Impact of gastric neoplasms location on clinical outcome of patients treated by endoscopic submucosal dissection

Abstract

BACKGROUND

The location of gastric neoplasms can influence the level of technical difficulty and performance of endoscopic submucosal dissection (ESD). There are few studies that analyze the influence of tumor location in the stomach on ESD outcomes.

AIM

To compare the clinical efficacy and safety of ESD in the proximal vs distal stomach.

METHODS

A retrospective analysis was conducted on patients admitted in chronological order who received gastric ESD between 2009 and 2024. Patients were stratified into two groups based on tumor location: Group 1 included patients with tumors in the lower third of the stomach, while Group 2 included those with tumors in the middle or upper third. The following parameters were evaluated for each group: procedure duration, curative resection rate, en bloc resection rate, complete resection rate, incidence of complications, and depth of neoplastic invasion.

RESULTS

The mean procedure time was 97.07 minutes for lesions located in the distal stomach and 129.08 minutes for those in the proximal stomach (P = 0.0011). En bloc resection rates for ESD in the distal and proximal stomach were 97.9% and 85.7%, respectively (P = 0.0016), while complete resection rates were 93.9% and 73.4%, respectively (P = 0.0002). Curative resection was achieved in 90.9% of distal lesions compared to 65.3% of proximal lesions (P = 0.0001). Submucosal invasion was identified in 4.0% of distal lesions and 14.2% of proximal lesions (P = 0.013).

CONCLUSION

ESD performed in the proximal stomach requires a longer procedural time compared to ESD in the distal stomach, independent of lesion size and histopathological characteristics. Additionally, proximal gastric ESD is associated with reduced clinical efficacy and increased incidence of submucosal invasion.

Key Words: Stomach neoplasms; Adenocarcinoma; Learning curve; Gastric topography; Endoscopic submucosal dissection

Core Tip: The location of gastric neoplasms in endoscopic submucosal dissection (ESD) may affect the level of technical difficulty and the efficacy and safety profile. There is limited scientific evidence assessing the clinical impact of gastric tumor location on ESD outcomes. In tumors in the proximal stomach, it is essential to carefully and individually select those cases that would benefit from gastric ESD eradication.

INTRODUCTION

Gastric cancer is one of the most common malignant neoplasms of the gastrointestinal tract, currently ranking fifth in incidence (5.6% of all new cancer cases) and fourth in mortality (7.7% of all cancer deaths) worldwide[1]. The early detection of superficial gastric neoplasms has recently increased due to several factors such as improved endoscopist training in early-cancer detection, greater availability of image-enhanced endoscopes and the implementation of screening programs in at-risk populations. Nevertheless, the endoscopic detection of early gastric neoplasms remains challenging, particularly in the proximal stomach, as it requires a combination of proper pre-procedure gastric cleansing and a dedicated systematic inspection of the entire gastric mucosa to avoid blind spots and to reduce the rate of missed lesions. Asian studies have reported that proximal gastric tumors are frequently associated with a high rate of submucosal invasion at diagnosis[2-9].

Among treatment options for superficial gastric lesions, endoscopic submucosal dissection (ESD) is recognized as the standard of care, showing similar results to gastrectomy with lower morbidity while preserving the affected organ. A major limitation in the clinical application of gastric ESD is the technical complexity and long learning curve required for its execution. Thus, ESD dissemination in the West has been much slower than Eastern countries. This technical difficulty can vary significantly depending on certain factors, including location of the gastric neoplasm, size of the lesion, degree of submucosal fibrosis, and depth of neoplastic invasion[10-27]. There are very few studies, mostly from Asia, that compare the clinical impact of tumor gastric topography with efficacy-safety profiles, clinical outcome and ESD procedure duration. The aim of our study was to comparatively analyze the clinical effectiveness, procedure duration and safety of ESD procedures in the proximal vs distal segments of the stomach.

