Comparison of Hybrid Surgery and Two-Level ACDF in Treating Consecutive Cervical Degenerative Disc Disease: A Systematic Review and Meta-Analysis

Abstract

Study Design

Systematic review and meta-analysis.

Objective

This meta-analysis aimed to compare hybrid surgery (HS) and two-level anterior cervical discectomy and fusion (ACDF) in the treatment of consecutive two-level cervical degenerative disc disease (CDDD).

Methods

Comprehensive searches were conducted in PubMed, Embase, and Web of Science. Extracted data from the selected studies included operative time, intra-operative blood loss, C2-C7 range of motion (C2-C7 ROM), superior adjacent segment range of motion (SAS ROM), inferior adjacent segment range of motion (IAS ROM), complication incidence, neck disability index (NDI) score, Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score. Meta-analysis was conducted using RevMan 5.3.

Results

A total of 626 patients from 11 studies who underwent either HS or two-level ACDF for CDDD were analyzed. Compared to ACDF in the non-ROI-C cage group, HS better preserved post-operative and final follow-up C2-C7 ROM (post-operation: MD 10.08, 95% CI 6.58 to 13.58, P < 0.01; final follow-up: MD 7.62, 95% CI 5.83 to 9.42, P < 0.01). HS significantly reduced post-operative and final follow-up SAS ROM and IAS ROM at the final follow-up. Additionally, HS resulted in less intraoperative blood loss than ACDF when blood loss reached 90 mL or more. Analysis of functional scores (NDI, JOA, and VAS), operative time, and complication rates showed no significant differences between HS and ACDF.

Conclusion

HS achieved better radiographic outcomes compared to two-level ACDF, with comparable clinical outcomes, reduced intraoperative blood loss, and a similar complication rate. However, further high-quality randomized controlled trials are needed.

Introduction

Cervical degenerative disc disease (CDDD) is characterized by the degeneration of cervical intervertebral discs caused by cumulative wear and tear factors.^1-3 The typical clinical manifestations of CDDD include neck pain, stiffness, as well as radiating pain or numbness in the upper limbs. ⁴ Surgical intervention for CDDD has received significant global attention, especially in cases of two-level CDDD.^5-7

Anterior cervical discectomy and fusion (ACDF) is a reliable therapeutic method that enables direct decompression and improves nerve function for CDDD. ⁸ Nevertheless, ACDF significantly influences the motion of adjacent discs, potentially causing adjacent segment degeneration (ASD). ASD remains a major concern following ACDF, with clinical studies demonstrating a 25-30% radiographic ASD incidence at a 10-year follow-up after single-level ACDF. ⁹ The risk further increases with two-level ACDF due to increased fusion mass rigidity, with clinical studies reporting a 10.0% reoperation rate for symptomatic ASD within 7-year follow-up. ¹⁰

Cervical disc replacement (CDR), also known as cervical disc arthroplasty (CDA), is a surgical procedure designed to preserve the intervertebral disc height and segmental activity as much as possible, thereby reducing the risk of ASD that may occur after ACDF. ¹¹ Although short-term clinical results have been well established, there is still a scarcity of studies that address long-term efficacy. ¹²

In recent years, hybrid surgery (HS), which combines ACDF and CDR, has emerged as a noteworthy alternative for CDDD treatment.^13-15 Biomechanical studies suggest that HS reduces the intradiscal pressure of adjacent segments compared to two-level ACDF, offering superior biomechanical properties to prevent ASD. ¹⁶ However, there is insufficient evidence regarding the long-term clinical efficacy and safety of HS. This study aimed to evaluate the postoperative and final follow-up surgical outcomes of HS vs two-level ACDF for managing two-level CDDD, providing surgical decision-making reference for the treatment of two-level CDDD.

Materials and Methods

Search Strategy and Selection Criteria

Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, ¹⁷ this systematic review and meta-analysis employed a comprehensive search strategy across Embase, PubMed, and Web of Science from their inception until March 2024. The combined terms used for search included: (“cervical” OR “neck” OR “cervical vertebrae”) AND (“disc disease” OR “degeneration” OR “herniation” OR “degenerative disc disease”) AND (“2-level” OR “two level”) AND (“ACDF” OR “fusion” OR “discectomy” OR “anterior cervical discectomy and fusion” OR “cervical disc arthroplasty” OR “CDA” OR “artificial disc replacement” OR “cervical disc replacement” OR “hybrid surgery” OR “HS” OR “hybrid ACDF” OR “hybrid cervical disc replacement” OR “ACDF with disc arthroplasty”). Two independent researchers (YY and WL) reviewed the relevant studies in the reference lists. Disagreements were resolved by a third professor-level researcher (YH).

