Introduction

The endoscopic diagnosis of lateral margin of superficial Barrett's esophageal adenocarcinoma (BEA) has been reported as challenging due to chronic inflammation. However, accurate lateral diagnosis is crucial when endoscopic treatment is indicated, as en bloc resection is necessary to prevent local recurrence. Nevertheless, the features of BEA with unclear demarcation remain poorly understood. Therefore, we aimed to clarify the clinicopathological characteristics and cause of BEA with unclear demarcation.

Aims & Methods

In this retrospective study, we reviewed cases of BEA resected by endoscopic submucosal dissection or surgery between January 2010 and September 2022 at two institutions. The lesions were classified into two groups; the clear demarcation group (CD group) and the unclear demarcation group (UD group). We then compared clinicopathological findings between the two groups. Furthermore, we aimed to elucidate the differences in pathological structures between the cancerous mucosa and the surrounding mucosa. To achieve this, we measured the length and width of the foveolar, as well as the width of marginal crypt epithelium (MCE). Subsequently, we compared these measurements in both cancerous and surrounding mucosa in each CD and UD group.

Results

		HR	95%CI	p value
Use of PPI	Negative	1	Reference
	Positive	1.39	0.35-5.58	0.634
Reflux esophagitis	Negative	1	Reference
	Positive	0.83	0.14-4.82	0.841
Barrett's esophagus	SSBE	1	Reference
	LSBE	10.38	2.14-50.19	0.004
Morphology	0-IIa	1	Reference
	0-IIc	4.06	0.83-19.83	0.083
	0-IIb	6.97	0.75-64.69	0.087

We analyzed 68 cases of BEA, with 47 in the CD group and 21 in the UD group. Univariate analysis showed that long-segment Barrett’s esophagus (OR; 8.44, 95% CI;2.64-27.00, p=0.00) and macroscopic type, 0-Ⅱb (OR; 8.43, 95% CI;1.36-52.06, p=0.022) as the significant risk factors for the UD group. Subsequently, multivariate analysis revealed long-segment Barrett’s esophagus as the sole significant risk factor (OR; 10.38, 95% CI;2.14-50.19, p=0.004) (Table.1).
Regarding pathological analysis, while the length and width of foveolar between the cancerous and surrounding mucosa in the CD group showed significant differences (p=0.03, and 0,00), these were not significantly different in the UD group (p=0.53, and 0.72). However, the width of MCE in the cancerous area was significantly shorter than that in the surrounding mucosa in both CD and UD group.

Conclusion

The significant risk factor for BEA with unclear demarcation was the long-segment Barrett’s esophagus. Additionally, we revealed that the primary pathological cause of unclear demarcation was the similarity of pathological structures between cancerous and surrounding mucosa. However, the width of MCE, which is recognized as white zone in endoscopy, was significantly different between the cancerous and surrounding mucosa in both groups, and this may be a key finding of endoscopic lateral diagnosis for all BEA lesions.

Introduction

With the recent rise in the occurrence of esophageal adenocarcinoma (EAC) in Western nations, there is an escalating worry regarding Barrett’s esophagus (BE). In contrast, Asian countries exhibit a lower prevalence of BE compared to their Western counterparts. Given the annual increase in chronic gastroesophageal reflux disease (GERD) cases, there is an expectation of a concurrent rise in the prevalence of BE. Consequently, we are embarking on a multicenter prospective study to assess the current prevalence of BE and pinpoint its risk factors in Taiwan.

Aims & Methods

Aim: to evaluate current prevalence and risk factors of Barrett's esophagus in Taiwan.
Methods: We carried out a prospective multicenter study involving consecutive outpatients who underwent upper gastrointestinal endoscopy for various upper gastrointestinal symptoms. Biopsies were taken from endoscopically suspected esophageal metaplasia (ESEM), clearly visible at least 1 cm above the gastroesophageal junction during endoscopy. The biopsy procedure involved obtaining standardized random samples, with four pieces taken every 2 cm from the four quarters of the esophagus exhibiting the ESEM lesion. BE was defined based on the histological confirmation of specialized intestinal metaplasia in the metaplastic esophageal epithelium.

Results

A total of 8925 subjects were enrolled in this study. The prevalence of BE was 2.6%. A total of 228 subjects with BE were detected among 751 ESEM subjects. Short segment BE (78.1 % , n = 178) was more prevalent than long segment BE (22.9 % , n = 50). The prevalence of GERD symptoms, erosive esophagitis (EE), and hiatal hernia (HH) was 52.5%, 27.3% and 7.85%, respectively. Multivariate analysis disclosed that old age [odds ratio (OR) = 1.59; 95% CI, 1.20-2.11; P <0.01], male gender (OR = 2.27; 95%CI, 1.65-3.11; P < 0.01),alcohol consumption (OR = 1.70, 95%CI, 1.19-2.44; P< 0.01), GERD symptoms (OR = 1.45, 95%CI, 1.10-1.92; P< 0.01), EE (OR = 1.94, 95%CI, 1.47-2.56; P< 0.01) and presence of hiatal hernia (OR = 2.49; 95%CI, 1.78-3.47; P < 0.001) were significant risk factors predicting BE.
Risk factors for Barrett esophagus: multivariable analysis.

