Endoscopic Lumbar Interbody Fusion,Minimally Invasive Transforaminal Lumbar Interbody Fusion,and Open Transforaminal Lumbar Interbody Fusion for the Treatment of Lumbar Degenerative Diseases: A Systematic Review and Network Meta-Analysis

Abstract

Study Design

network meta-analysis

Objective

To compare the clinical efficacy and safety of endoscopic lumbar interbody fusion (Endo-LIF), minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), and open transforaminal lumbar interbody fusion (OTLIF) in the treatment of lumbar degenerative diseases (LDDs).

Method

A literature search was conducted in the PubMed, Embase, and Cochrane Library databases. Studies comparing Endo-LIF, MIS-TLIF and OTLIF published from September 2017 to September 2022 for the treatment of LDD were retrieved. Data were extracted from preset clinical outcome measures, including operation time, estimated intraoperative estimated blood loss (EBL), length of hospital stay (LOS), complications, visual analog scale (VAS) score, Oswestry disability index (ODI) score, etc.

Result

Thirty-one studies with 3467 patients were included in this study. Network meta-analysis showed that in the comparison of the 3 procedures, Endo-LIF was superior to MIS-TLIF and OTLIF in terms of reducing EBL, LOS, time to ambulation, and VAS score of back pain. MIS-TLIF was superior to Endo-LIF in terms of ODI improvement, and OTLIF required the shortest intraoperative fluoroscopy time. There was no significant difference in operative time, complication rate, fusion rate, VAS score of leg pain, or JOA score among the 3 procedures.

Conclusion

Endo-LIF, MIS-TLIF and OTLIF each have their own advantages and disadvantages and show similar results in many respects, except for better early outcomes achieved with the more minimally invasive procedure.

Keywords

lumbar degenerative disease transforaminal lumbar interbody fusion endoscopic lumbar interbody fusion systematic review network meta-analysis

Introduction

Lumbar interbody fusion is a commonly used surgical treatment for lumbar degenerative diseases (LDDs).¹ Traditional surgical methods include posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF), but the 2 methods damage the posterior anatomy of the spinal column, cause a large amount of bleeding, require a long time to retract the nerve, and have a long postoperative bed rest time, which easily produces complications that affect the treatment effect and prognosis of patients.^1,2 Considering the continuous technical improvement of TLIF surgery, minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been widely used for treating LDDs in recent years due to the advantages of minimal tissue damage and short postoperative recovery time.³ Considering that transforaminal endoscopic lumbar discectomy (TELD) causes less trauma and sufficient decompression in the treatment of lumbar disc herniation, the endoscopic technique has also been applied to the endoscopic lumbar interbody fusion (Endo-LIF) surgical technique.

Endo-LIF has significant advantages in the treatment of lumbar degenerative disease, including endoscopic direct insertion into the interbody disc space and complete removal of the cartilage endplate under clearly enlarged endoscopy without causing damage to the bony endplate.⁴ Good endplate preparation facilitates interbody fusion. Alternatively, Endo-LIF may be performed under local infiltration or epidural anesthesia⁵ to reduce anesthesia-related risks, which is significant for patients who are unable to receive general anesthesia. Endo-LIF surgery is less traumatic and allows retention of the basic structure behind the spine.⁶ Because of its similar approach to that of OTLIF, most of the literature has named it Endo-TLIF. To ensure the rigor of the surgical expression, we still call this technique Endo-LIF.

At present, many scholars have conducted meta-analyses on MIS-TLIF and open TLIF (OTLIF). The advantages of MIS-TLIF seem to focus on the perioperative index, in which the long-term functional outcome is not significantly different from OTLIF, while the meta-analysis of Endo-LIF and MIS-TLIF also has similar results.^7-11 Moreover, because Endo-LIF and traditional TLIF have been rarely compared, evidence-based medicine studies have noted the difficult progression of OTLIF to Endo-LIF. Therefore, this paper collected relevant literature and compared the effectiveness and safety of the above 3 similar approach methods by network meta-analysis to provide an evidence-based basis for clinical practice.

Methods

In this study, evidence selection, qualitative synthesis, and meta-analysis were conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guidelines and the AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. The protocol of this study is registered on International prospective register of systematic reviews (PROSPERO, CRD 42023387572).