MATERIALS AND METHODS

Patients

This retrospective study was conducted at a single center. Information was obtained from a prospective database that included patients in chronological order undergoing ESD for superficial gastric lesions, all treated by the same specialist. Inclusion criteria included patients with incipient gastric neoplasms referred for endoscopic resection. Prior to ESD, all participants were evaluated by high-resolution white light endoscopy and image-enhancing endoscopy to confirm their suitability for the procedure. In cases where significant submucosal invasion was suspected, preoperative staging was further refined using endoscopic ultrasonography and computed tomography. Patients identified during staging as having advanced tumors with extensive submucosal involvement (or deeper) or those with medical conditions that contraindicated general anesthesia or endoscopic intervention were excluded from the study.

Patients treated between 2009 and 2024 were consecutively enrolled and categorized into two distinct groups based on tumor location. Group 1, termed the distal stomach group, included superficial gastric neoplasms situated the lower third of the stomach, specifically the antrum and incisure. Group 2, referred to as the proximal stomach group, comprised patients with lesions in the upper and middle thirds of the stomach, encompassing the body, fundus, and cardia. For each group, the following parameters were analyzed: Procedure time (in minutes), rates of en bloc, complete resections, curative resections, incidence of adverse events, tumor dimensions, histopathological findings of the excised specimen, and depth of tumor invasion.

The curative resection rate, en bloc resection rate and complete resection rate with free margins (R0 resection) were determined in accordance with the latest Japanese clinical guidelines[2]. The criteria used to define curative treatment for gastric carcinoma were as follows: (1) Endoscopic curability A: Predominantly differentiated type, tumors limited to the mucosa (pT1a), negative resection margins (complete R0 resection), absence of lympho-vascular invasion, absence of ulceration or ulcer scar, regardless of size. Long diameter ≤ 2 cm, predominantly undifferentiated type, pT1a, absence of ulceration or ulcer scar, negative resection margins, and absence of lympho-vascular invasion. Long diameter ≤ 3 cm, predominantly differentiated type, pT1a, finding of ulceration (or ulcer scar), negative resection margins, and absence of lympho-vascular invasion; and (2) Endoscopic curability B: Resected en bloc, long diameter ≤ 3 cm, predominantly of the differentiated type, negative resection margins, absence of lympho-vascular invasion and tumors limited to the superficial submucosa (pT1b/SM1) within < 500 μm from the muscularis mucosae. Histopathological assessment was performed according to World Health Organization classification[3,4].

ESD procedures

All patients who underwent gastric ESD were admitted to the hospital. The procedures were performed by a single endoscopist under general anesthesia. The operator was trained by experienced endoscopists in a high-volume referral center in Japan and has currently performed over 350 gastrointestinal tract ESD procedures. After a detailed endoscopic assessment with high-definition white light endoscopy and virtual chromoendoscopy, neoplasms deemed suitable for ESD were classified based on the Paris classification system. All ESD procedures were performed using standardized equipment, which included either a Flush Knife BT 2.0 or 2.5 (Fujifilm Co., Tokyo, Japan) connected to an electrosurgical unit (ERBE VIO 200S, 200D, or 300D, Tübingen, Germany), a 4-mm distal cap (Elastic Touch, Top Co., Tokyo, Japan) affixed to the endoscope tip, and a 25-gauge injection needle (Boston Scientific Co., MA, United States) for delivering the submucosal solution. Each ESD was performed following a structured sequence of steps: (1) Lesion marking (demarcation) was performed using diathermy in Soft Coagulation mode (effect 6, 30 watts); (2) Submucosal injection was performed to elevate the lesion, utilizing 0.4% sodium hyaluronate in teardrops form (Adaptis Fresh^®, Legrand Laboratory, Brazil)[5]; (3) Mucosal incision was executed in Endocut I mode (effect 2, cut duration 3, cut interval 2); (4) Dissection of the submucosal layer followed using Forced Coagulation mode (effect 3, 50 watts); and (5) Pre-hemostasis of visible blood vessels was performed using Soft Coagulation mode (effect 6, 100 watts). Depending on vessel size, hemostasis was achieved with the dissection knife or with coagulation forceps (Coagrasper; Olympus Co., Tokyo, Japan). Postoperatively, all patients were prescribed a proton pump inhibitor regimen for 4 weeks and sucralfate for 2 weeks.

