Predicting histological ulceration in early gastric cancer (EGC) during endoscopic examination is crucial for endoscopists deciding on the treatment modality. The aim of this study was to investigate the endoscopic factors that can predict histological ulcerations in EGCs.
We retrospectively analyzed patients who underwent endoscopic submucosal dissection (ESD) for EGC. Clinical features and endoscopic characteristics of EGC such as location, histological differentiation, longest diameter, tumor morphology, mucosal break, converging fold, color change, and surface irregularity were reviewed. Histological ulceration was defined based on ESD specimens.
A total of 633 EGC lesions from 613 patients were included and histological ulcerations were found in 90 lesions (14.2%). Presence of converging folds, tumor morphology, and color changes on endoscopic examination were related to histological ulceration in the univariate analysis and converging folds along with color changes were statistically significant factors in the multivariate analysis. Kaplan–Meier analysis showed that patients with histological ulcerations in EGCs tended to have higher marginal recurrence rates.
Mucosal breaks are not equivalent to histological ulcerations. Rather, the existence of converging folds and color changes during endoscopic examination suggest histological ulcerations. Endoscopists should consider these factors when they decide the treatment modality for EGCs.
Endoscopic submucosal dissection (ESD) has become one of the major treatment modalities in early gastric cancer (EGC) for the last few decades [
To avoid unnecessary procedures, endoscopists should cautiously select patients who meet the criteria for ESD. The size of the lesions can be measured during endoscopic examinations, and histological differentiation is confirmed after endoscopic biopsy. However, the presence of histological ulcerations may be difficult to determine before ESD. The presence of ulceration in EGC is closely related to the depth of invasion and lymphovascular invasion [
We previously reported that most endoscopists tend to consider mucosal breaks in EGCs as ulcerations [
We retrospectively reviewed patients who underwent ESD for EGC from May 2002 to January 2017 at Incheon St. Mary’s Hospital, The Catholic University of Korea. Patients diagnosed with non-epithelial tumors, carcinomas other than adenocarcinomas, and gastric adenomas were excluded. Patient follow-up lasted until the cut-off date of October 31, 2018. Patients were divided into 2 groups according to the presence or absence of histological ulcerations after ESD. Demographic features such as age and sex were analyzed and compared between the groups. This study was approved by the Institutional Review Boards of The Catholic University of Korea.
Four gastrointestinal pathologists reviewed the whole specimen according to the Vienna Classification [
Two endoscopists (JL and BWK) reviewed and analyzed the endoscopic images obtained before ESD and discussed with each other until a conclusion was reached. At least 3 endoscopic images from different angles for EGCs were reviewed and analyzed. Endoscopic characteristics of EGCs such as tumor location, tumor size, tumor morphologies, mucosal breaks, converging folds, color changes, and surface irregularities were compared between the groups. Tumor location was classified into 3 parts based on the longitudinal axis of the stomach: upper, middle, or lower third. Tumor size was defined as the longest diameter measured with biopsy forceps during endoscopic examination. Tumor morphology was classified into 4 types according to the Paris classification [
Demographic features and endoscopic factors were compared between the groups according to the presence of histological ulcerations using the χ-squared tests or independent
Baseline characteristics are presented in
We compared 6 endoscopic factors (longest diameter, tumor morphologies, mucosal breaks, converging folds, color changes, and surface irregularities) between the groups. Among them, tumor morphologies, converging folds, and color changes were statistically significant in the univariate analysis (
The mean follow-up duration was 66.4 months (range, 21–196 months) for all patients; 39.9 months (range, 21–88 months) in patients with histological ulcerations, and 61.0 months (range, 21–196 months) in patients without histological ulcerations. There was no difference in recurrence rate between patients with or without histological ulcerations (13.3% vs. 12.9%,
In this study, we found that converging folds and color changes of EGCs on endoscopic examination were closely related to histological ulcerations. Most endoscopists intuitively judge that EGC lesions have ulcers when they observe mucosal breaks in the lesions [
Ulcerations in EGCs may be healed without any medical treatment. Moreover, the healing process in EGCs is quite similar to that seen in benign ulcers [
Discoloration of the mucosa in EGCs usually results from the changing vascularity within the carcinomatous mucosa [
Mucosal breaks do not indicate ulcerations. In this study, only half of the patients with mucosal breaks showed histological ulcerations. Considering that even experienced endoscopists sometimes consider erosive lesions in EGCs as ulcerations [
Although, it was not statistically significant, the incidence of marginal recurrence rates was higher in patients with histological ulcers in EGCs than in those without. To identify the correlation between histological ulcers and marginal recurrence in EGCs, a large prospective study should be conducted in the future.
