Impact of tumor location on clinical outcomes of gastric endoscopic submucosal dissection

Abstract

AIM: To determine whether there is a correlation between the location of the lesion and endoscopic submucosal dissection (ESD) outcome.

METHODS: From January 2008 to December 2010, ESD of 1443 gastric tumors was performed. En bloc resection rate, complete resection rate, procedure time and complication rate were analyzed according to the tumor location.

RESULTS: The rates of en bloc resection and complete resection were 91% (1318/1443) and 89% (1287/1443), respectively. The post-ESD bleeding rate was 4.3%, and perforation rate was 2.7%. Tumors located in the upper third of the stomach were associated with a longer procedure time and significantly higher rates of incomplete resection, piecemeal resection, and perforation than tumors below the upper third of the stomach. Posterior wall lesions had significantly longer procedure times and higher rates of incomplete resection and piecemeal resection than lesions in other locations. In multivariate analysis, posterior wall lesions and upper third lesions were significantly associated with incomplete resection and perforation, respectively. In post-ESD bleeding analysis, location was not a significant related factor.

CONCLUSION: More advanced endoscopic techniques are required during ESD for lesions located in the upper third or posterior wall of the stomach to decrease complications and improve therapeutic outcomes.

Core tip: Location of the tumor is one of the most important clinical factors for complete resection and complications of endoscopic submucosal dissection (ESD) for early gastric cancer. Nonetheless, few studies have evaluated clinicopathologic outcomes of ESD according to the subdivision of tumor location. Based on our data, posterior wall lesions and upper third lesions were significantly associated with incomplete resection and perforation, respectively. Therefore, endoscopists should recognize the need for more advanced endoscopic techniques when performing ESD for lesions located in the upper third or posterior wall of the stomach to decrease the rate of serious complications and improve clinical outcomes.

INTRODUCTION

Advances in diagnostic technology and the increasing prevalence of screening programs have increased the rate of early gastric cancer (EGC) detection. EGCs that are confined to the mucosa and lack lymph node metastasis can be cured by endoscopic resection, such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)[1-4]. Compared with EMR, ESD may achieve complete resection not only of larger lesions but also of ulcerative lesions. In addition, ESD allows for a precise histological assessment of resected specimens and may reduce the risk of residual disease and local recurrence[5].

The factors affecting successful ESD include several characteristics of lesions such as location, presence of ulceration and histology[6,7]. In a recent multicenter study, scarred lesions, undifferentiated lesions and lesions located in the upper third required more advanced ESD techniques, because the complete resection rate is lower with these lesions than with other lesions[7]. In addition, the location of the tumor is one of the most important clinical factors for whether or not complete resection is possible or whether or not complication occurs. However, few studies have evaluated clinicopathologic outcomes of ESD according to the subdivision of tumor location in the longitudinal portions of the stomach and cross-sectional circumference divided into four equal parts. Therefore, we conducted this study to evaluate the level of difficulty of the procedure and clinicopathologic outcomes according to the tumor location.

MATERIALS AND METHODS

Patients

We analyzed 1319 patients with 1443 lesions who underwent ESD for gastric tumors at Yonsei University Health Care Center between January 2008 and December 2010.

Endoscopy with standard upper gastrointestinal endoscopes (GIF Q260 and H260, Olympus, Japan), chromoendoscopy with indigo carmine, and biopsies of the lesions with standard biopsy forceps (FB-21K-1; Olympus, Japan) were initially performed to determine the feasibility of ESD. Endoscopic ultrasonography (EUS) with radial scanning echoendoscopes (EG-3679URK, Pentax, Japan and GF-UE260, Olympus, Japan) was performed in case of carcinoma to evaluate the depth of invasion. Patients with lesions confirmed to be gastric cancer underwent abdominal computed tomography (CT) scans to determine if lymph node or distant metastasis was present. For this study, the endoscopic findings of EGC were classified as elevated (types I or IIa), flat (type IIb), depressed (types IIc, IIc+III, or IIa+IIc) or mixed (types IIa+IIb, IIb+IIc, IIa + IIc, III+IIa or III+IIb).

Gastric tumor lesions were classified according to their location in the upper, middle, and lower thirds of the stomach, and also to location in the cross-sectional circumference divided into four equal parts (anterior wall, posterior wall, lesser curvature or greater curvature).

