Abstract
Study design
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Systematic review; meta-analysis.
Purpose
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Lumbar degenerative disease is frequent and has a tremendous impact on patients’ disability and quality-of-life. Open and minimally invasive procedures have been used to achieve adequate decompression and fusion. Endoscopic lumbar interbody fusion (Endo-LIF) is emerging as an alternative, trying to reduce morbidity, while achieving comparable to superior clinical outcomes. The aim of this work is to perform a systematic review and meta-analysis to investigate how Endo-LIF compares to open or minimally invasive procedures.
Methods
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Electronic databases (MEDLINE, Scopus, Web of Science, Cochrane) were systematically reviewed using the query: ‘(percutaneous OR endoscop*) AND (open OR minimal* invasive) AND lumbar AND fusion’. PRISMA guidelines were followed.
Results
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Twenty-seven articles were included (25 cohort study, 1 quasi-experimental study, and 1 randomized control trial; for meta-analytical results, only observational studies were considered). Endo-LIF conditioned longer operative time, with significantly lower blood loss, bedtime, and hospital length of stay. Early post-operative back pain favored endoscopic techniques. Endo-LIF and non-Endo-LIF minimally invasive surgery displayed comparable results for most back and leg pain or disability outcomes, despite Endo-LIF having been associated with higher disability at late follow-up (versus Open-LIF). No differences were found regarding fusion rates, cage subsidence, or adverse events. Definitive conclusions regarding fusion rate cannot be drawn due to low number of studies and unstandardized fusion definition.
Conclusion
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Endo-LIF is an effective and safe alternative to conventional lumbar interbody fusion procedures. Evidence shortcomings may be addressed, and future randomized control trials may be performed to compare techniques and to validate results.
Introduction
Lumbar degenerative disease (LDD) encompasses a series of common conditions, including disc degeneration (with or without herniation), spondylolisthesis, and/or spinal stenosis, with a worldwide estimated annual incidence of over 250 million individuals (1, 2). LDD can present with varying symptoms and severity, remaining one of the most relevant causes of disability and work absenteeism due to its substantial impact on patient’s quality of life (3).
Treatment strategies for LDD may include conservative and/or surgical options. The latter may range from single-level discectomy and/or decompression to multi-level decompression and/or fusion procedures. Lumbar interbody fusion (LIF), which can be performed from posterior (PLIF), transforaminal (TLIF), lateral (LLIF), oblique (OLIF), or anterior (ALIF) approaches, involves the placement of an implant or structural graft within the intervertebral space (after discectomy and endplate preparation), in order to stabilize a painful segment, while allowing adequate direct or indirect decompression of neural elements and restoration of sagittal and/or coronal balance (4).
Minimally invasive surgery (MIS) has also been developed for the management of LDD. While trying to minimize structural damage and iatrogenic lesions, MIS approaches intend to improve post-operative pain and reduce recovery time (5). Moreover, endoscopic spine surgery has been developed and increasingly used to treat LDD. Nowadays, discectomy and decompression procedures are routinely performed under direct endoscopic visualization, with minimal tissue disruption (6, 7). Recently, endoscopic LIF (Endo-LIF) has been described and used (8, 9). However, a clear non-inferiority or superiority has not been established. Therefore, considering that Open-LIF remains the gold-standard procedure and the diversity of MIS-LIF techniques and approaches currently performed, the main aim of this work is to conduct a systematic review and meta-analysis to investigate how Endo-LIF compares to any other LIF techniques, whether open or minimally invasive. In addition, we aim to identify variables associated with differences in the comparison between Endo-LIF and other LIF techniques.
Methods
This systematic review complies with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (10).
Search and retrieval strategy
Electronic databases (MEDLINE, Scopus, Web of Science, and Cochrane) were systematically reviewed using the following query: ‘(percutaneous OR endoscop*) AND (open OR minimal* invasive) AND lumbar AND fusion’. A complementary manual search on Google Scholar and a reference review of included studies were conducted to identify any potential additional studies that could meet the inclusion criteria. The research was performed on January 2, 2023. No restrictions based on publication language, date, or status were applied. Titles and abstracts of all retrieved references were independently screened by two authors, who subsequently assessed those selected records for eligibility through an independent full-text analysis. Any disagreements were settled by mutual consensus or reconciled by a senior author.
Inclusion/exclusion criteria and study outcomes
Randomized clinical trials and prospective or retrospective cohort studies were included if they met the following inclusion criteria: (1) comparison of Endo-LIF with Open-LIF or MIS-LIF, (2) for the treatment of LDD, (3) with a report of at least one of the following outcomes: operative time, estimated blood loss, post-operative bedtime or hospital length of stay, back or leg pain (assessed through visual analog scale – VAS), disability (assessed through Oswestry disability index – ODI), fusion rate, cage subsidence, or adverse events.