Study Selection

The inclusion criteria for this study were as follows:

• (1) Target population: the patients diagnosed with two-level CDDD.

• (2) Interventions: the patients unerwent HS or two-level ACDF.

• (3) Outcomes: (1) operation parameters: operation time, blood loss; (2) radiographic outcomes: C2-C7 range of motion (C2-C7 ROM), superior adjacent segment range of motion (SAS ROM), inferior adjacent segment range of motion (IAS ROM); (3) clinical outcomes: neck disability index (NDI) score, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score; and (4) complication rate. The eligible study included at least one of the radiographic and clinical outcomes.

• (4) Article types: any clinical articles that had been published in a peer-reviewed journal, excluding case reports, reviews, biomechanical analysis, letters, and conference abstracts.

Duplicate or multiple publications of the same research, studies with incorrect subjects, and studies lacking essential data were excluded.

Data Extraction

Two researchers independently extracted the following data from each selected study: (1) study characteristics (main author, publication year, study design, intervention, sample size, gender, mean age, device information, and follow-up); (2) operation details (operation time, and blood loss); (3) postoperative data (measurement within one month after surgery) and final follow-up radiographic outcomes (C2-C7 ROM, SAS ROM, and IAS ROM); (4) clinical outcomes (NDI score, JOA score, and VAS score for neck and arm); and (5) complications.

Assessment of Methodological Quality

Two researchers (YY and WL) independently evaluated the quality of the literature following the PRISMA recommendations. ¹⁸ The methodological quality of each included study was evaluated following the Methodological Index for Non-Randomized Studies (MINORS). ¹⁹ Studies were scored and categorized as poor quality (≤14), moderate quality (15-22), or good quality (23-24). The Risk of Bias Assessment tool for Nonrandomized Studies (RoBANs) was utilized to evaluate the bias in each study included. ²⁰

Statistical Analysis

Statistical analysis was performed using Review Manager 5.3. The heterogeneity among the studies was evaluated through the Cochran Q test (with P ≤ 0.05 indicating significant heterogeneity) and the I² test (with values > 0%, > 50%, and > 75% indicating low, moderate, and high heterogeneity, respectively). ²¹ Random-effect models were employed when high heterogeneity was detected (I² ≥ 50% and P value for Q test ≤ 0.05), while fixed-effect models were used in the presence of low heterogeneity (I² < 50% and P value for Q test > 0.05). ²² Additionally, if the parameter exhibits I² > 50% and P < 0.05, it was validated through subgroup analysis or sensitivity analyses. P < 0.05 was defined as significant difference. Continuous outcomes were presented as the mean difference (MD) along with its corresponding 95% confidence interval (95% CI), while dichotomous outcomes were expressed as odds ratio (OR) with associated 95% CI.

Results

Literature Search

The comprehensive search strategy produced 2504 publications, and after removing duplicates, 1714 potentially relevant articles remained. Screening the titles and abstracts of 1714 publications led to the exclusion of studies that did not meet the inclusion criteria. After excluding 1457 publications, the full-text assessments were conducted in 257 publications, which included 11 studies published between 2009 and 2022, comprising a total of 626 patients for analysis (Figure 1).^{8,13,14,23-30} Notably, the surgical cases included in Xiong 2018 ²⁵ involved patients with two-level CDDD who underwent HS or ACDF between 2009 and 2012, while those in Xiong 2020 ²⁵ comprised patients who underwent HS or ACDF between March 2015 and May 2016. The surgical periods in these two studies did not overlap. Consequently, both studies were included in this meta-analysis.

Figure 1.

Diagram illustrating the process of selecting the studies included in this meta-analysis.

Study Characteristics

The included studies involved a total of 626 patients who underwent treatment for CDDD, with 296 patients in the HS group and 330 patients in the two-level ACDF group. In different studies, the mean age of patients in the HS group ranged from 43.4 to 58.4 years, while it ranged from 47.3 to 60.5 years in the two-level ACDF group. Devices such as the Mobi-C disc, Prodisc-C disc, and ROI-C cage were utilized during surgery in both the HS and two-level ACDF groups. Detailed information is shown in Table 1.

