REVIEW ARTICLE

Minimally invasive versus open transforaminal lumbar interbodyfusion for treatment of degenerative lumbar disease: systematicreview and meta-analysis

Kevin Phan1,2• Prashanth J. Rao1,2

• Andrew C. Kam2• Ralph J. Mobbs1

Received: 22 January 2015 / Revised: 21 March 2015 / Accepted: 22 March 2015

� Springer-Verlag Berlin Heidelberg 2015

Abstract

Purpose While open TLIF (O-TLIF) remains the main-

stay approach, minimally invasive TLIF (MI-TLIF) may

offer potential advantages of reduced trauma to paraspinal

muscles, minimized perioperative blood loss, quicker re-

covery and reduced risk of infection at surgical sites. This

meta-analysis was conducted to provide an updated

assessment of the relative benefits and risks of MI-TLIF

versus O-TLIF.

Methods Electronic searches were performed using six

databases from their inception to December 2014. Relevant

studies comparing MI-TLIF and O-TLIF were included.

Data were extracted and analysed according to predefined

clinical end points.

Results There was no significant difference in operation

time noted between MI-TLIF and O-TLIF cohorts. The

median intraoperative blood loss for MI-TLIF was sig-

nificantly lower than O-TLIF (median: 177 vs 461 mL;

(weighted mean difference) WMD, -256.23; 95 % CI

-351.35, -161.1; P \ 0.00001). Infection rates were sig-

nificantly lower in the minimally invasive cohort (1.2 vs

4.6 %; relative risk (RR), 0.27; 95 %, 0.14, 0.53;

I2 = 0 %; P = 0.0001). VAS back pain scores were sig-

nificantly lower in the MI-TLIF group compared to O-TLIF

(WMD, -0.41; 95 % CI -0.76, -0.06; I2 = 96 %;

P \ 0.00001). Postoperative ODI scores were also sig-

nificantly lower in the minimally invasive cohort (WMD,

-2.21; 95 % CI -4.26, -0.15; I2 = 93 %; P = 0.04).

Conclusions In summary, the present systematic review

and meta-analysis demonstrated that MI-TLIF appears to

be a safe and efficacious approach compared to O-TLIF.

MI-TLIF is associated with lower blood loss and infection

rates in patients, albeit at the risk of higher radiation ex-

posure for the surgical team. The long-term relative merits

require further validation in prospective, randomized

studies.

Keywords Minimally invasive � Transforaminal lumbar

interbody fusion � TLIF � Lumbar � Spine � Degenerative

Introduction

Degenerative spinal diseases are one of the most common

comorbidities in elderly patients, leading to discogenic

back pain and spinal instability [1, 2]. Transforaminal

lumbar interbody fusion (TLIF) is one of the surgical op-

tions used for the stabilization and treatment of degen-

erative lumbar disease such as disc degeneration and

spondylolisthesis which has failed conservative manage-

ment. TLIF was initially developed as a modification of the

posterior lumbar interbody fusion (PLIF) approach [3, 4],

with added advantages of direct, unilateral access to the

intervertebral foraminal area whilst reducing interruption

to the spinal muscles and structural integrity [5–9]. While

open TLIF (O-TLIF) is an established approach for

Electronic supplementary material The online version of thisarticle (doi:10.1007/s00586-015-3903-4) contains supplementarymaterial, which is available to authorized users.

& Kevin Phan

kphan.vc@gmail.com

Ralph J. Mobbs

ralphmobbs@hotmail.com

1 Neurospine Clinic and Neurospine Surgery Research Group

(NSURG), Prince of Wales Private Hospital, Randwick,

Sydney, NSW 2031, Australia

2 Department of Neurosurgery, Westmead Hospital, Sydney,

Australia

123

Eur Spine J

DOI 10.1007/s00586-015-3903-4

degenerative lumbar disease, there are still concerns sur-

rounding the associated long hospital stays, excessive

blood loss and postoperative complications associated with

an open procedure [10–12].

The advent of minimally invasive procedures in the

surgical realm led to the logical progression of O-TLIF to

minimally invasive TLIF (MI-TLIF) over the past decade.