Systematic reviews and meta-analyses, cadaveric and animal articles, biomechanical studies, expert opinions, commentary articles, case and technical reports without a precise case analysis, as well as studies assessing non-fusion techniques or patients with traumatic, infectious, and/or neoplastic pathology or with degenerative disease of the cervical and thoracic segments were excluded.
Regarding the Endo-LIF technique, we only considered studies describing a full-endoscopic procedure. For data collection and analysis on pain and disability, authors agreed to define three post-operative periods: early (<2 weeks; when data on multiple periods under 2 weeks were presented, 1-week post-operative values were considered), intermediate (6 months), and late (1 year to last follow-up; when multiple data were presented, 1-year follow-up values were considered). Fusion rates were classified according to the methods and records available in each article.
Data extraction and quality assessment
Data extraction from included articles was independently performed by two authors using a purposely built form, and conflicts were resolved by consensus. We extracted data on the number of participants per group and on the assessed outcomes (for binary outcomes, we extracted information on the number of participants per group who developed each outcome; for continuous outcomes, information on the pre- and post-intervention mean values and on the respective spread measures was collected). Other variables for which data were extracted included the study design, publication year, study location, patients’ demographic data, number of instrumented levels, type of cage (material; expandability), and bone graft (when used).
We performed a careful analysis to identify multiple publications from the same study, so that each study was only considered once. Quality assessment of included studies was performed with RoBRisk2 Tool from the Cochrane Foundation (for randomized clinical trials – RCT) or the Newcastle–Ottawa scale (for cohort studies) (11, 12). Two authors independently applied these scores for each study, and in the presence of conflicts, the lowest value was considered.
Statistical analysis
Mean differences (MD) and risk ratios (RR) were used to report the results of continuous and dichotomous variables, respectively. We performed random-effects meta-analyses of MD or RR (comparing outcomes in Endo-LIF with those in MIS-LIF or Open-LIF), using the restricted maximum likelihood method. Heterogeneity was assessed using Cochran’s Q-statistic test and the I2 statistic – a P-value <0.10 or an I2 ≥ 50% was considered to represent substantial heterogeneity. To explore sources of heterogeneity, we performed leave-one-out sensitivity analyses, subgroup analyses, and meta-regression. We tested the following variables in univariable meta-regression models (performed as long as there were ten primary studies for the outcome being assessed): year of publication, number of Endo-LIF portals, and type of Endo-LIF approach. The latter two variables were also tested in subgroup analyses for pain and disability. For fusion outcomes, subgroup analysis also tested for cage expandability and type of bone graft used. All analyses were performed using the meta package from software R.
Results
Study selection
We identified a total of 3258 records in the database search. We removed 1620 duplicate records and excluded 1549 articles by title and abstract reading, and 53 by full-text analysis (Fig. 1). Three additional articles were excluded by missing full text, and six articles by linguistic reasons (the full content of these articles was not written in a language understood by the authors, and despite efforts made to obtain relevant information by contacting corresponding authors, no answers were provided).
PRISMA flow diagram regarding literature search.
Citation: EFORT Open Reviews 9, 6; 10.1530/EOR-23-0167
A total of 27 articles were included (Table 1), comprising 953 patients in the Endo-LIF group and 1011 undergoing either Open-LIF (n = 320) or MIS-LIF (n = 691). Most studies were cohort studies (n = 25; 18 being retrospective (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30), five prospective (31, 32, 33, 34, 35), and two not specified (36, 37)). A quasi-experimental study (38) and a RCT (39) were also included. Given the fact that only one RCT was found and that it is not advisable to pool together results from observational studies and RCTs in the same meta-analyses, our meta-analytical results are solely based on data from observational studies.
Descriptive characteristics of included articles.