Statistical analysis

The data were tabulated using Microsoft Excel for Windows 2010 (Microsoft Corp., Redmond, WA, United States) and statistical analysis was performed using STATA version 16 and SPSS version 25. Univariate analysis to compare the means of the continuous quantitative variables between both groups was performed using the t-test, while the Z-test was used to compare proportions of qualitative variables between both groups. P < 0.05 was considered statistically significant.

Ethical considerations

The study consisted of a retrospective assessment of the clinical impact of superficial gastric neoplasm location on the performance of gastric ESD and was performed in accordance with the principles outlined in the Declaration of Helsinki. It focused exclusively on the statistical analysis and descriptive evaluation of patients who underwent gastric ESD and met the established inclusion criteria. The research was conducted at an endoscopic referral center in Brazil, following approval from the Institutional Review Board on May 6, 2020, and after obtaining informed consent from all participants. All procedures adhered to ethical standards for scientific research, including strict measures to ensure patient data confidentiality.

RESULTS

Throughout the study period, a total of 150 patients scheduled for gastric ESD were evaluated. The procedure was halted in two patients due to the detection of a non-lifting sign, and these cases were excluded from further analysis and were managed accordingly. One patient was referred for surgical gastrectomy, with histopathology confirming deep submucosal invasion, while the other was placed under endoscopic surveillance. As a result, 148 lesions were ultimately included in the analysis. Among the analyzed patients, 83 were female (56.0%) and 65 were male (44.0%). The average age for the group of neoplasms located in the distal and proximal stomach was 66.9 years (23-89 years) and 64.8 years (19-87 years), respectively. Each group consisted of the following number of patients: Group 1 (distal neoplasms): 99 patients; group 2 (proximal neoplasms): 49 patients. Figure 1 shows the distribution of gastric lesions according to location.

Figure 1  Schematic of the location of stomach lesions.

In group 1, the mean ESD procedure time, en bloc, complete and curative resection rate were 97.07 minutes (range: 30-300 minutes), 97.9% (97/99), 93.9% (93/99), and 90.9% (90/99), respectively. In group 2, those features were 129.08 minutes (range: 40-300 minutes), 85.7% (42/49), 73.4% (36/49), and 65.3% (32/49), respectively. The difference between group 1 and 2 was statistically significant for all parameters as demonstrated in Table 1. Tumor size and histopathological results of the resected specimen were separately analyzed in regard to procedure duration for each gastric segment. For lesions ≥ 30 mm, the mean procedure time for the distal and proximal stomach group were 111.90 (range: 50-300 minutes) and 154.76 minutes (range: 60-300 minutes), respectively (P < 0.001). For a diagnosis of gastric adenocarcinoma, the procedure times for the distal and proximal stomach group were 112.62 minutes (range: 50-300 minutes) and 136.05 minutes (range: 40-300 minutes), respectively (P = 0.017). Table 2 shows a detailed comparative analysis between both groups with a separate evaluation according to tumor size and final histological diagnosis.

Table 1 Comparative outcomes of endoscopic submucosal dissection performance between both gastric segments, n (%).

	Distal stomach, n = 99	Proximal stomach, n = 49	P value
Procedure time, minutes	97.07 ± 42.82	129.08 ± 63.91	0.0011
Overall en bloc resection rate	97 (97.9)	42 (85.7)	0.0016
Overall complete resection rate	93 (93.9)	36 (73.4)	0.0002
Overall curative resection rate	90 (90.9)	32 (65.3)	0.0001
Overall adverse events rate	5 (5.0)	1 (2.0)	0.1911

Table 2 Comparison of procedure time between both gastric segments according to lesion size and histological analysis.

	Procedure time, distal stomach (n = 99) (minutes)	Procedure time, proximal stomach (n = 49) (minutes)	P value
Neoplasm size
< 30 mm	83.04 ± 37.55	108.65 ± 44.58	< 0.001
≥ 30 mm	111.90 ± 44.00	154.76 ± 72.34	< 0.001
Histological type of resected specimen
Benign neoplasms	90.88 ± 37.07	111.66 ± 44.47	0.002
Low grade dysplasia	78.38 ± 24.30	96.87 ± 19.19	< 0.001
High grade dysplasia	92.72 ± 36.82	158 ± 78.07	< 0.001
Adenocarcinoma	112.62 ± 50.95	136.05 ± 67.44	0.017

Another separate analysis was conducted comparing both groups in terms of tumor depth. Proximal tumors presented submucosal invasion in 14.2% of patients (7/49), while submucosal invasion was noted in only 4.0% of the cases in the distal stomach (4/99) (P = 0.013). There was also a predominance of deep submucosal invasion in the gastric neoplasms located proximally (P = 0.035). Table 3 shows the comparative analysis of tumor invasion depth between both groups.

