MINIMALLY INVASIVE LUMBAR ARTHRODESIS AND PERCUTANEOUS PEDICLE SCREWS: A SYSTEMATIC REVIEW

ABSTRACT A systematic review of the literature was performed in order to organize, evaluate, and select evidences available about the safety and efficacy of minimally invasive percutaneous arthrodesis with percutaneous pedicle screws in the treatment of patients with degenerative disc disease (and other spinal pathologies) as compared to conventional arthrodesis. PubMed, EMBASE and Cochrane Library databases were consulted to locate clinical trials and case reports/case series published in English between 2014 and 2019. After selection according to the inclusion/exclusion criteria, 21 of the 197 articles identified were chosen for a complete reading and used for the present review. Although the level of evidence of most of the studies included made the demonstration of efficacy and superiority among the surgical techniques reviewed difficult, the findings related to the minimally invasive procedure indicate a safe and reliable approach for the treatment of lumbar diseases. Level of evidence II; Systematic review of literature.


INTRODUCTION
Arthrodesis (or fusion) is a commonly used technique for the treatment of degenerative lumbar diseases [1][2][3] and its use has grown substantially in recent decades, 4 however, the conventional approaches and instrumentations used in open procedures demand extensive tissue dissection, which is associated with traumas, blood loss, reoperation rates, and substantial costs. [5][6][7] With these issues in mind, minimally invasive fusion is proposed in pathological spinal conditions, 8 significantly reducing blood loss and tissue damage, and making the patient's faster recovery and better rehabilitation possible. [9][10][11][12] In minimally invasive lumbar arthrodesis surgeries, the placement of percutaneous pedicle screws provides fusion without extensive incisions, which reduces the probability of complications. 13 The objective of this systematic review was to investigate evidence related to the safety and efficacy of minimally invasive percutaneous arthrodesis with percutaneous pedicle screws in the treatment of patients with degenerative disc disease (and other pathological spinal conditions) as compared to conventional open arthrodesis.

METHODS
This systematic review was conducted in accordance with the PRISMA statement 14,15 and was registered in the PROSPERO database as number CRD42019133252. The inclusion criteria were articles related to patients with degenerative disc disease and arthrosis or facet joint degeneration, degenerative scoliosis/adult scoliosis, spinal instability, a history of previous lumbar spine surgery, spinal canal stenosis, spinal fractures of traumatic, neoplastic, osteoporotic, infectious, and/or rheumatological origins treated with minimally invasive percutaneous arthrodesis with percutaneous pedicle screws or conventional open arthrodesis, written in English, including clinical trials and case series/reports. Incomplete texts were excluded. The PubMed, Cochrane Library, and EMBASE databases were used to locate articles published from 2014 to April 2, 2019. The title and abstract of each article were analyzed to eliminate duplicate articles and the full text of potentially relevant articles was retrieved for analysis. Subsequently, the texts were examined by two independent reviewers, who applied the Oxford Centre for Evidence-Based Medicine (OCEBM) scale 16 to all of the articles in order to classify them according to level of evidence. The following items (when available) were collected from each article: author(s); year of publication; study design; number of participants; mean age, sex, and diagnosis of the participants; intervention; control group; instrumentation; graft/implant used; surgical time (minutes); blood loss (ml); complications/adverse events; reoperation/revision; duration of follow-up (months); outcome measurements; Visual Analog Scale or VAS (pain); Oswestry Disability Index or ODI; and conclusions.