| Study | Country | Study design | No. of participants (male) | Age* (years) | Study quality | Lumbar pathology | Endo-LIF | Open/MIS-LIF | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Endo-LIF | Open/MIS LIF | Endo-LIF | Open/MIS- LIF | |||||||
| Pang et al. (31) | China | PCS | 30 (16) | 22 (12) | 60.35 ± 12.31 | 60.18 ± 10.26 | 7 | Stenosis | Uni TF | Open PLIF |
| Park et al. (13) | South Korea | RCS | 71 (26) | 70 (20) | 68 ± 8 | 66 ± 9 | 6 | Mixed | Bi IL | Open PLIF |
| Liu et al. (32) | China | PCS | 27 (12) | 33 (13) | 63.89 ± 8.44 | 63.7 ± 9.69 | 6 | Mixed | Bi IL | Open PLIF |
| Lim et al. (14) | South Korea | RCS | 23 (10) | 36 (14) | 62.7 ± 4.1 | 58.2 ± 8.2 | 6 | Mixed | Uni TF | MIS TLIF |
| Han et al. (36) | China | NOS | 39 (18) | 43 (23) | 60.35 ± 8.04 | 60.98 ± 6.62 | 7 | Mixed | Uni TF | MIS TLIF |
| Zhang et al. (15) | China | RCS | 32 (12) | 30 (14) | 53.1 ± 12.8 | 55.7 ± 14.2 | 7 | Listhesis | Uni TF | MIS TLIF |
| Ge et al. (16) | China | RCS | 41 (21) | 43 (19) | 59.6 ± 7.6 | 62.7 ± 10.4 | 7 | Mixed | Uni TF | MIS TLIF |
| Kim et al. (17) | South Korea | RCS | 32 (17) | 55 (25) | 70.5 ± 8.26 | 67.3 ± 10.7 | 6 | Mixed | Bi IL | MIS TLIF |
| He et al. (37) | China | NOS | 30 (18) | 30 (18) | 51.6 ± 13.4 | 55.9 ± 14.3 | 6 | Mixed | Uni IL | Open PLIF |
| Lin et al. (18) | China | RCS | 41 (15) | 48 (18) | 61.85 ± 10.45 | 62.98 ± 10.52 | 6 | Stenosis | Uni IL | MIS TLIF |
| Song et al. (38) | China | QE | 31 (17) | 31 (11) | 59.1 ± 8.77 | 54.81 ± 9.46 | 7 | Mixed | Uni TF | MIS TLIF |
| Xiao et al. (19)# | China | RCS | 23 (10) | 23 (7) | 54.13 ± 9.56 | 57.61 ± 5.98 | 6 | Mixed | Uni TF | Open TLIF |
| Zhao et al. (20) | China | RCS | 40 (23) | 38 (20) | 56.93 ± 1.66 | 57.01 ± 0.95 | 7 | Mixed | Uni TF | MIS TLIF |
| Lv et al. (39) | China | RCT | 54 | 48 | – | – | † | Mixed | Uni TF | MIS TLIF |
| Wang et al. (21) | China | RCS | 32 (21) | 38 (23) | 39.6 ± 14.49 | 43.47 ± 12.29 | 7 | Mixed | Mixed | MIS TLIF |
| Li et al. (22) | China | RCS | 22 (12) | 30 (18) | 52 ± 8.8 | 50.7 ± 8.9 | 6 | Mixed | Uni IL | MIS TLIF |
| Yin et al. (33) | China | PCS | 56 (10) | 58 (10) | 60.5 ± 9.56 | 60.64 ± 7.42 | 6 | Stenosis | Uni TF | Open PLIF |
| Xue et al. (23) | China | RCS | 20 (11) | 20 (12) | 46.3 ± 17.2 | 48.4 ± 13.6 | 8 | Mixed | Uni TF | MIS TLIF |
| Jin et al. (24) | China | RCS | 16 (9) | 32 (18) | 61.2 ± 8.9 | 63.9 ± 7.6 | 8 | Listhesis | Uni TF | OLIF |
| Kang et al. (25)# | South Korea | RCS | 47 (17) | 32 (17) | 66.87 ± 10.41 | 66.38 ± 9.45 | 6 | Mixed | Bi TF | MIS TLIF |
| He et al. (26) | China | RCS | 28 (14) | 28 (13) | 59.8 ± 10.9 | 54.2 ± 10.3 | 6 | Listhesis | Uni IL | Open PLIF |
| Chang et al. (34) | China | PCS | 26 (15) | 32 (14) | 57.2 ± 13.5 | 56.1 ± 12.1 | 6 | Mixed | Uni TF | MIS TLIF |
| Gatam et al. (27) | Indonesia | RCS | 72 (26) | 73 (28) | 55.1 ± 5.12 | 52.3 ± 6.13 | 8 | Listhesis | Bi IL | MIS TLIF |
| Kim et al. (28) | South Korea | RCS | 33 (14) | 22 (7) | – | – | 6 | Mixed | Uni TF | MIS TLIF |
| Ao et al. (35) | China | PCS | 35 (16) | 40 (22) | 52.8 ± 7.5 | 53.68 ± 7.24 | 7 | Mixed | Uni TF | MIS TLIF |
| Shi et al. (29) | China | RCS | 32 | 32 | 59.3 ± 6.2 | 59.2 ± 5.5 | 8 | Mixed | Uni TF | MIS TLIF |
| Wu et al. (30) | China | RCS. | 20 (11) | 24 (14) | 53.4 ± 12.6 | 53.5 ± 10.3 | 6 | Mixed | Uni TF | Open TLIF |
#All articles refer to single-level surgery, except from Xiao, 2022 (19) (not specified) and Kang, 2021 (25) (double-level surgery); *Values are mean ± s.d.; †Some concerns.