MI-TLIF offers potential advantages of reduced trauma to

paraspinal muscles, minimized perioperative blood loss,

quicker recovery and reduced risk of infection at surgical

sites [13–15].

There is still a lack of robust clinical evidence for the

safety and efficacy of MI-TLIF compared with conven-

tional O-TLIF. Earlier systematic reviews and meta-ana-

lyses have attempted to evaluate the safety and

complications of MI-TLIF compared to O-TLIF [16, 17].

However, these were limited by smaller patient numbers

and studies, as well as analysis of overlapping patient

populations [18]. In the last 2 years alone, over double the

number of studies have been reported in the literature and

have been published [11, 12, 19–30] from unique centres,

reflecting the rapid popularity of the minimally invasive

approach worldwide. Therefore, the present meta-analysis

was conducted to provide an updated assessment of the

relative benefits and risks of MI-TLIF versus O-TLIF.

Methods

Literature search strategy

The study was conducted following the Preferred Report-

ing Items for Systematic Reviews and Meta-analyses

(PRISMA) [31]. Electronic searches were performed using

Ovid Medline, PubMed, Cochrane Central Register of

Controlled Trials (CCTR), Cochrane Database of System-

atic Reviews (CDSR), ACP Journal Club, and Database of

Abstracts of Review of Effectiveness (DARE) from their

date of inception to December 2014. To achieve the

maximum sensitivity of the search strategy, we combined

the terms: ‘‘minimally invasive’’, ‘‘open’’, ‘‘transforaminal

lumbar interbody fusion’’, ‘‘TLIF’’, as either key words or

MeSH terms. A full search strategy is presented in Sup-

plementary Table 1. The reference lists of all retrieved

articles were reviewed for further identification of poten-

tially relevant studies and assessed using the inclusion and

exclusion criteria.

Selection criteria

For the purposes of this review, ‘‘minimally invasive sur-

gery’’ was defined as surgery conducted through a tube,

cylindrical retractor blades or sleeves via a muscle-dilating

or muscle-splitting approach. Conventional or open surgery

was defined as surgery via an approach which includes

elevating or stripping the paraspinal muscles to gain access

to the spine, even if by a limited midline incision. Eligible

studies for the present systematic review and meta-analysis

included studies comparing MI-TLIF versus O-TLIF for

the treatment of degenerative lumbar disease. End points

included average operation times, intraoperative blood

loss, hospital stay, total complications, reoperations, dural

tears, infections, postoperative VAS scores for back and leg

pain and postoperative ODI scores. Studies that did not

include operation parameters or complications as end

points were excluded. When institutions published dupli-

cate studies with accumulating numbers of patients or in-

creased lengths of follow-up, only the most complete

reports were included for quantitative assessment at each

time interval. Reference lists were also hand searched for

further relevant studies. All publications were limited to

those involving human subjects and in the English lan-

guage. Abstracts, case reports, conference presentations,

editorials, reviews and expert opinions were excluded.

Data extraction and criteria appraisal

All data were extracted from article texts, tables and fig-

ures. Discrepancies between the two reviewers were re-

solved by discussion and consensus. Because quality

scoring is controversial in meta-analyses of observational

studies, two reviewers independently appraised each article

included in our analysis according to a critical review

checklist of the Dutch Cochrane Centre proposed by

MOOSE [32, 33]. The final results were reviewed by senior

investigators (R.J.M.).

Statistical analysis

For comparative studies, relative risk (RR) was used as a

summary statistic for dichotomous variables, and weighted

mean different (WMD) was used for continuous variables.

In the present study, both fixed- and random-effect models

were tested. In the fixed-effects model, it was assumed that

treatment effect in each study was the same, whereas in a

random-effects model, it was assumed that there were

variations between studies. v2 tests were used to study

heterogeneity between trials. I2 statistic was used to esti-

mate 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. In

Eur Spine J

123

an alternative way to account for heterogeneity, subgroup

analysis was performed based on follow-up duration

(B24 months, [24 months) and procedure technique

(unilateral versus bilateral screw fixation). All P values

were two sided. All statistical analysis was conducted with

Review Manager Version 5.2.2 (Cochrane Collaboration,

Software Update, Oxford, UK).

