t

ttrdebsolftoE

a

EDITORIAL

Barrett’s esophagus: should we burn it all?

Hrg

rcmnLwiwtiestatatTsoamepwptmoottn

Controversy continues on the issue of whether non-neoplastic Barrett’s esophagus and Barrett’s esophaguswith premalignant lesions such as low-grade intraepithe-lial neoplasia (LGIN) and high-grade intraepithelial neo-plasia (HGIN) should be eradicated endoscopically byusing ablative methods. The main argument in the past forendoscopic ablation using photodynamic therapy (PDT)or argon plasma coagulation (APC) was that it is capable ofpreventing cancer, against the background of the dramaticincrease in the incidence of esophageal adenocarcinomaduring the past few decades. There is no doubt that Bar-rett’s esophagus is a precancerous lesion, and Barrett’swith premalignant lesions in particular is associated with asignificant risk of malignant transformation.

The main arguments against endoscopic ablation inpatients with non-neoplastic Barrett’s esophagus are thevery low rate of malignant transformation,1 adverse post-treatment events such as pain and fever, and major com-plications such as perforations, stenosis, and bleeding.2 Inaddition, none of the methods available have been shownto achieve 100% complete ablation of Barrett’s metaplasia;buried glands with neoplastic potential2,3 may persist, andhere is therefore a need for continued surveillance.

In view of these facts, it has generally been acceptedhat non-neoplastic Barrett’s esophagus should not bereated endoscopically. In contrast to non-neoplastic Bar-ett’s esophagus, true premalignant lesions (LGIN, HGIN)etected in a Barrett’s segment and confirmed by a secondxperienced pathologist have to be treated endoscopicallyecause there is a high risk of progression to cancer, andynchronous cancer is often already present. The methodf choice in these cases is endoscopic resection if theesions are detectable. Endoscopic resection is mandatoryor these lesions because it allows histological classifica-ion of the resected specimen, in contrast to ablative meth-ds, which destroy the tissue that is treated. At least inurope, this therapeutic approach is widely accepted.

The development and introduction of radiofrequencyblation (RFA), with initially good results,4,5 revived de-

bates on whether all types of Barrett’s esophagus (non-neoplastic and premalignant) should be burned by usingthis new ablative method. Arguments in favor of RFA werethe high rate of eradication of premalignant lesions (LGIN,

Copyright © 2012 by the American Society for Gastrointestinal Endoscopy0016-5107/$36.00

8http://dx.doi.org/10.1016/j.gie.2012.09.010

www.giejournal.org Vo

GIN) as well as Barrett’s metaplasia, the relatively lowate of major complications, and the low rate of buriedlands.3

In this issue of Gastrointestinal Endoscopy, Tsai et al6

eport the results of a study using 3-dimensional opticaloherence tomography (3D-OCT) to determine the treat-ent response to RFA in patients with non-neoplastic oreoplastic short-segment Barrett’s esophagus, includingGIN and HGIN. A prototype endoscopic 3D-OCT deviceas used in the study. Two-dimensional OCT is a volumetric

maging technique that provides resolution of the GI wallith an imaging depth of up to 1 mm. The development of

he new 3D-OCT device makes it possible to combine greatermaging depth with faster imaging speed. The wall of thesophagus was scanned before and after RFA by using apecially designed OCT catheter, which is inserted throughhe endoscope’s biopsy channel. The imaging depth ofpproximately 2 mm made it possible to measure thehickness of the Barrett’s epithelium before and after ther-py. The main prerequisite for measurement is good con-act between the 3D-OCT probe and the esophageal wall.he entire Barrett’s segment was scanned every 1 mmeveral times, and the average and maximum thicknessesf the Barrett’s epithelium were recorded. The presence orbsence of unburned Barrett’s epithelium that had beenissed during RFA and of buried glands were recorded for

ach patient after 2 RFA sessions. The study included 33atients. Complete eradication of the Barrett’s epitheliumas achieved in 13 patients, but not in the other 20atients. The main predictive factor for a response to RFAreatment was the thickness of the Barrett’s epitheliumeasured before RFA. Patients with complete eradicationf Barrett’s epithelium had an average maximum thicknessf less than 300 �m compared with a thickness greaterhan 400 �m in patients with incomplete eradication. Sta-istical analysis showed that a cutoff threshold of a thick-ess of 333 �m achieved the best predictive accuracy, at

When curative endoscopic therapy is carried outin patients with early Barrett’s cancer, a precisehistopathological assessment of the neoplasia ismandatory.

