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Abstract

Background:

The resection of large superficial esophageal neoplastic lesions (SENLs) presents significant challenges for traditional endoscopic submucosal dissection (ESD). Endoscopic submucosal tunnel dissection (ESTD) has emerged as an alternative that potentially reduces resection difficulty.

Objectives:

We aimed to compare ESTD and ESD in the treatment of large SENLs.

Design:

Meta-analysis of randomized controlled trials (RCTs).

Data sources and methods:

We systematically searched MEDLINE, EMBASE, Cochrane Library, and Wanfang Data for RCTs comparing ESTD with ESD for large SENLs until July 1, 2024. The grading of recommendations assessment, development, and evaluation framework was used to assess the certainty of the evidence, whereas trial sequential analysis (TSA) was used to control for random errors and evaluate conclusion validity.

Results:

Four RCTs involving 315 patients were included. The pooled analysis showed that ESTD was significantly faster than ESD (mean differences 5.06, 95% confidence interval: 3.31–6.80; p < 0.01; I² = 0%; low certainty of evidence). TSA indicated a desired sample size of 162, with the cumulative Z curve crossing the trial sequential monitoring boundary. ESTD also had lower rates of major complications and post-operation esophageal stricture (low certainty of evidence). No significant differences were found in en bloc and curative resection rates.

Conclusion:

With low certainty, ESTD appears superior to ESD for large SENLs, offering faster resection and fewer complications, with similar en bloc and curative resection rates.

Trial registration:

This meta-analysis protocol was registered on PROSPERO (CRD42024520754).

Plain language summary

Is ESTD better than ESD in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis

Endoscopic Submucosal Dissection (ESD) is an effective treatment for early esophageal cancer but poses a higher risk of procedural failure and postoperative stricture for large lesions. Endoscopic submucosal tunnel dissection (ESTD) is an enhanced technique derived from ESD, which may improve procedural speed and reduce postoperative complications. Our meta-analysis included all available randomized controlled trials (RCTs) comparing the safety and efficacy of ESTD versus ESD for large esophageal lesions to provide high-quality evidence for clinical practice. We analyzed 4 RCTs involving 315 patients. The results demonstrated that ESTD significantly reduced operation time and postoperative stricture risk compared to ESD. Overall, our study supports that ESTD is superior to ESD for resecting large esophageal lesions.

Keywords

endoscopic submucosal dissection endoscopic submucosal tunnel dissection large superficial esophageal neoplastic lesions systematic review and meta-analysis tunnel endoscopy

Introduction

Esophageal cancer ranks as the eighth most common malignancy worldwide, representing the sixth leading cause of cancer-related mortality.¹ In 2022, it accounted for approximately 510,716 new cases and 455,129 deaths globally.² Early detection and intervention are crucial for reducing the mortality rate of this disease, hereby patients with superficial esophageal carcinoma can achieve a 5-year survival rate exceeding 90%.³

Endoscopic submucosal dissection (ESD) is a well-established technique for excising superficial esophageal neoplastic lesions (SENLs), with multiple guidelines citing it as the treatment of choice due to its high en bloc resection rate and low risk of postoperative recurrence.^4–7 However, ESD is time-consuming and challenging in large SENLs that exceed half of the esophageal circumference or have a longitudinal diameter greater than 20 mm. Circumferential dissection diminishes the efficacy of submucosal injections, increasing their frequency and complicating the procedure. Moreover, the narrow lumen and thin wall of the esophagus can cause the resected mucosa to obstruct the lumen, thereby impeding the operational space.⁸

Endoscopic submucosal tunnel dissection (ESTD), an evolution of ESD, represents a novel approach within the digestive endoscopic tunnel technique. Unlike conventional ESD, which starts with circumferential dissection, ESTD begins by creating submucosal tunnels through incisions on the anal and orofacial sides of the lesion-proximate mucosa before finally dissecting the margins on both sides.⁹ This technique offers several advantages, including prolonged retention of the submucosal solution, reduced need for additional injections, and improved visualization of the surgical field. Several studies have shown that ESTD provides practical advantages over ESD, particularly in terms of faster resection speeds.^8–10 Given the correlation between longer operation times and increased procedure-related complications,¹⁰ resection speed serves as a crucial indicator in evaluating endoscopic procedures. Moreover, research indicates that ESTD achieves a higher R0 resection rate and lower incidence of procedure-related complications compared to ESD.^8,9 However, existing guidelines lack clear recommendations for treating large esophageal lesions with ESTD versus ESD, due to insufficient evidence from clinical trials. Current meta-analyses have not addressed the challenges of large-area lesions and show considerable heterogeneity. Moreover, key efficacy and safety outcomes, such as en bloc resection and complication rates, remain controversial.^11–14 Therefore, higher-quality meta-analyses are urgently needed to inform clinical practice.