Literature Inclusion and Exclusion Criteria

Inclusion criteria: (1) Studies involving patients with clinically confirmed LDDs, including degenerative lumbar stenosis, degenerative lumbar spondylolisthesis, and degenerative lumbar disc herniation; (2) Studies with patients who underwent open transforaminal lumbar interbody fusion (OTLIF), MIS-TLIF or Endo-LIF; (3) Studies reporting surgical time, intraoperative estimated blood loss (EBL), length of hospital stay (LOS), postoperative drainage volume, intraoperative fluoroscopy time, time to ambulation, fusion rate, adverse events, visual analogical score of low back pain (VAS-BP), visual analogy score of leg pain (VAS-LP), Oswestry dysfunction index (ODI) score and Japanese Orthopedic Association (JOA) score, with a follow-up time of at least 12 months. (4) Studies designed as a randomized controlled trial or cohort study. The definitions of outcomes are shown in Supplemental File 1.

The exclusion criteria were as follows: (1) studies involving patients with infectious diseases, spinal trauma, deformity or tumors, history of lumbar surgery, or acute cauda equina syndrome; (2) studies on other surgical methods, such as anterior lumbar fusion, oblique lumbar fusion or posterior lumbar fusion; (3) studies involving modified methods, such as surgical robot assistance or O-arm navigation; and (4) reviews, meta-analyses, cadaveric studies, experimental articles, expert opinions, case reports, technical reports, case‒control studies, and cross-sectional studies.

Literature Search

A computer search of the Embase, PubMed and Cochrane Library databases was performed to collect comparative trials of TLIF or endoscopic lumbar fusion, and then the full texts of relevant papers were manually searched. Papers must have been written in English. The databases were searched between September 2017 and September 2022. The search strategy is shown in Supplemental File 2.

Literature Screening, Data Extraction and Bias Risk Assessment in the Included Studies

Two researchers, Jin and Liu, independently screened and extracted the relevant literature and cross-checked it. If there were differences, they discussed and resolved them. The literature screening process was as follows. After the literature was reviewed with EndNote X9, the literature that did not conform based on the title and abstract was excluded. The researchers then decided whether to include the literature by reading the full text and the exclusion criteria and inclusion criteria. The extracted data included author name, time of publication, sample size, sex and age of patients, follow-up time, observation outcomes, etc. The quality evaluation of the included randomized controlled experiments was conducted according to the criteria in the Cochrane risk-of-bias tool, and the quality evaluation of the included cohort studies was performed by using the Newcastle‒Ottawa Scale (NOS).¹² Low-quality studies with scores below 6 points were excluded.

Statistical Analysis

Treatment effects were expressed as the mean differences (MD) and 95% credibility intervals (CI) for continuous data or as risk ratios (RR) and 95% confidence intervals for categorical data. Network meta-analysis was performed using the frequentist model with a graph-theoretical method by R (version 4.1.2) package net Meta (version 2.1-0). We used the network plot command of Stata version 16.0 (Stata Corp, College Station, TX) to draw the network plots.¹³ The estimator was based on weighted least-square regression with the Moore–Penrose pseudoinverse method.¹⁴ We conducted pairwise meta-analysis with the DerSimonian–Laird random-effects model to estimate the variance in heterogeneity between studies.¹⁵ League tables of the relative treatment effects were used to visualize comparisons of network estimations. Global and local statistical heterogeneity was assessed with generalized Cochran’s Q.¹⁶ Local inconsistency of direct and indirect results was assessed with the node-splitting method for all comparison loops, and indirect results were derived from direct and network results by the back-calculation method.^17,18 Funnel plots were used to identify publication bias and small-study effects for outcome measures that were reported in more than 10 studies.

Results

Literature Screening Results and the Characteristics and Quality of the Included Literature

According to the set search strategy, a total of 1120 studies were found, and 760 documents were obtained after removal of duplicate literature. Fifty-two studies were selected after primary screening, and 31 documents that met the requirements were selected by reading the full text^2,6,19-47 (Figure 1). Thirty-one studies were included, and the total number of patients included was 3467, including 441 with Endo-LIF, 1591 with MIS-TLIF, and 1435 with OTLIF. The quality evaluation results are shown in Supplementary Files 3 and 4, and the general features of the included literature are shown in Supplementary File 5.

Figure 1.

Flow chart of selected articles.