Publication bias

Evidence of publication bias was sought using Begg and

Egger methods. Contour-enhanced funnel plot was per-

formed to aid in interpretation of the funnel plot. Possible

asymmetry was investigated using trim-and-fill analysis.

Results

Included studies

A total of 358 references were identified through six

electronic database searches (Fig. 1). After exclusion of

duplicate or irrelevant references, 324 potentially relevant

articles were retrieved. After detailed evaluation of these

articles, 42 studies remained for assessment. After applying

the selection criteria, 21 articles [11, 12, 14, 15, 19–30, 34–

38] were selected for qualitative and quantitative analysis.

The study characteristics are summarized in Table 1. Of

the 21 included articles, 966 patients undergoing MI-TLIF

were compared with 863 patients undergoing O-TLIF.

The included studies comprised 11 prospective studies

and 10 retrospective observational studies (Table 1). Of the

prospective studies, two studies [26, 38] were randomized

whilst nine studies were observational by design. There

were 6 studies which investigated 100 or more patients in

total [12, 22, 23, 25, 27, 36], with the remaining 15 studies

investigating fewer than 100 patients in total. The inclusion

criteria for patients in each study are summarized in

Table 1, with the majority involving patients with degen-

erative disc disease or spondylolisthesis.

The quality of the included studies was appraised using

a checklist proposed by the Dutch Cochrane Centre by

MOOSE. From this assessment, the majority of studies had

clear definitions for study populations, clear definitions of

Fig. 1 PRISMA flowchart of

systematic review and meta-

analysis comparing minimally

invasive (MI-TLIF) versus open

transforaminal lumbar interbody

fusion (O-TLIF)

Eur Spine J

123

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Eur Spine J

123

outcomes and outcome assessment, and independent

assessment of outcome parameters. Eight studies also did

not effectively discuss important confounders and prog-

nostic factors which further undermine the validity of their

data. The quality appraisal is presented in Supplementary

Table 2.

Baseline characteristics

Baseline characteristics of the included patients are sum-

marized in Table 2. For the MI-TLIF cohort, the mean age

ranged from 41.8 to 68.6 years, compared to 43.1–68 years

for the O-TLIF cohort. The proportion of males ranged

from 17.5 to 69.4 % and 17.5 to 74.2 % for MI-TLIF and

O-TLIF, respectively. The proportions of MI-TLIF versus

O-TLIF patients undergoing surgery for L5/S1, L4/5, L3/4

and L2/3 segments were not significantly different between

the cohorts.

Assessment of operation parameters

The operation parameters are summarized in Fig. 2. The

median operation duration for the minimally invasive ap-

proach was 185 min (range: 104–456 min), compared to

186 min (range: 113–375 min) for the conventional open

approach. There was no significant difference in operation

time noted between MI-TLIF and O-TLIF cohorts (WMD,

4.74; 95 % CI -58.55, 68.03; I2 = 100 %; P = 0.88).

However, significant heterogeneity was detected amongst

the included studies. The median intraoperative blood loss

for MI-TLIF was 177 mL (range: 55–456 mL) compared

with 461 mL (range: 125–961 mL) for the O-TLIF ap-

proach. This difference was significantly different (WMD,

-256.23; 95 % CI -351.35, -161.1; P \ 0.00001) and

was maintained upon subgroup analysis regardless of

whether the procedure used bilateral or unilateral pedicle

screw fixation. Significant heterogeneity (I2 = 98 %) was

detected amongst studies reporting intraoperative blood

loss. The hospital duration for MI-TLIF was also sig-

nificantly shorter than that of the O-TLIF cohort (WMD,

-1.86; 95 %, -2.69, -1.04; I2 = 96 %; P \ 0.00001).

The median hospital stay for MI-TLIF and O-TLIF was

4.7 days (range: 2.3–10.6 days) and 8.0 days (range:

2.9–14.6 days), respectively. X-ray exposure time was

significantly higher in the MI-TLIF group compared to

O-TLIF by 37 s (WMD, 37.27; 95 % CI 13.78, 60.77;

I2 = 98 %; P = 0.002).

