Clinico-pathologic determinants of non-e-curative outcome following en-bloc endoscopic submucosal dissection in patients with early gastric neoplasia

Abstract

Background: Endoscopic submucosal dissection (ESD) is gaining enormous popularity in the treatment of early gastric cancers (EGCs) in many institutions across the world. However, appropriate selection of candidates for endoscopic resection is crucial to sufficiently mitigate non-e-curative (NEC) resection. This study aims at identifying the various clinico-pathologic factors that independently predict the NEC outcome and depth of submucosal invasion following ESD procedure in patients with EGC.

Methods: Multiple logistic regression analysis was applied to investigate factors that independently predict both non-curability phenomenon and the level of submucosal invasion in patients with early gastric neoplasia. Statistical Packages for the Social Sciences version 23 was used for analysis.

Results: A total of 153 patients (162 EGC lesions) underwent en-bloc ESD after which the rate of complete resection and non-e-curative outcome were 95% and 22.2%, correspondingly. Multivariate analysis depicted that tumor location in the upper two third of stomach (odds ratio [OR], 5.46; 95% confidence interval [95% CI], 1.65-18.12; p = 0.006), tumor size > 2 cm (OR, 7.63; 95% CI, 2.29-25.42; p = 0.001), histologically undifferentiated tumor (OR, 15.54; 95% CI, 1.65-146.22; p = 0.001), and tumors with 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc (OR, 9.77; 95% CI, 1.23-77.65; p = 0.031) were all independent predictors of NEC resection for early gastric tumors. Additionally, location in the upper two third of the stomach (OR, 8.88; 95% CI, 2.90-27.17; p < 0.001), ulcerated lesions (OR, 3.70; 95% CI, 1.15-11.90; p = 0.028), lesions with > 2 cm (OR, 2.94; 95% CI, 1.08-8.02; p = 0.036) and those with poor differentiation (OR, 6.51; 95% CI, 2.23-18.98; p = 0.001) were found to have significant association with submucosal invasion.

Conclusions: Tumors located in the upper two third of the stomach having a larger size (> 2 cm), poor histo-differentiation and a gross type of 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc were significantly associated with a risk of NEC after ESD procedure. Thus, early gastric tumors displaying these features need to be handled carefully during endoscopic resection. Our findings may shed light on the pre-procedural detection of clinicopathologic factors that determine non-e-curability in patients with EGC.

Keywords: Clinico-pathologic factors; ESD; Early gastric cancer; Non-e-curative resection.

Fig. 1

Flowchart for patients with early gastric neoplasia who underwent ESD. ESD = Endoscopic submucosal Dissection, EGC = early gastric cancer, JGCA = Japanese Gastric Cancer Association, UD = Undifferentiated, U = Ulcer, SM1= Submucosal invasion < 500 μm LVI = Lympho-vascular invasion, UL= Ulceration, LNM = lymph node metastasis type

Fig. 2

Endoscopy-based macroscopic sub-classification of type ‘0’ early gastric lesions. A) Protruding [0-I], with ≥ 3 mm elevation. B) Superficial elevated [0-IIa], with < 3 mm elevation. C) Superficial flat lesions [0-IIb], tumors with no elevation or depression. D) Superficial depressed [0-IIc], tumors with slight depression. E) Excavated [0-III], tumors which are deeply depressed. F) Superficial elevated and depressed lesions with predominant elevated type [0-IIa + IIc]. G) Superficial elevated and depressed lesions with predominant superficial depressed type [0-IIc + IIa]. H) Superficial flat and depressed lesions with predominant superficial flat type [0-IIb + IIc].

Fig. 3

Different stages of early gastric neoplasia according to the depth of invasion (total magnification = 100x & 200x, scale = 100 & 200 μm). Hematoxylin and Eosin staining. (A1/A2) Gastric high grade dysplasia displaying complex glandular structure, significant cellular atypia, nuclear pseudo-stratification, hyperchromasia and poor nuclear polarization. (B1/B2) Cancer invading lamina propria. (C1/C2) Invasion involving the muscularis mucosae layer. (D1/D2) Gastric cancer that infiltrates into the submucosal layer but less than 500 μm depth from the muscularis mucosae, there is also associated lymphatic invasion. (E1/E2) Submucosal invasion greater than 500 μm from the muscularis mucosae with positive vertical margin