Meta-Analysis
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2016; 22(39): 8831-8843
Published online Oct 21, 2016. doi: 10.3748/wjg.v22.i39.8831
Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists
Harsha Moole, Jaymon Patel, Zohair Ahmed, Abhiram Duvvuri, Sreekar Vennelaganti, Vishnu Moole, Sowmya Dharmapuri, Raghuveer Boddireddy, Pratyusha Yedama, Naveen Bondalapati, Achuta Uppu, Prashanth Vennelaganti, Srinivas Puli
Harsha Moole, Jaymon Patel, Zohair Ahmed, Department of Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL 61637, United States
Harsha Moole, Department of Medicine, Apogee Medical Group, Davenport, IA 52804, United States
Abhiram Duvvuri, Sreekar Vennelaganti, Division of Gastroenterology and Hepatology, Kansas City Veteran Affairs Medical Center, Kansas City, MO 64128, United States
Vishnu Moole, Sowmya Dharmapuri, Raghuveer Boddireddy, Pratyusha Yedama, Department of Medicine, NTR University of Health Sciences, Andhra Pradesh 520008, India
Naveen Bondalapati, Department of Medicine, Barnes Jewish Christian Medical Group, Christian Hospital, St. Louis, MO 63136, United States
Achuta Uppu, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, United States
Prashanth Vennelaganti, Division of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, MO 66160, United States
Srinivas Puli, Division of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, IL 61637, United States
Author contributions: Moole H conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, critical revision, and final approval; Patel J acquisition of data, analysis and interpretation of data, drafting the article, final approval; Ahmed Z acquisition of data, analysis and interpretation of data, drafting the article, final approval; Duvvuri A interpretation of data, revising the article, final approval; Vennelaganti S interpretation of data, revising the article, final approval; Moole V acquisition of data, interpretation of data, drafting the article, revising the article, final approval; Dharmapuri S interpretation of data, revising the article, final approval; Boddireddy R acquisition of data, analysis and interpretation of data, drafting the article, final approval; Yedama P acquisition of data, analysis and interpretation of data, drafting the article, final approval; Bondalapati N acquisition of data, analysis and interpretation of data, drafting the article, final approval; Uppu A acquisition of data, analysis and interpretation of data, drafting the article, final approval; Vennelaganti P interpretation of data, revising the article, final approval; Puli S conception and design of the study, critical revision, final approval.
Conflict-of-interest statement: The authors deny any conflict of interest.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Harsha Moole, MD, Clinical Associate, Department of Medicine, University of Illinois College of Medicine at Peoria, 1 Illini Dr, Peoria, IL 61637, United States. harsha1778@yahoo.co.in
Telephone: +1-309-6557257 Fax: +1-844-8936705
Received: July 11, 2016
Peer-review started: July 12, 2016
First decision: August 19, 2016
Revised: September 4, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: October 21, 2016
Processing time: 101 Days and 15.4 Hours
Abstract
AIM

To evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists.

METHODS

Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.

RESULTS

Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett’s esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27).

CONCLUSION

When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett’s esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Keywords: Barrett’s esophagus; Low grade dysplasia; High grade dysplasia; Esophageal adenocarcinoma; Annual incidence of progression; Systematic review; Meta-analysis

Core tip: Current estimates suggest that annual incidence of progression from low grade dysplasia (LGD) to high grade dysplasia and/or esophageal adenocarcinoma is 0.5% to 4% per year. Current estimates are based on diagnosis made by one pathologist. Recent studies indicate that when the diagnosis of LGD is made by two or more expert pathologists, LGD progression is grossly underestimated. When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett’s esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.