RESULTS
The initial search of the PubMed, Cochrane Library, and EMBASE data bases using "intervertebral disc degeneration", "arthropathies", "spondylolysis", "scoliosis", "spinal stenosis"; "spinal fractures", "arthrodesis", "spinal fusion", "pedicular screws", and "minimally invasive surgical procedures", adapting the keywords to each of the databases and including synonyms, with filters for clinical trials or case reports/series, written in English, published between 2014 and 2019, identified 197 articles. After the elimination of duplicates, 162 articles remained. Two authors reviewed the titles and abstracts of the remaining works, selecting them according to the inclusion criteria. Only clinical trials and case reports/series related to minimally invasive percutaneous arthrodesis with percutaneous pedicle screws for the treatment of patients with degenerative disc disease (and other pathological spinal conditions) were included, resulting in 40 articles. Publications in languages other than English were also excluded in this step. The final step was to fully review each of the 40 eligible articles, comprising 2 prospective randomized controlled studies, 1 prospective non-randomized controlled study, and 18 case reports/series, resulting in a total of 21 articles for inclusion in the systematic review. (Figure 1) A total of 230 participants/cases (129 who were submitted to minimally invasive procedures and101 to conventional open procedures) were included in this systematic review. Most of the results came from patients/participants diagnosed with stenosis (54.3%) or spondylolisthesis (14.8%). The results were expressed as mean values ± standard deviations. The data collected from the 3 clinical trials and the 18 case reports/series are summarized in Table 1. Mean participant age: The 3 clinical trials had similar mean participant ages, as shown in Table 1. Considering all the selected case reports/series together, the mean age of the 30 participants was 52.2 ± 22.2 years. Diagnosis: The most reported diagnosis was stenosis, found in the 3 clinical trials 18,24,28 and 3 case reports. 17,20,37 A total of 62 participants with stenosis were described in minimally invasive procedures and 63 in open procedures. The second most reported diagnosis was spondylolisthesis, present in 1 clinical trial 28 and in 4 case reports. 17,20,27,34 A total of 19 participants with this pathology were described in minimally invasive procedures, while 15 were described in open procedures. Other diagnoses are described in Table 1. Intervention: Five different fusion procedures were reviewed: 215 cases of lumbar fusion, 1 case of thoracic fusion, 9 cases of thoracolumbar fusion, 2 cases of thoracolumbosacral fusion, and 3 cases of lumbosacral fusion. Among them, 129 were performed by minimally invasive approach, while open procedures were applied in 101 cases. Lumbar fusion was the main technique used for the treatment of spondylolisthesis 17,20,27,28,34 and stenosis. 17,18,20,24,28,37 Control: Only the three clinical trials had control groups. Kim et al. (2018) 18 had a conventional open posterior lumbar interbody fusion group (Cop-PLIF) as the control for Robot-PLIF. Kim et al. (2015), 24 also with an interventional group that underwent Rom-PLIF, had a Cop-PLIF group for comparison. In turn, Wang et al., 28 who had minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) as the intervention, described open transforaminal lumbar interbody fusion (TLIF) as the control procedure. Instrumentation: The use of pedicle screws was reported in all the studies included. It is important to mention that 11 studies 17,19,21,22,28,[30][31][32]34,35,37 refer to instrumentation with percutaneous pedicle screws and 12 18,20,23,24,[26][27][28][29]33,[36][37][38] refer to pedicle screws. Some of them specify other types of instrumentation used in conjunction with the screws: cage (6 studies), 20,21,28,[35][36][37] rod (1 study), 32 and percutaneous s2AI screws (1 study). 33 Tender et al. 27 reported the use of cage and plate in one of their cases and the use of plate only in another of the cases reported, however, these instruments were used without pedicle screws (which are mentioned only during the revision surgery). Graft/Implant: Fifteen studies report the use of grafts or implants in the surgical procedures. Among these, only 2 describe the use of implants. 