Table 1.

General Characteristics of the Included Studies.

Study	Design	Sample Size		Gender (M/F)		Mean Age (yr)		Surgical Level		Device Information		Mean Follow-Up (mo)
		HS	ACDF	HS	ACDF	HS	ACDF	HS	ACDF	HS	ACDF	HS	ACDF
Sharm, 30 2022	RC	27	22	20/7	14/8	43.4	53.3	C3-C5 (1) C4-C6 (8) C5-C7 (18)	C3-C5 (1) C4-C6 (8) C5-C7 (18)	NA	NA	37.2	48.0
Xiong, 26 2020	RC	48	43	22/26	20/23	53.42	56.33	C3-C5 (6) C4-C6 (32) C5-C7 (10)	C3-C5 (4) C4-C6 (30) C5-C7 (9)	Mobi-C disc + ROI-C cages	ROI-C cage	28.85	29.76
Wang, 8 2018	PC	30	33	14/16	16/17	58.4	59.9	C3-C5 (2) C4-C6 (19) C5-C7 (9)	C3-C5 (4) C4-C6 (23) C5-C7 (6)	ProDisc-C/Mobi-C disc + cage	Cage	84.4	83.7
Xiong, 25 2018	RC	20	22	12/8	15/7	54.40	55.77	C3-C5 (3) C4-C6 (4) C5-C7 (13)	C3-C5 (2) C4-C6 (6) C5-C7 (14)	Bryan disc + cage	Cage	77.25	79.68
Duan, 29 2017	RC	29	39	14/15	15/24	58.0	60.5	C3-C5 (4) C4-C6 (16) C5C7 (9)	C3-C5 (6) C4-C6 (22) C5-C7 (11)	Prodisc-C/Mobi-C disc + cage	Cage	84.2	85.5
Ji, 14 2017	PC	20	20	10/10	12/8	45.7	48.0	C3-C5 (3) C4-C6 (8) C5-C7 (9)	C3-C5 (4) C4-C6 (6) C5-C7 (10)	Mobi-C disc + cage	Cage	36 - 60	36 - 60
Grasso, 13 2015	PC	20	20	10/10	11/9	44.2	47.3	NA	NA	Prodisc-C/Mobi-C disc + ROI-C cage	ROI-C cage	24 - 40	24 - 40
Mende, 28 2015	RC	47	64	21/26	43/21	48.7	52.0	NA	NA	NA	NA	NA	NA
Shen, 27 2013	RC	18	30	11/7	19/11	54.2	54.9	C4-C6 (12) C5-C7 (6)	C4-C6 (21) C5-C7 (9)	Bryan disc + cage	Cage	24.1	24.1
Liu, 24 2012	RC	17	17	13/4	14/3	53.7	56.4	C4-C6 (11) C5-C7 (6)	C4-C6 (11) C5-C7 (7)	Prodisc-C disc + cage	Cage	6	6
Shin, 23 2009	PC	20	20	10/10	12/8	45.7	48.0	NA	NA	Mobi-C disc + cage	Zephir plate	> 24	> 24

PC, prospective Cohort; RC, retrospective Cohort; HS, hybrid surgery; ACDF, anterior cervical discectomy and fusion; NDI, neck disability index; JOA, Japanese orthopaedic association; VAS, visual analogue scale; C2-C7 ROM, C2-C7 range of motion; SAS ROM, superior adjacent segment range of motion; IAS ROM, inferior adjacent segment range of motion; NA, not available.

Assessment of Methodological Quality

MINORS scores ranged from 16 to 23 in the included studies, which indicated that two studies possessed good methodological quality and nine studies had moderate methodological quality (Table 2). The risk of bias for all selected studies was illustrated in Figure 2.

Table 2.

MINORS Scores of Included Studies (Criteria Scoring 0 = not Reported, 1 = reported but Inadequate, 2 = reported and Adequate).