Assessment of major end points

The total complications outcome was reported by 11 studies

(Fig. 3). No significant difference in total complications

was found between the MI-TLIF and O-TLIF cohorts (14.9

vs 20 %; RR, 0.77; 95 %, 0.52, 1.15; I2 = 32 %;

P = 0.20), with no significant heterogeneity detected.

There were also no differences between minimally invasive

and open cohorts in terms of reoperations required (5.5 vs

6.4 %; RR, 0.71; 95 % CI 0.44, 1.13; I2 = 0 %; P = 0.15).

No significant heterogeneity amongst the studies was de-

tected for reoperations. No significant differences in major

outcomes were also noted in studies reporting follow-up

B24 months and [24 months. Furthermore, the use of bi-

lateral screw versus unilateral screws did not show any

significant differences upon subgroup analysis; however,

there were fewer studies to analyse and this may be a

function of inadequate statistical power.

Assessment of safety and complications

Specific complication outcomes are reported in Fig. 4 and

Table 3. No difference was found between MI-TLIF and

O-TLIF cohorts in terms of dural tears (2.6 vs 4.7 %; RR,

0.59; 95 % CI 0.28, 1.22; I2 = 9 %; P = 0.15). However,

the infection rates were significantly lower in the

minimally invasive cohort (1.2 vs 4.6 %; RR, 0.27; 95 %,

0.14, 0.53; I2 = 0 %; P = 0.0001), with no significant

heterogeneity detected. A similar trend was seen for bi-

lateral screw fixation in MI-TLIF vs open TLIF and also

for unilateral screw fixation in MI-TLIF vs open TLIF.

Surgical procedure-related complications are summa-

rized in Table 3. There was no significant difference be-

tween the MI-TLIF and O-TLIF cohorts for graft

malposition (P = 0.66), screw malposition (P = 0.97),

neurological deficit (P = 0.55), haematomas (P = 0.45),

non-union (P = 0.94) and cerebrospinal fluid (CSF) leak

(P = 0.39). The lack of statistically significant differences

was also observed when subgroup analysis was performed,

in both the bilateral screw TLIF analysis and unilateral

screw TLIF analysis.

Assessment of pain scores

VAS back pain and leg pain scores as well as ODI scores

were the most commonly used measures amongst the in-

cluded studies for assessment of clinical outcomes. Sum-

mary changes of VAS and ODI scores are portrayed in

Table 4, whilst the comparison between the MI-TLIF and

O-TLIF cohorts in terms of postoperative VAS and ODI

scores is summarized in Fig. 5. A descriptive method was

used to extract mean changes, given that the standard de-

viations were poorly reported by the included studies. From

Fig. 5, postoperative VAS back pain scores were sig-

nificantly lower in the MI-TLIF group compared to O-TLIF

(WMD, -0.41; 95 % CI -0.76, -0.06; I2 = 96 %;

P \ 0.00001), with significant heterogeneity detected.

Postoperative ODI scores were also significantly lower in

Eur Spine J

123

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Eur Spine J

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the minimally invasive cohort (WMD, -2.21; 95 % CI

-4.26, -0.15; I2 = 93 %; P = 0.04). Significant hetero-

geneity was also detected. Upon subgroup analysis in

bilateral versus unilateral screw groups, differences in

postoperative ODI and VAS back pain scores were

mitigated and no longer significant.

Fig. 2 Forest plots comparing MI-TLIF and O-TLIF in terms of a operation time; b intraoperative blood loss; c hospital stay

Eur Spine J

123

Publication bias

Inspection of the funnel plot (Fig. 6) showed no apparent

asymmetry for total complications. Trim-and-fill analysis

indicated that no studies were missing. The effect size was

unchanged by trim-and-fill analysis, 0.779 (95 % CI

0.576–1.055). Publication bias was assessed with Egger’s

score (t value 0.694, P = 0.507) which was not significant,

and Begg’s score (z value 0.894, P = 0.371) was non-

significant. These results suggest that publication bias was

likely not a limiting factor.