–, missing data; Bi, biportal; Endo, endoscopic; IL, interlaminar; LIF, lumbar interbody fusion; MIS, minimally invasive surgery; NOS, cohort study, not otherwise specified; OLIF, oblique lumbar interbody fusion; PLIF, posterior lumbar interbody fusion; PCS, prospective cohort study; RCS, retrospective cohort study; RCT, randomized controlled trial; QE, quasi-experimental; TF, transforaminal; TLIF, transforaminal lumbar interbody fusion; Uni, uniportal.
Risk of bias
Quality assessment of included studies was performed. For the RCT, there were some concerns regarding randomization process and deviation from intended interventions, with a low risk of missing outcome data, outcome measurement, and selection of the reported results. Most cohort studies scored 6–8 on the Newcastle-Ottawa scale (Table 1 and Supplementary Table 1, see section on supplementary materials given at the end of this article).
Surgical- and hospital-related outcomes
For all surgical- and hospital-related outcomes (operative time, bedtime, hospital length of stay, and estimated blood loss), we detected severe heterogeneity (I2 = 73–99%; Q-Cochran test P-value <0.001) when performing meta-analysis. Endo-LIF was associated with a longer operative time when compared to both MIS-LIF (MD = 31.0 min; 95% CI (26.6; 45.4); P < 0.001; I2 = 98%) and Open-LIF (MD = 67.5 min; 95% CI (29.1; 106.0); P < 0.001; I2 = 98%). On the other hand, Endo-LIF associated with lower bedtime compared to Open-LIF (MD = −32.0 h; 95% CI (−41.9; −22.1); P < 0.001; I2 = 73%), with a similar non-statistically significant tendency for the comparison with MIS-LIF (MD = −6.2 h; 95% CI (−12.7; 0.4); P = 0.064; I2 = 93%). Hospital length of stay (vsMIS-LIF: MD = −2.0 days; 95% CI (−3.2; −0.8); P < 0.001; I2 = 95% // vs Open-LIF: MD= −2.9 days; 95% CI (−4.4; −1.5); P < 0.001; I2 = 95%) and estimated blood loss (vsMIS-LIF: MD = −85.0 mL; 95% CI (−120.2; −49.7); P < 0.001; I2 = 99% // vsOpen-LIF: MD = −182.6 mL; 95% CI (−277.2; −88.0); P < 0.001; I2 = 99%) also favored Endo-LIF (Table 2, Figs. 2 and 3). Leave-one-out analysis revealed that the heterogeneity for hospital length of stay lowered from 95% to 50% when excluding data from Jin et al. (24), with an additional reduction in the hospitalization period (MD = −3.6 days; 95% CI (−4.1; −3.0); P = 0.025; I2 = 50%) in the Endo-LIF group (vs Open-LIF).
Meta-analytical results for surgical- and hospital-related outcomes.
| Outcome | Endo-LIF vs MIS-LIF | Endo-LIF vs Open-LIF | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies, n | Patients, n | MD (95% CI) | P | I2 | QC-P | Studies, n | Patients, n | MD (95% CI) | P | I2 | QC-P | |
| Operative time (min) | 15 | 1041 | 31.0 (16.6; 45.4) | <0.001 | 98% | <0.001 | 9 | 621 | 67.5 (29.1; 106.0) | <0.001 | 98% | <0.001 |
| Bedtime (h) | 4 | 300 | −6.2 (−12.7; 0.4) | 0.064 | 93% | <0.001 | 3 | 212 | −32.0 (−41.9; −22.1) | <0.001 | 73% | 0.026 |
| Hospital length of stay (days) | 11 | 767 | −2.0 (−3.2; −0.8) | 0.001 | 95% | <0.001 | 6 | 314 | −2.9 (−4.4; −1.5) | <0.001 | 95% | <0.001# |
| Estimated blood loss (mL) | 12 | 833 | −85.0 (−120.2; −49.7) | <0.001 | 99% | <0.001 | 8 | 480 | −182.6. (−277.2; −88.0) | <0.001 | 99% | <0.001 |
#Performing leave-one-out sensitivity analyses, omitting Jin, 2020 (24), results: −3.6 (−4.1; −3.0; P < 0.001) (50%).
CEndo, endoscopic; I 2, heterogeneity; LIF, lumbar interbody fusion; MD, mean difference; MIS, minimally invasive surgery; QC-P, Q Cochran’s P value.
