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INTRODUCTION
Current guidelines advise esophagectomy for submucosal esophageal adenocarcinoma (T1b EAC). However, data from retrospective studies suggest that endoscopic follow-up (FU) may be a valid alternative in patients without signs of lymph node metastases (LNM) at baseline. In this international multicenter, prospective cohort study (NCT03222635), we aim to evaluate the safety of a watchful waiting strategy with regular endoscopic FU in patients treated endoscopically for T1b EAC.

METHODS
This ongoing prospective study is conducted in 19 hospitals in Europe and Australia, and aims to include 141 patients with 5-year FU. After radical endoscopic resection of T1b EAC, patients are re-staged with endoscopic ultrasound (EUS) and CT/PET. In the absence of LNM or distant metastases (N0M0), and upon consent for endoscopic FU, patients are included and undergo strict endoscopic FU with gastroscopy and EUS every 3 months during year 1 and 2, every 6 months during year 3 and 4, and at year 5. CT/PET is repeated after 1 year. We divided our cohort into two groups: high-risk (submucosal invasion ≥500um, a/o poorly/undifferentiated tumor (G3-4), a/o lymphovascular invasion (LVI+)), and low-risk if high risk features are absent. Primary outcome parameters are 5-year disease specific survival and overall survival; secondary outcome parameters are rate of LNM and local recurrence.

RESULTS
Since July 2017, 120 patients (100 men, median 68 yrs) were included with a median FU of 22 (IQR 10-32) months: 80 high-risk and 40 low-risk patients. 6 patients (5% [95CI 1.0-9.0]) were diagnosed with LNM (table 1) after median FU of 8 (IQR 5-16) months. Of these 6 patients, 2/6 were referred for neoadjuvant chemo(radio)therapy with esophagectomy (ypT0N0M0, ypT0N1M0), 1/6 underwent esophagectomy only (pT0N2M0), 3/6 underwent selective surgical resection of the tumor-positive LN.

7 patients (6% [95CI 2.0-10.0] were diagnosed with an intra-luminal tumor recurrence not eligible for endoscopic re-treatment after median FU of 7 (IQR 6-15) months. 5 had initial ESD and 2 cap-based EMR. Of these 7 patients, 2/7 underwent esophagectomy (pT1bN0M0, pTisN0M0), 1/7 had neoadjuvant chemoradiotherapy and esophagectomy (ypT1aN0M0), 2/7 underwent chemoradiotherapy only, 1/7 had palliative radiotherapy, 1/7 refused additional treatment. No distant metastases were diagnosed during FU in both cohorts. 6 patients died, all non EAC-related deaths. 3 patients discontinued FU due to old age. 2 patients were lost to FU.

CONCLUSION
The interim analysis from our ongoing prospective study suggest that in patients with radically removed high- or low-risk T1b EAC, without LNM at baseline, a strict endoscopic follow-up protocol is feasible and curative therapy remains possible in those patients who develop LNM (5%) or a local intra-luminal recurrence (6%) during FU. Most patients demonstrate uneventful FU.

Background: Objective assessments of esophageal varices (EVs) are inadequate. The recurrence of variceal bleeding after endoscopic variceal ligation (EVL) is associated with residual blood flow underlying EVL or incomplete treatment of perforating veins connecting to the EVs. To overcome these problems, we established the novel through-the-scope Doppler probe method (DOP), which has advantages in managing EVs (Fig. 1). This study aimed to develop a strategy for managing EVs and validate it.
Methods: The first study included 54 varices of 20 patients with a history of esophageal variceal rupture from June 2019 to December 2020 who underwent DOP at a tertiary hospital. Variceal velocities were compared based on the size and endoscopic variceal findings. In addition, we assessed the effectiveness of our strategy to reduce the recurrence of variceal bleeding in twelve patients with EVs from January 2021 to July 2021.
Results: Doppler imaging was observed in all 54 varices. The velocity of varices (cm/s) was significantly higher in EVs with a larger size (y = 1.567x – 1.329, R²= 0.826), greater form (F1, 4.03 ± 1.22; F2, 8.75 ± 1.91; F3, 10.75 ± 2.87; P=0.02), blue color (blue 7.68 ± 2.94 vs white 4.04 ± 1.54; P<0.001), and red color sign positive (RC-positive 9.33 ± 2.40 vs. RC-negative 4.22 ± 1.31; P<0.001). We developed the strategy for managing EVs based on the results (Fig. 2). The cutoff value for EV velocity (>5 cm/s to treat) was correlated with EV color (blue vs. white; the area under the curve was 0.89). In the validation study, perforating veins were identified in nine out of twelve patients who underwent DOP. Repeat EVL was performed until the variceal velocity reached decreased value (≤5 cm/s). No recurrence of variceal bleeding occurred during the follow-up period (mean 11.7 ± 3.2 months). No adverse events associated with DOP were observed.
Conclusion: This was the first study on the evaluation of the hemodynamics of EVs using DOP. EV velocities were related to the variceal size, form, blue color, and red color sign positive. The Developed strategy using DOP may be an objective and effective treatment for EVs. Further large-scale, long-term comparative studies are warranted.