A meta-analysis based on randomized controlled trials (RCTs) is considered the highest level of evidence for clinical medicine that can provide authoritative guiding recommendations. To the best of our knowledge, this is the first systematic review and meta-analysis to specifically include RCTs focused on large SENLs, aiming to compare the treatment efficacy and safety of ESTD versus ESD.

Methods

This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Supplemental Material 1).¹⁵ The study protocol was registered on PROSPERO (CRD42024520754).

Literature search strategy

A comprehensive literature search was conducted across databases including MEDLINE, EMBASE, Cochrane Library, and Wanfang Data up to July 1, 2024. The search terms utilized both MESH terms and free text, encompassing “esophageal carcinoma,” “superficial esophageal neoplastic lesions,” “endoscopic tunnel submucosal dissection,” “ESTD,” “endoscopic submucosal dissection,” and “ESD.” The detailed search strategy is outlined in Supplemental Material 2. No restrictions were applied regarding language. Furthermore, the reference lists of all primary studies and review articles were manually scrutinized for additional relevant studies.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (a) RCTs published as full-text articles in any language; (b) adult participants aged 18 years or older; and (c) diagnosis of large SENLs confirmed through esophagogastroduodenoscopy and biopsy, meeting the eligibility criteria for endoscopic resection according to the Japanese guidelines for the diagnosis and treatment of esophageal cancer.⁵ The pathological assessment process of included studies was standardized and rigorous. A large lesion was defined based on a size greater than 20 mm or involving more than half of the esophageal circumference, in accordance with previous RCTs^10,16; (d) studies comparing the use of ESTD and ESD in the treatment of large SENLs.

The exclusion criteria were as follows: (a) studies involving patients diagnosed with other diseases, such as gastric lesions, rectal lesions, or subepithelial tumors originating from the muscularis propria; (b) studies with single-arm designs or lacking an appropriate control group; (c) non-RCTs, including observational cohort studies, case–control studies, case reports, case-series, or reviews; (d) animal studies; (e) studies lacking sufficient data or identified as duplicate publications; and (f) studies published without full text.

Outcome measures

The primary outcome was dissection speed, a highly sensitive indicator, and a crucial evaluation metric for endoscopic procedures. Dissection speed is defined as the specimen area divided by the procedure time. Specimen area was calculated using the ellipse formula as follows: area (mm²) = (transverse diameter/2) × (longitudinal diameter/2) × π, while procedure time was defined as the time interval from the marking of the lesion to the complete removal of the specimen.¹⁰

The secondary outcomes primarily included en bloc resection, curative resection, major complications, as well as postoperative esophageal stricture (ES). Other secondary outcomes included delayed bleeding and perforation. En bloc resection was defined as the complete removal of the lesion in one piece without fragmentation.¹⁰ Curative resection referred to en bloc resection with lateral and vertical margins free of tumor cells without lymphovascular invasion, and tumor depth confined within the submucosa up to 200 μm.¹⁶ Delayed bleeding was defined by clinical symptoms (hematemesis, melena, or a decrease in hemoglobin of >2 g/dL since the patient’s latest laboratory test) occurring from the end of ESD to 28 days post-procedure.¹⁷ Perforation was diagnosed if a visible defect was noted during the procedure with extraluminal organs, fatty tissues, or space visualized through the lesion, or if symptoms of chest irritation appeared suddenly post-procedure, accompanied by free air on chest x-ray or CT.¹⁸ ES was defined as the inability to pass a standard 11-mm diameter endoscope through the stenosis after at least 1 month of endoscopic follow-up.¹⁹ Major complications were a composite outcome, which was defined as the occurrence of any of the three most common complications of ESD and ESTD, that is, bleeding, perforation, or stenosis.²⁰

Study selection

The literature search results were imported into the literature management software (Endnote X9), and the Bramer Method²¹ was used to remove duplicates. The team utilized shared EndNote files and synchronized all information from the included literature to ensure consistency within the team. Based on predefined criteria, two investigators (K.P. and Y.Z.) independently screened the titles and abstracts of relevant studies to identify potentially eligible articles. Subsequently, the full texts of the included articles were reviewed based on the inclusion and exclusion criteria. In case of any disagreements, consensus was reached through discussion involving a third reviewer (H.L.).