Eligibility criteria for ESD were as follows: (1) differentiated adenocarcinoma (well- to moderately-differentiated tubular adenocarcinoma) or dysplasia confirmed histologically by forceps biopsy; (2) depth of invasion limited to the mucosa or submucosa (≤ 500 μm penetration into the submucosa) as determined by EUS; (3) lesions without ulceration, regardless of size, or 30 mm or less in size with ulceration; or (4) undifferentiated adenocarcinoma or intramucosal cancer without ulcer findings ≤ 20 mm in size[8].

Endoscopic resection

All procedures were performed by an attending gastroenterologist, and five attending physicians were involved in the procedures. All ESDs were performed under conscious sedation using intravenous propofol or midazolam. Vital signs were continuously monitored during the procedure. After identifying the target lesion, marking dots were made circumferentially about 5 mm lateral to the margin of the lesion using a needle knife (KD-10Q, Olympus, Japan) or argon plasma coagulation (ERBE Elektromedizin, Germany). Epinephrine (1:10000 dilution) was then injected submucosally around the lesion, and an initial short incision was made in the mucosa with a needle knife to allow submucosal insertion of the tip of an insulation-tipped (IT) knife (KD-611L, Olympus, Japan). Circumferential mucosal cutting was performed outside the marking dots, and an additional submucosal injection was carried out. Finally, direct dissection of the submucosal layer was performed, and endoscopic hemostasis with specialized hemostatic forceps (FD-410LR, Olympus, Japan) was performed when needed.

Histologic evaluation of resection efficacy

All resected specimens were systematically sectioned at 2 mm intervals centered on the part of the lesion closet to the margin and the site of the deepest invasion. Histological assessment was based on the Vienna classification[9].

Final pathologic diagnoses were classified as low grade dysplasia (LGD), high grade dysplasia (HGD), differentiated EGC, and undifferentiated EGC.

Outcome measures

Patient data, including patient age, gender, previous medication history, the size, number and location of lesions, procedure start and end times, endoscopic findings, pathology, and complications, were collected.

Complete resection of en bloc resected tumors was defined as the lateral and vertical margins being free of tumor cells on histologic examination. Complete resection of tumors resected in a piecemeal fashion was defined as complete removal of the entire lesion, including sufficient tumor-free margins after perfect reconstruction of all pieces.

Procedure time was defined as the time from marking to complete removal, including the time required for hemostasis. Complication data included whether a complication occurred and details regarding bleeding, perforation and other factors related to the type of complication.

Clinicopathologic evaluation

To identify factors affecting the success of ESD, we analyzed lesion characteristics, procedure, and the procedure result. Analyzed lesion characteristics included the presence of ulceration, macroscopic morphology, size and location of the tumor.

Procedure results were analyzed for curability. Resection was deemed complete when removal was achieved with tumor-free lateral and vertical margins and there was no lymphovascular involvement or lymph node metastasis. Incomplete resection was defined as any resection that did not meet the curative criteria described above.

Follow-up

Endoscopic surveillance by esophagogastroduodenoscopy (EGD) was performed 3, 6, 12, and 24 mo after ESD for EGC to exclude local recurrence, as well as synchronous, and metachronous lesions. After 24 mo, EGD was carried out annually. Moreover, abdominal CT scans were performed every 6 mo for the first year and annually thereafter, to detect lymph node or distant metastasis. In cases with adenomas, endoscopic surveillance by EGD was scheduled for 3, 12, and 24 mo after ESD.

Statistical analysis

The data were analyzed using Pearson’s χ² test, unpaired t-test, Fisher’s exact test, and the Mann-Whitney U test. P values < 0.05 were considered significant. To identify related risk factors for complications and complete resection, predictors with P values < 0.05 in the univariate analysis were included in a backward, stepwise multiple logistic regression model. All data analyses were conducted using a statistical software package (SPSS version 18.0, Chicago, IL, United States).

