The endoscopic submucosal dissection (ESD) technique was introduced to facilitate
However, the procedural complexity of ESD, especially for gastric neoplasms, tends to vary with the lesion location and vascularity, presence of ulcers, scars, and fibrosis. These factors also determine the risk of intraoperative complications such as perforation and catastrophic hemorrhage, more so in inexperienced hands. Therefore, the success of ESD, to a large extent, depends upon an in-depth understanding of the specific attributes of the lesion.
Recently, several studies have examined the technical challenges in performing ESD with respect to lesion location and procedural time. Scarred and undifferentiated lesions as well as those located in the upper third of the stomach were reported to be typically challenging and required more time [
In this study, all the situations in which procedure time was considered to be different are discussed and classified as new locations. Furthermore, the procedure time for each location is examined with regard to both the mucosal CIS and SDS.
According to the training standards proposed by Tsuji et al. [
Study outline. Operators newly enrolled during the observation period and their first two cases.
Differentiated type, undifferentiated type, and mixed type (differentiated and undifferentiated) with an undifferentiated component of <20 mm were used according to the expanded criteria of ESD [
Adenomas that were considered precancerous included the following: (1) lesions >20 mm in diameter, (2) those with a depression, (3) those with rapid growth in a short time, and (4) those showing high-grade atypia on biopsy [
All cases of undifferentiated mixed type gastric cancer between April 1, 2009, and July 31, 2014, in which ESD was indicated as per the Japanese guidelines were reviewed [
Prior to the observation period, six operators who met the criteria discussed each of the listed items for which the procedural complexity was expected to differ. These included the mucosa (pyloric, fundic, and cardiac areas), state of the submucosa (vascularity, ulcers, scars, and hidden fibrosis observed for the first time at dissection), and maneuverability of the endoscope and device when different from the type of scope used normally. On the basis of this discussion, a total of 12 locations were identified (Figure
Twelve locations divided according to the consideration of a variable situation. 1: the lesion across the esophagogastric junction (AEGJ); 2: fornix; 3: lesser curvature of the body; 4: greater curvature of the body; 5: anterior wall of the body; 6: posterior wall of the body; 7: lesion across the angle; 8: lesser curvature of the antrum; 9: greater curvature of the antrum; 10: anterior wall of the antrum; 11: posterior wall of the antrum; 12: lesion across a pylorus ring (APR).
The 12 locations were as follows: 1: lesion at the esophagogastric junction (AEGJ); 2: fornix; 3: lesser curvature of the body; 4: greater curvature of the body; 5: anterior wall of the body; 6: posterior wall of the body; 7: lesion across the angle; 8: lesser curvature of the antrum; 9: greater curvature of the antrum; 10: anterior wall of the antrum; 11: posterior wall of the antrum; and 12: lesion across the pylorus ring (APR) (Figure
Resected specimens were obtained by placing markings for the incision line 10 mm outside the lesion; then resection was performed outside this line for undifferentiated and mixed type lesions. For all other cases, markings for the incision line were placed 5 mm outside the lesion margin, and the incision was made outside this line. As the resected specimens were oval, the area and circumference were calculated from the long and short axes. Furthermore, the CIS per unit length (mm/min) and SDS per unit area (mm2/min) were calculated for each location. Lastly, these were divided into three groups according to the median resected length/min and the median unit area for each location from the CIS and SDS in order of size. Next, these groups were further stratified according to procedure time (fast, moderate, and late groups).