Quality Assessment for Included Studies	Shin 2009	Liu 2012	Shen 2013	Mende 2015	Grasso 2015	Ji 2017	Duan 2017	Xiong 2018	Wang 2018	Xiong 2020	Sharm 2022
1. A clearly stated aim	2	2	2	2	2	2	2	2	2	2	2
2. Inclusion of consecutive patients	2	1	1	2	1	2	2	2	2	2	2
3. Prospective collection of data	2	2	2	2	2	2	2	2	2	2	2
4. Endpoints appropriate to the aim of the study	2	2	1	2	2	2	2	2	2	2	2
5. Unbiased assessment of the study endpoint	2	0	0	0	0	2	0	0	0	0	0
6. Follow-up period appropriate to the aim of the study	2	2	1	2	2	2	2	2	2	2	2
7. Loss to follow up less than 5%	2	2	2	2	0	2	2	0	1	2	2
8. Prospective calculation of the study size	1	1	1	2	0	1	2	1	1	1	1
Item 9-12 only for comparative studies
9. An adequate control group	2	2	2	2	2	2	2	2	2	2	2
10. Contemporary groups	2	2	2	2	1	2	2	2	2	2	2
11. Baseline equivalence of groups	2	2	2	2	2	2	2	2	2	2	2
12. Adequate statistical analyses	2	2	2	2	2	2	2	2	2	2	2
Total MINORS SCORE	23	20	18	22	16	23	22	19	20	21	21

Figure 2.

Risk of Bias Assessment tool for Nonrandomized Study (RoBANS). Green indicates a low risk of bias; red signifies a high risk; yellow represents an unclear risk of bias.

C2-C7 ROM

Overall, four studies reported the post-operative C2-C7 ROM among 205 patients, and subgroup analysis was conducted by dividing the studies into two subgroups based on whether ROI-C was applied during surgery (Figure 3A). In the subgroup with the ROI-C cage, the results indicated no significant statistical difference between ACDF and HS (P > 0.05) and no heterogeneity (P > 0.05, I² = 0%). In the subgroup without the ROI-C cage, the results revealed a significant difference between HS and ACDF (MD 10.08, 95% CI 6.58 to 13.58, P < 0.01). Additionally, the subgroup analysis led to reduced heterogeneity (I² = 0%). Furthermore, HS was found to maintain C2-C7 ROM better than ACDF at the final follow-up (MD 7.62, 95% CI 5.83 to 9.42, P < 0.01; Figure 3B) with mild heterogeneity (I² = 10%).

Figure 3.

Forest plot comparing HS with two-level ACDF regarding C2-C7 ROM (upper: ROI-C cage; lower: Non-ROI-C cages) (A) postoperatively and (B) at the final follow-up.

SAS ROM

The postoperative SAS ROM showed a significant reduction after HS in comparison to ACDF (MD -2.54, 95% CI -5.01 to −0.07, P = 0.04; Figure 4A), and there was no significant heterogeneity observed (P > 0.05). Moreover, HS resulted in less SAS ROM in comparison to ACDF at the final follow-up (MD -3.53, 95% CI -4.65 to −2.41, P < 0.01; Figure 4B), again without significant heterogeneity (P > 0.05).

Figure 4.

Forest plot comparing HS with two-level ACDF regarding SAS ROM (A) postoperatively and (B) at the final follow-up.

IAS ROM

The results revealed a notable decrease in IAS ROM at the final follow-up after HS when compared to ACDF (MD -3.38, 95% CI -4.64 to −2.12, P < 0.01; Figure 5B), with no significant heterogeneity observed (P > 0.05). Additionally, postoperative IAS ROM did not exhibit a significant statistical difference between HS and ACDF (MD -0.30, 95% CI -1.35 to 0.75, P = 0.58; Figure 5A) and showed no heterogeneity (I² = 0).

Figure 5.

Forest plot comparing HS with two-level ACDF regarding IAS ROM (A) postoperatively and (B) at the final follow-up.

NDI Scoring

The analysis revealed no significant statistical difference in postoperative NDI scores between HS and ACDF (MD -0.12, 95% CI -1.30 to 1.05, P = 0.84; Figure 6A), with mild heterogeneity observed (I² = 13%). Similarly, the final follow-up NDI scores following HS did not exhibit a significant statistical difference when compared to ACDF (MD -0.56, 95% CI -1.47 to 0.35, P = 0.23; Figure 6B), and there was no heterogeneity present (I² = 0%).

Figure 6.

Forest plot comparing HS with two-level ACDF regarding NDI scores (A) postoperatively (B) at the final follow-up; and regarding JOA scores (C) postoperatively and (D) at the final follow-up.

