Comparison of endoscopic submucosal dissection and surgery for early signet-ring cell carcinoma of the stomach: a multicenter study

Introduction

Gastric cancer is the fifth leading cause of cancer-related death worldwide (1). Among its histological subtypes, signet-ring cell carcinoma (SRCC) is traditionally considered an aggressive entity with poor prognosis, accounting for 3.4% to 18% of gastric malignancies in Asia (1,2). However, this perception is largely based on data from advanced-stage disease. Accumulating evidence demonstrates that early gastric SRCC—confined to the mucosa or submucosa—exhibits markedly different biological behavior, with substantially lower rates of lymph node metastasis (LNM) and favorable long-term outcomes compared to its advanced counterpart (3,4).

Previous studies have suggested that early gastric SRCC has a relatively low risk of LNM and a favorable prognosis, indicating that less-invasive endoscopic therapies might be suitable (5,6). Despite this growing evidence, endoscopic submucosal dissection (ESD) has not been universally accepted as the standard of care, primarily due to the scarcity of high-quality comparative studies evaluating ESD against surgical resection. More importantly, previous literature often evaluated SRCC as a single entity without distinguishing between pure SRCC and mixed SRCC. Recent evidence highlights that mixed SRCC exhibits significantly greater malignant potential, deeper infiltration, and a higher risk of LNM and lymphovascular invasion (LVI) compared to pure SRCC (7,8). Evaluating these distinct subtypes together may severely confound clinical outcomes and therapeutic decision-making.

Previous comparative studies evaluating ESD versus surgery for early SRCC have typically not distinguished between pure and mixed histology (3,4). Because mixed SRCC exhibits greater malignant potential, deeper infiltration, and higher LNM rates than pure SRCC (4-8), pooling these subtypes may obscure the true therapeutic window for endoscopic treatment in lower-risk pure SRCC. The critical gap, therefore, is not a direct comparison of pure versus mixed SRCC, but rather a rigorous evaluation of ESD versus surgery within a homogeneous pure SRCC cohort to determine whether this specific subtype—when strictly selected—can be managed endoscopically without compromising oncological safety. The aim of this multicenter retrospective study is to evaluate the perioperative safety and short-term oncological outcomes of ESD versus radical gastrectomy in a strictly defined cohort of patients with early pure gastric SRCC, and to generate hypotheses that may inform future randomized trials and refine patient selection criteria. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0278/rc).

Methods

Patients

The clinical data of patients with early SRCC who underwent endoscopy or surgery at Beijing Chaoyang Hospital, Beijing Tiantan Hospital and Feicheng People’s Hospital from April 2018 to April 2024 were collected and retrospectively analyzed. The enrolled patients were consecutive patients. Tumor staging was performed according to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification. Early gastric cancer was defined as clinical T1 (cT1) with no evidence of nodal or distant metastasis (cN0, cM0). All patients underwent preoperative staging with contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis. Endoscopic ultrasound (EUS) was performed in 89 patients (71.8%)—including all 44 ESD patients and 45 surgical patients—to assess the depth of invasion and regional lymph node status. Magnifying endoscopy with narrow-band imaging (M-NBI) was performed in all ESD candidates to assess mucosal and microvascular patterns. Patients with clinical evidence of distant metastasis (M1) or bulky regional lymphadenopathy on CT or EUS were excluded.

The inclusion criteria were as follows: (I) patients who had received conventional surgical treatment or ESD; (II) patients for whom pure SRCC was pathologically confirmed after surgery and whose tumors were confined to the mucosal and submucosal layers; and (III) patients whose postoperative follow-up period was more than 12 months. A minimum follow-up of 12 months was required to ensure adequate time for the first two complete surveillance cycles (postoperative endoscopy and contrast-enhanced CT). Patients with shorter follow-up were those lost to follow-up or transferred to other hospitals, not because of early recurrence. Importantly, no patient in the screened cohort experienced recurrence or disease-related death within 12 months of the index procedure; therefore, the follow-up threshold did not result in exclusion of early events. The exclusion criteria were as follows: (I) previous history of gastric tumor or gastric surgery; (II) postoperative pathology involving components of other poorly differentiated adenocarcinomas or other types of tumors; (III) postoperative pathology suggesting that the tumor infiltrated the intrinsic muscular layer of the stomach wall or deeper; and (IV) missing clinical and pathological data. The choice between ESD and surgical gastrectomy was based on the Japanese Gastric Cancer Association (JGCA) treatment guidelines, endoscopic assessment of lesion characteristics (size, depth, macroscopic type), presence of ulceration, and patient preference after multidisciplinary discussion. Patients meeting the absolute or expanded indications for ESD underwent endoscopic resection, whereas those with deep submucosal invasion (≥ sm2), suspected LNM, or lesions not meeting ESD criteria underwent surgical gastrectomy with lymph node dissection. Informed consent was obtained from all individual participants included in the study. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The protocol was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (No. KY2022-059-02) on May 26, 2022. Beijing Chaoyang Hospital and Feicheng People’s Hospital were informed and agreed with this study.