Network Plot, Constancy Detection, and Publication Bias Test

The network plot for each outcome measure in this study is shown in Figure 2. Most outcome measures in this study lacked a direct comparison between OTLIF and Endo-LIF. The node splitting method was used to test the 4 closed-loop outcome indicators, and the results showed P > .05, indicating that the results of direct and indirect comparison are consistent, and therefore, the possibility of inconsistency is small. (Figure 3). The reason for the publication bias for EBL, VAS-LP and operation time may be that the included literature was mainly cohort studies, and the level of evidence was not high (Figure 4).

Figure 2.

Network plots. The circular size in the evidence network graph indicates the sample size of the outcome in the corresponding operation, the connection line indicates that the 2 techniques have evidence of direct comparison, and the thickness of the connection line indicates the number of directly compared studies. AE, adverse event; LOS, length of hospital stay; EBL, estimated blood loss; JOA, Japanese orthopedic association score; ODI, oswestry dysfunction index; VAS-BP, visual analogical score of back pain; VAS-LP, visual analogical score of leg pain.

Figure 3.

Node splitting of 4 outcomes. LOS, length of hospital stay; EBL, estimated blood loss; ODI, oswestry dysfunction index; MD, mean differences; CI, credibility intervals.

Figure 4.

Funnel plots of publication bias. AE, adverse event; LOS, length of hospital stay; EBL, estimated blood loss; JOA, Japanese orthopedic association score; ODI, oswestry dysfunction index; VAS-BP, visual analogical score of back pain; VAS-LP, visual analogical score of leg pain.

Analysis Results

The network meta-analysis prediction intervals are summarized in Figure 5.

Figure 5.

Forecast Interval Summary of each outcome. AE, adverse event; LOS, length of hospital stay; EBL, estimated blood loss; JOA, Japanese orthopedic association score; ODI, oswestry dysfunction index, VAS-BP, visual analogical score of back pain, VAS-LP, visual analogical score of leg pain.

Endo-LIF vs MIS-TLIF

Endo-LIF had less intraoperative blood loss (MD: −69.76.95% CI: −99.08 to −40.44), an earlier time to ambulation (MD: −2.82.95% CI: −.44 to −.21), a shorter LOS (MD: 2.75.95% CI:1.56 to 3.94), and more significant improvement in VAS-BP scores (MD: .26.95% CI: .16 to .67) than MIS-TLIF. The ODI improvement was more obvious with MIS-TLIF (MD: 1.82, 95% CI: .24 to 3.39). The differences in AE, fusion rate and other remaining indicators were not statistically significant.

MIS-TLIF vs OTLIF

MIS-TLIF had less intraoperative blood loss (MD: −121.41.95% CI: −142.86 to −99.96), less drainage volume (MD: −98.81.95% CI: −152.67 to −44.94), an earlier time to ambulation (MD: −3.47.95% CI: −6.50 to −.44), a shorter LOS (MD: 1.32.95% CI: .93 to 1.89), a longer fluoroscopy time (MD: 27.22.95% CI: 15.17 to 39.27), and more significant improvement in VAS-BP scores (MD: .55.95% CI: .12 to .98) than OTLIF. The differences in AE, fusion rate and other remaining indicators were not statistically significant.

MIS-TLIF vs OTLIF

Endo-LIF had less intraoperative blood loss (MD: −191.16.95% CI: −226.10 to −156.23), an earlier time to ambulation (MD: −6.29.95% CI: −10.29 to −2.29), less drainage volume (MD: −157.50.95% CI: −247.11 to −67.89), a shorter LOS (MD: 1.27.95% CI: .53 to 3.03), more significant improvement in VAS-BP scores (MD: .81.95% CI: .21 to 1.40), and a longer fluoroscopy time (MD: 42.16.95% CI: 22.28 to 62.04) than OTLIF. The differences in AE, fusion rate and other remaining indicators were not statistically significant.

Discussion

Key Findings

To compare the clinical efficacy of Endo-LIF, MIS-TLIF, and OTLIF in patients with LDD, we combined 4 RCTs and 27 cohort studies involving a total of 3467 participants. The main finding of the current network meta-analysis was that Endo-LIF demonstrated better near-term efficacy, fewer severe complications, and more significant relief in low back pain than the other 2 procedures. The long-term outcomes were similar for all 3 procedures, demonstrating that the long-term outcomes of Endo-LIF surgery can achieve the same results as open surgery.