JOA Scoring

The results indicated no significant statistical difference in postoperative JOA scores between HS and ACDF (MD 0.13, 95% CI -0.21 to 0.48, P = 0.45; Figure 6C), exhibiting moderate heterogeneity (I² = 53%). Additionally, the final follow-up JOA scores for HS did not show a significant statistical difference when compared to ACDF (MD 0.07, 95% CI -0.09 to 0.22, P = 0.40; Figure 6D), with mild heterogeneity (I² = 48%).

VAS Scoring for Neck and Arm

We noted that the VAS scores for neck and arm from Grasso et al, ¹³ Duan et al, ²⁹ and Wang et al ⁸ were consistent, as their articles did not specify the region targeted by the VAS scores. The results revealed no significant statistical difference in postoperative VAS for the neck (MD -0.18, 95% CI -0.59 to 0.23, P = 0.39; Figure 7A) with moderate heterogeneity (I² = 53%) and VAS for the neck at the final follow-up (MD -0.23, 95% CI -0.65 to 0.19, P = 0.28; Figure 7B) with moderate heterogeneity (I² = 73%) when comparing HS with ACDF. The sensitivity test indicated that no specific study significantly contributed to the overall heterogeneity. Likewise, the results did not show a significant statistical difference between the two surgeries in the postoperative VAS for the arm (MD -0.09, 95% CI -0.36 to 0.18, P = 0.50; Figure 7C) with mild heterogeneity (I² = 35%) and VAS for the arm at the final follow-up (MD 0.04, 95% CI -0.10 to 0.19, P = 0.57; Figure 7D) without heterogeneity (I² = 0%).

Figure 7.

Forest plot comparing HS with two-level ACDF regarding VAS scores for neck (A) postoperatively (B) at the final follow-up; and regarding VAS scores for arm (C) postoperatively and (D) at the final follow-up.

Operation Time and Intra-operative Blood Loss

Operation time was reported in ten studies,^{8,13,14,23-27,29,30} showing a MD of 3.72 (95% CI -15.38 to 22.82), with no significant statistical significance (P = 0.70) (Figure 8A). The heterogeneity was substantial (I² = 99%), and a sensitivity test identified no specific study as a significant contributor to the overall heterogeneity. Nine studies reported intra-operative blood loss during the surgery (Figure 8B),^{8,14,23-27,29,30} and subgroup analysis was conducted by dividing the studies into two subgroups based on whether blood loss was 90 mL or more, or less than 90 mL (Figure 8B). In the subgroup with blood loss of 90 mL or more, the results showed an MD of −30.39 (95% CI -46.81 to −13.96) with a significant statistical difference (P < 0.01). The heterogeneity decreased in the subgroup analysis (I² = 63%). In the subgroup with less than 90 mL of blood loss, the results did not show a significant statistical difference between HS and ACDF (MD 3.85, 95% CI 0.05 to 7.64, P = 0.05). Furthermore, the subgroup analysis led to a reduced heterogeneity (I² = 27%).

Figure 8.

Forest plot comparing HS with two-level ACDF. (A) Mean difference in operation time (B) subgroup analysis for mean difference in blood loss (upper:>= 90cc; lower: <90cc).

Incidence of Complication

The complications after HS or ACDF were extracted comprehensively, with a total of 75 events reported after HS and 66 events after ACDF (OR 1.90, 95% CI 0.86 to 4.17, P = 0.11; Figure 9A), showing moderate heterogeneity (I² = 64%). Furthermore, HS exhibited a significant increase in the incidence of heterotopic ossification (HO) compared to ACDF (OR 6.74, 95% CI 3.01 to 15.08, P < 0.01; Figure 9B), exhibiting mild heterogeneity (I² = 42%). A detailed list of complications that occurred postoperatively is provided in Table 3.

Figure 9.

Forest plot comparing HS with two-level ACDF regarding (A) complications and (B) HO.

Table 3.

Reported Complications of the Included Studies.