There are some limitations in this study. First, this study had a retrospective design and was conducted at a single center; thus, selection bias may exist. Second, this study included ESD cases and did not include surgical specimens. Third, the interval between diagnostic biopsy and ESD was not assessed due to limited data. We could not obtain the biopsy date when the diagnostic endoscopy was not performed in our hospital. Fourth, the size of the mucosal break was not measured accurately due to the retrospective design.
In conclusion, mucosal breaks are not equivalent to histological ulcerations. The existence of converging folds and color changes in EGCs during endoscopic examination suggest histological ulcerations. Endoscopists should consider these endoscopic factors when deciding the treatment modality for EGCs.
Representative images of endoscopic factors associated with histological ulcerations. (A) Mucosal break (white-dotted circle); (B) Converging fold (white arrows); (C) Color change (white-dotted circle); (D) Irregular surface (white-dotted circle).
Recurrence rates. (A) Overall recurrence (
Baseline Characteristics of 633 Lesions from 613 Patients
Characteristics | Total (n=633) | Histological ulceration (+) (n=90) | Histological ulceration (–) (n=543) | |
---|---|---|---|---|
Sex |
0.449 | |||
Male | 434 (68.6%) | 64 (73.6%) | 370 (70.3%) | |
Female | 179 (31.4%) | 23 (26.4%) | 156 (29.7%) | |
Mean age |
65.2±9.5 | 64.7±9.4 | 65.3±9.5 | 0.541 |
Tumor location | 0.791 | |||
Upper | 30 (4.7%) | 4 (4.4%) | 26 (4.8%) | |
Middle | 219 (34.6%) | 34 (37.8%) | 185 (34.1%) | |
Lower | 384 (60.7%) | 52 (57.8%) | 332 (61.1%) | |
Tumor size |
0.416 | |||
≤10 | 207 (32.7%) | 29 (32.2%) | 178 (32.8%) | |
11–20 | 247 (39.0%) | 40 (44.4%) | 207 (38.1%) | |
21–30 | 107 (16.9%) | 15 (16.7%) | 92 (16.9%) | |
≥31 | 72 (11.4%) | 6 (6.7%) | 66 (12.1%) | |
Differentiation | 0.552 | |||
Differentiated | 587 (92.7%) | 82 (91.1%) | 505 (93.0%) | |
Undifferentiated | 46 (7.3%) | 8 (8.9%) | 38 (7.0%) | |
Depth of invasion | 0.483 | |||
Mucosa | 545 (86.1%) | 76 (84.4%) | 469 (86.4%) | |
sm1 | 39 (6.2%) | 8 (8.9%) | 31 (5.7%) | |
sm2 | 49 (7.7%) | 6 (6.7%) | 43 (7.9%) |
SD, standard deviation.
Sex ratio and mean age were calculated from 613 patients and others were calculated from 633 lesions.
Tumor size was defined as the longest diameter of the early gastric cancer.
Endoscopic Factors that Can Predict Histological Ulcerations
Endoscopic factors | Histological ulceration (+) (n=90) | Histological ulceration (–) (n=543) | ||
---|---|---|---|---|
Univariate analysis | Multivariate analysis | |||
Tumor morphology | 0.013 | 0.054 | ||
Elevated | 13 (14.4%) | 149 (27.4%) | ||
Flat | 25 (27.8%) | 165 (30.4%) | ||
Depressed | 27 (30.0%) | 136 (25.0%) | ||
Mixed | 25 (27.8%) | 93 (17.1%) | ||
Mucosal breaks | 0.549 | - | ||
Yes | 44 (48.9%) | 247 (45.5%) | ||
No | 46 (51.1%) | 296 (54.5%) | ||
Converging folds | 0.001 | 0.005 |
||
Yes | 22 (24.4%) | 63 (11.6%) | ||
No | 68 (75.6%) | 480 (88.4%) | ||
Color changes | 0.008 | 0.020 |
||
Yes | 80 (88.9%) | 415 (76.4%) | ||
No | 10 (11.1%) | 128 (23.6%) | ||
Surface irregularity | 0.054 | - | ||
Yes | 45 (50.0%) | 213 (39.2%) | ||
No | 45 (50.0%) | 330 (60.8%) |
Odds ratio, 2.27; 95% confidence interval, 1.27–4.05.
Odds ratio, 2.33; 95% confidence interval, 1.14–4.76.