RESULTS

Gastric tumor characteristics

During the study period, ESD was performed in 1319 patients with 1443 gastric tumors. Baseline clinicopathologic characteristics of the gastric tumors and the clinical outcomes of ESD are shown in Table 1. Mean age was 63.0 ± 9.4 years. The lesions consisted of 733 (50.8%) EGCs and 710 (49.2%) dysplastic lesions. Submucosal invasion occurred in 7.3% of cases. Mixed-type endoscopic morphology was the most common (63.4%). With respect to size and location, tumors less than 20 mm in size (71.7%), those located in the lower third (85.4%) and those located in the lesser curvature (33.3%) were most common. The mean tumor size was 15.72 ± 8.81 mm. The mean procedure time was 61.8 ± 47.0 min. The complete resection rate was 89% (1287/1443), and the en bloc resection rate was 91.3% (Table 1). The post-ESD bleeding rate was 4.3%, and the perforation rate was 2.7%. Most cases of bleeding (60/63) were treated by endoscopic hemostasis such as hemoclipping, argon plasma coagulation or epinephrine injection. Two cases were treated by angiographic embolization. Only one case required surgery for bleeding control.

Table 1.

Baseline characteristics of gastric tumors n (%)

Characteristic	Value
Gender (female:male)	1:2.18 (454:989)
Age, yr, mean ± SD	63.0 ± 9.4
Tumor size, mm
< 20	1034 (71.7)
≥ 20	409 (28.3)
Macroscopic appearance
Elevated	310 (21.5)
Flat	128 (8.9)
Depressed	90 (6.2)
Mixed	915 (63.4)
Ulcer	71 (4.9)
Invasion depth
Mucosa	612 (42.4)
Submucosa	106 (7.3)
LocationI
Lower third	1233 (85.4)
Middle third	112 (7.8)
Upper third	98 (6.8)
Location II
Anterior wall	294 (20.4)
Lesser curvature	481 (33.3)
Posterior wall	405 (28.1)
Greater curvature	263 (18.2)
Histology
Low grade dysplasia	534 (37.0)
High grade dysplasia	176 (12.2)
Differentiated EGC	655 (45.4)
Undifferentiated EGC	78 (5.4)
Procedure time, min	61.8 (± 47.0)
Curability
Complete resection	1287 (89.0)
Incomplete resection	156 (11.0)
Resectability
En bloc	1318 (91.3)
Piecemeal	125 (8.7)
Perforation	39 (2.7)
Post-ESD bleeding	63 (4.3)

EGC: Early gastric cancer; ESD: Endoscopic submucosal dissection.

Around half of all perforation cases (20/39) were minute or micro-perforations, while the remaining ones were overt perforations. Only two such cases required surgery. All other cases were treated by conservative care. There was no mortality in the present study.

Endoscopic outcomes according to the location

We compared the clinical outcomes of ESD in relation to detailed tumor location. Upon division into upper third and other lesions, the upper third lesion group had significantly higher percentages of incomplete resections (19.4% vs 10.2%, P = 0.005) and piecemeal resections (15.3% vs 8.2%, P = 0.015) compared with other tumor locations. Additionally, upper third lesions required a longer procedure time (90.51 min vs 59.71 min, P < 0.001) and were associated with a higher perforation rate (9.2% vs 2.2%) (Table 2). There was no significant difference in the frequency of post-ESD bleeding.

Table 2.

Comparison of the upper third and non-upper third groups n (%)

	Upper third	Non-upper third	P value
Tumor size, mm
< 20	70 (71.4)	964 (71.7)	0.520
≥ 20	28 (28.6)	381 (28.3)
Ulcer	2 (2.0)	69 (5.1)	0.172
Pathology
Dysplasia	45 (45.9)	665 (49.4)	0.501
Carcinoma	53 (54.1)	680 (50.6)
Curability
Incomplete resection	19 (19.4)	137 (10.2)	0.005
Complete resection	79 (80.6)	1208 (89.8)
Resectability
En bloc	83 (84.7)	1235 (91.8)	0.015
Piecemeal	15 (15.3)	110 (8.2)
Procedure time, min, mean ± SD	90.51 ± 58.06	59.71 ± 45.46	< 0.001
Perforation	9 (9.2)	30 (2.2)	< 0.001
Post-ESD bleeding	4 (4.1)	57 (4.2)	0.600

ESD: Endoscopic submucosal dissection.