Studies	HS		Two-Level ACDF
	Number	Events	Number	Events
Shin 2009	0/20	None	0/20	None
Liu 2012	0/20	None	0/20	None
Shen 2013	Not report clearly	NA	Not report clearly	NA
Grasso, 2015	Not report clearly	NA	Not report clearly	NA
Mende 2015	16/47	Subsided implants (11); operative revisions (5)	33/64	Subsided implants (31); operative revisions (2)
Duan 2017	16/29	ASD (5); HO (10); implant subsidence (1)	10/39	ASD (8); C5 nerve root palsy (1); implant subsidence (1)
Ji 2017	11/20	Non-fusion (2); HO (9)	8/20	Non-fusion (1); HO (7)
Xiong 2018	5/20	Vertebral SWD (2); HO (1); ASD (1); byran disc migration (1)	2/22	ASD (2)
Wang 2018	10/30	HO (10)	4/33	Dysphagia and hoarseness (3); C5 palsy (1)
Xiong 2020	10/48	Mild dysphagia (8); HO (2)	9/43	Mild dysphagia (9)
Sharma 2022	7/27	HO (7)	0/22	NA

HO, heterotopic ossification; SWD, sagittal wedge deformity; ASD, adjacent segment degeneration.

Disscusion

The optimal surgical strategy for treating consecutive two-level CDDD remains controversial, with HS demonstrating potential as a viable alternative to traditional two-level ACDF.^30-32 Reported drawbacks of ACDF, including reduced cervical mobility and accelerated ASD, appear to be mitigated by HS. This innovative technique combines the benefits of both ACDF and CDR, demonstrating superior clinical advantages in the treatment of multilevel CDDD. ³³ This meta-analysis evaluated HS vs ACDF across radiographic outcomes, clinical outcomes, operative details, and complications. Our results indicated that HS was superior to ACDF in preserving cervical ROM and minimizing ASD. Notably, HS achieved comparable neurological functional recovery to ACDF while providing these additional biomechanical benefits, providing data reference for guiding clinical decision-making when selecting appropriate surgery for CDDD.

HS Achieves Better Radiographic Parameters Changes

The preservation of C2-C7 ROM is essential for patients with CDDD to maintain the physiological cervical mobility, which enhances long-term quality of life by avoiding the stiffness associated with two-level cervical fusion. ³⁴ It was reported that HS can better preserve the C2-C7 ROM compared to two-level ACDF, and patients return to work sooner after HS compared to ACDF. ³⁵ All included studies in this study measured C2-C7 ROM by the Cobb angle between maximal flexion and extension on lateral radiographs, ensuring methodological consistency. This result is consistent with previous meta-analysis,^36-38 and our study expanded the analysis to long-term follow-up results. ³⁷ Notably, our subgroup analysis revealed significantly reduced C2-C7 ROM in the ACDF group without ROI-C implantation compared to HS. Additionally, the use of ROI-C in ACDF procedures enhanced cervical mobility, achieving ROM preservation comparable to HS.

The results of this meta-analysis also indicated that HS limited increases in SAS/IAS ROM compared with ACDF. This result is consistent with another 5-year retrospective study, ⁸ which demonstrated no significant compensatory motion in adjacent segments after HS, while both SAS and IAS ROM increased significantly in the ACDF group. The increase of SAS and IAS ROM after cervical surgery reflects postoperative biomechanical compensation, indicating that adjacent segments receive more stress. ³⁹ A finite element analysis also demonstrated that increased ROM can lead to elevated intradiscal pressure and facet joint forces, which may accelerate the postoperative ASD. ⁴⁰ Therefore, HS may prevent ASD by reducing the adjacent segmental ROM to reduce the segmental loads.

The choice of operation levels designated for either HS or ACDF substantially influences postoperative cervical motion. The upper cervical spine, known for its high mobility, poses significant surgical risks. ⁴¹ Fusion in this area can greatly restrict overall cervical rotation, leading to compensatory movements in adjacent segments and accelerating ASD. ⁴² The revision surgery of the upper cervical spine using ACDF was found to significantly increase ROM and intradiscal pressure in adjacent segments, suggesting the occurrence of ASD after a secondary ACDF. ⁴³ Moreover, upper cervical level surgery carries a higher risk of nerve injury and dysphagia. ⁴⁴ A clinical study involving 358 patients who underwent ACDF analyzed the causes of postoperative dysphagia, identifying that upper cervical spine surgery is a significant risk factor for this condition. Many studies have demonstrated that the C5-7 level, due to its greater range of flexion-extension motion, frequently exhibits degenerative changes in the lower cervical spine and endures a higher biomechanical load.^45,46 Additionally, the stress significantly increases in the C6-7 segments after a C5-6 fusion, making it more susceptible to degeneration. ⁴⁷ Liang et al. ⁴⁸ demonstrated that using the hybrid construct with CDA for the revision of ASD in the upper adjacent segment after one-level ACDF significantly reduced biomechanical respondes while inducing minimal kinematic changes in adjacent segments compared with conventional ACDF revision.