In the network meta-analysis of EBL, time to ambulation, and LOS, Endo-LIF had the best results, followed by MIS-TLIF, and OTLIF had the worst results. The Endo-LIF procedure reduces the extent of paravertebral muscle stripping, preserves more posterior spinal structures, and reduces the strain on the cauda equina, resulting in less disruption, less bleeding, and a shorter postoperative recovery time.⁶ Continuous saline flushing and certain water pressure during Endo-LIF may be one of the main factors in reducing bleeding. However, Endo-LIF and MIS-TLIF require repeated intraoperative fluoroscopy to determine the position of the working channel, pedicle screws and cages, thus exposing the patient and surgeon to higher radiation doses. Our results show no significant difference in fluoroscopy time between Endo-LIF and MIS-TLIF, but both are higher than OTLIF. Studies of postoperative drainage have shown that Endo-LIF and MIS-TLIF drainage are similar, and both are lower than OTLIF. In addition, percutaneous endoscopic TLIF (PE-TLIF) can be performed under local infiltration or epidural anesthesia^5,48 to reduce anesthesia-related risks and provide real-time neurofeedback to patients, which has important implications for patients who cannot tolerate general anesthesia. It has been reported in the literature that endoscopic local anesthesia in patients undergoing TLIF can provide a similar outcome for patients undergoing OTLIF under general anesthesia, with a shorter operative time and hospital stay.⁴⁹ Endoscopic TLIF without general anesthesia is a novel and promising short-segment lumbar fusion that is safer for surgery in middle-aged and elderly patients and patients with renal impairment.⁵⁰

In terms of long-term outcomes beyond 1 year, the differences between the 3 procedures were mainly in the relief of low back pain, with Endo-LIF showing the most relief and OTLIF the least. Our study showed that patients with Endo-LIF had the most relieve back pain among the 3 procedures, followed by MIS-TLIF and OTLIF, and that MIS-TLIF had a slight advantage over Endo-TLIF in terms of resolution of functional impairment, but there was no significant difference between the 2 procedures when compared with OTLIF. In conclusion, there was no significant difference in the alleviation of pain, dysfunction, and clinical symptoms between these 3 procedures.

The description of the fusion rate varies widely from study to study. Most studies determined fusion by observing the presence of bridging trabeculae bone between vertebrae on computed tomography (CT) scan.²⁹ Fusion rates assessed by radiological, clinical, and unspecified methods were all included in our scope of inclusion. However, if both radiological fusion and clinical fusion were mentioned in the article, we would include fusion rates assessed by radiological methods. Our results showed that the fusion rates of the 3 surgeries were not significantly different from each other. Subchondral bone injury or incomplete endplate preparation may lead to cage subsidence, displacement or fusion failure after TLIF.^51,52 In contrast, Endo-LIF has a clearer field, and the cartilage endplate can be completely removed under clearly enlarged endoscopy without damage to the bone endplate.⁵³ Good endplate preparation can reduce the probability of cage displacement and subsidence, improve the fusion rate and is an important link to promote interbody fusion.⁵⁴ However, it is worth noting that Endo-LIF is not as widely applicable for endplate treatment as traditional surgery, and the bone graft volume and bone graft area are small, which increases the displacement and collapse of the postoperative cage.

In the safety analysis, we combined the data of all reported complications according to the Clavien‒Dindo surgical complication classification and found that among 309 Endo-LIF patients, 9 had grades I-II (2.91%), 2 had grade III (.65%), and 4 had neuro events.⁵⁵ Among 904 MIS-TLIF patients, 41 had grade I-II complications (4.54%), 11 had grade III complications (1.22%), 3 had grade IV complications (.33%), and 14 had CSF (cerebrospinal fluid) events. Among 760 OTLIF patients, 54 had grade I-II complications (7.11%), 23 had grade III complications (3.03%), 3 had grade IV complications (.39%),⁵⁵ and 22 had neurological events. The results showed that Endo-LIF had the highest safety profile in terms of both the frequency and severity of adverse events, with MIS-TLIF being the next safest and OTLIF the lowest. However, network meta-analysis showed no significant difference in the total AE incidence between the 3 procedures. As an emerging technology, the complication rate of Endo-LIF varies from 0 to 28.6%, and most complications are mild and resolved with conservative management.⁵⁶ Moreover, there is a correlation between the choice of surgical access and complications, with Endo-LIF via the trans-Kambin approach having the potential to damage the exiting nerve root,⁵⁶ while the posterior-lateral approach may injure the traveling nerve root.⁵⁷