Table 3 Comparison of neoplastic invasion in depth between both gastric segments, n (%).

	Distal stomach	Proximal stomach	P value
Adenocarcinoma
Intramucosal	33.3 (33/99)	20.4 (10/49)	0.052
Submucosal invasion	4.0 (4/99)	14.2 (7/49)	0.013
SM1 invasion	25 (1)	28.5 (2)	0.106
SM2 invasion	75 (3)	71.4 (5)	0.035

SM: Submucosal.

DISCUSSION

The factors that increase the technical difficulty of gastric ESD prolong procedure times and affect intervention efficacy-safety profiles are highly relevant issues for endoscopists that practice ESD, particularly for novice operators. The detailed analysis of neoplasms in the proximal segments of the stomach is crucial to achieve an optimal minimally invasive therapeutic approach to gastric cancer in this area, which is often a more challenging clinical scenario even for expert ESD operators. In the present study, proximal tumors present with significantly more submucosal invasion, require longer procedure times to achieve en bloc resection and ultimately lead to poorer clinical outcomes in terms of curability compared to gastric distal tumors. Nevertheless, there were no safety differences between the two groups in terms of adverse events. To our knowledge, this is the first Western study to comprehensively assess the importance of gastric neoplasm location on the clinical effectiveness and procedure duration for gastric ESD. Figures 2 and 3 show illustrative pictures of ESD in the lower third and upper-middle third of the stomach, respectively, performed on the same patient in a single session.

Figure 2 Illustrative pictures of endoscopic submucosal dissection in the lower third of the stomach. A: A 33-year-old woman presented with an elevated-type lesion (0-IIa) in the lower third of the stomach (gastric antrum); B: Markings were placed for endoscopic submucosal dissection, mucosal incision was started at the distal margin of the lesion; C: Submucosal injection to lift the lesion with 0.4% sodium hyaluronate in a teardrops form; D: Submucosal layer dissection; E: Complete tumor resection was achieved en bloc; F: Histological analysis of the endoscopic submucosal dissection specimen that revealed high grade dysplasia.

Figure 3 Illustrative pictures of endoscopic submucosal dissection in the upper-middle third of the stomach. A: A 33-year-old woman presented with a flat-type lesion (0-IIb) in the upper-middle third of the stomach (gastric body); B: Markings were placed for endoscopic submucosal dissection. Mucosal incision was started at the distal margin of the lesion; C: Mucosal incision; D: Submucosal layer dissection; E: Complete tumor resection was achieved en bloc; F: Histological analysis of the endoscopic submucosal dissection specimen that revealed predominantly undifferentiated (diffuse) mixed-type adenocarcinoma.

