Foulis, Alan K.

Fullarton, Grant M.

Going, James J.

Moyes, Lisa H.

Oien, Karin A.

English

PubMed

Lisa H Moyes

Karin A Oien

Alan K Foulis

Grant M Fullarton

James J Going

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Prevalent low-grade dysplasia: the strongest predictor of malignant progression in Barrett's columnar-lined oesophagus

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LETTERPrevalent low-grade dysplasia:the strongest predictor ofmalignant progression inBarrett’s columnar-linedoesophagusDear Professor Emad El-Omar,We read with interest the work by Duitset al1 who ﬁnd that validated low-gradedysplasia (LGD) is highly predictive ofmalignant progression in Barrett’soesophagus (BO). Yachimski2 stresses theneed for this important ﬁnding to be vali-dated in other centres. Our experience ofprevalent LGD as a predictor of malignantprogression in BO in the West of Scotlandstrongly reinforces the conclusions of ourcolleagues in the Netherlands.Patients with BO diagnosed between1994 and 2009 at one centre (GlasgowRoyal Inﬁrmary (GRI)) all had BO visibleendoscopically, with biopsy-proven meta-plastic glandular mucosa in the tubularoesophagus. Exclusions for residenceoutside GRI catchment area, severecomorbidities, refusal of surveillance, lossto follow-up, high-grade dysplasia (HGD)or oesophageal adenocarcinoma (OA) atdiagnosis (or ascertained within 1 year ofindex endoscopy), or being indeﬁnite fordysplasia (n=15) left 145 short (≤3 cm)and 577 long (>3 cm) patients with BOin surveillance.Biopsy protocol was by endoscopist’schoice. Endoscopy was biennial withoutLGD, and 3–6 monthly after LGD ascer-tainment. Patients with new HGD or OAwere offered endoscopic treatment orsurgery. Proton pump inhibitors (PPIs)were prescribed throughout. Death and itscauses were ascertained from the regionalregistrar. Follow-up was from entry toprogression, death or 31 December 2012.Age and BO length thresholds weretaken as <65, 65–74, >75 years; ≤3 cm,>3 cm. Progression-free survival was exam-ined with the Kaplan–Meier estimator andCox’s proportional hazards regression ofprogression to HGD or OAwith the follow-ing factors: prevalent dysplasia as originallyreported, age, gender, segment length andsocial deprivation, using R V.3.0.2, withlibraries survival andmuhaz.Our 722-person cohort of 437 men(1st quartile:median:3rd quartile53:63:72 years) and 285 women(61:69:78 years) underwent 74 989months’ follow-up (75:109:137 months).N=58 patients with prevalent dysplasiawere slightly older (median 67 vs64 years, p<0.05) and more likely to bemale (40 men, 18 women, p<0.02). Ofthese 58, 21 (36%) progressed to HGD(9) or OA (12) at overall rates of 2.0%and 2.7% per annum, respectively(p<0.001).Of the 664 patients without identiﬁedprevalent dysplasia, 85 progressed:54 (8%) to LGD at 0.93% per annum.Only 10 (1.5%) developed HGD at0.17% per annum and 21 (3.2%) OA, at0.36% per annum. LGD was powerfullypredictive of progression, with HR 10.8(95% CI 5.9 to 18.1) for progression toHGD and 7.3 (95% CI 3.6 to 14.7) forprogression to OA. No other factor wasprognostic independent of LGD.Figure 1A shows malignant progression(to HGD/OA) stratiﬁed by prevalent LGDstatus. Comparison with ﬁgure 3 of Duitset al1 shows an identical proportion ofpatients with LGD with malignant pro-gression in our cohort and in the Dutchcohort (ﬁgure 1B).Our patients with BO and prevalentLGD had a 10-fold hazard of progressionto HGD and sevenfold to OA comparedwith those without dysplasia. Kaplan–Meier plots for progression to HGD/OAin our patients with LGD and those vali-dated by Duits et al are almost identical:this is good evidence that what we callLGD in Glasgow and what our expert col-leagues in Amsterdam and Nieuwegeincall LGD are indeed the same.Our analysis is of histopathology reportsas originally issued by reporting patholo-gist(s), but throughout the study period,specialist GI pathologists, AKF, JJG andKAO, were readily available to colleaguesfor discussion and case review. We are notspecial, and we think any motivated groupof GI histopathologists should achieve riskstratiﬁcation equally good or better. Westrongly endorse present recommendationsfor peer review and audit of dysplasia diag-noses in BO.3 Radiofrequency ablation(RFA) prevents progression of LGD inBO,4 but it is not universally accepted thatmalignant progression occurs oftenenough in LGD to justify RFA. We thinkvalidated LGD (purged of spurious diag-noses) is a genuine marker of high progres-sion risk in BO, which should be activelysought in new BO cases and when found,should be treated.Lisa H Moyes,1 Karin A Oien,2,3 Alan K Foulis,2Grant M Fullarton,1 James J Going2,31Department of Surgery, Glasgow Royal Inﬁrmary,Glasgow, UKFigure1 (A) Kaplan–Meier curves for malignant progression (to HGD