Post-operative pain and disability
Post-operative back pain
Meta-analytical results on post-operative back pain are summarized in Table 3, Figs. 4 and 5, and Supplementary Tables 2 and 3. Endo-LIF was associated with significant early improvement in back pain compared to MIS-LIF (MD = −1.1; 95% CI (−1.6; −0.6); P < 0.001) and Open-LIF (MD = −1.0; 95% CI (−1.3; −0.7); P < 0.001), despite substantial heterogeneity (I2 = 95% and 61%, respectively). Leave-one-out analysis for Endo-LIF vs Open-LIF revealed decreased heterogeneity omitting results from Yin et al. (33) (MD = −0.9; 95% CI (−1.1; −0.7); P < 0.001; I2 = 14%). Meta-regression analyses revealed that the year of publication could be a moderator of heterogeneity for early post-operative back pain (meta-regression coefficient = 0.5; 95% CI (0.2; 0.8); I2 = 91%).
Meta-analytical results for post-operative back and leg pain and disability outcomes.
| Outcome | Endo-LIF vs MIS-LIF | Endo-LIF vs Open-LIF | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies, n | Patients, n | MD (95% CI) | P | I2 | QC-P | Studies, n | Patients, n | MD (95% CI) | P | I2 | QC-P | |
| Back pain (VAS) | ||||||||||||
| Early post-op | 12 | 826 | −1.1 (−1.6; −0.6) | <0.001 | 94% | <0.001 | 6 | 390 | −1.0 (−1.3; −0.7)#4 | <0.001 | 61% | 0.024 |
| Intermediate post-op | 6 | 440 | −0.1 (−0.2; 0.1) | 0.414 | 0% | 0.568 | 6 | 388 | −0.5 (−1.1; 0.1)#5 | 0.119 | 90% | <0.001 |
| Late post-op | 11 | 764 | −0.1 (−0.2; 0.0) | 0.065 | 0% | 0.963 | 6 | 471 | −0.3 (−0.5; −0.1)#6 | 0.003 | 60% | 0.029 |
| Leg pain (VAS) | ||||||||||||
| Early post-op | 10 | 705 | −0.2 (−0.5; 0.1)#1 | 0.268 | 89% | <0.001 | 7 | 531 | 0.0 (−0.3; 0.2) | 0.824 | 64% | 0.010 |
| Intermediate post-op | 5 | 378 | −0.1 (−0.2; 0.1) | 0.341 | 0% | 0.481 | 6 | 388 | −0.2 (−0.3; 0.0) | 0.022 | 0% | 0.665 |
| Late post-op | 10 | 705 | 0.0 (−0.1; 0.1) | 0.905 | 0% | 0.918 | 6 | 471 | 0.0 (−0.1; 0.)#7 | 0.860 | 27% | 0.233 |
| Disability (ODI) | ||||||||||||
| Early post-op | 6 | 436 | −2.2 (−4.0; −0.5)#2 | 0.012 | 78% | <0.001 | 2 | 108 | −0.8 (−3.0; 1.4) | 0.458 | 0% | 0.761 |
| Intermediate post-op | 7 | 524 | −0.8 (−2.2; 0.7)#3 | 0.271 | 77% | <0.001 | 6 | 388 | −1.8 (−4.2; 0.6)#8 | 0.144 | 79% | <0.001 |
| 1-year post-op | 17 | 1235 | 0.3 (−0.2; 0.8) | 0.246 | 0% | 0.622 | 6 | 471 | 0.9 (0.1; 1.6) | 0.032 | 9% | 0.357 |
#1Performing leave-one-out sensitivity analyses, omitting Ge et al. (16), MD (95% CI): 0.0 (−0.2; 0.1); P = 0.488; I2 = 0%; #2Performing leave-one-out sensitivity analyses, omitting Song et al. (38), MD (95% CI): −3.1 (−4.4; −1.8); P < 0.001; I2 = 0%; #3Performing leave-one-out sensitivity analyses, omitting Ge et al. (16), MD (95% CI): −0.2 (−0.9; 0.6); P = 0.670; I2 = 24%; #4Performing leave-one-out sensitivity analyses, omitting Yin et al. (33), MD (95% CI): −0.9 (−1.1; −0.7); P < 0.001; I2 = 14%; #5Performing leave-one-out sensitivity analyses, omitting Xiao et al. (19), MD (95% CI): −0.2 (−0.4; 0.0); P = 0.034; I2 = 50; #6Performing leave-one-out sensitivity analyses, omitting Yin et al. (33), MD (95% CI): −0.4 (−0.5; −0.2); P < 0.001; I2 = 10%; #7Performing leave-one-out sensitivity analyses, omitting Yin et al. (33), MD (95% CI): −0.1 (−0.1; 0.2); P = 0.313; I2 = 0%; #8Performing leave-one-out sensitivity analyses, omitting Xiao et al. (19), MD (95% CI): −1.0 (−2.0; 0.0); P = 0.038; I2 = 4%.