The main endoscope used was GIF Q260J (Olympus, Tokyo, Japan); in duodenum bulb, a reverse maneuver is not possible with the GIF-Q260J, so, in all lesions of duodenum bulb, we used GIF-Q260 (Olympus, Tokyo, Japan). When a closed approach was difficult, the endoscope was changed to GIF 2TQ260M (Olympus, Tokyo, Japan). For the injection solution, a mixture of normal saline with 1% indigo carmine dye was used. In the event of poor uptake, an adequate amount of sodium hyaluronate with high viscosity was used. For basic techniques, we performed a precut in the region of the mucosa using a dual knife (KD-650, Olympus, Tokyo, Japan). Then, a mucosal circumferential incision was made using the dual knife or insulation-tipped (IT) knife 2 (KD-611L, Olympus, Tokyo, Japan). Submucosal dissection was performed using the IT knife 2 and/or a dual knife (especially if a dual knife was used for the scar tissue). In the event of active bleeding or if prominent blood vessels were present, hemostasis was ensured using a coagrasper (FD-410LR, Olympus, Tokyo, Japan). A high-frequency surgical unit for cutting and coagulation (Erbotom VIO300D, ERBE, Tubingen, Germany) was employed.
Curative resection was defined as per the expanded criteria of ESD [
This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Boards at Juntendo University Hospital.
Interquartile range (IQR) was calculated to determine variations in incisional circumference length (per unit length) for each location and the dissected area. With regard to operator skill differences for each location, large deviations were marked with an “
Outliers were defined as “cases exceeding 1.5 times the interquartile range above the third quartile.” Data pertaining to categorical variables are presented as constituent ratios. Between-group differences in case of normally distributed variables were assessed using one-way Analysis of Variance; nonnormally distributed variables were assessed using Kruskal-Wallis or Steel-Dwass tests, as appropriate. Fisher’s exact test or
In this classification system, we found a significant difference between different groups for all CIS and SDS in each location, demonstrating the validity of this classification method (
A total of 10 operators participated in the study: six operators who completed the training program prior to the observation period and had experience performing ESD on at least three patients, plus four newly added operators with ESD experience of at least three patients. On the basis of operator adaptations, 341 lesions remained for 10 operators. Furthermore, we excluded five cases that finally became piecemeal and snaring resection. In addition, we excluded one case in which the procedure was discontinued. Among the cases in which
A total of 302 lesions were examined in the study; the male-to-female ratio was 2.5 : 1. Macroscopically, flat, and depressed types accounted for >95% of the total lesions. The median tumor diameter was 11 mm, and the median size of the resected specimen was 34 mm. The most common histological tumor type was differentiated adenocarcinoma (81.8%); mixed types containing a differentiated type and ≤20 mm undifferentiated types accounted for 4.0%; lesions of an undifferentiated type accounted only for 1.7% of the total number of lesions. Adenomas represented 11.9% of the cases. In addition, there was one case of a neuroendocrine tumor and one of a hyperplastic polyp. Ulcers or scars were confirmed in 7.9% of cases, and hidden fibrosis in 11.6%. Moreover, much time to hemostasis was observed in 16.9% of the cases. Complications involving perforation occurred in 2.3% and delayed bleeding in 3% of cases, comparable to results that have been reported elsewhere (Table
Baseline characteristics of gastric tumors.
Characteristics | Value | (%) |
---|---|---|
Sex (females : males) | 80 : 222 (1 : 2.5) | |
Age, years, median (range) | 73 (40–92) | |
Morphology | ||
Protruded (0-I) | 11 | (3.7) |
Flat (0-II b, 0-II a) | 143 (6, 137) | (47.4) |
Depressed (0-II a + II c, 0-IIc) | 147 (138, 9) | (48.8) |
Submucosal tumor | 1 | (0.3) |
Tumor size (mm), median (range) | 11 (2–60) | |
Specimen size (mm), median (range) | 34 (14–110) | |
Histology | ||
Adenoma | 36 | (11.9) |
Differentiated type | 247 | (81.8) |
Mix type (differentiated + undifferentiated type (<20 mm)) | 12 | (4) |
Undifferentiated type | 5 | (1.7) |
| 2 | (0.7) |
Ulcer or scar | 24 | (7.9) |
Hidden fibrosis | 35 | (11.6) |
Much time to hemostasis | 51 | (16.9) |
Perforation | 7 | (2.3) |
Delayed bleeding | 9 | (3.0) |
The breakdown of the number of cases according to 12 classified locations is shown in Table
Classification of lesions by location (
Location number | | (%) |
---|---|---|
1: AEGJ | 5 | (1.7) |
2: fornix | 7 | (2.3) |
3: lesser curvature of the body | 33 | (10.9) |
4: greater curvature of the body | 21 | (7.0) |
5: anterior wall of the body | 22 | (7.3) |
6: posterior wall of the body | 46 | (15.2) |
7: across the angle | 34 | (11.3) |
8: lesser curvature of the antrum | 45 | (14.9) |
9: greater curvature of the antrum | 17 | (5.6) |
10: anterior wall of the antrum | 34 | (11.3) |
11: posterior wall of the antrum | 34 | (11.3) |
12: APR | 4 | (1.3) |
AEGJ: across the esophagogastric junction; APR: across the pyloric ring.