and/or OA) in Glasgow BOcases with prevalent LGD (red curve) and without (blue). Grey shading represents 95% CI. Numbersin follow-up are given above the x axis. (B) duplicates the ﬁrst 5 years of these curves andsuperimposes (in orange) the curve for malignant progression of LGD, validated by Duits et al1 in theNetherlands. The LGD curves are very close at 5 years. BO, Barrett’s oesophagus; HGD, high-gradedysplasia; LGD, low-grade dysplasia; NL, Netherlands; OA, oesophageal adenocarcinoma.Gut Month 2015 Vol 0 No 0 1PostScript Gut Online First, published on June 17, 2015 as 10.1136/gutjnl-2015-309978Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& BSG) under licence. group.bmj.com on July 31, 2015 - Published by http://gut.bmj.com/Downloaded from 2Department of Pathology, South Glasgow UniversityHospital, Glasgow, UK3Institute of Cancer Sciences, University of Glasgow,Glasgow, UKCorrespondence to Dr James J Going, Department ofPathology, South Glasgow University Hospital, GlasgowG51 4TF, UK; gqxa02@udcf.gla.ac.ukAcknowledgements The important role ofconsultant surgeon Mr Robert C Stuart in establishingBarrett’s Oesophagus services at Glasgow RoyalInﬁrmary is respectfully acknowledged.Contributors LHM, GMF and JJG designed the study.AKF, KAO and JJG were responsible for histopathologyreporting. LHM collated the data. LHM and JJG analysedit. LHM and JJG drafted the manuscript with input from allauthors. JJG had access to all data, and takesresponsibility for its integrity and accuracy of data analysis.Competing interests GMF has received consultancyfees for Barrx/Covidien RFA meetings.Provenance and peer review Not commissioned;internally peer reviewed.Data sharing statement We would be content forinterested parties to.Open Access This is an Open Access articledistributed in accordance with the Creative CommonsAttribution Non Commercial (CC BY-NC 4.0) license,which permits others to distribute, remix, adapt, buildupon this work non-commercially, and license theirderivative works on different terms, provided theoriginal work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/To cite Moyes LH, Oien KA, Foulis AK, et al. GutPublished Online First: [please include Day Month Year]doi:10.1136/gutjnl-2015-309978Received 14 May 2015Revised 29 May 2015Accepted 1 June 2015Gut 2015;0:1–2. doi:10.1136/gutjnl-2015-309978REFERENCES1 Duits LC, Phoa KN, Curvers WL, et al. Barrett’soesophagus patients with low-grade dysplasia can beaccurately risk-stratiﬁed after histological review by anexpert panel. Gut 2015;64:700–6.2 Yachimski P. What we talk about when we talk aboutdysplasia. Gut 2015;64:695–6.3 Fitzgerald RC, di Pietro M, Raganuth K, et al. BritishSociety of Gastroenterology guidelines on thediagnosis and management of Barrett’s oesophagus.Gut 2014;63:7–42.4 Phoa KN, van Vilsteren FG, Weusten BL, et al.Radiofrequency ablation vs endoscopic surveillance forpatients with Barrett esophagus and low-grade dysplasia:a randomized clinical trial. JAMA 2014;311:1209–17.2 Gut Month 2015 Vol 0 No 0PostScriptgroup.bmj.com on July 31, 2015 - Published by http://gut.bmj.com/Downloaded from Barrett's columnar-lined oesophaguspredictor of malignant progression in Prevalent low-grade dysplasia: the strongestJ GoingLisa H Moyes, Karin A Oien, Alan K Foulis, Grant M Fullarton and James published online June 17, 2015Gut  http://gut.bmj.com/content/early/2015/06/17/gutjnl-2015-309978Updated information and services can be found at: These include:References#BIBLhttp://gut.bmj.com/content/early/2015/06/17/gutjnl-2015-309978This article cites 4 articles, 3 of which you can access for free at: Open Accesshttp://creativecommons.org/licenses/by-nc/4.0/non-commercial. See: provided the original work is properly cited and the use isnon-commercially, and license their derivative works on different terms, permits others to distribute, remix, adapt, build upon this workCommons Attribution Non Commercial (CC BY-NC 4.0) license, which This is an Open Access article distributed in accordance with the CreativeserviceEmail alertingbox at the top right corner of the online article. Receive free email alerts when new articles cite this article. Sign up in theCollectionsTopic Articles on similar topics can be found in the following collections  (211)Open accessNoteshttp://group.bmj.com/group/rights-licensing/permissionsTo request permissions go to:http://journals.bmj.com/cgi/reprintformTo order reprints go to:http://group.bmj.com/subscribe/To subscribe to BMJ go to:group.bmj.com on July 31, 2015 - Published by http://gut.bmj.com/Downloaded from 

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Prevalent low-grade dysplasia: the strongest predictor of malignant progression in Barrett's columnar-lined oesophagus

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