Clinical Characteristics and Influencing Factors of Postoperative Pain in Patients Undergoing Gastric Endoscopic Submucosal Dissection

ABSTRACT

Background

To comprehensively analyze the clinical characteristics of patients who underwent gastric endoscopic submucosal dissection (ESD) and explore the incidence and influencing factors of postoperative pain.

Methods

The clinical data of patients who underwent gastric ESD at our center from 2009 to 2024 were retrospectively analyzed. Pain severity was assessed using a visual analogue scale, with a score ≥ 4 defined as postoperative pain. Based on the presence or absence of postoperative pain, patients were divided into a pain group and a control group. Independent factors influencing postoperative pain were identified using multivariate logistic regression analysis. To control for confounding bias, patients in the case and control groups were matched by sex and lesion size, and the matched participants were further analyzed using a conditional logistic regression model.

Results

In total, 993 patients were analyzed. The incidence of postoperative pain was 9.1% (95% confidence interval [CI], 7.3–11.1). In the univariate analysis, sex, operation duration, anesthesia method, intraoperative electrocoagulation, nasogastric tube placement, and postoperative vomiting were significantly associated with postoperative pain. Multivariate analysis identified eight independent factors: male sex (odds ratio [OR], 0.61; 95% CI, 0.37–0.97; p = 0.04), operation duration (OR, 1.29; 95% CI, 1.03–1.63; p = 0.02), protuberant lesions (OR, 0.43; 95% CI, 0.26–0.71; p < 0.01), antral lesions (OR, 1.84; 95% CI, 1.10–3.05; p = 0.01), intubation general anesthesia (OR, 0.40; 95% CI, 0.22–0.72; p = 0.002), intraoperative electrocoagulation (OR, 0.32; 95% CI, 0.19–0.55; p < 0.01), nasogastric tube placement (OR, 2.005; 95% CI, 1.12–3.57; p = 0.01), and postoperative vomiting (OR, 3.24; 95% CI, 1.40–7.47; p = 0.005). Conditional logistic regression analysis further identified diabetes mellitus (OR, 2.50; 95% CI, 1.03–6.06; p = 0.04).

Conclusion

Female sex, diabetes mellitus, concave‐type lesions, lesions in the gastric antrum, non‐intubation general anesthesia, absence of intraoperative electrocoagulation, prolonged operation duration, nasogastric tube placement, and postoperative vomiting were independent factors associated with moderate to severe pain after gastric ESD. For patients at increased risk of postoperative pain, appropriate prophylactic and therapeutic measures during the perioperative period may effectively alleviate pain following gastric ESD.

Endoscopic submucosal dissection (ESD) causes post‐procedural pain. Independent influencing factors for pain after gastric ESD: Female gender, diabetes mellitus concavitive lesions lesions on the gastric antrum non‐intubation general anesthesia without intraoperative electrocoagulation, prolonged operation, nasogastric tube, and postoperative vomiting.

Abbreviations

BMI

body mass index

CA125

carbohydrate antigen 125

CA199

carbohydrate antigen 199

CEA

carcinoembryonic antigen

CI

confidence interval

ESD

endoscopic submucosal dissection

OR

odds ratio

PLA

people's liberation army

p‐value

probability value

R0

resection with no residual tumor

STROBE

strengthening the reporting of observational studies in epidemiology

Vs

versus

1. Introduction

Endoscopic submucosal dissection (ESD) is a minimally invasive procedure recommended by clinical practice guidelines and expert consensus for the treatment of early gastric cancer, esophageal cancer, and their precursors, as well as flat, depressed, and laterally spreading colorectal lesions [1]. Compared with traditional endoscopic mucosal resection, ESD offers higher overall, R0, and curative resection rates, along with a lower local recurrence rate [2]. However, ESD is also more technically challenging and time‐consuming, and it requires greater proficiency from the endoscopist. It carries relatively higher rates of adverse events, including bleeding, perforation, and stenosis [3]. In addition to these complications, post‐procedural pain is a common adverse event following ESD [4]. Pain not only significantly affects patients' quality of life but also leads to unnecessary examinations, prolonged hospital stays, and increased medical costs [5, 6, 7, 8]. Identifying high‐risk groups for post‐ESD pain through risk factor analysis and implementing timely pain prevention and management strategies holds substantial clinical value. Previous studies have identified factors influencing post‐ESD pain, including sex, age, residence, alcohol consumption, lesion size, lesion location, proton pump inhibitor use, and procedure duration. However, there is a paucity of studies on this topic in China [9, 10, 11], with most focusing on esophageal lesions and limited by small sample sizes and incomplete clinical data [12, 13].