Two reviewers (H.L. and Y.Z.) independently extracted all relevant data from the included studies using a standardized data extraction sheet. Following data extraction, another reviewer (K.H.) reviewed the extracted data. Any discrepancies were resolved through re-extraction, analysis, and discussion.

Data collection

Two reviewers (H.L. and Y.W.) collected information and data from the included studies. The specific extracted information encompassed the following:

(1) General information: Year of publication and author’s name.

(2) Methods: Study design, study date, number of study centers and location, randomization methodology, allocation concealment, blinding, withdrawals, and follow-up.

(3) Participants: Inclusion and exclusion criteria, participant number, age, sex, as well as the location, size, and circumferential extent of esophageal lesions.

(4) Interventions: Description of the intervention, control groups, and any concomitantly used medications.

(5) Outcomes: primary and secondary outcomes as mentioned above.

Statistical analysis

Measures of treatment effect and heterogeneity

The meta-analysis was conducted using RevMan (Cochrane, version 5.4.1) for the statistical analysis. A random-effects model was employed to obtain pooled data, after which the DerSimonian and Laird method was used to estimate between-study variance. For dichotomous data, including outcomes such as en bloc resection, curative resection, delayed bleeding, perforation, stricture, and major complications, effect sizes were calculated as risk ratios (RRs) with 95% confidence intervals (CIs). For continuous outcomes, such as dissection speed, mean values, and standard deviations (SDs) of observed changes in each arm of the trial were extracted. Effect sizes were calculated using mean differences (MDs) with 95% CIs. In cases where data were reported as medians, minimum and maximum values, and/or first and third quartiles, a data transformation method was utilized to convert them into mean values and SDs, ensuring consistency among the pooled results.^22,23 Because a random-effects model was used as the pooling method, the approach proposed by Higgins et al.²⁴ was used to compute the prediction intervals. Forest plots were generated to visually represent the point estimates from each study in relation to the summary of the pooled estimates, whereby the width of point estimates in the Forest plots corresponded to the weight to assigned the corresponding study.

In case of missing values, we contacted the investigators or study sponsors to obtain the missing data if possible. Otherwise, we utilized established methods for imputation, including informative missing RRs for dichotomous outcomes and the difference of means for continuous outcomes.^25,26

The heterogeneity of studies was assessed using Cochran’s Q test based on inverse variance weights and by calculating the I² statistic. I² ⩾ 60% indicated moderate to substantial levels of heterogeneity. In cases where I² > 80% (indicating substantial heterogeneity), we refrained from conducting meta-analysis and instead presented the results using forest plots without pooled estimates.²⁷

Risk of bias and certainty of evidence

Two reviewers (K.H. and Y.Z.) independently assessed the risk of bias for each study using criteria outlined in the Cochrane Collaboration Risk of Bias tool.^27,28 Each potential source of bias was categorized as high, low, or having some concerns. Conflicts were resolved through consensus or by involving a third author (H.L.).

In addition, we applied the grading of recommendations assessment, development, and evaluation (GRADE) framework to assess the certainty of evidence for main outcomes, including primary outcomes and several important secondary outcomes such as dissection speed, en bloc resection, curative resection, and major complications.²⁹ GRADE Pro-version 3.6 software was used (http://gradepro.org/; McMaster University, Hamilton, ON, Canada).

Publication bias was assessed qualitatively based on the characteristics of the included studies rather than using funnel plots, as there were fewer than 10 included RCTs.

Trial sequential analysis

Trial sequential analysis (TSA) was used to control for the risk of random errors resulting from low sample sizes and repeated significance testing in meta-analyses. This approach allows researchers to adjust the thresholds for statistical significance and determine whether further trials are necessary.³⁰ The analysis was conducted using TSA software version 0.9 beta (Copenhagen Trial Unit, Centre for Clinical Intervention 213 Research, Copenhagen, Denmark).³¹ For discontinuous data, we set the effect measure to “RR” and the model to “Random-effects (DL)” in TSA software. The required sample size for the primary outcome was conservatively calculated based on the incidence in RCTs with a low risk of bias, with a power (1−β) of 80% and type I error α of 5%. Anticipated risk reduction was also set based on RCTs with a low risk of bias. The statistical significance of the meta-analysis was assessed by examining the position of the cumulative Z curve relative to the conventional boundary, trial sequential monitoring boundary (TSMB), and futility boundary. A stable and firm conclusion was reached if the cumulative Z curve crossed the TSMB or entered the futility area below the futility boundary.³²

Results

Search results and study characteristics

As depicted in Figure 1, our search across four databases yielded 217 records, from which 56 duplicate studies were excluded. Subsequently, 157 studies were further excluded as they did not meet the predefined selection criteria. Ultimately, four RCTs were included in this meta-analysis.^10,16,33,34

Figure 1.