Characteristics of the cases in the 12 locations.
Location | | Mean age | Sex | Ulcer or scar (%) | Hidden fibrosis (%) | Much time to hemostasis (%) | Tumor size (mm), median | Circumference (mm), median | Resected area (mm2), median |
---|---|---|---|---|---|---|---|---|---|
1 | 5 | 64.4 | 1 : 4 | 1/5 (20) | 1/5 (20) | 3/5 (60) | 12 | 206.9 | 3187.1 |
2 | 7 | 72.1 | 2 : 5 | 1/7 (14.3) | 2/7 (28.6) | 3/7 (42.9) | 10.5 | 182.3 | 2637.6 |
3 | 33 | 72.4 | 7 : 26 | 2/33 (6.1) | 8/33 (24.2) | 10/33 (30.3) | 13.5 | 195.3 | 2901.4 |
4 | 21 | 69.5 | 3 : 18 | 2/21 (9.5) | 2/21 (9.5) | 3/21 (14.3) | 16 | 201.8 | 3165.1 |
5 | 22 | 72.4 | 4 : 18 | 1/22 (4.5) | 2/22 (9.1) | 5/22 (22.7) | 14 | 200 | 3132.2 |
6 | 46 | 70.1 | 12 : 34 | 4/46 (8.7) | 8/46 (17.4) | 13/46 (28.3) | 14.5 | 182.2 | 2637.6 |
7 | 34 | 74.1 | 10 : 24 | 4/34 (11.8) | 6/34 (17.6) | 9/34 (26.5) | 18 | 226.8 | 4042.8 |
8 | 45 | 72.6 | 14 : 31 | 4/45 (8.9) | 4/45 (8.9) | 2/45 (4.4) | 18.5 | 219.2 | 3733.5 |
9 | 17 | 71.5 | 3 : 14 | 2/17 (11.8) | 1/17 (5.9) | 0/17 (0) | 10.5 | 182.5 | 2625 |
10 | 34 | 72.2 | 12 : 22 | 1/34 (2.9) | 0/34 (0) | 1/34 (2.9) | 12 | 183.6 | 2512 |
11 | 34 | 74.4 | 9 : 25 | 1/34 (2.9) | 0/34 (0) | 2/34 (5.9) | 12 | 173.1 | 2373.8 |
12 | 4 | 76 | 3 : 1 | 1/4 (25) | 1/4 (25) | 0/4 (0) | 14 | 211.1 | 3504.2 |
| |||||||||
| 0.24 | <0.05 | <0.01 | <0.01 |
1: the lesion across the esophagogastric junction (AEGJ); 2: fornix; 3: lesser curvature of the body; 4: greater curvature of the body; 5: anterior wall of the body; 6: posterior wall of the body; 7: the lesion across the angle; 8: lesser curvature of the antrum; 9: greater curvature of the antrum; 10: anterior wall of the antrum; 11: posterior wall of the antrum; 12: the lesion across the pylorus ring (APR).
Mucosal circumference incision speed and submucosal dissection speed cut (speed per minute) in descending order.