This study comprehensively characterizes the clinical profiles of patients undergoing gastric ESD, with the dual aims of identifying risk factors associated with postoperative pain and providing evidence‐based insights to improve perioperative management strategies for this patient population.

2. Materials and Methods

2.1. Study Design

This retrospective case‐control study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Norms for Reporting Observational Studies [14]. The study follows the ethical principles outlined in the Declaration of Helsinki (2013) [15] and was reviewed and approved by the Ethics Committee of the First Medical Center of the PLA General Hospital (No. S2024‐358‐01). The requirement for informed consent was waived because of the retrospective design and the use of anonymized data.

2.2. Study Subjects

The study included adult patients who underwent gastric ESD at the Endoscopy Center of the Digestive Medicine Department, First Medical Center, PLA General Hospital, between April 2009 and April 2024. The inclusion criteria were an age of 18 years or older and meeting established indications for gastric ESD. Patients were excluded if they met any of the following conditions: concurrent peptic ulcer; regular use of pain medications; history of upper gastrointestinal surgery; presence of multiple lesions; postoperative complications such as delayed bleeding or perforation; postoperative infection; unsuccessful ESD; severe cardiovascular, renal, hepatic, neurological, or psychological disorders; pregnancy or lactation; significant missing data; or duplicate case entries.

2.3. Surgical Procedure and Perioperative Management

ESD procedures were performed according to standard operational protocols. The main steps included circumferential marking, submucosal injection, circumferential incision, submucosal dissection, and wound management. Perioperative management followed current clinical guidelines and expert consensus. Key management measures involved obtaining informed consent, completing all relevant preoperative examinations and carefully evaluating the indications for ESD, enforcing a fasting period of at least 6 h and water restriction for 2 h before the procedure, administering either intravenous general anesthesia or general anesthesia with endotracheal intubation, and providing proton pump inhibitors intravenously for the first 3 days followed by oral administration for 4 to 8 weeks. Indications for ESD were noninvasive tumors (e.g., intraepithelial low‐grade dysplasia/neoplasia, intraepithelial high‐grade dysplasia/neoplasia, carcinoma in situ, or suspected invasive carcinoma) and lesions smaller than 2 cm in diameter without ulceration in cases of differentiated mucosal carcinoma.

2.4. Postprocedure Pain Assessment and Patient Grouping

Pain intensity was assessed using a visual analogue scale [16], which evaluates pain experienced either currently or within the past 24 h. The scale consists of a 0‐ to 10‐cm line divided into 10 equal parts, where “0” indicates no pain and “10” represents the worst possible pain. A pain nurse records the score by marking the position indicated by the patient. Higher scores reflect greater pain intensity and are categorized as mild (1–3), moderate (4–6), and severe (7–10). A score of ≥ 4 is defined as moderate to severe pain. Pain assessments were conducted from 1 h postoperatively until discharge. Based on the presence or absence of moderate to severe pain following ESD, patients were classified into either the pain group or the control group.

2.5. Data Collection

Clinical data were collected using the electronic medical record system and included demographic characteristics, lesion‐related features, preoperative clinical findings, preoperative laboratory results, ESD procedure‐related data, postoperative clinical features, postoperative complications, postoperative medication regimens, postoperative pain scores, and comprehensive postoperative nursing measures. Detailed variables for data collection are listed in Appendix Table A1. The area of the resected lesion was calculated using the formula: Area (cm²) = maximum length (cm) × maximum width (cm).