Discussion

The clinical application of the MI-TLIF has not been

matched with clinical evidence, as there is still a lack of

adequately powered, multicentre randomized trials which

directly compares the minimally invasive and open fusion

approaches. From the current available evidence, the pre-

sent systematic review and meta-analysis demonstrated

that: (1) no difference in operation duration was found

between MI-TLIF and O-TLIF; (2) MI-TLIF was associ-

ated with less intraoperative blood loss; (3) MI-TLIF was

associated with increased X-ray exposure; (4) O-TLIF

approach was associated with significantly higher rates of

infection; and (5) patients who underwent MI-TLIF had

significantly lower VAS and ODI pain scores compared to

patients undergoing O-TLIF.

Given the limited working space and surgical vision,

MI-TLIF has often been reported to have a complex

learning curve and thus associated with longer operative

times. To assess and define the learning curve for MI-TLIF,

Lee and colleagues [39] reported a prospective case series

of 86 patients with degenerative lumbar disease who un-

derwent unilateral transforaminal approach with

Fig. 3 Forest plots comparing MI-TLIF and O-TLIF in terms of a total complications; b reoperations

Eur Spine J

123

percutaneous pedicle screws. The operative time decreased

as the series progressed and an asymptote was reached after

30 cases. The surgeons’ experience significantly correlated

with reduced operation time and intraoperative blood loss,

suggesting that the minimally invasive approach may be a

safe and effective treatment operation once the initial

Fig. 4 Forest plots comparing MI-TLIF and O-TLIF in terms of a dural tears; b infections

Table 3 Summary effect of

surgical complications in meta-

analysis comparing MI-TLIF

with O-TLIF

Surgical complications n/N MI-TLIF N/N O-TLIF RR (95 % CI) I2 (%) P value

Graft malposition 4/463 4/358 0.74 (0.19–2.84) 0 0.66

Screw malposition 12/571 6/391 0.98 (0.39–2.49) 0 0.97

Neurological deficit 20/400 7/244 1.28 (0.57–2.86) 0 0.55

Haematoma 7/330 7/229 0.63 (0.19–2.10) 21 0.45

Non-union 4/253 3/235 1.08 (0.14–8.65) 36 0.94

CSF leak 9/459 14/417 0.61 (0.20–1.88) 23 0.39

n number of affected patients, N number of total patients, RR relative risk, CI confidence interval

Eur Spine J

123

learning curve is traversed. These results are corroborated

by other studies [40, 41], which show significant reduced

complication rates and operation durations in the later

phase of their MI-TLIF series. Additionally, the increased

use of navigation imaging during pedicle screw placement

may also increase operation durations while increasing the

surgeon’s exposure to potentially harmful ionizing ra-

diation [42, 43]. In the present meta-analysis, no significant

difference was found between MI-TLIF and O-TLIF co-

horts in terms of operation duration, which is likely at-

tributed to the varying surgical expertise and experience

amongst the included studies. In comparison to other

minimally invasive PLIF, MI-TLIF tends to have reduced

operation duration since the decompression and cage is

inserted unilaterally.

Proponents of the minimally invasive fusion procedure

emphasize its potential advantages of reduced iatrogenic

tissue injury and complication rates. In the present, there is

a significant reduction in blood loss and infection rates in

the MI-TLIF group. These trends are not surprising, given

that MI-TLIF employs a tubular retraction which preserves

the contralateral ligament and bony attachments of para-

spinal muscles, thereby reducing potential bleeding. The

minimal muscle dissection and bone removal also will

reduce complications attributed to blood clot accumulation

and tissue fluid accumulation [23]. The need for smaller

incisions and minimal open exposure of MI-TLIF also

significantly reduced the opportunity for bacteria entry and

hence infection of the surgical sites. In contrast, O-TLIF

involves a large midline incision and extensive dissection.