Rank | Mucosal circumference incision speed | Submucosal dissection speed | ||||
---|---|---|---|---|---|---|
Location | Median (mm/min) range | Interquartile range | Location | Median (mm2/min) | Interquartile range | |
1 | 9 | 19.3 (3.8–39.3) | 18.3 | 10 | 214.6 (47.1–942) | 174.5 |
2 | 10 | 18.0 (5.9–81.7) | 10.9 | 9 | 204.1 (55.8–653.1) | 309.3 |
3 | 11 | 15.6 (3.8–95.8) | 13.7 | 11 | 175.1 (34.1–576.9) | 201.2 |
4 | 8 | 13.9 (3.3–35.2) | 11.3 | 8 | 118.2 (19.3–502.4) | 114.1 |
5 | 4 | 12.8 (4.2–24.0) | 8.6 | 3 | 116.7 (23.1–440.4) | 159.4 |
6 | 3 | 12.4 (2.9–34.1) | 10.7 | 5 | 116.0 (15.2–338.2) | 92.7 |
7 | 5 | 11.5 (2.6–35.5) | 10.4 | 4 | 96.4 (55.9–316.5) | 61.2 |
8 | 2 | 10.0 (3.1–30.4) | 12.5 | 6 | 93.5 (7.6–506.6) | 80.1 |
9 | 7 | 9.2 (2.5–40.3) | 8.15 | 7 | 92.5 (20.9–474.4) | 125.9 |
10 | 6 | 8.2 (1.7–26.5) | 6.6 | 1 | 91.1 (12.8–157) | 97.7 |
11 | 1 | 7.6 (2.9–11.2) | 6.4 | 2 | 66.6 (7.6–141.3) | 49.2 |
12 | 12 | 4.5 (3.3–6.1) | 2.2 | 12 | 43.5 (12.2–236.4) | 170.9 |
| ||||||
| <0.01 | <0.01 |
A high rate of hidden fibrosis was observed in fornix, location 2 (28.6%), and the lesser curvature of the body, location 3 (24.2%) (Figure
Variations of lesser curvature. (a, b) Easy case of submucosa. (c, d) “Hidden fibrosis.” (e, f) Many perforating vessel case.
Much time to hemostasis was in the following, in descending order: (1) AEGJ (location 1), 60%; (2) fornix (location 2), 42.9%; (3) lesser curvature of the body (location 3), in 30.3%; (4) posterior wall of the body (location 6), 28.3%; (5) lesion across the angle (location 7), 26.5%; (6) anterior wall of the body (location 5), 22.7%; and (7) greater curvature of the body (location 4), in 14.3%, with a higher rate at the lesser curvature of the body (location 3) than at the greater curvature of the body (location 4).
Table
Table
Interquartile range of the mucosal incision and submucosal dissection speed. This figure shows a graph of the mucosal incision and submucosal dissection speed of each of the 12 locations. By noting the interquartile range, the variation in the rate was clear.
Regarding CIS, while the speed was faster for lesions of the antrum than for those at other locations, it was slowest for the antral area along the lesser curvature, location 8 (median: 13.9 mm/min). The overall incisional speed was slower for the gastric body than for the antral area and was the slowest for location 6, the posterior wall of the gastric body (median: 8.2 mm/min). The second slowest location (i.e., 11th position) was location 1, AEGJ (median: 7.6 mm/min), and the slowest location was location 12, APR (median: 4.5 mm/min).
In contrast, the greatest IQR was found for the antral area along the greater curvature, location 9. Although the incisional speed was slow in the AEGJ and APR, the IQR was small, with little variation in speed.
With respect to SDS, as expected, the overall speed was fast for antral lesions; however, when dissecting areas around the antrum, the speed was slowest for location 8, the lesser curvature of the antrum (median: 118.2 mm2/min). The antrum exhibited a large IQR, and, overall, the speed tended to vary greatly at the same sites of the antrum. The variation was particularly high in location 9, the greater curvature of the antrum. For the gastric body, the speed was the slowest for location 6, the posterior wall, similar to the case for CIS. However, the greatest variation in the dissection speed was observed for location 3, the lesser curvature (IQR: 159.40). The SDS for the AEGJ, APR, and fornix was lower than that for other locations.
