated and assessed for asymmetry. The funnel plot for operative time detected a significant outlier study (Figure 5), indicating potential publication bias influencing the reported outcome. However when this study was removed, significance at both overall and cohort study levels between groups remained absent. Asymmetry was not observed in the remaining funnel plots.

Figure 5

Figure 5

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DISCUSSION

The use of MIS to treat degenerative disease such as spondylolisthesis is increasing. Although the concept of MIS is an attractive one, there needs to be clear clinical evidence of its efficacy and safety compared with conventional OS. Meta-analyses of the available comparative studies showed MIS is associated with (1) significantly lower intraoperative blood loss than OS, (2) significantly shorter hospitalization than OS, and (3) no greater complication, functional or pain outcomes than OS. This is the first review to analyze these outcomes with respect to spondylolisthesis only.

This review did not detect significant difference in follow-up functional or pain outcomes between spondylolisthesis patients treated by MIS or OS when comparing ODI and VAS measures. The pooled results of the meta-analyses agree with recent systematic reviews6–9 that have analyzed general degenerative lumbar diseases. Some studies17,22,24 in this review were specific to comorbid populations, which may have influenced functional and pain outcome results.27 Future studies report that these factors will allow for a greater understanding of postoperative functional and pain outcomes in both MIS and OS.

The significant reduction in both intraoperative blood loss and length of hospitalization demonstrated in MIS is intuitive. Similar results have been shown in systematic reviews6–9 reporting on lumbar disease in general. There is less spinal muscle atrophy and blood supply disturbances in MIS than is seen in OS. Smaller incisions and less retraction may promote faster recovery. This is particularly applicable for those with hematologic and immune-related conditions who especially benefit from less blood loss and less infection exposure risk. What may prove most significant, however, is that our meta-analysis demonstrated no increased association with complications compared to OS. These results suggest that MIS can offer an alternative option in spondylolisthesis management, which involves less surgical trauma but maintains the patient-rated outcomes and complication rates seen in OS patients.

The meta-analysis for operative time demonstrated no significant difference between MIS and OS groups. However, the considerable heterogeneity observed may reflect the documented steep transition from conventional OS to mastering novel MIS.28,29 Previous systematic reviews6,7,9 studying general degenerative lumbar disease have proposed that operative time can vary between surgeons who are at different points along the learning curve. MIS surgery requires a firm grasp of the relevant anatomy, familiarity with the novel instrumentation, and comfort with the restricted view.6 The potential correlation between less experience and case-load explains why there remain studies30–32 that have observed greater operative times in MIS than OS in treating general lumbar disease. Longitudinal studies33,34 have in fact demonstrated significant decrease in operative time with increasing number of MIS performed for degenerative lumbar diseases. Future studies should analyze for benefits yet to be established as MIS operating times normalize to shorter durations.

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Strengths and Limitations

Strengths of this study include extensive literature search strategy, strict adherence to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines,14 quality of evidence analysis by GRADE protocol, and assessing the interstudy publication risk by funnel plots. This enabled us to produce the first systematic review and meta-analysis of outcomes for MIS versus OS specifically for spondylolisthesis. Ultimately, the findings of this study require confirmation by a large, multi-institutional prospective randomized controlled trial with significant follow up. Until then, this study represents the highest level of evidence justifying the clinical significance of MIS in treating spondylolisthesis.

This study was restricted by a number of limitations, one of which was the scarcity of data relating to the comparative outcomes of spondylolisthesis spinal fusion surgery, especially for isthmic and higher-grade spondylolistheses. Only two studies18,26 in this review reported isthmic spondylolisthesis outcomes and these were only collectively reported with degenerative spondylolisthesis outcomes. Whether the clinical and radiological outcomes of this study were influenced by low representation of isthmic spondylolisthesis is unclear. A recent study35 investigating the outcomes of MIS and OS with TLIF between low-grade isthmic and degenerative spondylolistheses showed significant radiological difference only with respect to disc restoration height, not fusion or clinical, functional, and pain outcomes. Moreover, the diverse definition of MIS in the included studies (percutaneous, mini-open, and muscle splitting approaches) could have caused broader spread of the surgical outcomes for that group, potentially confounding the results of the meta-analysis.

There is a risk of selection bias, as our study consisted only of lower quality retrospective and prospective studies with no randomized controlled trials. Considerable heterogeneity exists between these studies for many of the outcomes. This can be attributed to a number of factors: intersurgeon variability in experience and case-load; subjective nature of most outcome measures; and inherent heterogeneity of surgical procedures such as TLIF and PLIF. Outcome differences between spondylolisthesis procedures have been reported in the literature. For example, OS PLIF can be associated with a higher incidence of complications and poorer perioperative outcomes relative to OS TLIF.36 In an attempt to control for heterogeneity, random-effects meta-analysis was used rather than fixed-effects meta-analysis. This was to allow for the assumption that effect across studies is distributed similarly rather than the same.

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CONCLUSION

This systematic review is the first review of current literature comparing MIS versus OS spinal fusion outcomes for the treatment of grade I and grade II spondylolisthesis specifically. MIS was associated with lower intraoperative blood loss, shorter hospital stay than OS and has comparable rates of complications and pain and functionality improvement overall. Subgroup analysis of prospective trials also associated MIS with longer operative time and better functional outcomes. However, only low to very low qualities are available in current literature, and no randomized controlled trials exist that specifically look at the outcomes of spondylolisthesis treated either by MIS or OS spinal fusion literature only. Such studies in the future will validate the findings of this study.

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References

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Keywords:

degenerative spondylolisthesis; isthmic spondylolisthesis; minimally invasive surgery; posterior lumbar interbody fusion; spinal fusion; spine; spondylolisthesis; systematic review; transforaminal interbody fusion

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