This is often performed using high-force retraction of

paraspinal muscles, increasing blood loss, surgical trauma

and increased risk of infection. Other surgical complica-

tions, including dural tear, graft and screw malposition, and

haematomas were similar between the groups. Total com-

plications and reoperation rates were also comparable be-

tween MI-TLIF and O-TLIF. Minimized surgical trauma

and complications also justify the significantly shorter

hospitalization for the MI-TLIF cohort observed. However,

hospital stay results should be interpreted with caution,

given the different health-care systems and reimbursement

schemes in different countries, factors which could not be

accounted for in this analysis. Some groups have also re-

ported an increased incidence of adjacent-level revision

surgery at long-term follow-up in the O-TLIF cohort, po-

tentially due to the less destabilizing nature of MI-TLIF

[12]. However, there have been few reports of this phe-

nomenon and it thus requires further validation in

Table 4 Improvement of functional outcomes

References Mean back pain VAS improvement Mean leg pain VAS improvement Mean ODI improvement

MI-TLIF O-TLIF MI-TLIF O-TLIF MI-TLIF O-TLIF

Wong et al. [12] -4.12 -2.77 -7.47 -6.6 -26.8 -18.2

Tian et al. [19] -3.56 -3.71 -5.3 -5.34 -26.33 -26.47

Sulaiman et al. [20] -4.2 -2.1 NR NR -28 -12

Singh et al. [21] NR NR NR NR NR NR

Parker et al. [22] -4.8 -4.9 -3.5 -4.2 -21.3 -18.7

Lo et al. [23] NR NR NR NR NR NR

Gu et al. [24] -5.4 -5.6 -5.9 -5.9 -27.2 -28.4

Zairi et al. [25] NR NR NR NR NR NR

Seng et al. [11] -4.3 -5.9 -5.1 -4.7 -27.7 -29.8

Rodriguez-Vela et al. [26] -3.7 -2.57 -4.93 -4.39 -16.76 -9.09

Lau et al. [27] NR NR NR NR NR NR

Cheng et al. [28] -4.1 -4.3 NR NR NR NR

Brodano et al. [29] -5.5 -5.5 NR NR -32 -34

Archavlis et al. [30] -4.4 -3.8 -4 -3.8 -23 -24

Mobbs et al. [14] -5.5 -4.9 NR NR -32 -24

Wang et al. [38] -5.8 -5.3 NR NR -27.3 -26.4

Wang et al. [37] -6.3 -6.3 NR NR -30.4 -26.3

Villavicencio et al. [36] -4 -4.8 NR NR NR NR

Shunwu et al. [35] -4.5 -3.6 NR NR -25 -24.8

Schizas et al. [15] -4.2 -2.2 NR NR -22 -27

Schuefler et al. [34] NR NR NR NR NR NR

NR not reported, MI-TLIF minimally invasive transforaminal lumbar interbody fusion, O-TLIF open transforaminal lumbar interbody fusion,

n number of affected patients, N number of total patients, RR relative risk, CI confidence interval

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adequately powered prospective trials. Overall, results

from the present meta-analysis suggest that MI-TLIF can

be performed safely with reduced intraoperative blood loss

and infection rates compared to conventional open ap-

proaches. However, it must be noted that any advantages of

MI-TLIF is offset by the increased radiation exposure to

the surgical team.

Minimized surgical trauma via the use of tubular re-

tractors and reduced paraspinal muscle dissection is likely

responsible for the significant reduction in postoperative

VAS and ODI pain scores in the MI-TLIF cohort versus

O-TLIF. From the present meta-analysis, the mean differ-

ence in VAS back pain scores was 0.4 points lower for MI-

TLIF, and 2.2 points lower for ODI score in MI-TLIF

compared to O-TLIF. However, these differences in pain

outcomes are inconsistently reported in the literature, with

studies by Seng et al. [11] demonstrating significantly

worse pain outcomes in the MI-TLIF group. To alterna-

tively assess pain outcomes, Mobbs et al. [14] looked at

opioid analgesia as a surrogate marker for pain outcomes

following fusion surgery, with no difference in usage or

dosage between MI-TLIF and O-TLIF cohorts, which is a

contradictory significant difference in VAS and ODI

scores. Other problems with the use of pain scores are the

heterogeneity in the follow-up protocols among the in-

cluded studies, making it difficult to ascertain the temporal

extent of the improvement in pain scores. Prior studies

have suggested that improvements in pain and disability

outcomes are significant for 12 months, after which little

further improvement occurs [44, 45]. Investigations by

Datta et al. [46] have also suggested that score improve-

ment is directly associated with shorter durations of intra-

muscular pressures. Thus, for operations performed during

Fig. 5 Forest plots comparing MI-TLIF and O-TLIF in terms of a postoperative VAS back pain scores; b postoperative ODI

Fig. 6 Funnel plot for total complications in MI-TLIF versus O-TLIF

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123

the early phase of the learning curve, longer operation

durations may be associated with poorer VAS and ODI

pain score outcomes. Overall, the current results suggest

that MI-TLIF is an effective alternative to O-TLIF with at

least equivalent pain score outcomes and potentially re-

duced pain scores in some cases.

