Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2018; 24(39): 4472-4481
Published online Oct 21, 2018. doi: 10.3748/wjg.v24.i39.4472
Barrett’s esophagus with high grade dysplasia is associated with non-esophageal cancer
Nir Bar, Naama Schwartz, Michal Nissim, Naomi Fliss-Isacov, Shira Zelber-Sagi, Revital Kariv
Nir Bar, Naama Schwartz, Michal Nissim, Naomi Fliss-Isacov, Shira Zelber-Sagi, Revital Kariv, Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
Nir Bar, Naama Schwartz, Michal Nissim, Naomi Fliss-Isacov, Revital Kariv, Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
Shira Zelber-Sagi, School for Public Health, University of Haifa, Haifa 31905, Israel
Author contributions: Kariv R designed the study; Nissim M and Bar N collected the data; Schwartz N, Fliss-Isakov N and Bar N did the statistical analysis; Bar N, Kariv R, and Zelber-Sagi S prepared the manuscript; Bar N, Kariv R, Zelber-Sagi S, Fliss-Isacov N and Schwartz N critically reviewed the manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Review board (protocol number 0022-09).
Informed consent statement: Informed consent was waivered by the Institutional review board.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Revital Kariv, MD, Doctor, Department of Gastroenterology, Tel Aviv Medical Center, Weitzman 6 street, Tel Aviv 6423906, Israel.
Telephone: +972-3-6974458 Fax: +972-3-6974868
Received: July 30, 2018
Peer-review started: July 30, 2018
First decision: August 27, 2018
Revised: September 3, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 21, 2018
Research background

Patients with Barrett’s esophagus (BE) are at risk for esophageal adenocarcinoma, and surveillance is recommended. However, non-esophageal cancer is the leading cause of death in this population. This raises questions about the focus we give to surveillance for esophageal cancer, and the need for broader cancer surveillance.

Research motivation

We wanted to better describe the non-esophageal cancer morbidity in patients with BE, and specifically in patients with high grade dysplasia (HGD). Finding that patients with HGD carry a higher non-esophageal cancer risk can direct efforts and resources for cancer prevention.

Research objectives

We aimed to describe the non-esophageal cancer morbidity in patients with BE, and to test whether patients with HGD have a higher risk as compared to low grade dysplasia. Indeed, in this study we have shown that compared to non-HGD, patients with HGD have a lower all cancer and non-BE cancer free survival. The significance of these findings is in the recognition of the importance of total cancer surveillance in these patients. In addition, by comparing non-esophageal cancer morbidity in HGD and less dysplastic BE, we show the added value of information received in surveillance endoscopies. These findings put the foundations for larger cohort studies, preferably multi-center for reaching a significant number of patients.

Research methods

Endoscopic and histologic data were collected, and cancer morbidity data were retrieved from the national cancer registry. We compared non-esophageal cancers, all cancers and mortality between patients with HGD and less dysplastic BE. Cancer free survival analysis was done.

Research results

We found patients with HGD had a worse non-BE cancer free survival and all cancer free survival. The higher frequency of non-esophageal cancer in patients with HGD raises the question as to the reason for this association. Further population based and mechanistic studies are required to further investigate these reasons.

Research conclusions

Our study shows that HGD may act as a marker for all cause cancer outcome, not just esophageal cancer. Perhaps it reflects a behavioral, environmental and genetic inclination towards malignancy. After endoscopic treatment for the dysplasia, we should focus our efforts to teach these patients about healthier lifestyle, and modifiable cancer risk factors such as smoking cessation and weight reduction. Perhaps in this population, screening for other malignancies may hold a different cost-effective profile.

Research perspectives

Patients with BE and HGD have a higher non-esophageal cancer risk, on top of esophageal cancer risk. This should be confirmed in more prospective studies and population-based studies. This may shift the focus of esophageal based surveillance to a more holistic cancer prevention program for certain patients. Future research should include larger cohorts of patients from multiple centers, with detailed endoscopic and histologic data as well as other cancer risk factors including obesity measures and lifestyle behaviors as smoking, physical activity and dietary intake to better encompass risk stratification and prevention potential.