23,34 The other 13 studies report the use of different types of grafts, as shown in Table 1  Records identified in other sources (n = 0) Records after removal of duplicate articles (n = 162) Blood loss: Eleven studies reported blood loss during the surgical procedures, only one of which was a clinical trial. 28 In this study the authors described mean blood loss of the minimally invasive procedures (274 ± 99 ml) and of the open procedures (645 ± 163 ml) (p < 0.01). Ntourantonis et al., 29 reported blood loss during the surgical procedure in their case report, but did not provide volume information. The mean blood loss for the 9 case reports/series that did report this information was 330.5 ± 255.0 ml. Complications/adverse events: Among the 21 studies selected, there was an overall complications rate of 57.1% (12 studies -2 clinical trials and 10 case reports/series), as shown in Table 1. Four studies 17,20,22,36 reported the absence of complications, while five studies 24,26,33,37,38 did not report any information about complications or adverse events. Reoperation or revision: Five studies 18,24,27,31,34 reported the need for reoperation or revision of the surgical procedure, although only one of these 27 described the procedure. Tender et al., reported 2 cases of patients with degenerative spondylolisthesis, who had undergone lateral lumbar fusion with cage and/or plate. Due to complications related to the surgical procedures, the patients were submitted to a second procedure: the placement of pedicle screws in L4-L5 and S1 and facet joint graft (case 1) and bilateral foraminotomy of L3-L4 followed by instrumented posterolateral fusion of L3-L4 (case 2). Wang et al., 28 reported the absence of reoperation or revision surgery. Outcome measurement: Of the 21 studies, only the 3 clinical trials published outcome measurements. Kim et al., 18 in a study conducted to compare the robot-assisted posterior fusion surgical technique (Robot-PLIF) with conventional posterior fusion (Freehand-PLIF) in patients with degenerative spinal disease through clinical outcomes, used the Visual Analog Scale (or VAS), the Oswestry Disability Index (or ODI), and the SF-36 questionnaire, in addition to radiological evaluation of fusion status (by computed tomography) and flexion/ extension and disc degeneration by X-ray, to measure outcomes. Kim et al., 24 reported using cumulative sum control analysis for quality control monitoring of the accuracy of pedicular screw insertion and computed tomography of the accuracy of screw insertion for quality control monitoring of robot-assisted fixation. Wang et al., 28  Intergroup analyses were not shown. As for the case reports/series, none of them reported statistical analysis, although a decrease in scores was observed between the pre-and postoperative periods. As regards the ODI in the clinical trials, Kim et al., 18 evaluated the Robot-PLIF and Freehand-PLIF group scores during pre-and postoperative periods without significant differences between the groups in either period. Wang et al., 28 assessed the ODI in minimally invasive and open procedure groups. Once again, no statistically significant differences were observed between the groups and no intragroup analysis was shown. None of the case reports/series demonstrated statistical analysis, although a decrease in the scores had been observed between the pre-and postoperative periods. Follow-up: The mean duration of follow-up, considering 18 studies ( 3 studies 24,33,38 did not report this information) was 10.1 ± 9.3 months. In the clinical trials the mean duration was 24.1 ± 17.0 months. 18,28 In the cases reports/series this duration was 8.6 ± 7.4 months. Tender et al., 27 did not report the exact number of months of follow-up ("> 18 months") in one of their 2 cases. Main conclusions: Table 2 summarizes the main conclusions of the studies included in the systematic review, according to the respective authors. Regarding their clinical trials, Kim et al. (2018) 18 and Kim et al., 24 reported that minimally invasive techniques can be beneficial to patients. Wang et al., 28 concluded that minimally invasive fusion is safe and reliable. The case reports/series presented quite specific and very diversified conclusions, making it impossible to group them.