Treatment process

ESD was performed by experienced endoscopists using standard electrosurgical knives and submucosal injection solutions. The surgical resection method (proximal gastrectomy, distal gastrectomy, or total gastrectomy) was determined on the basis of the anatomical location of the gastric tumor. D1+β or D2 lymph node dissection was performed according to the gastric cancer diagnosis and treatment guidelines of the JGCA (9). D1+β lymph node dissection included dissection of some lymph nodes at the second station in addition to standard D1 dissection (of lymph nodes at the first station around the stomach). D2 lymph node dissection involved systematic dissection of the first and second station lymph nodes.

Pathological assessment

Specimens after ESD

Resected specimens were stretched, pinned flat on a corkboard, and fixed in 10% neutral buffered formalin. The fixed specimens were serially sectioned at 2-mm intervals perpendicular to the closest margin. Pathological assessment was performed in accordance with the JGCA classification. The evaluation focused on the horizontal and vertical margins, predominant histologic type, depth of tumor invasion, and the presence of LVI and perineural invasion (PNI). Pure SRCC was defined according to the World Health Organization (WHO) Classification of Digestive System Tumours as a tumour in which ≥95% of the neoplastic cells exhibit classic signet-ring morphology (intracytoplasmic mucin with eccentrically displaced nucleus). Cases with any component of non-signet-ring adenocarcinoma (e.g., tubular, papillary, or poorly cohesive non-signet-ring cells) exceeding 5% were classified as mixed SRCC and were excluded from the analysis. This 95% threshold was predefined and applied uniformly by two independent gastrointestinal pathologists.

Postoperative specimens

Fresh samples were dissected and flattened by specialist pathologists along specific anatomical positions and fixed with neutral buffered formaldehyde for 24–48 hours to ensure stable tissue morphology. Subsequently, continuous cuts were made at intervals of 4 mm perpendicular to the long axis of the tumor, and the position of each margin was marked to prepare standardized histological sections. Systematic pathological assessment covered core parameters such as tumor differentiation grade (G grade), depth of gastric wall invasion (T stage), surgical margin status (R0/R1), and the number of regional lymph node metastases (N stage). A central pathology review was conducted for all included SRCC cases. Two dedicated gastrointestinal pathologists, who were not involved in the original clinical diagnosis, independently re-evaluated all haematoxylin-and-eosin-stained slides and, where available, immunohistochemistry for pancytokeratin and E-cadherin. Discrepancies were resolved by consensus.

Observation indicators and follow-up

Baseline demographic data, including sex, age, body mass index (BMI), comorbidities, and tumor marker levels, were collected. BMI was calculated as weight in kilograms divided by the square of height in meters (kg/m²). Smoking was defined as current or former smoking of ≥10 pack-years. Alcohol consumption was defined as current or former intake of ≥20 g ethanol per day for ≥5 years. Endoscopic characteristics (tumor location, macroscopic type based on the Paris classification, and the presence of ulceration) and preoperative CT findings were documented. Postoperative pathological parameters were systematically recorded, specifically noting the maximum tumor diameter, the precise depth of invasion—subdivided into epithelium (m1), lamina propria (m2), muscularis mucosae (m3), superficial submucosa (sm1, <500 µm), and deep submucosa (sm2, ≥500 µm)—and the presence of LNM (9). LNM was defined as follows: in the ESD group, LNM was defined as radiologically or pathologically confirmed LNM during postoperative follow up; in the surgical group, LNM was defined as either pathologically detected LNM in the resected surgical specimen or LNM identified during postoperative follow up.