PRISMA flow chart of the flow of information through the different phases of the systematic review and meta-analysis process.

All studies were published between 2018 and 2022, involving a total of 315 patients, 158 having received ESTD and 157 receiving ESD. All studies were conducted in China. The procedures for both ESTD and ESD were thoroughly described, with typical ESTD images provided in Supplemental Figure 1. No traction techniques were employed. The included studies met the definition of large lesions, characterized by a diameter of at least 20 mm or a circumferential involvement greater than 50%. The lesion sizes and circumferential extents were comparable between the ESTD and ESD groups. In addition, two studies reported the use of preventive steroid treatments during the procedures, applying the same preventive strategy for both ESTD and ESD groups. The detailed baseline characteristics of the included studies are summarized in Table 1.

Table 1.

Baseline characteristics of the included studies.

Author, year	Country	Study design	Patients (n)		Age (years),mean ± SD		Gender (n),M/F		Location of lesions (n)^a		Size of lesions (mm), mean ± SD		Circumferential extent		Pathological type of lesions	Procedure for stenosis prevention
Author, year	Country	Study design	ESTD	ESD	ESTD	ESD	ESTD	ESD	ESTD	ESD	ESTD	ESD	ESTD	ESD	Pathological type of lesions	Procedure for stenosis prevention
Fan et al. (2018)³³	China	RCT	25	24	58.93 ± 6.76	57.48 ± 4.92	13/12	13/11	12/9/4	8/10/6	⩾20 mm		⩾30%		ESCC	Oral corticosteroids
Zheng et al. (2019)³⁴	China	RCT	37	37	61.6 ± 10.2	63.7 ± 7.9	23/14	27/10	7/19/11	5/23/9	26.6 ± 5.6	25.7 ± 6.4	NR		HGIN, ESCC	NR
Ding et al. (2019)¹⁶	China	RCT	20	20	62.90 ± 9.596	64.85 ± 8.671	4/16	5/15	0/14/6	0/12/8	NR		⩾50%		HGIN, in situ carcinoma, ESCC	Endoscopic local corticosteroid injection followed by oral corticosteroids
Han et al. (2022)¹⁰	China	RCT	76	76	61.5 ± 8.6	63.2 ± 7.7	57/19	54/22	13/43/20	10/45/21	38.75 ± 3.12	39.75 ± 3.96	52/22/2^b	52/21/3^b	HGIN, ESCC	NR

Location of lesions: upper/middle/lower.

Circumferential extent: <50%/50%–100%/100%.

ESCC, esophageal squamous cell carcinoma; ESD, endoscopic submucosal dissection; ESTD, endoscopic submucosal tunnel dissection; HGIN, high-grade intraepithelial neoplasia; NR, not reported; RCT, randomized controlled trial; SD, standard deviation.

Risk of bias assessment and summary of main findings

The risk of bias in the eligible studies was assessed as shown in Figure 2. One RCT had a low risk of bias, whereas the other three presented some concerns in three to four items.

Figure 2.

The methodological quality of included studies according to the Cochrane Collaboration tool for assessing the risk of bias. (a) Risk of bias summary. (b) Risk of bias graph.

We evaluated the certainty of evidence for the main outcomes mentioned above using the GRADE methodology, as presented in Table 2.

Table 2.

Summary of main findings.

Outcomes	Anticipated absolute effects^a (95% CI)		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)
Outcomes	Risk with ESD	Risk with ESTD	Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)
Dissection speed	The mean dissection speed was 13.55 mm²/min	MD 5.06 mm²/min more (3.31 more to 6.8 more)	—	266 (3 RCTs)	⨁⨁◯◯^b Low
En bloc resection	975 per 1000	994 per 1000 (955–1000)	RR 1.02 (0.98–1.05)	315 (4 RCTs)	⨁⨁◯◯^b Low
Curative resection	818 per 1000	916 per 1000 (818–1000)	RR 1.12 (1.00–1.26)	275 (3 RCTs)	⨁⨁◯◯^b Low
Major complications	287 per 1000	143 per 1000 (89–232)	RR 0.50 (0.31–0.81)	315 (4 RCTs)	⨁⨁◯◯^b Low
Post-operation esophageal stricture	223 per 1000	134 per 1000 (82–221)	RR 0.60 (0.37–0.99)	315 (4 RCTs)	⨁⨁◯◯^b Low

Population: patients with large SENL. Intervention: ESTD. Comparison: ESD. GRADE Working Group grades of evidence—High certainty: we are very confident that the true effect lies close to that of the estimate of the effect; Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect; Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

Downgrade two levels for risk of bias and imprecision.