2.6. Statistical Analysis

Continuous variables following a normal distribution were expressed as mean ± standard deviation; otherwise, they were presented as median [interquartile range]. Independent‐samples t‐tests and non‐parametric rank sum tests were used to compare the two groups, as appropriate. Dichotomous variables were expressed as count (percentage), with comparisons made using the χ ² test or Fisher's exact test, depending on suitability. For unordered multinomial variables, a clinically relevant category was selected as the reference, and dummy variables were created accordingly. For continuous variables with missing values, if the proportion of missing data was less than 20%, mean imputation was applied.

To explore factors influencing post‐ESD pain, a univariate analysis was first conducted. Variables that were statistically significant (p < 0.1) [17] in the univariate analysis or deemed clinically relevant were included in a multivariate logistic regression model. Variable selection was performed using the stepwise regression method to identify independent influencing factors. To control for confounding bias, matching was carried out based on sex (tolerance 0) and lesion area (tolerance 2 cm²), using a 1:3 matching ratio between the case and control groups. Conditional logistic regression was then applied to the matched patients for multivariate analysis to further investigate influencing factors. A two‐sided p‐value of < 0.05 was considered statistically significant. Statistical analyses were performed using MedCalc Statistical Software (version 19.6.4) and R software (version 4.2.0).

3. Results

3.1. Baseline Characteristics of Included Patients

In total, 993 eligible patients were included in the study, of whom 90 experienced moderate to severe postoperative pain, resulting in an incidence rate of 9.1% (95% confidence interval [CI], 7.3–11.1). The patients inclusion flowchart was showed in Figure 1. The median time to the first pain episode was 6 [2–11] h. The median age of the included patients was 59 [51–67] years, and 64.4% (640/993) were male. In the case group, CA125 levels (9.7 [8.73–11.69] vs. 9.63 [6.96–10.43] U/mL, p < 0.01), resected lesion area (9 [4–14.8] vs. 7.5 [2.7–14] cm², p = 0.04), the proportions of depressed‐type (21.1% vs. 12.5%, p = 0.02) and elevated‐type (66.7% vs. 53.6%, p = 0.01) lesions, the duration of fasting and water restriction (4 [3–5] vs. 3 [3, 4] hours, p < 0.01), and the time to first meal (4.5 [4–6] vs. 4 [3, 4] h, p < 0.01), were all significantly higher than those in the control group. Conversely, the proportions of male patients (54.4% vs. 65.4%, p = 0.03), use of intubation for general anesthesia (78.8% vs. 89.1%, p < 0.01), and pathologically confirmed cancer (22.2% vs. 35.9%, p < 0.01) were significantly lower in the case group than in the control group. No statistically significant differences were observed between the two groups in terms of body mass index, underlying diseases, blood pressure, other laboratory tests, or lesion locations. The detailed baseline characteristics of the included patients are presented in Table 1.

Figure 1.

Patient screening flowchart.

Table 1.

Baseline characteristics of included patients.