The second slowest SDS (i.e., the 11th position) was the fornix, and the slowest was for the APR. The fornix was at the eighth place with respect to CIS but at the eleventh place for SDS. The greatest IQR for SDS was observed for location 9, the greater curvature of antrum (IQR = 309.3).
The results are shown in Table
Subgroup analyses by procedure time for mucosal incision and submucosal dissection on ESD.
Mucosal incision | Submucosal dissection | |||||||
---|---|---|---|---|---|---|---|---|
Location | Rate, median | Interquartile range | | Location | Rate, median | Interquartile range | | |
Fast group | 8, 9, 10, 11 | 15.6 | 12 | 8, 9, 10, 11 | 170.5 | 178.7 | ||
Moderate group | 2, 3, 4, 5 | 12.4 | 10.6 | | 3, 4, 5, 6 | 97.7 | 79.7 | |
Late group | 1, 6, 7, 12 | 8.2 | 6.7 | | 1, 2, 7, 12 | 89.2 | 90.4 | 0.42 |
1: the lesion across the esophagogastric junction (AEGJ); 2: fornix; 3: lesser curvature of the body; 4: greater curvature of the body; 5: anterior wall of the body; 6: posterior wall of the body; 7: the lesion across the angle; 8: lesser curvature of the antrum; 9: greater curvature of the antrum; 10: anterior wall of the antrum; 11: posterior wall of the antrum; 12: the lesion across the pylorus ring (APR).
With regard to CIS, a significant difference was observed between the fast and moderate groups and between the moderate and late groups (
With regard to the ESD difficulty by location, the longest reported procedure time has been reported for the upper third of the posterior wall [
In the present study, unlike conventional location classification methods, we incorporated several key variables that determine procedural complexity. Additionally, we also examined CI and SD as separate factors. Using this classification system, we found a significant difference between different groups for all CIS and SDS in each location, demonstrating the validity of this classification method (
Undifferentiated lesions have been reported to be more difficult to assess [
Regarding the overall ESD, the incisional and dissection speed was faster in the case of antral lesions than those for other locations. However, the IQR tended to vary greatly during the actual dissection (Figure
The SDS varied greatly in lesions in the lesser curvature of the body, relative to that in other locations of the body (IQR = 159.4). The gastric angle and lesser curvature of the body are sites in which ulcers and scars are common. However, in the lesser curvature of the body, hidden fibrosis is often incidentally discovered during endoscopic dissection, regardless of the lack of scars; of note, we also found fibrosis in 24.2% of the dissections in this area in the present study. Therefore, increased time is required for detachment when the submucosa is not sufficiently lifted by local injection. Furthermore, the lesser curvature of the body can be difficult to approach with a scope or device depending on the shape of the stomach. Moreover, some lesions were viewed perpendicularly, which may have been responsible for the high variability in the incisional speed among lesions located at the same gastric body site. Moreover, it was initially believed that the greater curvature had more blood vessels and hemostasis. However, in clinical practice, more cases of much time to hemostasis were observed for the lesser curvature lesions (30.3% versus 14.3% for the greater curvature lesions) (Table
While increased perilesional vascularity in the case of ulcers, scars, and hidden fibrosis is believed to be another potential reason for the occurrence of many blood vessels, several perforating branches of blood vessels to submucosa in the lesser curvature are also contributory factors. However, a difference in the presence or absence of blood vessels and fibrosis in the lesser curvature greatly affects the procedure; therefore, it is not straightforward to predict the time required for dissection. Consequently, we suggest that expert operators with experience in difficult situations always be prepared to take turns at any time.
Differences in CIS and SDS between the fast, moderate, and late groups were found in the fornix (location 2) and in the posterior wall of the body (location 6). The fornix was classified in the moderate group for CIS, but the late group for SDS. This is because the scope and device end up perpendicular to the lesion and thus it is difficult to maneuver horizontally as both the submucosa and muscularis were thin.