Gastric neoplasms located in the middle-upper third of the stomach present different clinicopathologic characteristics compared to those located in more distal segments. Proximal stomach tumors are strongly associated with an Epstein-Barr virus infection, which can present as a Helicobacter pylori co-infection, generating a greater chronic inflammatory component in the gastric mucosa in this type of neoplasm[6-8]. One of the most critical characteristics of gastric cancer in proximal segments is the higher rate of deep submucosal invasion at the time of diagnosis, reducing the possibility of cure by endoscopic resection techniques such as ESD. This higher frequency of submucosal invasion could be explained by inadequate evaluation of the proximal segments of the stomach during upper digestive endoscopy, leading to late-stage diagnosis or difficulties in characterizing subtle neoplasms in the proximal stomach. Figueirôa et al[9] elaborated a meta-analysis in which they included 105 studies (52126 ESD procedures), most of them from Asia. The authors demonstrated that lesions in the upper-middle third of the stomach were associated with a significantly higher risk of submucosal invasion compared to lesions in the lower third [odds ratio (OR) (upper) = 3.20, 95% confidence interval (CI): 1.04-9.86, and OR (middle) = 2.11, 95%CI: 1.41-3.16]. They also demonstrated that early gastric cancers (EGCs) in the upper third of the stomach showed higher probabilities of deep submucosal invasion compared to EGCs in the middle (OR = 2.11, 95%CI: 1.18-3.79) and lower third (OR = 3.35, 95%CI: 1.45-3.81). Our study confirmed these findings, showing a higher rate of submucosal invasion and deep submucosal invasion in EGCs in the proximal stomach, but in a Latin American population. A relevant aspect to highlight in our study is the greater proportion of undifferentiated adenocarcinomas (diffuse type) in the proximal stomach. According to the main international clinical guidelines, this type of adenocarcinoma has very restricted indications for ESD treatment, being limited to intramucosal tumors smaller than 20 mm. For this reason, most of these patients were referred for gastrectomy.

ESD is now regarded as the primary therapeutic approach for the removal of superficial gastric neoplasms. However, there are special situations that increase the technical complexity of this procedure even in expert hands[10-12]. The location of the lesions in the proximal gastric segments is one of the most critical factors in the performance of ESD. The poor maneuverability of the endoscope in this area, along with other lesion-specific factors, such as size greater than 30 mm or submucosal fibrosis, prolong the procedure time, reduce the clinical effectiveness in terms of en bloc, complete, curative resection, and increase the rate of adverse events[13-18]. Thus, in many of these cases, total or subtotal gastrectomy is indicated for lesions in the proximal stomach, leading to higher morbidity and mortality rates. However, ESD in highly experienced endoscopic centers is still a safe and effective technique for proximal lesions. Kim et al[19] retrospectively enrolled 135 patients with neoplasms located in the proximal stomach who underwent ESD and were divided into two groups: Remnant stomach and entire stomach. In the entire stomach group, the authors demonstrated high rates of en bloc resection (92%; 46/50) and complete resection (88.0%; 44/50), with low complication rates (4.0%; 2/50). The main international clinical guidelines establish the lower third of the stomach as the propitious segment to begin performing ESD, due to its accessibility and better maneuverability[20-22]. Gastric topography is a determining aspect of the ESD learning curve, reflected in the need for a greater number of cases performed by an operator to achieve competence and mastery in gastric ESD of proximal segments compared to those needed for distal segments[23-25]. Suzuki et al[26] prospectively elaborated a multicenter study across 41 institutions (9715 patients/10926 lesions) enrolling lesions with indication for ESD for EGC or suspected EGC to analyze different short-term parameters, as well as the main factors that could influence its execution, demonstrating a longer procedure time (> 120 minutes) for lesions located in the middle-upper third of the stomach (P < 0.0001). They also identified other factors that prolonged procedure time, including lesion size > 20 mm, submucosal invasion, presence of ulcer, and local recurrence. Our study reaffirms these results in a Western cohort between proximal and distal segments of the stomach. It should be noted that this study incorporated an exhaustive analysis of the learning curve of the endoscopist who performed all of the procedures included in this series. The findings revealed that this factor did not have a statistically significant impact on the clinical outcomes. In contrast, gastric topography was identified as the only influential factor in our results. Tables 4 and 5 show a detailed analysis of the endoscopist’s learning curve in the distal and proximal stomach, respectively, divided into three chronological periods.

Table 4 Gastric endoscopic submucosal dissection learning curve analysis for distal stomach, n (%).

