Comparing Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion in Obese and Nonobese Patients: A Systematic Review and Meta-Analysis

Background: Our study aimed to compare the outcomes of obese and nonobese patients following minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Methods: Relevant studies comparing the outcome of MIS-TLIF between obese and nonobese patients were involved to make a systematic literature review and meta-analysis. All of the comparative studies published in PubMed, MEDLINE, and Web of Science databases as recently as 10 July 2020, were included. Primary outcomes (complications) and secondary outcomes (Oswestry Disability Index (ODI) score, visual analog scale (VAS) score, the length of hospital stay, the duration of surgery, and the estimated blood loss) were assessed between obese patients and nonobese patients. Statistical analysis was performed by Review Manager 5.3 and forest plots were made for each outcome. Results: Nine studies were enrolled in this meta-analysis. BMI correlated signicantly with complications, and postoperative complications occurred more frequently in obese patients. Additionally, obese patients after MIS-TLIF were associated with similar Oswestry Disability Index (ODI) score, Visual Analog Scale score for back pain(BP-VAS), and Visual Analog Scale score for leg pain(LP-VAS) scores in early ( ≤ 6 months after MIS-TLIF) and late period ( ≥ 24 months after MIS-TLIF). There was no signicant difference in intraoperative complications, duration of surgery, length of hospital stay, and estimated blood loss between the two groups. Conclusion: Obese patients should not be excluded from MIS-TLIF procedures due to worry about higher postoperative complication rates. Understanding common postoperative complications after MIS-TLIF will improve the treatment of obese patients with the degenerative lumbar disease. for the of hospital stay, with obese patients at 2.87d and nonobese patients at 2.86d. random effect is in the length of hospital stay obese patients and


Introduction
Transforaminal lumbar interbody fusion (TLIF) was rst introduced in 1982,which could signi cantly reduce the amount of the nerve root retraction and thecal sac [1]. Then, the minimally invasive technique was rst introduced by Foley et al for the TLIF surgery in 2000 [2]. Nowadays, MIS-TLIF has been a well-known surgical procedure for the management of various spine diseases such as spondylolisthesis and degenerative disk disease [3]. MIS-TLIF was reported to have a similar curative effect as open-TLIF with the potential advantages of less pain and estimated blood loss and shorter length of hospital stay [4].
Obesity, one of the most serious public health issues, has an increasing prevalence in recent years, and its impact on orthopedic surgery continues to draw more attention to orthopedic surgeons [5][6][7]. Currently, over half of Americans are obese or overweight, and obesity is linked to a variety of diseases, including diabetes and osteoarthritis, and has thus been a focus of health care initiatives [8][9][10]. Consequently, spinal surgeons must consider the in uence of obesity on MIS-TLIF because of the increasing number of obese patients with degenerative lumbar diseases requiring MIS-TLIF [11].
Many previous studies had proven that obese patients incline to have inferior surgical outcomes than patients of normal weight undergoing operation [12][13][14][15][16]. MIS-TLIF has been reported to improve the surgical treatment of obese patients by minimizing the size of surgical skin incision and cavity, and the number of surgical trauma [3]. Some cohort studies [17][18][19][20] have demonstrated that MIS-TLIF was safe for obese patients. However, no meta-analysis has been performed to investigate the in uence of obesity on clinical outcomes in patients with MIS-TLIF. Besides, no randomized controlled trial (RCT) has been conducted to compare the outcomes of MIS-TLIF between obese and nonobese patients.
Consequently, we searched all relevant literatures to perform a meta-analysis in an attempt to investigate the in uence of obesity on outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in patients with degenerative lumbar disease.

Literature Retrieval Strategy
Our research literature was obtained by searching the Web of Science, Medline, and PubMed databases. The literature search was based on the PRISMA statement and guidelines [21]. "Minimally invasive transforaminal lumbar interbody fusion", "TLIF", "MIS-TLIF", "obese", "minimally invasive" and "BMI" were used as the Medical Subject Headings (MeSH) or Emtree in the search strategy. The search terms were rst based on the title and abstract, and the full text was retrieved if a decision could not be made from the summary.