CI, confidence interval; ESCC, esophageal squamous cell carcinoma; ESD, endoscopic submucosal dissection; ESTD, endoscopic submucosal tunnel dissection; GRADE, grading of recommendations assessment, development and evaluation; MD, mean difference; NR, not reported; RCT, randomized controlled trial; RR, risk rate.

Effect of interventions on outcomes

Primary outcomes

Dissection speed

Three RCTs assessed the mean dissection speed during the lesion resection procedure. Meta-analysis revealed that ESTD was significantly faster than ESD (MD 5.06, 95% CI: 3.31–6.80; p < 0.01; I² = 0%; n = 266; RCTs = 3; low certainty of evidence; Figure 3(a)). TSA indicated that the required information sizes were reached, at 162. The cumulative Z curves for the primary outcome crossed both the conventional boundary and the TSMB, suggesting the robustness of this result (Figure 3(b)).

Figure 3.

Forest plots (a) and TSA (b) illustrate the primary outcome as dissection speed.

Important secondary outcomes

En bloc resection rate

All four RCTs reported the en bloc resection rate, revealing no significant difference between the ESTD and ESD groups (RR 1.02, 95% CI 0.98–1.05; p = 0.35; I²= 0%; n = 315; RCTs = 4; low certainty of evidence; Figure 4(a)).

Figure 4.

Forest plots illustrate important secondary outcomes. (a) En bloc resection rate. (b) Curative resection rate. (c) Rate of major complications. (d) Rate of post-operation esophageal stricture.

Curative resection rate

Three RCTs reported the curative resection rate, showing no significant difference between the ESTD and ESD groups (RR 1.12, 95% CI 1.00–1.26; p = 0.05; I²= 27%; n = 275; RCTs = 3; low certainty of evidence; Figure 4(b)).

Major complications

All four RCTs reported the rate of major complications, which was significantly lower in the ESTD than in the ESD group (RR 0.5, 95% CI: 0.31–0.81; p < 0.01; I²= 2%; n = 315; RCTs = 4; low certainty of evidence; Figure 4(c)).

Post-operation ES

All four RCTs reported the stricture rate, whereby ESTD had a lower rate of post-operation stricture than ESD (RR 0.6, 95% CI 0.37–0.99; p < 0.05; I²= 0%; n = 315; RCTs = 4; low certainty of evidence; Figure 4(d)).

Other secondary outcomes

There was no difference between the ESTD and ESD groups in the rates of delayed bleeding (RR 0.29, 95% CI 0.06–1.36, p > 0.05, n = 315, RCTs = 4) and perforation (RR 0.41, 95% CI 0.06–2.63, p > 0.05, n = 315, RCTs = 4; Supplemental Figure 2).

Discussion

ESD faces challenges in treating large SENLs, such as obstructed endoscopic views and the need for multilayer submucosal injections.³⁵ To address these challenges, ESTD was introduced by von Delius et al.³⁶ in 2007 and clinically applied by Linghu et al.⁹ in 2013. ESTD utilizes a dual knife to create a submucosal tunnel, enhancing the en bloc resection success rate while minimizing injury to the muscular layer, which is particularly beneficial for circumferential SENLs.³⁷ However, there is a lack of meta-analysis comparing the efficacy and safety of ESTD and ESD, leading to a lack of international guidelines on this topic. This systematic review and meta-analysis included all RCTs that compared the outcomes of ESTD versus ESD in treating large SENLs. We found low certainty of evidence that ESTD was superior to ESD for large SENLs, with significantly faster dissection speed and lower rate of complications, while maintaining similar en bloc and curative resection rates.

Rapid operation was one of the notable advantages of ESTD, as confirmed by our meta-analysis, in agreement with previous studies.¹² In large SENLs, traditional ESD procedures can be time-consuming due to rapid submucosal liquid diffusion and unclear operative views. By contrast, the establishment of a tunnel in ESTD prevents mucosal rolling, offering improved visibility and reducing the need for submucosal injections.