	Phase I (n = 33)	Phase II (n = 33)	Phase III (n = 33)	P value
En bloc resection	33 (100)	33 (100)	31 (93.9)	0.540
Complete resection (R0)	30 (90.9)	33 (100)	30 (90.9)	1.0
Curative resection	28 (84.8)	33 (100)	29 (87.8)	1.0
Size (mean), mm	26.4 (10-60)	29.8 (15-60)	24.7 (10-60)	0.495
Procedure time, mean ± SD, minutes	98.2 ± 49.9	94.0 ± 38.4	99.0 ± 40.4	0.863
Adverse events
Overall adverse event rate	0	2 (6.0)	3 (9.0)	0.296
Digestive bleeding	0	2 (6.0)	2 (6.0)	0.540
Perforation	0	0	1 (3.0)	0.540
Histological type of lesions
Benign neoplasms	7 (21.2)	6 (18.1)	6 (18.1)	0.540
Low grade dysplasia	3 (9.0)	6 (18.1)	10 (30.3)	0.296
High grade dysplasia	8 (24.2)	9 (27.2)	7 (21.2)	1
Adenocarcinoma (according to depth of tumor invasion)
Intramucosal	13 (39.3)	12 (36.3)	8 (24.2)	0.296
SM1 invasion	0	0	1 (3.0)	0.540
SM2 invasion	2 (6.0)	0	1 (3.0)	1

SM: Submucosal.

Table 5 Gastric endoscopic submucosal dissection learning curve analysis for proximal stomach, n (%).

	Phase I (16 cases)	Phase II (16 cases)	Phase III (17 cases)	P value
En bloc resection	15 (93.7)	14 (87.5)	13 (76.4)	0.296
Complete resection (R0)	14 (87.5)	11 (68.7)	11 (64.7)	0.540
Curative resection	12 (75.0)	10 (62.5)	10 (58.8)	0.540
Size (mean), mm	17.2 (10-35)	28.6 (15-40)	32.7 (12-80)	0.035
Procedure time, mean ± SD, minutes	110.3 ± 52.8	126.2 ± 63.6	145.0 ± 67.2	0.348
Adverse events
Overall adverse event rate	0	0	5.8 (1/17)	0.540
Digestive bleeding	0	0	5.8 (1/17)	0.540
Perforation	0	0	0	1
Histological type of lesions
Benign neoplasms	6 (37.5)	5 (31.2)	0	0.296
Low grade dysplasia	2 (12.5)	2 (12.5)	4 (23.5)	0.540
High grade dysplasia	1 (6.2)	2 (12.5)	9 (52.9)	0.296
Adenocarcinoma (according to depth of tumor invasion)
Intramucosal	3 (18.7)	5 (31.2)	2 (11.7)	1
SM1 invasion	1 (6.2)	0	1 (5.8)	1
SM2 invasion	3 (18.7)	2 (12.5)	1 (5.8)	0.296

SM: Submucosal.

There are few studies that compare the efficiency of gastric ESD between proximal and distal segments of the stomach[27]. Cho et al[28] compared the dissection speed between the upper-middle and lower third of the stomach of 356 ESDs, demonstrating greater difficulty in achieving fast dissection speed in the upper-middle third compared to the lower third (OR: 0.05 and 0.36). They also determined that the number of cases needed to achieve fast dissection speed was 15 for tumors located in the lower third of the stomach and 98 for tumors located in the upper-middle third. Our study corroborates these results, showing a statistically significant longer procedure time in the proximal stomach compared to distal stomach, regardless of lesion size or histological results of the resected specimen. Table 6 presents a comparative analysis of our results compared to other recently published case series in terms of clinical effectiveness of ESD in the proximal stomach.

Table 6 Comparative table of world-wide outcomes in gastric endoscopic submucosal dissection in proximal stomach.

Ref.	En bloc resection rate	Complete resection rate	Curative resection rate	Adverse events rate	Procedure time, mean ± SD (minutes)	Submucosal neoplastic invasion
Current study	85.7 (42/49)	73.4 (36/49)	65.3 (32/49)	2.0 (1/49)	129.08 ± 63.91	14.2 (7/49)
Cho et al[28], 2023	100 (12/12)	91.7 (11/12)	83.3 (10/12)	16.7 (2/12)	Not specified	Not specified
Kim et al[13], 2017	92.0 (46/50)	88.0 (44/50)	94.1 (16/17)	4.0 (2/50)	33 ± 18	17.6 (3/17)
Kang et al[27], 2017	92.5 (62/67)	94.0 (63/67)	Not specified	Not specified	Not specified	22.9 (20/67)
Yoon et al[14], 2014	84.7 (83/98)	80.6 (79/98)	Not specified	13.3 (13/98)	90.51 ± 58.06	Not specified