Curability for patients in the ESD group was stratified into eCura systems (eCura A, B, C) based on JGCA expanded criteria for early SRCC (undifferentiated intramucosal carcinoma, size ≤2 cm, without ulceration) (9). For patients with non-curative resection (eCura C-2), additional treatments, including radical surgery or adjuvant chemotherapy, were recorded. Follow-up consisted of esophagogastroduodenoscopy (EGD) at 3 months post-ESD and at 6 months post-surgery, followed by EGD and contrast-enhanced thoracoabdominal CT every 6 months for the first 3 years, and annually thereafter. Local recurrence was defined as the histological confirmation of identical tumor tissue at or within 1 cm of the primary resection site. Synchronous and metachronous multiple primary gastric cancers were defined as new lesions appearing within 12 months and beyond 12 months postoperatively, respectively (10).

Statistical analysis

Statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). Continuous variables following a normal distribution were presented as means ± standard deviations and compared using the independent Student’s t-test, whereas non-normally distributed data were expressed as medians (interquartile ranges) and compared using the Mann-Whitney U test. Categorical variables were presented as frequencies (percentages) and compared using the Chi-squared test or Fisher’s exact test, as appropriate. We employed propensity score matching (PSM) to create balanced cohorts. Sensitivity analyses included inverse probability of treatment weighting (IPTW) with stabilized weights, truncated at the 1st and 99th percentiles, to estimate treatment effects in the full cohort. Variables with a P value <0.10 in the univariate analysis were incorporated into a multivariate logistic regression model to identify independent risk factors for LNM, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). Given the limited number of events, only two clinically and statistically significant predictors were entered into the multivariate model to minimize overfitting. Goodness-of-fit was assessed using the Hosmer-Lemeshow test. A two-sided P value <0.05 was considered statistically significant.

Results

Baseline information

A total of 124 patients with early SRCC were enrolled from three centers, with a male–female ratio of 1:1.067, an average age of 52.27 years (30–73 years) and a median follow-up time of 51.56 months (12.23–91.83 months). The patients were divided into the ESD group (44 patients) and the surgical group (80 patients) according to the surgical method (Figure 1). There were no statistically significant differences in sex, age, height, weight, BMI, combined underlying diseases, family history of tumors, history of alcohol consumption, or tumor markers between the two groups (Table 1).

Figure 1 CONSORT flowchart of patient selection and propensity score matching. ESD, endoscopic submucosal dissection.

Preoperative endoscopic features

As shown in Table 2, regarding tumor location, lesions in the ESD group were more frequently located in the middle third of the stomach (38.6% vs. 16.3%), whereas those in the surgery group were predominantly found in the lower third (50.0% vs. 80.0%; P=0.002). Endoscopic ulceration was significantly less common in the ESD group compared to the surgery group (2.27% vs. 30.0%; P<0.001). Furthermore, the macroscopic appearance based on the Paris classification differed significantly between the two cohorts (P=0.02), with a higher prevalence of flat lesions (0-IIb) in the ESD group and depressed lesions (0-IIc) in the surgery group. No clinical evidence of LNM was detected preoperatively in either group.

Procedural outcomes and complication

All patients successfully underwent their respective procedures (Table 3). The ESD group demonstrated significantly shorter operative times (58.11±21.91 vs. 144.51±54.71 min, P<0.001) and reduced lengths of hospital stay (6.08±1.06 vs. 14.07± 5.14 days, P<0.001) compared to the surgery group. The overall complication rate was significantly lower in the ESD group [2.27% (1/44), delayed bleeding managed endoscopically] than in the surgery group [15.0% (12/80), including intestinal obstruction, gastroparesis, biliary fistula, and anastomotic stricture] (P=0.03).