Characteristics	Overall (N = 993)	Moderate to severe pain group (n = 90)	Control group (n = 903)	p
Age (years)	59 [51–67]	59.5 [50–67]	59 [51–66.7]	0.99
Male	640 (64.4)	49 (54.4)	591 (65.4)	0.03
BMI (m2/kg)	24.6 [22.3–26.6]	24.3 [22.7–27]	24.6 [22.3–26.5]	0.63
Hypertension	293 (29.5)	27 (30)	266 (29.4)	0.91
Diabetes	134 (13.5)	15 (16.6)	119 (13.2)	0.35
Coronary heart disease	62 (6.2)	4 (4.4)	58 (6.4)	0.45
Smoking	310 (31.2)	30 (33.3)	280 (31)	0.65
Alcohol consumption	339 (34.1)	27 (30)	312 (34.5)	0.38
Systolic blood pressure (mmHg)	128 [120–138]	130 [122–140]	128 [120–138]	0.12
Preoperative laboratory tests
White blood cell count (109/L)	5.7 [4.79–5.81]	5.7 [4.86–7.17]	5.7 [4.79–6.75]	0.33
Hemoglobin (g/L)	42 [40–44.1]	41.2 [39.4–43.7]	42 [40.1–44.1]	0.10
Platelet count (109/L)	204 [172–240]	208.5 [181–254]	204 [171–238]	0.10
Total bilirubin (μmol/L)	10.8 [8.4–14.2]	10.5 [7.7–13.7]	10.9 [8.5–14.2]	0.11
Blood creatinine (μmol/L)	74 [64–83.3]	73.7 [63–80]	74 [64–83.8]	0.18
CEA (ug/L)	2 [1.32–2.72]	2.08 [1.32–2.97]	2 [1.32–2.70]	0.73
CA125 (u/mL)	9.7 [7.02–10.58]	9.7 [8.73–11.69]	9.63 [6.96–10.43]	< 0.01
CA199 (u/mL)	9.51 [6.07–13.1]	10.9 [6.06–15.6]	9.42 (6.08–12.8)	0.14
Lesion location
Cardia	237 (23.8)	23 (25.5)	214 (23.7)	0.69
Fundus	144 (14.5)	7 (7.7)	137 (15.2)	0.05
Body of stomach	245 (24.6)	21 (23.3)	224 (24.8)	0.75
Angular part of stomach	92 (9.2)	11 (12.2)	81 (8.9)	0.31
Antrum of stomach	275 (27.7)	28 (31)	247 (27.3)	0.44
Lesion morphology
Flat	317 (32)	11 (12.2)	306 (33.9)	< 0.01
Depressed	132 (13.3)	19 (21.1)	113 (12.5)	0.02
Elevated	544 (54.8)	60 (66.7)	484 (53.6)	0.01
Intraoperative histopathology type
Atypical hyperplasia	287 (28.9)	34 (37.7)	253 (28)	0.05
Cancer	345 (34.7)	20 (22.2)	325 (35.9)	< 0.01
Other	361 (36.3)	36 (40)	325 (35.9)	0.45
Endotracheal general anesthesia	876 (88.2)	71 (78.8)	805 (89.1)	< 0.01
Duration of surgery (min)	80 [55–120]	82.5 [55–135]	80 [55–120]	0.16
Resection area (cm2)	7.5 [3–14]	9 [4–14.8]	7.5 [2.7–14]	0.04
Water fasting time (d)	3 [3–4]	4 [3–5]	3 [3–4]	< 0.01
First oral intake time (d)	4 [3–5]	4.5 [4–6]	4 [3–5]	< 0.01
Onset of pain (h)	—	6 [2–11]	—	—

Note: Data are presented as count (percentage) or median (interquartile range).

3.2. Univariate and Multivariate Logistic Regression Analysis

The univariate analysis showed that male sex (odds ratio [OR], 0.63; 95% CI, 0.40–0.97; p = 0.03), surgery duration (OR, 1.25; 95% CI, 1.03–1.53; p = 0.02), intubation for general anesthesia (OR, 0.45; 95% CI, 0.26–0.78; p = 0.004), intraoperative electrocoagulation (OR, 0.45; 95% CI, 0.28–0.72; p < 0.01), postoperative gastric tube placement (OR, 2.04; 95% CI, 1.19–3.48; p < 0.01), and postoperative vomiting (OR, 4.39; 95% CI, 2.03–9.46; p < 0.01) were significantly associated with moderate to severe pain following gastric ESD. In the multivariate analysis, male sex (OR, 0.61; 95% CI, 0.37–0.97; p = 0.04), surgery duration (OR, 1.29; 95% CI, 1.03–1.63; p = 0.02), elevated‐type lesions (OR, 0.43; 95% CI, 0.26–0.71; p < 0.01), antral lesion location (OR, 1.84; 95% CI, 1.10–3.05; p = 0.01), intubation for general anesthesia (OR, 0.40; 95% CI, 0.22–0.72; p = 0.002), intraoperative electrocoagulation (OR, 0.32; 95% CI, 0.19–0.55; p < 0.01), postoperative gastric tube placement (OR, 2.005; 95% CI, 1.12–3.57; p = 0.01), and postoperative vomiting (OR, 3.24; 95% CI, 1.40–7.47; p = 0.005) were identified as independent factors influencing moderate to severe pain after ESD (Table 2).

Table 2.

Univariate and multivariate logistic regression analysis results.