Endo, endoscopic; I2, heterogeneity; LIF, lumbar interbody fusion; MD, mean difference; MIS, minimally invasive surgery; ODI, Oswestry disability index; VAS, visual analog scale.
A non-statistically significant trend was observed at intermediate follow-up (vsMIS-LIF: MD = −0.1; 95% CI (−0.2; 0.1); P = 0.414; I2 = 0% // vs Open-LIF: MD = −0.5; 95% CI (−1.1; 0.1); P = 0.119; I2 = 90%). Significant results and decreased heterogeneity were observed for Endo-LIF vs Open-LIF when excluding results from Xiao et al. (19) (MD = −0.2; 95% CI (−0.4; 0.0); P = 0.034; I2 = 50%).
At late follow-up, Endo-LIF was associated with a significant decrease in post-operative back pain (MD = −0.3; 95% CI (−0.5; −0.1); P = 0.003; I2 = 0%) compared with Open-LIF, with no significant differences to MIS-LIF (MD = −0.1; 95% CI (−0.2; 0.0); P = 0.963; I2 = 60%). For this outcome, omitting results from Yin and collaborators (33) reduced heterogeneity to 10% and demonstrated significant reduction in VAS (MD = −0.4; 95% CI (−0.5; −0.2); P < 0.001) in the Endo-LIF group vs Open-LIF. In subgroup analysis, the interlaminar approach revealed lower late post-operative back pain levels compared with the transforaminal approach (MD = −0.5; 95% CI (−0.6; −0.3); I2 = 0 vs MD = −0.1; 95% CI (−0.2; 0.1); I2 = 0%, respectively).
Post-operative leg pain
The results on post-operative leg pain (Table 3, Figs. 6 and 7, Supplementary Tables 2 and 4) revealed substantial heterogeneity in the early follow-up period (64–89%) and low heterogeneity for both intermediate and late results (0–27%). No statistically significant differences were evident, with one exception: intermediate post-operative leg pain was lower in the Endo-LIF group compared with Open-LIF (MD = −0.2; 95% CI (−0.3; 0.0); P = 0.665; I2 = 0%). Leave-one-out analysis revealed a decrease in heterogeneity (from 89% to 0%) for early post-operative leg pain (in the comparison between Endo-LIF and MIS-LIF) when excluding the study from Ge et al. (16), but without significant changes in VAS. Moreover, subgroup analysis did not reveal significant moderators of heterogeneity.
Disability
Data on disability is depicted in Table 3, Figs. 8 and 9, and Supplementary Table 5. We observed a significant reduction in ODI at early follow-up in the Endo-LIF group compared with MIS-LIF (MD = −2.2; 95% CI (−4.0; −0.5); P = 0.012; I2 = 78%). On the other hand, Endo-LIF was associated with higher disability compared with open fusion procedures (MD = 0.9; 95% CI (0.1; 1.6); P = 0.032; I2 = 9%) at late follow-up. No other statistically significant differences were found. Leave-one-out analysis showed that omitting data from Xiao et al. (19) reduced heterogeneity (79–4%) and revealed a statistically significant reduction in intermediate post-operative ODI with Endo-LIF (vs Open-LIF: MD = −1.0; 95% CI (−2.0; 0.0); P = 0.038; I2 = 4%). Subgroup analyses revealed that the number of portals used in Endo-LIF may influence late disability: a statistically significant difference was found between uniportal (MD 0.6; 95% CI (−0.2; 1.4); I2 = 0%) and biportal (MD = 3.5; 95% CI (0.8; 6.2)) Endo-LIF.
Fusion and subsidence
Definite fusion was estimated in 66.5% (256/385) for Endo-LIF, 63.9% (188/294) for MIS-LIF, and 79.4% (123/155) for Open-LIF. When considering definitive and probable fusion, the estimated fusion rates increased to 94.0% (663/705) in Endo-LIF, 93.1% (446/479) in MIS-LIF, and 93.9% (279/297) with Open-LIF. There were 5.5% (20/365) subsidence cases among all Endo-LIF studies, 2.9% (3/105) in MIS-LIF, and 5.0% (14/282) in Open-LIF. Data on fusion and subsidence showed low to moderate heterogeneity (0–42%), with non-statistically significant differences between study groups (Table 4; Figs. 10 and 11) or on subgroup analysis (Supplementary Table 6).