Benefits of DOP: (<b>1</b>) Risk stratification according to variceal velocities, (<b>2</b>) Identification of perforating veins, (<b>3</b>) Confirmation of reduced blood flow after EVL, and (<b>4</b>) avoiding EVL for downhill cases. Each red arrow means blood stream of varices. Black bar represents the band after EVL.

Benefits of DOP: (1) Risk stratification according to variceal velocities, (2) Identification of perforating veins, (3) Confirmation of reduced blood flow after EVL, and (4) avoiding EVL for downhill cases. Each red arrow means blood stream of varices. Black bar represents the band after EVL.

A flow chart of the management of esophageal varices

A flow chart of the management of esophageal varices

Background: Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating long-segment early ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture.
Methods: We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area more than 10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared to a historical control group of 25 patients who received RFA without oral steroids (Figure 1). The primary endpoint was the frequency of post-RFA stricture (Figure 2 A-D). Secondary endpoints were the number of balloon dilation sessions and the adverse event rate.
Results: There were no significant differences in the worst pathology grade at baseline, length of unstained lesions between the two groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared to the control group, the oral prednisolone group had a significantly lower stricture rate (4%, 2/48 patients vs. 44%, 11/25 patients; P<0.0001) and a lower number of balloon dilation sessions (median 0, range 0-4 vs. median 6, range 0-10). There were two cases of asymptomatic candida esophagitis in the study group, and no severe adverse effects.
Conclusions: The oral administration of prednisolone showed promising results in preventing post-RFA stricture (Figure 2 E-H) for long-segment early ESCNs.

Background: Endoscopic submucosal dissection (ESD) for Barrett’s esophageal adenocarcinoma (EAC) is increasingly supported by societal guidance. While definitions of pathologically curative vs. non-curative ESD exist, data concerning how these definitions operate, as well as rates of recurrent malignancy over long periods of surveillance, are lacking. We hypothesize that ESD of EAC fulfilling criteria for pathologically curative resection will result in low rates of local/distant recurrence.

Methods: A multicenter retrospective study (including 6 academic centers from a larger collaborative in North America) was performed that included only patients who underwent ESD of EAC with endoscopic ± imaging surveillance for ≥1 year or until recurrence. We assessed demographic and procedural outcomes including rates of pathologically curative resection (R0, moderately/well differentiated, lack of lymphovascular invasion, and if T1b with submucosal invasion <500 µm). Primary outcomes included rates of recurrence, development of a metachronous lesion, and location of recurrence (i.e., local or distant/metastatic).

Results: 112 patients underwent ESD for EAC. Patients were predominantly male and Caucasian with median age of 70 years (Table 1A). Median tumor size on pathology was 26 mm, and 98% of tumors were located in the distal esophagus. 74 (66%) EACs were T1a, 37 (33%) were T1b, and 1 was unspecified T1. En bloc resection was achieved in 96% and complete histologic resection (R0) was achieved in 77%. 54 patients (48%) met criteria for curative resection and had endoscopic surveillance. 39 (35%) patients underwent endoscopic surveillance due to patient preference or comorbidities precluding surgery. The remaining 19 patients (17%) underwent surgical resection. Median follow-up was 35 months (IQR 20-50 months), which included a median of 3 endoscopies and 1 imaging study. Recurrences were less likely to occur in the curative resection group compared to non-curative resections followed endoscopically (11% vs. 28%, P=0.04), which was supported by multivariate analysis (OR 3.0 for non-curative, CI [1.0, 9.4], P=0.05; Table 1B). Median time to local or metastatic recurrence was 4-5 months in both groups. There was no significant difference in recurrence over time for patients with curative resection vs. those with non-curative resection who then underwent surgical resection (Figure 1).

Discussion: ESD of EAC with a pathologically curative resection results in very low rates of local or metastatic recurrence (2%) when performed in North American centers. Recurrence rates were significantly higher in those who did not achieve curative resection and were unwilling or unfit for surgery, which indicates that closer surveillance may be warranted in this population. As more patients undergo ESD for EAC, such data will help inform surveillance strategies.

Table 1

Figure 1

Makoto Nishimura

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