Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection

Abstract

Background: Although the criteria for the indication of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD-EGC) have been recently proposed, accumulating reports on the non-negligible rate of lymph node metastasis (LNM) after indicated ESD raise questions on the reliability of the current criteria.

Aim: To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.

Methods: We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center, a tertiary university hospital in Korea. To identify the risk factors of LNM of UD-EGC meeting the expanded criteria for ESD, we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4. We reviewed the clinical, endoscopic, and histologic features of the cases to identify features with a significant difference according to the presence of LNM. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios (ORs).

Results: Of the 4780 UD-EGC cases, 1240 (25.9%) were identified to meet the expanded indication for ESD. Of the 1240 cases, 14 (1.1%) cases had LNM. Among the various clinical, endoscopic, and histopathological features that were evaluated, mixed histology (tumors consisting of 10%-90% of signet ring cells) had a marginally significant association (P = 0.059) with the risk of LNM. Moreover, diffuse blurring of the muscularis mucosae (MM) underneath the tumorous epithelium, a previously unrecognized histologic feature, had a significant association with the absence of LNM (P = 0.028). Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM (OR: 0.12, 95%CI: 0.02-0.95; P = 0.045).

Conclusion: The risk of LNM is higher than expected when using the current expanded indication for UD-EGC. Histological evaluation could provide useful clues for reducing the risk of LNM.

Keywords: Endoscopic submucosal dissection; Gastric cancer; Lymph node metastasis; Undifferentiated carcinoma.

Figure 1

Flow chart of study patients. EGC: Early gastric cancer; SM: Submucosa; LVI: Lymphovascular invasion.

Figure 2

Blurring of muscularis mucosa underneath the tumorous epithelium. Representative images of tumors with diffuse, focal, and no blurring of muscularis mucosa. A: Diffuse blurring of muscularis mucosa (MM) was prominent enough to localize the tumor at scanning magnification (arrowhead); B: At higher magnification (40´), the thickness of MM appeared irregular due to collagen fibers disrupting the muscle fibers of MM; C: The majority of MM underneath the tumorous epithelium (both ends are marked by arrows) was undisrupted compared with adjacent MM underneath the non-tumorous epithelium, making the foci of MM blurring focal (arrowhead); D: With no blurring of MM, it was difficult to localize the tumor (both ends are marked by arrows) at scanning magnification based on the status of MM.

Figure 3

Endoscopic images of the cases with lymph node metastasis without exudate, mucosal break, converging fold, and tumor island. A: Case 1, B: Case 3, C: Case 5, D: Case 9.