Characteristics	Odd ratio	95% CI	P
Male	2.27	1.65-3.11	< 0.01
Old Age (50y/o)	1.59	1.20-2.11	< 0.01
Body mass index <25 25-30 >30	1 1.21 1.30	- 0.91-1.62 0.84-2.01	- 0.19 0.24
Smoking_Ever	1.19	0.86-1.63	0.30
Alcohol	1.70	1.19-2.44	< 0.01
GERD symptoms	1.45	1.10-1.92	< 0.01
Reflux esophagitis	1.94	1.47-2.56	< 0.01
Hiatal hernia	2.49	1.78-3.47	< 0.01

Conclusion

The prevalence of BE was identified as 2.6%. Notably, advanced age (>50), male gender, alcohol consumption, symptoms of gastroesophageal reflux disease (GERD), erosive esophagitis, and the presence of hiatal hernia emerged as independently significant risk factors for Barrett's esophagus.

References

1. Sharma P. Barrett Esophagus: A Review. Jama. 2022;328(7):663-71.
2. Marques de Sá I, et al. The global prevalence of Barrett's esophagus: A systematic review of the published literature. United European Gastroenterol J. 2020;8(9):1086-105.
3. Chang CY, et al. Current status of Barrett's esophagus research in Asia. J Gastroenterol Hepatol. 2011;26(2):240-6.
4. Shiota S, et al. Prevalence of Barrett's Esophagus in Asian Countries: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2015;13(11):1907-18.
5. Chang CY, et al. The application of Prague C and M criteria in the diagnosis of Barrett's esophagus in an ethnic Chinese population. Am J Gastroenterol. 2009;104(1):13-20.
6. Fock KM, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. Gut. 2016;65(9):1402-15.
7. Eusebi LH, et al. Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis. Gut. 2021;70(3):456-63.
8. Akiyama T, et al. Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men. BMC Gastroenterol. 2008;8:58.
9. Andrici J,et al. Hiatal hernia and the risk of Barrett's esophagus. J Gastroenterol Hepatol. 2013;28(3):415-31.

Introduction

In Western countries, endoscopic submucosal dissection (ESD) for early-stage Barrett’s esophageal adenocarcinoma (BEA) is usually combined with radiofrequency ablation (RFA) to eradicate the residual BE mucosa. In contrast, as RFA is not commercially performed in Japan, lesion-based ESD (L-ESD) has become the standard treatment for superficial BEA, followed by post-ESD surveillance. Although L-ESD is effective, metachronous recurrence may occur from preserved BE, and complete BE resection may be required depending on recurrence risk. While BE length has been associated with recurrence risk, it may not fully predict the recurrence. In Japan, image-enhanced magnification endoscopy with peri-lesional biopsies before ESD is used to assess lesion margins. Thus, we focused on the association between peri-lesional biopsy and the risk of metachronous recurrence.

Aims & Methods

We aimed to investigate clinicopathological features of BEA with metachronous recurrence after curative L-ESD, with a particular focus on peri-lesional biopsy. This was a retrospective, multicenter cohort study conducted at three high-volume Japanese institutions between April 2006 and August 2024. Patients with lesions assessed by image-enhanced magnification and peri-lesional biopsy before L-ESD were included. We excluded cases where lesions for which the definitive pathological diagnosis after L-ESD was not BEA. Patients were classified into two groups: no recurrence (non-R) and metachronous recurrence (MR). In peri-lesional biopsies, “negative” was defined when all biopsy specimens in each case showed no atypia or malignancy, and “non-negative” was defined when any specimen exhibited atypia or malignancy. We evaluated clinicopathological features and explored potential risk factors. The cutoffs for metachronous recurrence risk in the Prague C and M classification were also calculated using receiver operating characteristic curves.

Results

A total of 207 patients with 215 lesions were included. Of these, 200 patients (200 lesions) were in the non-R group, and 7 patients (15 lesions) in the MR group. In the non-R and MR groups, median ages were 67 and 77 years (p=0.19); long-segment BE rates were 26.5% and 85.7% (p=0.002); median Prague C lengths were 1 and 5 cm (p=0.007); and M lengths were 2 and 6 cm (p=0.002), respectively. Median tumor sizes were 15 and 13 mm (p=0.22); depths were pT1a: 69% and 86.7%, and pT1b: 31% and 13.3% (p=0.24); unclear or positive horizontal margins were 9.0% and 20.0% (p=0.17), respectively. The cutoff value for the risk of metachronous recurrence in the Prague C length was 5.0 cm (area under the curve [AUC]=0.78, 95% confidence interval [CI]: 0.56-0.99) and M length was 5.0 cm (AUC=0.83, 95%CI: 0.64-1.0).
The non-negative rate of peri-lesional biopsies was significantly higher in the MR group than in the non-R group (35.7% [5/15] vs. 12.5% [25/200]; p=0.04). In five lesions of the MR group, peri-lesional biopsies were all negative for the initial BEA (0% [0/22] of peri-lesional biopsies were non-negative), however, those for metachronous BEA were included non-negative species in each five lesion (50.0% [11/22] of peri-lesional biopsies were non-negative).