Postoperative pathological and follow-up outcomes

As shown in Table 3, there was no significant difference in the average diameter determined by postoperative pathology between the two groups of lesions (P=0.06). In the ESD group, both the horizontal and basal margins were negative, and the overall resection rate and complete resection rate were 100%. Both margins in the surgical group were negative. There was a significant difference in the depth of invasion between the two groups (P=0.02). The ESD group had a greater proportion of tumors confined to the laminal mucosa (45.45%), whereas the surgical group had a greater proportion of tumors infiltrating the muscularis mucosa (35%). No cases (0%) of LNM were observed in the ESD group, whereas 8 cases of LNM were detected in the surgical group; the difference in incidence was significant (proportions z-test, P=0.03). Four (9.09%) patients with submucosal infiltration in the ESD group underwent additional surgical operations, and no residual lesion or LNM was detected via postoperative pathology. Twelve patients (15%) in the surgical group received additional postoperative chemotherapy (capecitabine plus oxaliplatin). There was no significant difference in the follow-up time between the two groups. During the follow-up period, no recurrence or metastasis was detected in the ESD patients, whereas LNM occurred in 1 patient (1.25%) in the surgical group. Therefore, the LNM in the surgical group was 9 cases (11.25%). There were no disease-related deaths in either group.

Characteristics and outcomes before and after PSM

Before matching, significant differences were observed between the ESD and surgery groups in several baseline characteristics (Table S1). The surgery group had a higher proportion of ulceration (30.0% vs. 2.3%), deeper invasion (37.5% vs. 11.4% submucosal), and larger lesion size (2.1±1.4 vs. 1.6±1.2 cm). After PSM, all covariates achieved adequate balance with standardized mean difference (SMD) below 0.35. The most substantial improvements in balance were observed for sex (SMD 0.378→0.068), tumor location (SMD 0.614→0.039), and depth of invasion (SMD 0.590→0.157), indicating successful mitigation of selection bias.

Regarding endoscopic features, Paris classification and tumor location were comparable between groups after PSM (P=0.60 and P=0.24, respectively), suggesting that the matched cohorts had similar macroscopic appearances and anatomical distributions. This balance is clinically important because Paris classification and tumor location are known predictors of LNM risk in early gastric cancer.

After PSM, perioperative advantages of ESD remained significant. Operative time (60.7±23.4 vs. 151.1±53.3 min, P<0.001) and hospital stay (6.1±1.2 vs. 14.0±6.1 days, P<0.001) were significantly shorter in the ESD group. For the primary endpoint of LNM, the rate was 0% (0/29) in the ESD group and 3.4% (1/29) in the surgery group (P=0.31), indicating comparable oncological outcomes between matched groups. No significant difference was observed in follow-up duration (48.0±23.1 vs. 47.6±23.3 months, P=0.94).

IPTW sensitivity analysis

As a sensitivity analysis, IPTW with stabilized weights (truncated at the 1st and 99th percentiles) was applied to the full cohort. The weighted LNM rate was 0.0% in the ESD group versus 7.8% in the surgery group. A weighted two-proportion z-test showed a significant difference (z=2.351, P=0.02). Weighted logistic regression encountered quasi-separation because the ESD group had zero LNM events, rendering odds ratios uninterpretable; therefore, the weighted proportion comparison is reported instead. These results are detailed in Table S2.

Subgroup analysis based on expanded ESD indications

Subgroup analysis based on expanded ESD indications was performed to evaluate whether the oncological safety of ESD versus surgery differed among patients who met the JGCA expanded criteria (undifferentiated intramucosal carcinoma, ≤2 cm, no ulceration) versus those who did not. As shown in Table 4, 31 patients (70.45%) in the ESD group met the expanded criteria for ESD (undifferentiated intramucosal carcinoma with lesion diameter ≤2 cm and no ulcer formation) and were classified as eCuraA under endoscopic curability. Other lesions with ulcers, lesions larger than 2 cm, or infiltration into the submucosa were classified as eCuraC-2. Thirty patients (37.5%) in the surgical group met the expanded criteria for ESD, which significantly differed from the proportion of patients meeting these criteria in the ESD group (P<0.001). When the data of patients who met the expanded criteria for ESD were analyzed, none of the 31 patients in the ESD group had LNM, and 1 of the 30 patients in the surgical group had LNM. There was no statistically significant difference in terms of postoperative LNM between the two groups (0% vs. 3.3%, P>0.99).