Influencing factors	Univariate analysis				Multivariate analysis
	Coefficient	OR	95% CI	p	Coefficient	OR	95% CI	p
Age (Years)	−0.019832	0.98	0.81–1.17	0.83
Gender
Female	Ref.	—	—	—	Ref.	—	—	—
Male	−0.46056	0.63	0.40–0.97	0.03	−0.50093	0.61	0.37–0.97	0.04
BMI (kg/m2)
18.5–23.9	Ref.	—	—	—
≥ 28	0.016129	1.01	0.54–1.89	0.95
24–27.9	−0.34307	0.71	0.43–1.14	0.16
< 18.5	−1.25684	0.28	0.03–2.14	0.22
Lesion morphology
Depressed type	Ref.	—	—	—	Ref.	—	—	—
Elevated type	−0.55270	0.57	0.31–1.06	0.07	–0.83559	0.43	0.26–0.71	< 0.01
Flat type	−0.13808	0.87	0.46–1.63	0.66
Lesion location
Cardia	Ref.	—	—	—	Ref.	—	—	—
Fundus	0.020508	1.02	0.49–2.10	0.95
Body of stomach	−0.14534	0.86	0.45–1.65	0.66
Angular part of stomach	−0.52571	0.59	0.21–1.61	0.30
Antrum of stomach	0.30343	1.35	0.75–2.41	0.30	0.60966	1.84	1.10–3.05	0.01
Anesthesia Method
Intravenous general anesthesia	Ref.	—	—	—	Ref.	—	—	—
Endotracheal general anesthesia	−0.78763	0.45	0.26–0.78	0.004	−0.90911	0.40	0.22–0.72	0.002
Diabetes	0.27585	1.31	0.73–2.36	0.35
Smoking	0.10661	1.11	0.70–1.76	0.64
Alcohol consumption	−0.20849	0.81	0.50–1.30	0.38
Preoperative gastrointestinal symptoms	−0.16835	0.84	0.51–1.39	0.51
Preoperative proton pump inhibitors	0.10335	1.10	0.65–1.87	0.69
Preoperative mucosal protectants	0.19139	1.21	0.67–2.17	0.52
Duration of surgery (hours)	0.22840	1.25	1.03–1.53	0.02	0.26117	1.29	1.03–1.63	0.02
Lesion resection area (cm2)	0.0039973	1.004	0.98–1.02	0.64
Intraoperative Electrocoagulation	−0.78193	0.45	0.28–0.72	< 0.01	−1.11814	0.32	0.19–0.55	< 0.01
Protein glue	0.12151	1.13	0.66–1.92	0.65
Metal clips	0.075730	1.07	0.68–1.70	0.74
Postoperative gastric tube	0.71227	2.04	1.19–3.48	< 0.01	0.69564	2.005	1.12–3.57	0.01
Postoperative vomiting	1.47933	4.39	2.03–9.46	< 0.01	1.17590	3.24	1.40–7.47	0.005

3.3. Matching Results and Multifactorial Conditional Logistic Regression Analysis

Based on sex and resected lesion area, patients in the case group were matched with patients in the control group at a 1:3 ratio, resulting in 270 matched controls. The baseline characteristics of the case group and matched control group are presented in Appendix Table A2. No significant differences were observed between the two groups in terms of age, body mass index, laboratory test results, lesion location, lesion morphology, or surgery duration. Multivariate conditional logistic regression analysis revealed that intraoperative electrocoagulation (OR, 0.27; 95% CI, 0.12–0.58; p < 0.01), elevated‐type lesions (OR, 0.40; 95% CI, 0.16–0.99; p = 0.04), diabetes (OR, 2.50; 95% CI, 1.03–6.06; p = 0.04), postoperative vomiting (OR, 8.38; 95% CI, 2.31–30.37; p = 0.001), and intubation for general anesthesia (OR, 0.35; 95% CI, 0.15–0.80; p = 0.01) were independent factors associated with the occurrence of moderate to severe pain following gastric ESD (Table 3).

Table 3.

Multivariate conditional logistic regression analysis results.