One of the strategies to decrease the procedure time of gastric ESD in proximal segments, as well as to shorten the learning curve in this area is the use of traction devices. These approaches allow the endoscopist a better maneuverability of neoplasms located in the upper-middle third of the stomach, reducing the technical difficulty[29-31]. Yamada et al[32] retrospectively enrolled 63 lesions that underwent ESD in the greater curvature of the upper-middle third of the stomach, which were divided into two groups: ESD with the use of traction devices (26 lesions) and ESD without the use of traction devices (37 lesions). They demonstrated a shorter procedure time for the group with the use of traction devices (40 minutes) compared to the control group (77 minutes) (P = 0.01). Likewise, they observed a higher resection speed in the group with the use of traction devices (P = 0.02). In our study, traction devices were only used in seven recent cases (14.2%) of gastric neoplasia located in proximal segments, but the low number of cases did not allow for analysis about its effectiveness in facilitating the ESD procedure.

Recently, some authors have proposed the prophylactic closure of the ESD defect, aiming to reduce the risk of adverse events, such as delayed bleeding and perforation[33-35]. This recommendation may be particularly important in patients that require anti-thrombotic or anticoagulation medications, or when there is muscularis propria burn injury due to excessive use of electrocautery current. However, it is essential to consider certain technical aspects when attempting closure of anatomically narrow areas of the stomach, such as the cardia or pyloric channel, which can increase the risk of stricture. Currently, there is no international consensus on the performance of prophylactic closure after gastric ESD, unlike in other locations of the gastrointestinal tract, such as the duodenum or proximal colon[36,37]. Ego et al[38] conducted a retrospective study in 311 patients and 400 ESD procedures who received antithrombotic therapy and underwent gastric ESD for EGC. These patients were divided into two groups: those with (131 ESDs, 110 patients) or without (269 ESDs, 217 patients) prophylactic closure. Although there was a trend toward a lower rate of delayed gastrointestinal bleeding in the closure group, the difference was not statistically significant (P = 0.89). Other authors have proposed a second-look endoscopy 24 to 48 hours after ESD to assess the ulcer scar and add thermal coagulation or clipping to any bleeding or protruded vessels[39,40]. We have not adopted prophylactic closure of gastric ESD defects or routine postoperative second-look endoscopy in our center; nevertheless our rate of delayed bleeding has been only 3.3% (5/148), and we have not experienced any cases of delayed perforation.

Our study has some limitations. It reports the experience of a single endoscopist, who received training in Japan and has 15 years of accumulated experience. Therefore, the results presented in this manuscript may not be representative of endoscopic centers with less experience in ESD procedures, and therefore our results cannot be generalized. Furthermore, the number of cases in our series may be relatively limited compared to prior studies conducted in Asia. To the best of our knowledge, this represents one of the largest cohorts of gastric ESD from the West, prospectively elaborated on a consecutive and non-selective manner, aiming to capture the variability in the effectiveness, efficiency, and safety of gastric ESD across different anatomical regions of the stomach. Another limitation is that our study contains twice as many cases in the distal stomach compared to proximal lesions. Nevertheless, such observation was also noted in other studies and may hypothetically reflect the more strict indication for ESD in lesions in the proximal stomach, as well as the lower detection rate of early proximal tumors. An additional limitation is the lack of inclusion of local recurrence rates during long-term endoscopic follow-up in the different segments of the stomach. However, our study focuses on the analysis of parameters that are directly affected by gastric topography during ESD performance (efficacy, efficiency, and safety).

CONCLUSION

In conclusion, the proximal stomach is a highly challenging area to perform ESD, requiring prolonged procedure time and ultimately leading to worse clinical outcomes in terms of endoscopic curability. Therefore, in tumors in the proximal stomach, it is essential to carefully and individually select those cases that would benefit from gastric ESD eradication. Likewise, it is necessary to adopt certain strategies to improve the clinical outcome, such as careful preoperative staging to rule out deep submucosal invasion, greater availability of time for the ESD procedure, and referral to more experienced ESD operators that are familiar with the use of traction devices.