After dividing location according to posterior wall and other lesions, the posterior wall lesion group had a significantly longer procedure time (69.41 min vs 58.84 min, P < 0.001) and higher rates of incomplete resections (14.8% vs 9.2%, P = 0.002) and piecemeal resections (11.6% vs 7.5%, P = 0.013) than lesions in other locations (Table 3). There was no significant difference in the frequency of post-ESD bleeding or perforation between the two groups.

Table 3.

Comparison of the posterior wall and non-posterior wall groups n (%)

	Posterior wall	Non-posterior wall	P value
Tumor size, mm
< 20	278 (68.6)	756 (72.8)	0.065
≥ 20	127 (31.4)	282 (27.2)
Ulcer	21 (5.2)	50 (4.8)	0.771
Pathology
Dysplasia	216 (53.3)	494 (47.6)	0.053
Carcinoma	189 (46.7)	544 (52.4)
Procedure time, min, mean ± SD	69.41 ± 52.55	58.84 ± 44.39	< 0.001
Curability
Incomplete resection	60 (14.8)	96 (9.2)	0.002
Complete resection	345 (85.2)	942 (90.8)
Resectability
En bloc	358 (88.4)	960 (92.5)	0.013
Piecemeal	47 (11.6)	78 (7.5)
Perforation	14 (3.5)	25 (2.4)	0.27
Post-ESD bleeding	17 (4.2)	44 (4.2)	0.552

ESD: Endoscopic submucosal dissection.

Factors related to incomplete resection and complications

We analyzed the factors associated with complete resection complications of ESD such as perforation or bleeding. In univariate analyses, lesion size larger than 20 mm, upper third location, posterior wall location, carcinoma and procedure time longer than 60 min were significantly related to incomplete resection. In multivariate analysis, lesion size larger than 20 mm, posterior wall location, carcinoma and procedure time longer than 60 min were significantly related to incomplete resection (Table 4).

Table 4.

Multivariate analysis for incomplete resection

	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Tumor size, mm
< 20	1 (reference)
≥ 20	2.144 (1.526-3.011)	< 0.001	1.846 (1.283-2.654)	0.001
Ulcer
-	1 (reference)
+	1.210 (0.589-2.485)	0.604
SM invasion
-	1 (reference)
+	1.828 (0.811-4.119)	0.146
Location
Non-upper third	1 (reference)
Upper third	2.12 1(1.247-3.607)	0.006	1.576 (0.882-2.814)	0.124
Location
Non-posterior wall	1 (reference)
Posterior wall	1.707 (1.208-2.410)	0.002	1.687 (1.163-2.449)	0.006
Pathology
Dysplasia	1 (reference)
Carcinoma	4.921 (3.240-7.475)	< 0.001	4.675 (3.049-7.166)	< 0.001
Procedure time, min
< 60	1 (reference)
≥ 60	2.494 (1.772-3.509)	< 0.001	1.648 (1.142-2.379)	< 0.001

SM: Submucosa.

In addition, univariate predictors of perforation were lesion size larger than 20 mm, upper third location, procedure time longer than 60 min and piecemeal resection. In multivariate analysis, upper third location, procedure time longer than 60 min and piecemeal resection were statistically significantly related to perforation (Table 5).

Table 5.

Multivariate analysis for perforation

	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Tumor size, mm
< 20	1 (reference)
≥ 20	2.470 (1.304-4.678)	0.006	1.574 (0.807-3.071)	0.183
Ulcer
-	1 (reference)
+	1.637 (0.492-5.451)	0.422
SM invasion
-	1 (reference)
+	1.041 (0.238-4.550)	0.957
Location
Non-upper third	1 (reference)
Upper third	4.433 (2.042-9.623)	< 0.001	2.783 (1.138-6.803)	0.025
Location
Non-posterior wall	1 (reference)
Posterior wall	1.451 (0.746-2.820)	0.272
Pathology
Dysplasia	1 (reference)
Carcinoma	1.755 (0.905-3.405)	0.096
Procedure time, min
< 60	1 (reference)
≥ 60	8.143 (3.390-19.561)	< 0.001	4.985 (1.978-12.565)	< 0.001
Curability
Complete resection	1 (reference)
Incomplete resection	1.842 (0.799-4.248)	0.152
Resectability
En bloc	1 (reference)
Piecemeal	7.352 (3.748-14.423)	< 0.001	4.029 (1.987-8.170)	< 0.001

SM: Submucosa.