Influencing factors	Conditional logistic regression analysis
	Coefficient	OR	95% CI	p
Lesion morphology
Depressed type	Ref.	—	—	—
Elevated type	−0.9092	0.40	0.16–0.99	0.04
Anesthesia method
Intravenous general anesthesia	Ref.	—	—	—
Endotracheal general anesthesia	−1.0348	0.35	0.15–0.80	0.01
Intraoperative Electrocoagulation	−1.3057	0.27	0.12–0.58	< 0.01
Postoperative vomiting	2.1262	8.38	2.31–30.37	0.001
Diabetes	0.9170	2.50	1.03–6.06	0.04

4. Discussion

This retrospective case‐control study analyzed the clinical characteristics of 993 patients who underwent gastric ESD and found an incidence rate of 9.1% for moderate to severe postoperative pain. Multivariate analysis identified sex, diabetes, lesion morphology, lesion location, anesthesia method, intraoperative electrocoagulation, surgery duration, postoperative gastric tube placement, and postoperative vomiting as independent factors influencing the occurrence of moderate to severe pain following gastric ESD.

Previous studies have indicated that female patients undergoing gastric ESD have a significantly higher risk of postoperative pain than their male counterparts, with the risk being 1.6 to 2.8 times greater for female patients [10, 11]. Our findings demonstrate that the risk of pain in male patients is 39% lower than that in female patients. Large epidemiological surveys have shown that women experience a higher incidence, greater intensity, and longer duration of pain than do men. This difference may be attributed to hormonal levels, psychosocial factors, and epigenetic mechanisms, all of which contribute to increased pain sensitivity in women [18, 19, 20]. Kim et al. [11] found that antral lesions are more prone to postoperative pain after ESD than are lesions in other locations. In our study, the risk of postoperative pain for antral lesions was 1.84 times higher than that for cardia lesions. The anatomical structure and gastric emptying mechanism of the antrum, which involves more frequent contractions and peristalsis, may make antral ulcers more susceptible to irritation and pain following ESD. Extensive research has indicated that gastric depressed‐type lesions, because of their greater surgical difficulty and deeper wound depth, are more prone to postoperative complications [21]. Our study shows that patients with elevated‐type lesions have a 60% lower risk of pain than patients with depressed‐type lesions. Previous studies have also confirmed a positive correlation between the duration of gastric ESD procedures and the risk of postoperative pain [10, 11]. Our results indicate that with each additional hour of surgery, the risk of postoperative pain increases by 29%. The evidence presented above suggests that our study findings are consistent with previous research, demonstrating both clinical relevance and interpretability.

Other factors influencing postoperative pain following gastric ESD in this study include the anesthesia method, intraoperative electrocoagulation, nasogastric tube indwelling, and postoperative vomiting. The method of anesthesia affects both the anesthetic effect and postoperative pain in ESD [22]. The Chinese consensus recommends intravenous general anesthesia and endotracheal intubation general anesthesia for ESD procedures [23]. Endotracheal intubation general anesthesia provides better surgical conditions, significantly reduces the operative duration, leads to fewer postoperative complications, and improves satisfaction for both patients and surgeons [21]. Our study showed that compared with intravenous general anesthesia, endotracheal intubation general anesthesia reduced the risk of postoperative pain by 60%. Electrocoagulation, an endoscopic hemostasis technique, is critical for managing small vessel bleeding during ESD. The absence of prophylactic electrocoagulation is an independent risk factor for delayed bleeding after ESD [24]. Our study shows that patients who underwent intraoperative electrocoagulation had a 70% lower risk of postoperative pain compared with those who did not, suggesting that electrocoagulation may help reduce postoperative pain in addition to its hemostatic effect. However, excessive electrocoagulation should be avoided because repeated application can cause ischemic changes in the gastric wall and increase the risk of delayed perforation [25]. Because ESD creates large mucosal defects, some patients receive nasogastric tube indwelling postoperatively to facilitate decompression, drainage, and promote wound healing. However, as an invasive intervention, nasogastric tube indwelling can cause discomfort such as dry mouth, throat pain, nausea, and vomiting, and improper placement may irritate the gastric wall [26, 27]. In our study, the risk of pain in patients with postoperative nasogastric tube indwelling was twice that of patients without. This may be attributed not only to the mechanical irritation from the tube itself but also to the fact that such patients typically have larger resected lesions or experience complications like intraoperative perforation and bleeding. Because of pathological mechanisms such as oxidative stress and chronic inflammation, approximately 20% of patients with diabetes have difficulty with wound healing, which can lead to serious complications such as diabetic foot [28]. Diabetes is also a known risk factor for delayed healing of artificial ulcers after ESD [29]. Conditional logistic regression analysis in our study further indicates that diabetes increases the risk of postoperative pain after ESD by 2.5 times, likely related to the impaired healing capacity of ESD‐induced wounds in diabetic patients.