The dynamic nature of cervical spine biomechanics and complication rates changes over time, our study specifically emphasized the inclusion of long-term follow-up data to comprehensively evaluate postoperative outcomes. The C2-C7 ROM significantly decreases after ACDF, with no significant changes observed between the 2-year and 5-year follow-up periods. ⁴⁹ In contrast, HS demonstrated superior long-term motion preservation through partial maintenance of segmental mobility, which more closely approximates the spine’s natural biomechanics and significantly reduces adjacent segment loads in a long-term follow-up. ³⁶ A more than 5-year follow-up study indicated that both ACDF and HS remain relatively stable for ASD incidence. ⁵⁰ In our systematic investigation, we prioritized the inclusion of long-term follow-up studies to strengthen the clinical relevance of our findings. Among the included studies only one had a follow-up duration of less than two years among the studies we analyzed, while most reported follow-up periods longer than two years.

Comparable Clinical Outcomes Between HS and ACDF

The clinical outcomes scores, including NDI, JOA, and VAS scores for pain, are widely used to evaluate functional recovery and pain relief after cervical surgery.^8,26,30 The above functional and clinical outcomes primarily reflect symptom relief (like pain reduction and neurological recovery) resulting from decompression at the operative level. Both HS and ACDF effectively relieve nerve compression, achieving comparable short-term symptom improvement. ⁵¹ However, the biomechanical advantages of HS include superior cervical ROM preservation and reduced ASD incidence, serving as imaging-detectable benefits not fully captured by conventional clinical scoring systems. ¹⁶ Long-term follow-up studies and patient-reported outcome measures specific to quality of life may be necessary to capture these subtle but meaningful differences. In this meta-analysis, there were no significant differences in these clinical scores between HS and two-level ACDF postoperatively and at the final follow-up. The previous meta-analysis also demonstrated no significant differences in postoperative clinical scores between the HS group and the ACDF group. ³⁷

Operation Time and Blood Loss after HS

Operation time and blood loss are closely related to the size of trauma and recovery time after operation. The findings of this study indicated that the operation time for HS and two-level ACDF is comparable. However, the considerable heterogeneity among the included studies concerning operation time can be attributed to the individualized surgical procedures and varying surgical levels required for the patients. Regarding blood loss, the study highlights that the HS group experienced significantly less blood loss compared to the two-level ACDF group, particularly when blood loss exceeded 90 mL. A previous meta-analysis showed consistent results regarding blood loss comparison between the ACDF and HS groups. ³⁷ The main reason for the results in both meta-analyses might be that ACDF involves more extensive resection, leading to increased blood loss during surgery. ⁵²

Complications Rate Between HS and ACDF

The primary surgical risks and complications that are likely to occur include neck pain, dysphagia, non-fusion, and nerve root damage for both HS and ACDF.^34,53 This study found no significant statistical difference in the overall complication rate between HS and two-level ACDF. Among 1576 ACDF patients from a previous study, the most frequently reported adverse events were dysphagia, dural tears, cerebrospinal fluid leaks, and hoarseness. ⁵⁴ Dysphagia, especially delayed dysphagia, might be caused by scarring or adhesions around the spinal implant. ⁵⁴ An incidental dural tear frequently occurs postoperatively, often due to improper surgical procedures during the excision of the posterior longitudinal ligament. ⁵⁵

The occurrence of implant subsidence and revision surgery were the need for spine surgeons to pay enough attention.^28,29 One included study of this meta-analysis showed an implant subsidence rate of 48% in the two-level ACDF group, while the rate was only 23% in the HS group. ²⁸ The difference in the incidence of implant subsidence may be associated with the extent of intraoperative bone resection. ⁵⁶ Moreover, the location, size, and type of implant also influence postoperative implant subsidence. ⁵⁷ Two included studies reported the incidence of postoperative ASD,^25,29 and the results of the included studies demonstrated a higher occurrence of ASD in the ACDF group compared to the HS group. Posterior cervical motion redistribution occurs following ACDF, as the reduced ROM at the fused segments necessitates compensatory hypermobility in adjacent levels to preserve global cervical spine kinematics. This increased motion and stress on the intervertebral discs and facet joints accelerate degeneration in adjacent segments. ¹⁶ Although HS employs fusion in certain segments, the application of artificial disc mobility in others better preserves the normal kinematic pattern of the cervical spine. ⁵⁸