DISCUSSION
The main objective of this systematic review was to gather evidence related to the safety and efficacy of minimally invasive arthrodesis/fusion with percutaneous pedicle screws in the treatment of degenerative disc disease (and other pathological spinal conditions) when compared to conventional arthrodesis. A considerable number of studies related to this intervention were identified in the literature (21), although few of the studies reviewed dealt with randomized and controlled clinical trials (2) based on rigorously planned experimental design and, consequently, with more reliable results. Most of the studies included in this review (86%) were case reports and series, studies that present a low level of scientific evidence and are biased by their methodologies. Therefore, the main limitations of the present study are the lack of clinical trials and the small number of articles included with moderate or high levels of evidence.
The conclusions and parameters such as age and follow-up time, for example, are quite different among the case reports, making comparisons and assertive conclusions about the safety and efficacy of the minimally invasive techniques difficult. Among the 18 case reports/series presented in this systematic review, four 26,33,37,38 offered no information about complications or adverse events and only three 17,20,36 reported the absence of these situations. All these factors taken together allow only inferences about the safety and efficacy of the technique and of the instrumentation.
Clinical trials conducted to evaluate minimally invasive techniques suggest that these may be beneficial to patients, but the results presented were not significantly different from those obtained from open procedures or required longer follow-up periods, making it difficult to prove the superiority of one procedure over the other.
Despite the difficulty in demonstrating superiority, the findings regarding minimally invasive techniques indicate a safe and reliable procedure and attribute the inconclusive results to limitations related to study design, follow-up time, and number of participants. Of the three clinical trials selected, only two presented an experimental design that included a control group and a randomization technique. 18,24 The study by Kim et al.,18 emphasized that a follow-up of more than two years would be necessary to obtain more accurate data. Additionally, the authors argue that many participants did not have access to computed tomography in the postoperative period (only 28 in the minimally invasive group and 25 in the conventional group), a fact that may have influenced the conclusions. Kim et al.,24 in turn, suggested the differences in instrumentation (screw) used among the groups and the fact that operating time was not included in the performance quality measurement as possible limitations of the study. The third clinical trial selected, 28 although controlled, was not randomized. This study reports only three complications in the group treated with the minimally invasive procedure and one in the conventional procedure group, without the need for repair or surgical revision. The authors concluded, then, that the minimally invasive fusion technique is safe and reliable, but this conclusion was made based on a non-randomized, small, and specific (overweight and obese patients) population. It is worth mentioning, however, that almost all the studies showed that there were no serious adverse effects related to the use of a minimally invasive technique. These findings are corroborated by cohort and prospective studies not considered in this systematic review.
The scarcity of clinical trials with a high level of evidence, verified through the preparation of this systematic review, was also the subject of discussion of Park et al., 39 in a meta-analysis that included nine prospective cohort studies published up until December 2017, involving the comparison between minimally invasive lumbar fusion and the conventional technique. The results found in this study show that minimally invasive lumbar fusion techniques are more effective than open techniques in the treatment of spondylolisthesis in terms of improving function and reducing rates of infection, blood loss, and hospitalization time. However, there was no significant difference in parameters such as pain improvement, fusion rates, complications, or need for subsequent surgeries. In contrast, the prospective study by Giorgi et al., 40 which involved 66 participants and a two-year follow-up, reported satisfactory results obtained from the minimally invasive technique (fusion rate of 96.8% in radiographic analyses), with a low rate of postoperative complications (6.1%), demonstrating the need to conduct more robust studies to obtain significant and reliable results.

CONCLUSIONS
Although the level of evidence of most of the studies included makes it difficult to demonstrate efficacy and superiority among the surgical techniques reviewed, the findings around the minimally invasive procedure indicate a safe and reliable approach for the treatment of lumbar diseases. Many of the studies with lower levels of evidence present favorable results and add information to our understanding of the application of the technique and the instrumentation in rare and critical cases of lumbar disorders, while clinical trials, prospective studies and cohort studies may be more indicated and more reliable for the purpose of determining the best approach to choose for each patient in more generalized populations.
All authors declare no potential conflict of interest related to this article. The use of a multiexpandible cage allows a less invasive approach with satisfactory short-term clinical results. The minimally invasive approach seems to offer benefits to patients with neuromuscular scoliosis.

Brodano et al. (2014) b
The minimally invasive approach for the treatment of adolescent idiopathic scoliosis demonstrates deformity correction and advantages, but long-term data is needed.

Tender (2014) b
Attention to the caudal vertebral fracture as a potential complication following minimally invasive lumbar fusion. In patients with atherosclerosis, the lateral approach to the anterior lumbar spine may induce occlusion of the renal artery and renal infarction. Fixation with percutaneous pedicle screws may provide lasting benefits, although more in-depth investigations are necessary.