Risk factors for LNM

Multivariate logistic regression analysis was conducted to identify risk factors for LNM. After screening variables with P<0.10 in the univariate analysis, the multivariate model demonstrated that submucosal invasion (OR =4.80, 95% CI: 1.05–21.90, P=0.043) and the presence of ulceration (OR =5.20, 95% CI: 1.10–24.60, P=0.04) were independent risk factors for LNM. The treatment modality itself was not an independent risk factor (P=0.60). The model exhibited good calibration (Hosmer-Lemeshow test, P=0.68) (Table 5) We calculated the variance inflation factor (VIF) for the two retained predictors. The VIF values were 1.38 for submucosal invasion and 1.42 for ulceration, indicating negligible collinearity (VIF <2). A sensitivity analysis reclassifying the 4 ESD patients who underwent subsequent surgery to the surgery group yielded directionally consistent results, with the between-group difference becoming more pronounced (P=0.009).

Kaplan-Meier curves

Despite the limited number of events, we agree that visualizing follow-up completeness is valuable. We have generated Kaplan-Meier curves for (I) recurrence-free survival and (II) overall survival for the entire cohort and for the expanded-criteria subgroup (Figure 2). As expected, the curves are largely superimposed with wide confidence intervals due to the paucity of events, but they demonstrate that follow-up duration was comparable between groups and that censoring patterns were similar.

Figure 2 Kaplan-Meier survival curves for overall survival (A) and recurrence-free survival (B) after ESD and surgical resection. ESD, endoscopic submucosal dissection.

Discussion

ESD is widely recognized as the standard minimally invasive treatment for early-stage differentiated gastric cancer (9,11-13). However, the application of ESD in early SRCC remains controversial due to the historical perception of SRCC as an aggressive histological subtype prone to early metastasis (14-16). Recent advances have challenged this paradigm, demonstrating that early pure SRCC exhibits distinct biological behaviors with exceptionally low rates of LNM compared to mixed undifferentiated carcinomas (4-8). While previous literature largely evaluated SRCC as a single, homogenous entity, recent robust evidence has established that mixed SRCC—containing additional poorly differentiated components—has significantly higher malignant potential, deeper infiltration, and an increased risk of LNM compared to pure SRCC. Consequently, evaluating therapeutic outcomes without distinguishing these subtypes confounds clinical guidelines (17,18). By strictly limiting our cohort to patients with histologically confirmed early pure SRCC, our multicenter study minimizes this critical confounder, aiming to establish whether ESD can provide comparable oncological safety to radical gastrectomy in this specific, low-risk population.

Our findings confirmed that ESD demonstrated significantly more favorable perioperative parameters regarding perioperative outcomes, demonstrating shorter operative times, faster recovery, and lower postoperative complication rates, similar to previous research results (19,20). A major concern in observational studies comparing ESD with surgical resection is the inherent selection bias, as surgical candidates often present with more adverse pathological features, such as deeper invasion or ulceration. In our initial analysis, these imbalances could potentially confound the assessment of oncological safety. To overcome this limitation, we employed both PSM and IPTW methods to adjust for these baseline discrepancies. Both analyses consistently demonstrated that, after controlling for confounding variables, there were no statistically significant differences in critical oncological outcomes between the ESD and surgery groups. These robust statistical adjustments suggest that the observed equivalence in outcomes is not merely a result of risk stratification but reflects the genuine comparative effectiveness of the treatments in this specific cohort. Therefore, our findings provide stronger evidence supporting the oncological safety of ESD for carefully selected patients. The data analysis of this study revealed a significant difference between the two groups of lesions in terms of whether they were associated with ulcers, mainly because the expanded indication for ESD treatment was undifferentiated intramucosal carcinoma with a lesion diameter of less than 2 cm and no ulcer formation, and early SRCC lesions with ulcers did not meet the expanded indication for ESD. With a curable grade of eCuraC-2 and a higher risk of LNM, the guidelines recommend additional surgical resection combined with lymph node dissection. In addition, this study revealed a significant difference in the Paris classification between the two groups of lesions. Previous studies have shown that early gastric cancer of the superficial depression type or depression type is often accompanied by the possibility of submucosal invasion (21). Therefore, early SRCCs of the superficial depression type or depression type need to be fully evaluated before surgery, and treatment methods should be carefully selected. In addition, an analysis of the data of patients who met the expanded ESD indications in both groups revealed that there was no statistically significant difference in postoperative LNM among patients who met the expanded ESD indications. In the expanded-criteria subgroup, no significant difference in LNM was observed between treatment modalities. However, given the small sample size, low event rates, and retrospective design, these data are insufficient to claim therapeutic equivalence. They should be interpreted as hypothesis-generating and require validation in prospective studies.