Study selection criteria
There were several criteria for the study that we have included: (1) the study population was patients who underwent MIS-TLIF, (2) Essential data could be easily extracted or calculated from the original essay, (3) studies that reported more than two following variables: complication, estimated blood loss, length of hospital stay, duration of surgery and Oswestry Disability Index (ODI), visual analog score (VAS) for leg pain and back pain, (4) retrospective study listed the comparison between obese patients and nonobese patients.
Exclusion criteria were as follows: (1) studies such as review articles, book chapters, case reports, cadaver studies, and summaries of experience; (2) cell or animal studies; (3) the original data of the comparison outcomes could not be extracted.
Data extraction and quality assessment The following data were extracted independently from the nal eligible studies, the details include the rst author of the article, publication date, study design, study population characteristics (age, sex, and nation), the de nition (as BMI) of obesity and normally used, demographical data, the number of events for dichotomous outcomes, the mean and standard deviation (SD) for continuous outcomes. Two reviewers extracted the data independently and all disagreements between the investigators were resolved by discussion. According to the Cochrane Handbook for Systematic Reviews, the qualities of the selected studies were assessed by using the Newcastle-Ottawa Scale (NOS) [22].

Study outcomes
In our study, the primary outcome measures were the complications, and complications were further subdivided into intraoperative and postoperative complications. The secondary outcome measures included the VAS scores for back and leg pain, the ODI scores, and the duration of surgery, the length of hospital stay, and estimated blood loss. Meanwhile, ODI and VAS scores were classi ed into early (≤6 months after MIS-TLIF) and late (≥24 months after MIS-TLIF) period.

Dealing with Missing Data
When meeting missing or inadequate data, we considered contacting the authors of the identi ed literature to ensure that the data was available. When the mean and SD were necessary to combine in a separate study and the data were given for obese and morbidly obese respectively, we used the formula of Headrick et al [23] to calculate overall mean and SD.

Statistical analysis
Review Manager (Version5.3) was used to perform the meta-analysis. Odds ratios (ORs) and weighted mean differences (WMD) and associated con dence interval (CI) were used to analyze dichotomous and continuous variables. Studies for each outcome were combined to present an overall estimate of the effect in the form of a forest plot. P<0.05 was used as the level of signi cance and I 2 was set as the index to evaluate heterogeneity. If the I 2 ≥50% was shown in the metaanalysis, we chose to use the random-effects model as the heterogeneity was signi cant. Otherwise, the xed-effects model was suitable [24] .

Search and study selection
Initially, 262 documents were yielded in the electronic databases after screening the core terms. 129 duplicates were eliminated, then 115 of 129 records were removed based on their titles and abstracts. Subsequently, after downloading and identifying the full text, 9 articles without access to the inclusion criteria were excluded. Ultimately, this metaanalysis contained a total of 9 eligible studies [17][18][19][20][25][26][27][28][29] published between 1999 and 2018. The speci c process of literature identi cation and selection is shown in Figure 1.

Study characteristics
Nine retrospective studies with 1043 patients were enrolled in our meta-analysis and the characteristics and the general demographics of the identi ed studies were listed in Table 2 and Table 3. The sample size of the included studies ranged from 16 to 186, and the studies were published between 2008 and 2019. The 1043 patients all underwent MIS-TLIF, 412 obese patients, and 631 nonobese patients ( Table 2). The duration of surgery was reported in 6 studies, estimated blood loss was reported for 3 studies, the length of hospital stay was reported in 5 studies, and ODI and LP-VAS scores were reported in 2 studies, BP-VAS score was shown in 2 studies. The number of complications was reported in 6 studies (Table 4). According to the data extracted, ODI, LP-VAS, and BP-VAS scores were divided into early (≤6 months after MIS-TLIF) and late (≥24 months after MIS-TLIF) period. The NOS score as the aspect of methodological quality for each selected study were all over six points, revealing the high quality ( Table 1).