The posterior wall of the body was classified into the moderate group for SDS, but the late group for CIS. We believe that this was attributed to the fact that reverse maneuver was considered to be difficult for the circumferential incision, in addition to the fact that there were more large blood vessels and fat in the mucosa and submucosa than in the other sites. However, upon completion of the circumferential incision, not as many blood vessels or as much fat was observed in the submucosa as that at the time when the circumferential incision was performed, and, therefore, dissection was considered easier than the circumferential incision. Locations that became classified into the late group for both CIS and SDS included the following: location 1, AEGJ; location 7, across the angle; and location 12, APR.
Maneuverability for the AEGJ (location 1) is considered to be poor due to the following reasons: hemostatic treatment is difficult due to several palisade blood vessels traversing the submucosa; dissection is difficult due to inflammatory adhesions caused by gastroesophageal reflux disease or other conditions; the working space on the oral side of the lesion is narrow due to the requirement for the intraesophageal maneuver; and reverse maneuver on the anal side is difficult to move the scope closer to the lesion. The angle (location 7) has a sharp anatomical bend and, therefore, must be approached from various angles. It is also a common site for ulcers and scars, which cause adhesions and render the dissection more challenging. APR requires resection of the pylorus ring (location 12) and reverse maneuver in the narrow bulbous working space as well as precautions for prevention of duodenal perforation. Consequently, it was assumed to be the location in which numerous techniques were most required. For the reasons provided above, in APR, reverse maneuver was not possible with the GIF-Q260J typically used. In all cases, the scope had to be changed to GIF-Q260, which has the greatest flexibility in the tip structure. Furthermore, to ensure the working space for this location, it is important to use a scope without the tip hood mounted so as not to impede inversion.
Initially, we believed that the greater curvature belonged to the late group for both the CIS and SDS, on the basis of the mucosal thickness, blood vessels, and the amount of fat. However, in our analysis, it was found to belong to the moderate group.
Complications involving perforation occurred in 2.3% and delayed bleeding in 3% of cases, comparable to results that have been reported elsewhere (Table
The limitations of this study include the fact that it was a single-center study, and there may be a bias according to the endoscopist who performed the ESD.
In the present study, a more detailed classification of the resection sites was used than those that have been previously described; this inevitably reduced the sample size for each lesion location. However, a larger sample size would have made it challenging to perform a detailed study. Apart from location, we did not analyze other determinants of ESD duration and speed. However, we were able to clarify submucosal fibrosis and confirmed, for the first time upon dissection in the lesser curvature of the body, locations at which hemostasis can be difficult (e.g., the greater curvature of the body).
It has been reported that the prolongation of ESD duration increases the rate of complications [
In the present study, we compared CIS and SDS in ESD of gastric lesions and reported the CIS and SDS for different locations for the first time. On the basis of our results, we predicted the CIS and SDS according to different locations and clarified the underlying factors that affect procedural complexity and speed.
The authors declare that there are no competing interests or financial ties relevant to the publication of this paper.
Hironori Konuma (endoscopist of this study) collected, analyzed, interpreted the data, and drafted the manuscript. Kenshi Matsumoto (corresponding author and endoscopist of this study) planned and executed the study, analyzed and interpreted the data, and revised the manuscript. Yoichi Akazawa, Hiroyuki Komori, Misuzu Ueyama, Yuta Nakagawa, Tsutomu Takeda, Takashi Morimoto, Kohei Matsumoto, and Hiroya Ueyama were endoscopists of this study. Daisuke Asaoka and Mariko Hojo collected the data. Takashi Yao (Professor) provided the pathological analysis. Akihito Nagahara (Professor) was an endoscopist of this study. Professors Akihisa Miyazaki and Sumio Watanabe revised the paper.
The authors would like to thank Shizuru Matsuoka, a statistical specialist, for providing appropriate statistical advice.