Comparison with Previous Studies

Our study is the first network meta-analysis comparing the clinical outcomes of Endo-LIF, MIS-TLIF, and OTLIF. In a previous meta-analysis of Endo-LIF vs MIS-TLIF, the more consistent results were less intraoperative blood loss, shorter hospital stay, and no significant differences in long-term prognosis, complication rates, and fusion rates for Endo-LIF when compared to those for MIS-TLIF, but the surgical time was different. The results of Kou¹¹ and Guo’s⁵⁸ study showed that Endo-LIF surgery time was longer than the MIS-TLIF surgery time, while the results of Sousa’s¹⁰ study showed no significant difference in surgery time between the 2. The results of Kou and Guo seem to be more convincing in terms of the quality of the included studies; however, after including more literature, our results on the duration of surgery are in agreement with those of Sousa. Of interest is that in a meta-analysis of PE-TLIF vs MIS-TLIF, PE-TLIF had a shorter operative time.⁹ This advantage may be due to local infiltration anesthesia and epidural anesthesia, but it may also be due to the inconsistency of our findings with Kou and Guo.

Meta-analyses of MIS-TLIF and OTLIF are relatively well established, with the main consensus being that MIS-TLIF causes less intraoperative blood loss, a shorter hospital stay, and lower complication rates, while the operative time and long-term outcomes are roughly comparable to those of OTLIF.^7,8,59,60 MIS-TLIF showed better back pain relief in early meta-analyses,⁶⁰ but recent studies, especially analyses with a long-term follow-up of more than 2 years, have shown no significant difference in long-term back pain relief between the 2.⁷

Limitations

Our study has several limitations. First, there are few high-quality studies on Endo-LIF, and to ensure a sufficient sample size to perform a net meta-analysis, our inclusion criteria were broad, excluding only case‒control studies and cross-sectional studies and retaining retrospective cohort studies. In addition, the publication bias of this study was high due to the small sample size of the treatment group and other systematic errors. Second, Endo-LIF is a relatively new surgical technique, and essentially all of the comparative studies related to it were focused within 5 years. To reduce the influence of surgeon experience on the study results, we could only limit the search time to 5 years and therefore had to discard some of the earlier high-quality MIS-TLIF vs OTLIF comparative studies. Even so, differences in surgeon experience still affect the efficacy of Endo-LIF when compared with MIS-TLIF and OTLIF. Third, due to the scarcity of relevant studies, we had to abandon the analysis of some indicators, such as postoperative adjacent segment regression and time to return to work. The above limitations adversely affected the strength of the argumentation of this study, and more high-quality clinical trials are needed to obtain more reliable results in the future.

Conclusion

There was no significant difference in operative time, complication rate, fusion rate, VAS score of leg pain, or JOA score among the 3 procedures. However, among the above 3 surgical techniques, the more minimally invasive the procedure is, the better its early efficacy. In terms of mid- and long-term outcomes, Endo-LIF showed better low back pain relief, and MIS-TLIF showed better functional improvement. We also conducted the first meta-analysis on reductions in drainage, fluoroscopy time, time to ambulation, and JOA score with Endo-LIF, further demonstrating that minimally invasive technical development has a positive effect on the early outcome of patients undergoing lumbar interbody fusion.

Supplemental Material

Supplemental Material - Endoscopic Lumbar Interbody Fusion, Minimally Invasive Transforaminal Lumbar Interbody Fusion, and Open Transforaminal Lumbar Interbody Fusion for the Treatment of Lumbar Degenerative Diseases: A Systematic Review and Network Meta-Analysis

Supplemental Material for Endoscopic Lumbar Interbody Fusion, Minimally Invasive Transforaminal Lumbar Interbody Fusion, and Open Transforaminal Lumbar Interbody Fusion for the Treatment of Lumbar Degenerative Diseases: A Systematic Review and Network Meta-Analysis by Xijian Hu, Lei Yan, Xinjie Jin, Haifeng Liu, Jing Chai, and Bin Zhao in Global Spine Journal

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Author’s Note

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

ORCID iDs

Xijian Hu

Lei Yan

Supplemental Material

Supplemental material for this article is available online.

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