In this study, 9 patients in the surgical group had pathological LNM, and no patients in the ESD group had postoperative LNM. There was a statistically significant difference in the incidence of LNM between the two groups. Multivariate logistic regression analysis was conducted to identify risk factors for postoperative pathological LNM. The results suggested that submucosal infiltration (OR =4.80, P=0.043) and the presence of ulcers (OR =5.20, P=0.04) were independent risk factors for LNM. This finding is similar to previous research results (8). Therefore, rigorous preoperative screening of patients with intramucosal carcinoma and no ulcers for ESD treatment can effectively reduce the risk of LNM. For patients with ulcers or submucosal infiltration, surgical intervention combined with lymph node dissection remains a necessary option. In preoperative assessments, EUS should also be performed to precisely evaluate the depth of infiltration and ulcer status in order to optimize treatment decision making.

No disease-related deaths occurred in either group. There were no cases of recurrence or metastasis in the ESD group during the follow-up period, and 1 patient in the surgical group had postoperative LNM. The postoperative pathology of patients in the ESD group revealed 100% whole-block resection and complete resection, with no recurrence or metastasis. The follow-up results of the ESD group in this study were better than those in previous studies (8,22), mainly because the majority of patients in the ESD group met the expanded indications, the postoperative curative grade was eCuraA, and radical surgery was added in patients with eCuraC-2 grade. Therefore, great caution should be exercised in determining the indications for SRCC for ESD treatment before surgery Given the small overall sample size and particularly the limited ESD cohort, this study lacks adequate power to detect clinically meaningful differences in rare oncological endpoints or to claim formal equivalence. Therefore, the absence of statistically significant differences should not be misinterpreted as evidence of therapeutic parity.

This study has several limitations that warrant acknowledgment. First, the retrospective, non-randomized design introduces inherent selection bias; notably, patients in the surgery group harbored more high-risk features, such as deep submucosal infiltration and larger tumor sizes, and therefore the findings should not be interpreted as evidence of causal equivalence, but rather as generating hypotheses for future randomised trials. While the median follow-up of 51.6 months is sufficient for evaluating mid-term outcomes, the long-term recurrence patterns of ESD-treated pure SRCC require further validation through large-scale, prospective, randomized controlled trials. Finally, the single-country, Asian-only composition of our cohort limits external validity. Our findings require independent validation in Western populations before informing clinical practice outside East Asia. A major limitation of this study is its exclusive derivation from Asian centers. Screening practices, Helicobacter pylori prevalence, tumor biology, particularly SRCC and treatment thresholds differ substantially between Asian and Western populations. Contemporary Western data suggest that early gastric SRCC may exhibit more aggressive biological behavior and a higher propensity for nodal involvement than traditionally assumed from Asian cohorts (23,24). Consequently, our findings suggesting that ESD may be a viable option in highly selected patients should be extrapolated to Western settings with extreme caution and only after validation in local prospective cohorts.

Conclusions

For carefully selected patients with early gastric pure SRCC who strictly meet the expanded indications (intramucosal carcinoma, diameter ≤2 cm, without ulceration), ESD may be a feasible minimally invasive option with favorable perioperative outcomes. In this retrospective, hypothesis-generating analysis with limited sample size and low event rates, ESD was not associated with inferior short-term oncological outcomes compared to surgery. However, these findings should be interpreted with caution and do not establish therapeutic equivalence. For lesions with submucosal invasion or ulceration, or for patients not meeting expanded criteria, gastrectomy with lymph node dissection remains the recommended standard of care. Prospective randomized trials are needed to definitively compare long-term oncological outcomes between ESD and surgery in this population.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0278/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0278/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0278/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0278/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Informed consent was obtained from all individual participants included in the study. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The protocol was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (No. KY2022-059-02) on May 26, 2022. Beijing Chaoyang Hospital and Feicheng People’s Hospital were informed and agreed with this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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