Meta-analytical results for fusion, subsidence, and adverse events.
| Outcome | Endo-LIF vs MIS-LIF | Endo-LIF vs Open-LIF | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies, n | Patients, n | RR (95% CI) | P | I2 | QC-P | Studies, n | Patients, n | RR (95% CI) | P | I2 | QC-P | |
| Definitive fusion | 7 | 531 | 1 (0.9; 1.2)#1 | 0.969 | 42% | 0.114 | 4 | 303 | 0.9 (0.9; 1.0) | 0.246 | 0% | 0.640 |
| Probable or definitive fusion | 11 | 805 | 1.0 (1.0; 1.0) | 0.934 | 0% | 0.978 | 8 | 565 | 1.0 (1.0; 1.0) | 0.904 | 0% | 0.825 |
| Cage subsidence | 4 | 343 | 2.3 (0.5; 11.3)#2 | 0.294 | 27% | 0.249 | 3 | 307 | 0.8 (0.4; 1.7) | 0.647 | 0% | 0.459 |
| Adverse events | 5 | 593 | 0.4 (0.1; 1.3) | 0.129 | 0% | 0.965 | 4 | 407 | 0.6 (0.2; 1.8) | 0.381 | 1% | 0.386 |
#1Performing leave-one-out sensitivity analyses, omitting Wang et al. (21), RR (95% CI): 0.9 (0.8;1.0); P = 0.223, I2 = 0%; #2Performing leave-one-out sensitivity analyses, omitting Gatam et al. (27), RR (95% CI): 4.5 (0.9; 21.1); P = 0.060, I2 = 0%.
Endo, endoscopic; I2, heterogeneity; LIF, lumbar interbody fusion; MIS, minimally invasive surgery; RR, risk ratio; QC-P, Q Cochran’s P value.
Adverse events: dural tear, root tear, and infection
Overall, there were 31 dural tears (14 in Endo-LIF, 10 in MIS-LIF, and 7 in Open-LIF), 1 root injury in an Open-LIF, and 17 post-operative infections (1 in Endo-LIF, 7 in MIS-LIF, and 9 in open fusions). No vascular injuries were reported. There was very low heterogeneity when comparing procedures on adverse events as a whole, without statistically significant differences between different groups (Table 4; Figs. 10 and 11).
Discussion
Over the last decades, numerous LIF techniques have been described to address LDD. Despite the increasing use of MIS and endoscopic techniques, there has been an ongoing debate on which surgical procedure is superior to manage LDD. While most of the existing systematic reviews and meta-analyses limit their comparison to a specific approach (MIS-TLIF) (40, 41, 42, 43), we aimed to perform a systematic review and meta-analysis to provide an evidence-based judgment on the comparison between Endo-LIF and MIS-LIF or Open-LIF. This is one of the most extensive reviews on the topic (with 27 included articles) and, to the best of our knowledge, the first encompassing a comparison of Endo-LIF with both MIS and Open-LIF techniques. However, these results are mainly limited to single-level LDD (except from Xiao et al. (19) and Kang et al. (25)) and/or low-grade spondylolisthesis, in view of the characteristics of the included articles.
In our study, Endo-LIF was associated with longer operative time, significant improvement in other hospital-related outcomes and post-operative back pain, with overall similar post-operative leg pain, disability, fusion rates, and complications – suggesting that Endo-LIF may be effective, safe, and comparable in most domains to MIS and open techniques, for the management of LDD. However, for some analyses, we observed substantial heterogeneity, which may be explained by differences across studies, including the year of publication, endoscopic technique, and/or approach (uniportal versus biportal and interlaminar versus transforaminal).
Surgical- and hospital-related outcomes
Endo-LIF is a relatively new and unfamiliar procedure. Technical challenges, spatial orientation, limited surgical field, and surgeon’s experience may contribute to a steep learning curve and longer operative time, as evidenced in this analysis: on average, Endo-LIF took 31 min longer than MIS-LIF and 68 minutes longer than Open-LIF. Estimated blood loss was significantly lower in endoscopic procedures, probably due to smaller incisions, the use of low-profile instruments, and direct endoscopic visualization, allowing for reduced soft tissue trauma and more precise dissection and hemostasis. Results on blood loss reported high heterogeneity, which may be due to different measurement strategies and constant water irrigation without an effective suction system. Bedtime and hospital length of stay were significantly longer in the Open-LIF and MIS-LIF groups. Extensive surgical-induced trauma may have an impact on these outcomes – previous works suggested local and systemic effects induced by these surgical techniques, with reported higher levels of systemic inflammatory markers (creatine kinase protein, C-reactive protein, erythrocyte sedimentation rate, interleukin-6, and tumor necrosis factor-α) and elevated injury and fatty infiltration rates in multifidus muscles with open techniques compared to Endo-LIF (31, 32, 33, 36). Future studies may assess whether these findings may influence treatment decision-making, particularly for high morbidity and frail patients (44).