Moreover, univariate predictors of post-ESD bleeding were lesion size larger than 20 mm, procedure time longer than 60 min and piecemeal resection. In multivariate analysis, procedure time longer than 60 min and piecemeal resection were statistically significantly related to post-ESD bleeding (Table 6).

Table 6.

Multivariate analysis for post-endoscopic submucosal dissection bleeding

	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Tumor size, mm
< 20	1 (reference)
≥ 20	1.938 (1.151-3.362)	0.013	1.523 (0.886-2.619)	0.128
Ulcer
-	1 (reference)
+	1.377 (0.485-3.909)	0.547
SM invasion
-	1 (reference)
+	0.807 (0.276-2.358)	0.695
Location
Non-upper third	1 (reference)
Upper third	1.621 (0.957-2.745)	0.072
Location
Non-posterior wall	1 (reference)
Posterior wall	0.990 (0.559-1.754)	0.972
Pathology
Dysplasia	1 (reference)
Carcinoma	1.633 (0.963-2.770)	0.069
Procedure time, min
< 60	1 (reference)
≥ 60	2.804 (1.636-4.807)	< 0.001	2.120 (1.185-3.793)	0.011
Curability
Complete resection	1 (reference)
Incomplete resection	1.259 (0.587-2.698)	0.555
Resectability
En bloc	1 (reference)
Piecemeal	3.771 (2.040-6.971)	< 0.001	2.749 (1.433-5.276)	0.002

SM: Submucosa.

DISCUSSION

ESD has been widely accepted as an effective and safe treatment for gastric tumors[5,10]. To summarize previous studies, it is believed that the location of a lesion affects both the completeness of resection and whether complications are likely to occur[6,7,11-14]. These previous studies analyzed tumor location which is anatomically divided into three portions (upper, middle, and lower thirds) as a factor related to the clinical outcomes of ESD. Many studies reported that upper third location was associated with incomplete resection, longer procedure time and a higher rate of perforation[7,11,12]. However, even among tumors located in the same thirds of the stomach, the difficulty of the procedure and the clinical outcomes may be different according to the cross-sectional circumference, which is divided into four equal parts.

In our study, after dividing the upper third lesions from other lesions, it was found that the upper third lesion group had significantly higher percentages of incomplete resections (19.4% vs 10.2%) and piecemeal resections (15.3% vs 8.2%), longer procedure time (91 min vs 60 min) and a higher perforation rate (9.2% vs 2.2%). Furthermore, we analyzed clinical outcomes between posterior wall lesions and non-posterior lesions. The posterior wall lesion group had significantly longer procedure times and more frequent piecemeal and incomplete resections, which are likely explained in part by the difference in technical difficulty and poor visual field.

In previous studies, procedure time during ESD became longer as tumor locations became higher[7,15]. In addition, longer procedure time was needed for tumors located in the posterior wall[15]. These findings were consistent with our study results. As longer procedure times have been shown to be associated with increased risks of complications[16,17], we attributed the relationship between tumor location and complications to the longer procedure time of ESD for gastric tumors in the upper-third or the posterior wall of the stomach. As mentioned above, prolonged procedure time in cases involving the upper-third or the posterior wall location was caused primarily by technical difficulties and a poor visual field. During ESD for gastric tumors in the upper-third of the stomach, endoscopists cannot let the knife encroach on the submucosal layer beneath the tumor, and cannot control the direction and depth well adhering to the dissection plan[7]. Along these lines, the worse outcomes after ESD for those lesions in this study were also consistent with earlier studies that demonstrated lower rates of en bloc and curative resections in lesions of the upper portion of the stomach[6,7,12].

It is very important that we determine the factors related to complete resection, because clinically complete resection is the ultimate goal of ESD, and it is closely related to tumor recurrence rate after ESD[18,19]. We analyzed incomplete resection rates according to the tumor location, and independent factors related to incomplete resection. In multivariate analysis, lesions larger than 20 mm, posterior wall location, carcinoma and procedure time longer than 60 min were statistically significantly associated with incomplete resection. Interestingly, the significant factor of location for incomplete resection was being in the posterior wall in our study. The posterior wall location makes it technically difficult to use a knife during ESD in comparison with the anterior wall or lesser curvature locations. Furthermore, in this study, almost all cases of endoscopic resection were performed using a single channel endoscope and because this endoscope’s accessory channel opening is oriented at the 7 o’clock position, which is the opposite direction needed for posterior wall dissections, and makes ESD of posterior wall lesions difficult.