ESTD had a lower incidence of major complications the ESD, with a particularly notable reduced rate of post-operation ES. Previous studies reported ES as the most common complication of ESD,³⁸ particularly when lesions exceed half the esophageal circumference.³⁹ Our pooled results revealed a significantly lower ES rate with ESTD compared to ESD, leading to substantial improvements in the patient’s quality of life. Mechanistically, prolonged chronic inflammation is crucial for stricture formation. Prolonged inflammation can trigger the transformation of fibroblasts into myofibroblasts, resulting in excessive extracellular matrix deposition and disorganized cell accumulation.⁴⁰ Several studies suggested that ESTD may facilitate faster mucosal healing, potentially decreasing the duration of inflammation and lowering stricture incidence.^10,33 Muscular layer injury is another factor contributing to ES formation. Animal models indicate that muscle injury prompts the de-differentiation of myocytes into fibroblasts, promoting stricture formation.⁴¹ Consistently, large-scale clinical research identified muscular layer injury as an independent risk factor for post-ESD ES.⁴² Zheng et al.³⁴ found that ESTD induces less muscular layer damage and fewer electrocoagulation injuries at the wound base, implying that it may be less traumatic and reduces stricture occurrence. Although further robust evidence is needed, our review suggests that ESTD may be more effective than ESD in preventing ES.

Compared to previous meta-analyses,^11,12,14,37 our study presented several new key points. First, it is the first systemic review and meta-analysis based on RCTs, significantly enhancing the level of evidence and reducing heterogeneity in our analysis. Second, our meta-analysis focused specifically on the large-lesion subgroup of SENLs rather than SENLs as a whole, as this subgroup poses greater challenges for traditional ESD in clinical practice. Lastly, considering the limited number of eligible RCTs, we employed TSA to further evaluate the validity and reliability of our primary outcome, thereby enhancing the clinical guidance. In addition, the GRADE framework was also used to assess the certainty of evidence.

In spite of the encouraging findings, this study also has important limitations that should be considered. First, the number of included studies was small, and the sample sizes of included studies were limited, which reduced the reliability of the meta-analysis. However, we used TSA to demonstrate that the sample size was sufficient to support the findings of this meta-analysis, and we also used the GRADE approach to assess the credibility of the results. Second, all included studies were from China, which presents some concerns about the risk of bias, limiting the generalizability of these results in clinical practice. However, ESTD is a relatively new technique that was developed in China, and thus it is not surprising that the current RCTs are all from this region. We hope that our meta-analysis will serve as a catalyst for global interest in ESTD, encouraging more international studies and wider adoption of the technique in clinical practice. Third, some studies had missing data regarding lesion size, circumferential extent, use of prophylactic steroids, or the details of pathological assessment, which may reduce the accuracy of the findings and limit our ability to conduct subgroup analyses. We look forward to more high-quality RCTs with comprehensive and detailed reporting.

Conclusion

According to our meta-analysis, ESTD had superior efficacy and safety compared to ESD for resecting large SENLs, offering faster resection speed and fewer complications while maintaining similar rates of en bloc and curative resection. Further RCTs with a large sample size and low risk of bias are required to comprehensively compare the clinical applications of these two techniques.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251324227 – Supplemental material for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis

Supplemental material, sj-docx-1-tag-10.1177_17562848251324227 for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis by Huimin Liu, Yueyi Zhang, Yabing Wang, Ke Pang, Wenfeng Xi, Long Zou, Kun He, Qiang Wang and Liuye Huang in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-docx-2-tag-10.1177_17562848251324227 – Supplemental material for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis

Supplemental material, sj-docx-2-tag-10.1177_17562848251324227 for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis by Huimin Liu, Yueyi Zhang, Yabing Wang, Ke Pang, Wenfeng Xi, Long Zou, Kun He, Qiang Wang and Liuye Huang in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-docx-3-tag-10.1177_17562848251324227 – Supplemental material for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis

Supplemental material, sj-docx-3-tag-10.1177_17562848251324227 for Is endoscopic submucosal tunnel dissection better than endoscopic submucosal dissection in treating large superficial esophageal neoplastic lesions? A systematic review and meta-analysis by Huimin Liu, Yueyi Zhang, Yabing Wang, Ke Pang, Wenfeng Xi, Long Zou, Kun He, Qiang Wang and Liuye Huang in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

The authors would like to thank Dr Tao Wang for invaluable advice in the preparation of this manuscript.

Declarations

ORCID iD

Yueyi Zhang

Supplemental material

Supplemental material for this article is available online.

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