HO is a common complication after CDR or HS.^15,26,59 Typically, HO forms around the spinal implant, with factors like old age, gender, and genetic condition being significant risk contributors.^53,60 The results demonstrated that the incidence of HO in the HS group is markedly higher compared to the two-level ACDF group. HO formation after HS might be an essential aspect of the postoperative bone remodeling process. ⁶¹ The impact of HO on the progression of adjacent-level degeneration and clinical outcomes over a long-term follow-up after HS remains to be verified.^59,62

HS Strategy Design

Previous studies reported the potential kinematic changes at both the operative and adjacent levels when employing different hybrid strategies.^34,63,64 It was reported that HS involving disc replacement at a segment with higher ROM and fusion at a segment with lower ROM is effective. ⁶³ Li et al ⁶⁵ designed two hybrid strategies at the C4-C6 level: one combining ACDF at the C4-C5 level and CDR at the C5-C6 level (ACDF/CDR), and the other using ACDF at both levels (ACDF/ACDF). They found that facet stress at the cartilage between the index and infra-adjacent levels increases with all prostheses in the ACDF/ACDF group, while only DCI induces a significant increase in the ACDF/CDR group. Thus, the CDR/ACDF HS results in greater adjacent cartilage overloading compared to the ACDF/CDR HS, which may hasten the progression of ASD over time.

Surgeons will take into account the hybrid construct and the selection of the CDR prosthesis device when conducting HS.^45,65 The mechanical properties of different CDR devices vary, necessitating consideration of the quality and reliability of the chosen CDR device. The metal-on-polymer design is the most prevalent for CDR devices, featuring a polymer core encased by two metal components to create a sliding articulation mechanism. ⁶⁶ Mo et al ⁴⁵ analyzed the biomechanical performance of five CDR devices (Bryan, ProDisc-C, PCM, Mobi-C, and Discover) in HS for the treatment of bi-level CDDD, using a cervical spine finite element model. Their findings showed that the ROM at both the operative and adjacent levels for ball-socket prostheses, such as ProDisc-C, Mobi-C, and Discover, is comparable to that of a healthy spine. Conversely, for Byran and PCM, the ROM at the operative levels is less than that of a healthy spine and results in increased ROM at adjacent levels. Furthermore, Bryan and PCM cause more adjacent intradiscal pressures and stress on the bone-implant interface compared to a healthy spine. According to their results, HS using Bryan and PCM may be appropriate for patients at risk of facet joint degeneration, while HS with ProDisc-C, Mobi-C, and Discover may be better suited for patients at risk of vertebral osteoporosis.

Strengths and Limitations

To the best of our knowledge, this is the first meta-analysis to compare HS and two-level ACDF both in the postoperative period and at the final follow-up. In contrast to previous studies, our investigation focused on clinical literature concerning two-level consecutive CDDD. Moreover, our study not only compared postoperative outcomes but also examined relevant outcomes over the long-term follow-up. However, this meta-analysis has its limitations. First, certain literature did not clearly report postoperative results. We included studies with complete postoperative data to reduce bias and ensure accurate results. Second, the heterogeneity of some comparisons is considerable due to the different prostheses used in the surgeries. And we performed subgroup analysis to reduce heterogeneity and assess outcome consistency. Additionally, we still need more high-quality randomized controlled trials to obtain more reliable results.

Conclusions

This meta-analysis demonstrates that HS yields superior radiographic outcomes compared to two-level ACDF, including greater preservation of cervical ROM and a reduced risk of ASD. Notably, HS achieves comparable clinical functional outcomes while significantly reducing intraoperative blood loss without increasing the complication rate relative to two-level ACDF. These findings suggest that HS represents a viable alternative to traditional ACDF. However, further high-quality randomized controlled trials are needed to verify this conclusion.

ORCID iDs

Yihan Yang https://orcid.org/0009-0005-8254-8567

Weishi Liang https://orcid.org/0000-0003-3565-6504

Zhangfu Li https://orcid.org/0000-0002-0112-1678

Yong Hai https://orcid.org/0000-0002-7206-325X