During the ESD procedure, serious complications such as bleeding or perforation may occur. Risk factors for perforation were identified in a recent study by Yoo et al[20], who proposed that risk of perforation is associated with age, depth of invasion and length of the procedure. In our study, the perforation rate was significantly associated with upper third location. This may be due to the fact that lesions in the lower third are easily approached and manipulated by endoscopy, and thus it is technically easier to perform ESD and there is a lower chance of applying sufficient tension on the gastric wall to cause perforation. Another possible reason is that the lower or the mid-portion of the gastric wall is thicker than the upper portion of the stomach.

Previous reports showed that bleeding occurred more frequently in the corpus than in the antrum[11,21]. Okada et al[22] demonstrated that having a tumor located in the mid-third of the stomach was an independent risk factor for post-ESD bleeding. However, the relationship between tumor location and post-ESD bleeding remains controversial to date. In our post-ESD bleeding analysis, location was not a significant factor for post-ESD bleeding. Besides tumor location, various factors such as the patient’s underlying medical and drug history, the endoscopist’s experience and preventive coagulation of visible vessels in the resection area after ESD may affect post-ESD bleeding. A recent study demonstrated that post-ESD bleeding depends on how meticulously coagulation of visible vessels is performed after dissection[23]. Regrettably, we could not analyze the effect of underlying disease or anti-platelet agents on post-ESD bleeding because we had relatively few patients with chronic disease such as chronic renal failure or cirrhosis, and all the patients in our study who underwent ESD discontinued anti-platelet agents prior to the procedure.

Limitations of this study include the fact that it was a retrospective single-center study with a limited follow-up duration. Therefore, there may be a bias according to the endoscopist who performed the ESD. In addition, we did not include long-term follow-up data concerning recurrence, disease-free survival, and overall survival, which are important for evaluating the effect of risk factors on outcomes. Nevertheless, this study focused on outcomes after ESD for gastric tumors with reference to therapeutic efficacy and complications according to lesion location. Although we did not address long-term outcomes, this study revealed that the two main components for the feasibility of ESD, acceptable complete resection and complication rates, change according to the location of gastric tumors. In addition, the clinical implications of tumor location were based on large-volume data. Accordingly, we suggest that attention to gastric tumor location, particularly in the upper third or posterior wall, during ESD is needed to avoid incomplete resection and complications. We should also explain the possibility of further surgical treatment after ESD to patients with such lesions. Nonetheless, further investigations with long-term follow-up data concerning the clinical significance of tumor location are needed to support our recommendations.

In conclusion, ESD for gastric tumor is an effective and safe therapy. However, endoscopists should recognize the need for more advanced endoscopic techniques when performing ESD for lesions located in the upper third or posterior wall of the stomach in order to decrease the rate of serious complications and improve clinical outcomes.

COMMENTS

Background

Advances in diagnostic technology and the increasing prevalence of screening programs have increased the rate of early gastric cancer (EGC) detection. EGCs that are confined to the mucosa and lack lymph node metastasis can be cured by endoscopic resection, such as endoscopic mucosal resection and endoscopic submucosal dissection (ESD).

Research frontiers

Previous studies analyzed tumor location which is anatomically divided into three portions (upper, mid, and lower thirds) as a factor related to the clinical outcomes of ESD.

Innovations and breakthroughs

In this study, the perforation rate was significantly associated with upper third location. This may be due to the fact that lesions at lower third are easily approached and manipulated by endoscopy, and thus it is technically easier to perform ESD and there is a lower chance of applying sufficient tension on the gastric wall to cause perforation.

Applications

ESD for gastric tumor is an effective and safe therapy. However, endoscopists should recognize the need for more advanced endoscopic techniques when performing ESD for lesions located in the upper third or posterior wall of the stomach in order to decrease the rate of serious complications and improve clinical outcomes.

Peer review

This is an interesting study regarding on the technical aspect of gastric ESD, focused on the tumor location. The number of the subjects is large and the analysis is simple with clear results.