Extending treatment criteria for Barrett’s neoplasia: results of a nationwide cohort of 138 ESDs

Objective The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett’s esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed inNL. Design We retrospectively assessed ESD outcomes in NL, where treatment for BE neoplasia is centralized in 9 expert centers with jointly trained endoscopists and pathologists, and treatment/follow-up data collected in a joint database. ESD is restricted for selected cases. Results During median 121 minutes (p25-p75 90-180), 130 complete ESDs were performed with 97% (126/130) removed en-bloc. Pathology was HGD (5%), T1a-EAC (43%) or T1b-EAC (52%; 19%sm1, 33%≥sm2). The combined en-bloc and R0 rate was 87% [95%-CI 77-94%] for HGD/T1a-EAC and 49% [37-62%] for T1b-EAC. Upon R1 resection, 29% had residual cancer, in all cases detected at first follow-up endoscopy, while the remaining 71% had no residual cancer in esophagectomy specimen (n=6) or during median 9 months endoscopic FU (p25-p75 4-22) (n=18). Upon R0 resection, local recurrence rate during median 17 months (8-30) was 0% [0-5%]. Adverse events: 1% perforation [0-4%], 3% post-procedural bleeding [1-7%], 13% strictures [8-20%]. Conclusion In expert hands, ESD is safe and allows for removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter is, however, associated with a positive deep resection margin in half of the patients, yet only one third had actual persisting neoplasia at endoscopic FU. To better stratify R1-patients with an indication for additional surgery, repeat endoscopy after healing of the ESD wound may help in predicting residual cancer.

Expression of Intestinal Stem Cell and Cancer Stem Cell Markers in Submucosal Invasion and Its Prognostic Significance in Gastric Cancers

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Endoscopic diagnosis and treatment planning for colorectal polyps using a deep-learning model

We aimed to develop a computer-aided diagnostic system (CAD) for predicting colorectal polyp histology using deep-learning technology and to validate its performance. Near-focus narrow-band imaging (NBI) pictures of colorectal polyps were retrieved from the database of our institution. Of these, 12480 image patches of 624 polyps were used as a training set to develop the CAD. The CAD performance was validated with two test datasets of 545 polyps. Polyps were classified into three histological groups: serrated polyp (SP), benign adenoma (BA)/mucosal or superficial submucosal cancer (MSMC), and deep submucosal cancer (DSMC). The overall kappa value measuring the agreement between the true polyp histology and the expected histology by the CAD was 0.614–0.642, which was higher than that of trainees (n = 6, endoscopists with experience of 100 NBI colonoscopies in <6 months; 0.368–0.401) and almost comparable with that of the experts (n = 3, endoscopists with experience of 2,500 NBI colonoscopies in ≥5 years) (0.649–0.735). The areas under the receiver operating curves for CAD were 0.93–0.95, 0.86–0.89, and 0.89–0.91 for SP, BA/MSMC, and DSMC, respectively. The overall diagnostic accuracy of the CAD was 81.3–82.4%, which was significantly higher than that of the trainees (63.8–71.8%, P < 0.01) and comparable with that of experts (82.4–87.3%). The kappa value and diagnostic accuracies of the trainees improved with CAD assistance: that is, the kappa value increased from 0.368 to 0.655, and the overall diagnostic accuracy increased from 63.8–71.8% to 82.7–84.2%. CAD using a deep-learning model can accurately assess polyp histology and may facilitate the diagnosis of colorectal polyps by endoscopists.

Mid- and long-term outcomes of endoscopic resection for submucosal esophageal cancer types pT1b-SM1 and pT1b-SM2