This study has several clinical implications for the perioperative management of patients undergoing gastric ESD. By assessing pain‐related risk factors, high‐risk individuals can be more accurately identified, enabling the timely implementation of appropriate pain prevention measures. This, in turn, may reduce the incidence of postoperative pain, minimize unnecessary examinations, improve patient satisfaction, and shorten hospital stays. Possible measures to reduce postoperative pain include, but are not limited to, the following:

• 1.For female patients, strengthening doctor–patient communication and providing continuous pain education by nursing staff during hospitalization can enhance patients' understanding of postoperative pain following ESD, alleviate anxiety, and reduce fear [30].
• 2.For diabetic patients, regular blood glucose monitoring and timely adjustment of hypoglycemic medications during the perioperative period are essential to avoid excessive fluctuations and to maintain glucose levels within a reasonable range [31].
• 3.In terms of anesthesia choice, selecting endotracheal intubation general anesthesia whenever possible can provide favorable surgical conditions, ensure a smooth operation, and reduce postoperative pain.
• 4.During surgery, the use of electrocoagulation to manage minor bleeding may help reduce postoperative pain, and continuous improvement in surgical skills along with minimizing the operation time is essential.
• 5.Past studies have reported various drugs effective in preventing or alleviating postoperative pain following gastric ESD. Choi et al. [32] found that preoperative use of fentanyl transdermal patches significantly reduced postoperative pain and decreased the need for temporary analgesics, and Lee et al. [33] reported that a single intravenous injection of dexamethasone (0.15 mg/kg) effectively relieved abdominal pain at 6 h postoperatively compared with controls. In another randomized controlled study, injection of bupivacaine combined with triamcinolone at the surgical site significantly reduced pain at 6 h postoperatively [34]. Our study similarly found that the median time to the first onset of pain after gastric ESD was 6 h, suggesting that the 6‐h postoperative period may carry the highest risk for pain. In addition to the medications mentioned above, sedatives and hypnotics can also contribute to pain relief following ESD. A recent randomized controlled study conducted in China demonstrated that intraoperative use of dexmedetomidine (0.6 μg/kg/h) alongside intravenous anesthetics significantly reduced postoperative pain levels, decreased morphine consumption, and lowered the incidence of adverse events such as nausea and vomiting [35].

This study has several limitations. First, as a retrospective study, it may be subject to selection and confounding bias. However, we applied strict inclusion and exclusion criteria and matched key confounding factors during statistical analysis to mitigate these biases. Second, this is a single‐center study, which may limit the representativeness of the participants and the generalizability of the findings. To enhance statistical power, we included data from patients consecutively enrolled at our center over the past 15 years to maximize the sample size. Third, because of the long study period, evolving clinical practices and endoscopic technologies led to incomplete inclusion of certain variables. Finally, the causal relationship between exposures and outcomes in observational studies should be interpreted with caution. Prospective studies are needed to further investigate the factors influencing post‐ESD pain.

5. Conclusion

Independent factors influencing moderate to severe pain following gastric ESD include female sex, diabetes, depressed‐type lesions, antral lesions, use of non‐intubated intravenous general anesthesia, absence of intraoperative electrocoagulation, prolonged surgery duration, postoperative nasogastric tube placement, and postoperative vomiting. Implementing appropriate prophylactic measures during the perioperative period for high‐risk patients can effectively reduce pain following gastric ESD.

Author Contributions

Fen Deng: conceptualization (equal), writing – original draft (equal). Lei Tao: investigation (equal). Liru Pan: resources (equal). Xiaoyu Qiu: methodology (equal). Bing Li: formal analysis (equal). Jing Hao: resources (equal). Huihui Li: methodology (equal). Zhenzhen Zhang: investigation (equal). Weiwei Ding: resources (equal). Yingying Wang: data curation (equal). Bo Ning: project administration (equal), supervision (equal), writing – review and editing (equal).