Strengths and limitations

The present systematic review and meta-analysis has sev-

eral strengths. Firstly, PRISMA guidelines for systematic

reviews were strictly followed, with the PRISMA checklist

shown in Supplementary Table 3. The systematic review

was performed according to a ‘‘priori’’ design question and

inclusion criteria. A comprehensive literature search strat-

egy was used, and in contrast to earlier reviews on this

topic, the scientific quality of the included studies was

assessed using a well-known quality appraisal tool [32].

Furthermore, publication bias was assessed using funnel

plots. Quality assessment highlighted the poorer quality of

studies in terms of duration of follow-up and prognostic

indicators, therefore, providing tangible evidence that the

literature requires upgrade of evidence in terms of

adequately powered, randomized studies with long-term

follow-up. Prior meta-analyses based on fewer number of

studies suggest that there are no differences in VAS or ODI

functional outcomes between minimally invasive versus

open TLIF [17], or only described the differences without

statistical methods [16]. In contrast, our meta-analysis is

based on 21 studies and a total of 1829 patients, more than

twice the number of total patients, and thus was adequately

powered to detect a significant difference in functional

VAS and ODI outcomes. While infection rates were intu-

itively thought to be less in the minimally invasive ap-

proach, to our knowledge, our meta-analysis is the first to

show that pooled infection rates were lower in the

minimally invasive group.

The present study is also limited by several constraints.

Firstly, there is a lack of an official definition or consensus

on what procedures actually constitute ‘‘minimally inva-

sive surgery’’ compared to ‘‘standard open’’ surgery. The

transition between these two is not clearly defined, de-

pendent on individual surgical technique. Reduced skin

incisions likely have a more cosmetic effect, whilst the

damage to the musculature, fascia and insertion points,

facet joints and their capsules, as well as ligaments, is

likely to have reduced surgical trauma. Unfortunately,

these aspects were not well reported in the included studies

and thus a significant limitation not only of the present

study, but of the literature in general. Furthermore, the

majority of included studies were observational cohort

studies, with a similar ratio of retrospective and prospective

studies. There is a lack of clinically robust randomized

controlled trials. Therefore, the validity of the data avail-

able for meta-analysis may be undermined by selection

bias. Second, there is heterogeneity among the included

studies with regard to difference in surgical experience and

expertise, different inclusion and exclusion criteria, as well

as slight variations between centres in terms of MI-TLIF

and O-TLIF surgical techniques. To address the effect of

unilateral vs bilateral screw fixation on outcomes, we

performed subgroup analysis on our results. Similar trends

were seen for blood loss outcomes, infections and com-

plications for both unilateral and bilateral screw fixation

MI-TLIF techniques compared with open TLIF. Variations

in follow-up durations as well as inconsistent and unstan-

dardized reporting of pain score outcomes are also addi-

tional limitations of the present studies. To address this,

subgroup analysis was performed according to follow-up

duration (B24 months, [24 months), but similar trends

were observed. Future multi-center prospective registry or

randomized studies with long-term follow-up are required

to validate the trends observed.

Conclusion

In summary, the present systematic review and meta-ana-

lysis demonstrated that MI-TLIF was associated with re-

duced intraoperative blood loss, infection rates and

postoperative VAS and ODI pain scores compared to

O-TLIF, albeit with higher radiation exposure and risk for

the surgical team. No difference in operation duration and

total complications was detected. MI-TLIF appears to be a

safe and efficacious approach, but the long-term relative

merits require further validation in prospective, random-

ized studies.

Conflict of interest The authors have no conflict of interest what-

soever in the conduct of the study or its results.

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