Conclusion

BE length is an indicator for risk stratification of recurrence. In addition, given the high incidence of non-negative results in peri-lesional biopsies at the time of metachronous recurrence, the temporal progression of atypia in the surrounding BE may have advanced significantly until metachronous recurrence. This finding is crucial for determining the potential candidates for BE eradication.

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.

Aims & 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 no high risk features are present. 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, 134 patients (112 men, median age 69 ±10 years) were included with a median FU of 22 (IQR 11-35) months: 87 high-risk and 47 low-risk patients. 6 patients (4% [95%CI 0.2-8.8]) 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 (ypT0N1M0, ypT0N0M0), 1/6 underwent esophagectomy only (pT0N2M0), 3/6 underwent a selective surgical resection of the tumor-positive LN.
7 patients (5% [95%CI 0.8-9.6] 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), 3/7 underwent (chemo)radiotherapy only, of which 1 patient eventually died as result of stenosing EAC, 1/7 refused additional treatment. No distant metastases were diagnosed during FU in both cohorts. Five patients died during FU of a cause unrelated to EAC. Five patients discontinued FU due to old age. Two patients were lost to FU.

N=134	FU (months), Median (IQR)	Lymph node metastasis, N (% [95%CI])	Intra-luminal tumor recurrence*, N (% [95%CI])	Distant metastasis, N (%)	EAC-related death, N (% [95%CI])	Non-EAC related death, N (% [95%CI])
High-risk T1b (N=87)	19 (11-35)	4 (5% [0.1-9.1%])	5 (6% [1.0-10.4%])	0	1 (1% [0-4.0%])	4 (5% [0.1-9.1%])
Low-risk T1b (N=47)	22 (9-36)	2 (4% [0-10.0%])	2 (4% [0-10.0%])	0	0	1 (2% [0-7.3%])

*not eligible for endoscopic therapy

Conclusion

The preliminary 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 the window for curative therapy remains open for those patients who develop LNM (4%) or a local intra-luminal recurrence (5%) during FU. Most patients demonstrate uneventful FU.

Disclosure

No conflict of interests.

Introduction

Although the issue of post-colonoscopy colorectal cancer (PCCRC) has been widely discussed, the characteristics of overlooked Barrett's adenocarcinoma (BAC) remain unclear.

Aims & Methods

We aimed to identify the characteristics of BAC that were missed during screening gastroscopy. A retrospective review of 28 patients with superficial BAC who had undergone gastroscopy within three years prior to diagnosis was conducted. The patients were divided into two groups: “misdiagnosis of detection” (no images were appropriately taken of the area where the BAC was eventually diagnosed) and “misdiagnosis of malignancy” (the BAC was overlooked despite endoscopists having taken images of the location where the BAC eventually diagnosed).

Results

The study included 24 male patients with a mean age of 65. The interval months between endoscopy at diagnosis and the last endoscopy before diagnosis were less than 12 months (n=3, 11%), 12-23 months (n=23, 82%), and 24-36 months (n=2, 7%). Background Barrett’s esophagus was short-segment (SSBE, n=18, 64%) and long-segment (LSBE, n=10, 36%). The Paris classification of the lesions was 0-I (n=2, 7%), 0-IIa (n=13, 46%), 0-IIb (n=4, 14%), and 0-IIc (n=9, 32%). The median tumor size was 14.5mm (range 3-107). Tumor locations were located at 0-3 o’clock position (n=17, 61%), 3-6 (n= 5, 18%), 6-9 (n=2, 7%), 9-12 (n=3, 11%) and circumferential (n=1, 4%). Most cases were classified into “misdiagnosis of malignancy” (n=19, 68%). Comparing misdiagnosis of malignancy with misdiagnosis of detection groups, lesions located at the 0 to 3 o’clock position were more likely to be missed due to misdiagnosis of malignancy (15/19 vs. 3/9, P=0.03). In contrast, lesions within LSBE were more likely to be overlooked due to misdiagnosis of detection (6/9 vs. 4/19, P=0.03).

Conclusion

Our findings suggest that lesions located at the 0 to 3 o'clock position were frequently missed due to misdiagnosis as esophagitis, highlighting the importance of careful differential diagnoses between esophagitis and BAC at such sites. In contrast, most lesions within LSBE were likely missed due the lack of adequate observation. Therefore, careful observation of LSBE using all available modalities is recommended.