Discussion
Our meta-analysis demonstrated that obesity had no signi cant in uence on the duration of surgery, the estimated blood loss, and the length of hospital stay. Obese increased the risk of complications but not the intraoperative complication. Additionally, no signi cant effect was found in ODI, BP-VAS, and LP-VAS scores in both early and late periods after MIS-TLIF between the two groups.
Morbid obesity can be considered one of the biggest di culties in treating spinal surgery. Obese patients with inferior clinical outcomes may require surgical treatment via MI-TLIF [32][33][34]. This meta-analysis found that obese patients did not cost more duration of surgery when MIS-TLIF was used. Cole et al [4] found that the use of the minimally invasive tubular traction system can signi cantly decrease the time required for the long distances between the skin and spine of obese patients. Minimally invasive techniques could narrow the gap in the duration of surgery between obese and nonobese patients.
Compared with nonobese patients, traditional surgery requires a larger incision to deal with the relatively thick layer of adipose tissue in obese patients, causing more estimated blood loss. However, the xed-effects model found obesity had no signi cant in uence on estimated blood loss. Moreover, our study showed a minimal difference between the two groups for the length of hospital stay, with obese patients at 2.87d and nonobese patients at 2.86d. The random effect forest plot demonstrated that there is no signi cant correlation in the length of hospital stay between obese patients and nonobese patients. This result is consistent with other studies investigating obese patients with surgery [3,35]. Therefore, surgeons do not have to consider longer hospital stay for obese patients after MIS-TLIF.
ODI and VAS scores were used to assess the postoperative functional outcome, and there was no signi cant difference in the levels of BP and LP VAS and ODI scores in the early and late period after MIS-TLIF between obese and nonobese patients. Studies focusing on other fusion techniques also found no difference in VAS and ODI scores between obese and nonobese patients [36][37][38]. However, our study for pain and ODI after MIS-TLIF was based on the limited number of studies included. Large retrospective trials are required to compare the pain and ODI in obese patients and nonobese patients following MIS-TLIF.
Obesity was related to a higher incidence of complications. Many previous studies assumed that obese patients had a higher incidence of complications than patients who were of normal weight [12,15,16]. Nevertheless, several studies suggested no increased intraoperative complications rate in the obese with MIS-TLIF[39]. Therefore, complication results were further collected during the intraoperative period and postoperative period. We found that the difference was signi cant in postoperative complications and was not meaningful in intraoperative complications. Buyuk et al [18] and Krüger et al [29], whose studies were enrolled in the meta-analysis, had speci c records of intraoperative complications.
Among the obese MIS-TLIF groups, the intraoperative complication rate was reported as 2.3% (2/84) in the obese groups, including 2 durotomies and 1 genitourinary; for the normal MI TLIF groups, the intraoperative complication rate was reported as 3.8% (3/78), including 3 durotomies. A previous study demonstrated that obesity correlated marginally with the incidental durotomy[40]. However, according to our integrated data, the incidence of durotomy was 3.8% (3/78) in the normal group and 1.2% (1/84) in the obese group. We concluded that obese patients were at a higher complication risk particularly in the postoperative period and that the adverse events were mostly related to comorbidities of the obese population rather than the surgery itself. In our meta-analysis, long-term postoperative complications between the two groups were not analyzed due to the lack of data from the selected literature. The difference in long-term postoperative complications could better explain the effect of obesity on MIS-TLIF. Therefore, we suggested that long-term postoperative complications should also be used as a standard measure of outcome in future research.
LIMITATIONS Nonetheless, the current study has several limitations. Firstly, all enrolled studies were retrospective observational studies; such study designs could have unidenti ed biases or confounders. Secondly, heterogeneity was signi cant in some statistical analyses, possibly caused by different baseline among the trials and various outcome measurements in the studies. Thirdly, the non-standard de nition of "normal weight" that occurred in certain studies may cause some unavoidable differences in study populations. Despite these limitations, this meta-analysis was based on comparable characteristics between obese groups and normal groups and the results should be veri able.

Conclusion
Obesity has no signi cant in uence on the duration of surgery, estimated blood loss, length of hospital stay, ODI, and VAS scores on patients following MIS-TLIF. MIS-TLIF could offer comparable outcomes between obese and non-obese patients with degenerative lumbar disease, though the obese group had a higher risk of postoperative adverse events. It's important to evaluate the high risk of postoperative complications of obese patients before undergoing MIS-TLIF. Declarations Ethics approval and consent to participate Since our study is a meta-analysis, an Ethical Review Committee Statement is not required.

Consent for publication
Not applicable.

Availability of data and materials
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests
The author(s) declared no potential con icts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online.

Funding
This research did not receive any speci c grant from funding agencies in the public, commercial, or not-for-pro t sectors.
XXH and WJQ designed the study, interpreted and analyzed the patient data, and wrote the paper. All authors read and approved the nal manuscript. All authors have read the journal policies and have no issues relating to journal policies. All authors have seen the manuscript and approved to submit to your journal. The work described has not been submitted elsewhere for publication, in whole or in part.  Tables   Table 1 Quality assessment using Newcastle-Ottawa scoring Study Selection Comparability Outcome