Post-operative pain and disability
Overall, Endo-LIF was associated with statistically significant lower early post-operative back pain, with a similar tendency for intermediate to late back-VAS (including a significant improvement for late post-operative pain when compared with Open-LIF). Less invasiveness and lower iatrogenic lesions to surrounding anatomical structures may contribute to reducing post-operative back pain. However, some of these results need to be carefully interpreted due to the high heterogeneity. There were comparable results among different groups regarding post-operative leg pain, which may suggest similar effectiveness in neural decompression among the three techniques. Results for disability were somewhat conflicting, with lower ODI at early follow-up with Endo-LIF and at late follow-up with Open-LIF. However, according to criteria from Parker and collaborators (45), differences in these outcomes (pain and disability) do not exceed the threshold for minimum clinically important difference. Moreover, it may be important to compare uniportal to biportal techniques and interlaminar to transforaminal approaches, as subgroup and meta-regression analyses suggested potential differences that may have contributed to the reported heterogeneity.
Fusion and subsidence
One of the main goals of LIF is to promote arthrodesis between two vertebral bodies, which requires careful and effective vertebral endplate preparation – complete removal of the cartilaginous endplate, without damaging the bony structure. In this review, no statistically significant differences were found in fusion or cage subsidence outcomes. Attention should be drawn to ambiguous methods and criteria to assess fusion or subsidence (e.g. simple radiography vs computer tomography and time of follow-up imaging). Future studies may try to address whether endoscopic magnified visualization can allow for a more precise endplate preparation, as well as for the potential effect of continuous irrigation in washing out osteogenic factors.
Adverse events: dural tear, root tear, and infection
Complication rates are important for evaluating surgical safety. As the frequency of each adverse event was low, we were unable to conduct a meta-analysis of each individual type of complication but rather pooled together the occurrence of all complications. Despite this, there was low heterogeneity, and no significant differences were found in the frequency of overall adverse events, suggesting both techniques are comparable in terms of safety. This contrasts with data from Sik and colleagues, who observed a higher complication rate in Endo-LIF vs MIS-TLIF (46).
Limitations
Very few RCTs have been performed on this topic. Therefore, most included articles report results based on retrospective unicentric cohort studies, assessing small samples. Selection biases, losses to follow-up (poorly described in included studies) and information biases of primary studies may limit the conclusions drawn from this study. Nevertheless, consistent results were observed with observational studies and the RCT (39). For several outcomes, there was considerable heterogeneity, suggesting relevant clinical and/or methodological differences across primary studies. We attempted to explore sources of heterogeneity by performing sensitivity and subgroup analyses and meta-regression, despite being conditioned by missing data in a few primary studies. Given the fact that RCTs are the most adequate studies to assess the effectiveness of interventions, future well-designed RCTs (with larger samples) are required to provide evidence for both short- and long-term outcomes among these LIF techniques in the treatment of LDD.
Other non-assessed or poorly reported topics may be relevant for adequate comparison of these techniques, such as surgeons’ experience with each procedure, radiation exposure, the need for conversion to open surgery, post-operative radiographic outcomes, costs, and time to return to work. Some recently published articles report higher radiation exposure with Endo-LIF (18, 36, 38), and ways to address this shortcoming will be paramount. Surgical conversion from endoscopic to open or MIS procedures is poorly reported, with no apparent cases among the included articles (17, 36, 37). However, adequate analysis of these cases may provide valuable information on how to properly select cases and manage complications. Differences in spinopelvic balance may impact post-operative outcomes (47, 48, 49). Few studies reported on these outcomes regarding endoscopic fusion (24, 26, 37). Therefore, future studies may investigate how effective Endo-LIF can be in restoring spinopelvic balance (considering some technical issues, such as the use of expandable cages versus lordotic implants and eventual limitations of a smaller approach to perform adequate osteotomy procedures) both in the short and long-term, how it compares with Open-LIF and/or MIS-LIF, and the potential clinical relevance of these differences. Efficiency is another relevant dimension. MIS and endoscopic techniques are usually associated with costlier materials, and whether this is compensated by a lower hospital length of stay or post-operative pain is worth studying. Finally, time to return to work was rarely reported: Lv et al.(39) showed comparable return to work between the Endo-TLIF and MIS-TLIF groups. More studies may also focus on this topic.
Conclusion
For the management of LDD, endoscopic, minimally invasive, and open LIFs appear to have comparable efficacy and safety, considering fusion and adverse event rates. Endo-LIF compared favorably to MIS-LIF and Open-LIF in estimated blood loss, hospital-related outcomes (bedtime and length of stay), and post-operative back pain (mainly in the early follow-up period), although not exceeding the minimum clinically important difference for the latter outcome. Comparable results regarding post-operative leg pain and conflicting results on disability were observed. Endo-LIF was also associated with longer operative times, which may justify technical optimization and training.
Supplementary materials
This is linked to the online version of the paper at https://doi.org/10.1530/EOR-23-0167.
ICMJE Conflict of Interest Statement
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported here.
Funding Statement
This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
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