Background and study aims Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) are promising therapeutic options for early esophageal cancer (EC). The factors that can affect mid- and long-term survival in patients with submucosal EC (SM1 and SM2) have not been described in the literature. We aim to describe clinicopathological outcomes and factors that can affect the mid- and long-term survival in patients with resected submucosal tumors. Patients and methods We performed a retrospective analysis of patients who underwent endoscopic resection (ER) for submucosal tumors over a 20-year period. The final study population included 119 cases with 137 lesions. Information was collected according to the Japanese Classification of Esophageal Cancer 11-edition and factors affecting survival for 2 and 5 years after ER were analyzed. Results EMR was performed in 99 cases (72.3 %), ESD in 38 cases (27.7 %). There were no significant complications. Two- and 5-year survival rates were 91 % and 82 %, respectively. Mean age was 67.22 years (± 9.49 years), mortality caused by EC occurred in 13 cases (11 %). Factors that had a significant impact on long-term survival were age > 65 years (P = 0.0026), number of resected specimens (P = 0.0031), presence of another progressive disease (not EC) (P ≤ 0.001), recurrence (P = 0.0002), and relation between histopathological positive vertical margin and recurrence (P = 0.0112). Conclusions ER is viable treatment for esophageal submucosal cancer, selection between ESD/EMR can depend on tumor size and patient condition, and en bloc ER is the recommended technique for submucosal tumors. Long-term survival factors were identified.

Endoscopic features of submucosal invasion in undifferentiated type early gastric cancer sized less than 2 cm without ulceration.

76 Background: The prediction of invasion depth is important to decide the treatment modality for the undifferentiated type early gastric cancer (EGC) when size is less than 2 cm and had no ulceration. We aimed to identify the endoscopic features associated with submucosal invasion in the undifferentiated type EGC that meet the criteria of size and status of ulcer in the endoscopic submucosal dissection (ESD). Methods: A total of 120 patients with undifferentiated type EGC who received ESD or operation from August 2008 to December 2017 were enrolled in this study. All lesions met the ESD criteria except the invasion depth. We retrospectively reviewed endoscopic features of tumor before the resection and depth of invasion after resection. Results: In 120 undifferentiated EGCs, the mucosal and submucosal cancer were 97 and 23 lesions, respectively, In univariable analysis, discolor change, upper third location, the presence of deep/wide erosion were associated with submucosal invasion. Multivariable analysis revealed that upper/middle third location (odds ratio [OR] 8.0, 95% confidence interval [CI] 1.2-55.0; OR 7.9, 95% CI 1.8-35.1), erosion or polypoid (OR 41.8, 95% CI 4.1-427.9), and elevated type (OR 20.9, 95% CI 2.5-173.8) were significant risk factors. In 112 patients received gastrectomy with lymph nodes dissection, lymph node metastases were found in four cases (three mucosal cancer and one submucosal cancer). However, there was no lymph node metastasis in the lesions meeting the expanded ESD indication. Conclusions: The careful decision of treatment modality is needed for undifferentiated type EGC with erosion or elevated gross type located on the upper/middle third, although the tumor size and ulcer status meet the ESD indication.

Validation of treatment algorithm based on the Japan narrow-band imaging expert team classification for sub-centimeter colorectal polyps

Background and study aims Although cold polypectomy (CP) is widely used for colorectal polyps < 10 mm, appropriateness of indications for CP or endoscopic mucosal resection (EMR) are still unclear. The aim of this study was to validate the endoscopic treatment algorithm based on the Japan NBI Expert Team (JNET) classification. Patients and methods Consecutive patients with at least one colorectal non-pedunculated polyp < 10 mm between July 2014 and October 2016 were included in this retrospective study. During the period, EMR was performed for JNET ≥ 2B lesions and CP for JNET < 2A. Among a total of 3966 lesions, 3368 lesions with JNET ≤ 2A were resected by CP in compliance with the treatment algorithm but 565 resections for JNET ≤ 2A were not compliant (by EMR), while all 24 JNET > 2B lesions were removed by EMR in compliance with the algorithm. Polypectomy outcomes were compared between the compliant and non-compliant groups. Histological outcomes were analyzed in accordance with JNET classification. Results Post-polypectomy bleeding rate in the compliant group (0 %) was lower than that in the non-compliant group (0.53 %, P < 0.01). Proportion of lesions diagnosed as cancer (38 % vs 0.36 %, P < 0.01) or submucosal cancer (4.2 % vs 0.03 %, P = 0.012), and the lesion with free resection margin (91 % vs 64 %, P < 0.01) was higher in the JNET ≥ 2B than JNET ≤ 2A. Conclusion This study indicated our algorithm would be valid: CP is suitable for most polyps < 10 mm as incidence of post-polypectomy bleeding is low, whereas EMR is recommended for JNET ≥ 2B lesions for histological complete removal.