Ethics Statement

This study adheres to the ethical principles of the Declaration of Helsinki (2013) and has been approved by the Ethics Committee of the First Medical Center of the PLA General Hospital (No. S2024‐358‐01).

Consent

The requirement for informed consent was waived because of the retrospective nature of the study and use of anonymized data.

Conflicts of Interest

The authors declare no conflicts of interest.

1.

Table A1.

Detailed data collection variables.

Data category	Variables collected
Demographic characteristics	Age, gender, BMI, underlying diseases (hypertension, diabetes, coronary heart disease), smoking history, drinking history
Lesion characteristics	Location, shape, postoperative biopsy pathological nature
Clinical features	Blood pressure, anesthesia method, operation duration, lesion resection area, fasting and water deprivation duration, first meal time, first pain onset time, preoperative mucosal protectant, preoperative antacid, preoperative dyspepsia symptoms, postoperative gastric tube, postoperative vomiting, postoperative pain grade
Laboratory tests	White blood cell count, hemoglobin, platelet count, total bilirubin, serum creatinine, CEA, CA125, CA199
Surgical information	Surgical duration, resection area, intraoperative electrocoagulation, protein gel, metal clips

Table A2.

Baseline characteristics of the case group and the matched control group.

Characteristics	Case group (n = 90)	Matched group (n = 270)	p‐value
Age (year)	59.5 (50–67)	60 (51–66)	0.90
BMI (m2/kg)	24.8 ± 3.21	24.2 ± 3.29	0.16
Hypertension	27 (30)	81 (30)	1.00
Diabetes	15 (16.6)	26 (9.6)	0.10
Coronary heart disease	4 (4.4)	17 (6.3)	0.51
Smoking	30 (33.3)	72 (26.7)	0.22
Drinking	27 (30)	80 (29.6)	0.94
Systolic blood pressure (mmHg)	130 (122–140)	125.5 (117–137)	0.01
Preoperative laboratory tests
WBC (109/L)	5.70 (4.86–7.17)	5.59 (4.77–6.41)	0.18
Hemoglobin (g/L)	136.5 (126–147)	137 (127–146)	0.80
PLT (109/L)	208.5 (181–254)	204 (172–243)	0.20
Total bilirubin (μmol/L)	10.5 (7.7–13.7)	10.25 (7.9–13.3)	0.73
Serum creatinine (μmol/L)	73.8 (63.5–80)	73.3 (60.2–82)	0.84
CEA (μg/L)	2.08 (1.32–2.97)	1.94 (1.23–2.72)	0.50
CA125 (μ/mL)	9.7 (8.73–11.69)	9.16 (6.39–10.78)	0.001
CA199 (μ/mL)	10.89 (6.06–15.64)	9.25 (5.94–13.55)	0.24
Lesion site
Cardia	21 (23.3)	60 (22.2)	0.82
Gastric fundus	13 (14.4)	42 (15.6)	0.80
Gastric body	19 (21.1)	65 (24.1)	0.56
Angle of the stomach	5 (5.6)	29 (10.7)	0.14
Antrum of stomach	32 (35.6)	74 (27.4)	0.14
Preoperative lesion morphology
Sunk 0	16 (17.8)	38 (14.1)	0.39
Flat 1	34 (37.8)	83 (30.7)	0.21
Ridgy 2	40 (44.4)	149 (55.2)	0.07
General anesthesia with intubation	71 (78.9)	240 (88.9)	0.01
Surgical duration (min)	82.5 (55–135)	80 (55–120)	0.15
First drink of water (day)	4 (3–5)	3 (3–4)	< 0.01
first meal (day)	4.5 (4–6)	4 (3–5)	0.03
Postoperative pathological results
Atypical hyperplasia	31 (34.4)	71 (26.3)	0.13
Cancer	28 (31.1)	90 (33.3)	0.69
Others	31 (34.4)	109 (40.4)	0.31

Note: The data are presented as median (interquartile range), mean ± standard deviation, or n (%).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.