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.

Introduction

Superficial Barrett's adenocarcinoma (BAC) is a rare disease in Japan, and its clinicopathological characteristics are not well-defined. As a result, indications for endoscopic treatment have not been determined.

Aims & Methods

A histopathological study was performed to investigate whether there is a relationship between risk factors for lymph node metastasis and the mucin expression phenotypes of BAC. We conducted a retrospective analysis of a database comprising consecutive patients with superficial BAC treated by endoscopic or surgical resection. Immunohistochemical analysis was performed using the antibodies of MUC5AC, MUC6, MUC2, and CD10 to determine the classification of mucin expression phenotype.

Results

A total of 74 BAC lesions in 68 patients (54 males, median age 69 years) were identified. Mucin expression classification showed gastric (64%, complete gastric 24%, predominantly gastric 39%), intestinal (34%, complete intestinal 14%, predominantly intestinal 20%) or null (3%) phenotypes. Surgical treatment was performed in 30 patients, including additional treatment after ESD, and lymph node metastasis was observed in 4 patients (13%). Compared to the intestinal phenotype group, patients with gastric phenotype BAC had an almost significantly higher rate of lymphovascular invasion (38% vs 16%, P=0.06) and poorly differentiated component (23% vs 4%, P=0.09). All 4 lymph node metastasis-positive cases were in the gastric phenotype group (P=0.28).

Conclusion

Although our study did not show a direct relationship between the risk of lymph node metastasis and mucin expression phenotype of BAC, it did suggest BAC with gastric phenotype may be more likely to have lymphovascular invasion and poorly differentiated component. The endoscopic-specific findings of BAC with gastric phenotype are unknown. However, some specific endoscopic findings of gastric phenotype in gastric cancer are well-known, such as intralobular loop pattern or vessels within epithelial circle pattern. If we see such findings in BAC, due to a possible higher risk of lymphovascular invasion or poorly differentiated components, we should perform ESD rather than piecemeal EMR to obtain en-bloc tissue specimens for detailed pathological evaluation.

Disclosure

None

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

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

Oesophageal adenocarcinoma (OAC) is often diagnosed at a late stage and has a poor survival rate. Barrett’s oesophagus (BO) can progress to OAC in a stepwise fashion, although the annual risk of progression is low, at 0.22% per year.¹ Currently, patients with BO undergo regular endoscopic surveillance with biopsies, with the degree of dysplasia guiding further management. This is invasive and expensive, and there is interobserver variability between pathologists in the assessment of dysplasia. There is an urgent need for new approaches to risk-stratify patients with BO. Epigenetic changes can occur early in the neoplastic progression of BO, making them attractive for use as potential risk-stratification biomarkers.

Aims & Methods

We aimed to carry out a systematic review to investigate whether epigenetic biomarkers can predict the progression of patients with BO to high-grade dysplasia (HGD) or OAC. The review was registered in PROSPERO (CRD42024509643). To be eligible for inclusion, studies must have examined patients with BO that was non-dysplastic (NDBO), had low-grade dysplasia (LGD), or was indefinite for dysplasia (IND) at baseline. Eligible studies assessed any type of epigenetic biomarker of any source, including DNA methylation, histone modification, and non-coding RNA. Non-epigenetic biomarkers were excluded. Studies must have compared epigenetic biomarker levels between patients who progressed to HGD/OAC and those who did not. Included studies must have assessed progression of NDBO/LGD/IND to HGD/OAC.
Ovid MEDLINE, EMBASE, and Web of Science Core Collection were searched from inception to 27^th January 2025. The risk of bias of individual studies was assessed using the Newcastle-Ottawa Scale. A narrative synthesis of all included studies was performed. A random-effects meta-analysis was also conducted. Cochran’s Q test was used to test for heterogeneity, and the I² statistic was used to quantify its extent. A sensitivity analysis was performed to assess the robustness of the results.

Results

1633 abstracts were screened, 143 were taken forward to full-text assessment, and 12 studies were included in the final review. 10 assessed DNA methylation and 2 assessed microRNAs. There was substantial diversity across studies in the specific biomarkers assessed, definitions of progression, and statistical approaches used. Studies suggested that methylation levels of genes such as p16, RUNX3, HPP1, APC and OR3A4 could predict progression to HGD/OAC. Panels assessing methylation of multiple genes, and prediction models incorporating gene methylation data, also predicted progression. Additionally, certain microRNAs, such as miR-192, 194, 196a and 196b, were predictive of progression.
A meta-analysis of 4 studies assessing p16 methylation was performed, showing that p16 methylation was associated with an increased risk of progression of BO to HGD/OAC (pooled odds ratio (OR) 2.11, 95% confidence interval (CI) 1.19 – 3.76, p = 0.01). There was evidence of moderate heterogeneity (I² = 46.2%; Q = 5.57, p = 0.13). A sensitivity analysis was performed, excluding 1 study that had required a continuity correction to calculate the OR. This yielded a more precise estimate (pooled OR = 1.78, 95% CI = 1.36 – 2.32, p < 0.0001; I² = 4.5%), supporting the robustness of the association.

Conclusion

Epigenetic biomarkers, particularly p16 methylation, show promise in predicting progression of BO to HGD/OAC. However, the evidence base remains limited and heterogeneous. Given the potential clinical utility of risk prediction biomarkers in BO, this is an important area for further research.

References

1. Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study. JNCI J Natl Cancer Inst. 2011 Jul 6;103(13):1049–57.