7.9%, with a negative predictive value of 94.4% and a pos-

lume 76, No. 6 : 2012 GASTROINTESTINAL ENDOSCOPY 1113

tsR

itbtbtt

arisrwmuctrTdesabaciaRieFn

D

t

Ae3a

R

Editorial May

itive predictive value of 80%. The thickness of 333 �m cor-related not only with the presence or absence of endoscop-ically visible residual Barrett’s epithelium, but also with thepresence or absence of buried glands directly after RFA andduring the follow-up, with an accuracy of 87.5%.

The first studies of RFA reported positive results, with alow rate of severe complications and a high rate of erad-ication of non-neoplastic and neoplastic Barrett’s esopha-gus.4,5 In addition, the rate of buried glands also appearedo be lower with RFA compared with PDT and APC. Aystematic review noted a 0.9% rate of buried glands afterFA compared with 14.2% after PDT and 8% after APC.2,3

After these initially excellent results, RFA appeared to bethe new star in the world of endoscopic ablation.

The results recently reported by Zhou et al,7 which aren contrast to all of the previous results, were therefore allhe more disappointing. It was shown using 3D-OCT thaturied glands were present after RFA in 63% of the pa-ients. One explanation for this might be that the standardiopsies performed in earlier studies are not deep enougho detect buried glands. The extent of the malignant po-ential of buried glands is not yet known, but it does exist.8

These findings show that the ablative tools currently avail-able are still not optimal. After all the enthusiasm that fol-lowed the introduction of RFA, the question of whether itmakes sense to ablate Barrett’s epithelium now must befaced. At first glance, this question might seem difficult toanswer, but it is not. We only have to be aware of a few facts.

First, the findings by Zhou et al and Tsai et al onlyunderscore the general rational view that non-neoplasticBarrett’s epithelium should not be ablated endoscopically,even in the age of RFA. Second, ablative and thus destruc-tive methods should not be used as primary therapy for(detectable) neoplastic Barrett’s because LGIN and HGINare very often already taking place alongside adenocarci-noma. Our own group9 and others10 have confirmed thevalue of endoscopic resection of early Barrett’s cancer incertain conditions. These conditions are determined by thehistopathological assessment of the Barrett’s neoplasiawith regard to infiltration depth, differentiation, and lym-phatic or blood vessel invasion—all important risk factorsfor lymph node metastasis. When curative endoscopictherapy is carried out in patients with early Barrett’s can-cer, a precise histopathological assessment of the neopla-sia is mandatory, and this can only be achieved by endo-scopic resection, not by thermal destruction. Third, theindisputable value of ablative treatment for the residualnon-neoplastic Barrett’s epithelium after resection of theneoplastic areas is based on the fact that ablation leads toa dramatic reduction in the rate of metachronous neopla-sias detected during the follow-up.11-13 In a single-center,prospective, randomized trial, our group showed that in36.7% of the patients in the surveillance group who did notundergo ablation after resection, metachronous HGIN oradenocarcinoma developed, whereas it did not develop in

2.6% of those who received ablation as the second step

1114 GASTROINTESTINAL ENDOSCOPY Volume 76, No. 6 : 2012

fter resection.12 The discrepancy from the higher 16.5%ate of metachronous lesions reported by our group in Gutn 2008 is explained by the fact that in the early stage of thetudy, ablation was not performed near the time of theesection, but was added later during follow-up when itas found that without ablation, the rate of recurrent andetachronous lesions was more than 30%.14 The strategysed for curative endoscopic therapy for early Barrett’sancer was therefore changed. Endoscopic resection ofhe neoplasia is the first step, followed by ablation of theesidual non-neoplastic Barrett’s epithelium as the second.he correctness of this approach has been confirmed byata reported by the Amsterdam group.13 The only differ-nce is that we used APC for ablation, whereas the Am-terdam group used RFA. The question of which type ofblation should be used cannot be answered at presentecause 3D-OCT data after ablation using APC are not yetvailable. It is possible that the rate of buried glands isomparable to that after RFA, but it is also conceivable thatt might be lower, at least if high-energy APC is used forblation, because of the deeper ablation compared withFA. The thickness of the Barrett’s epithelium plays anmportant role in the success of eradication of Barrett’spithelium, as has been very clearly shown by Tsai et al.6

urther studies and technical improvements are thereforeeeded in this field to optimize ablation treatment.

ISCLOSURE

The author disclosed no financial relationships relevanto this publication.

Andrea May, MD, PhDDepartment of Internal Medicine II

HSK/Dr Horst Schmidt Kliniken GmbHWiesbaden, Germany

bbreviations: APC, argon plasma coagulation; HGIN, high-grade intra-pithelial neoplasia; LGIN, low-grade intraepithelial neoplasia; 3D-OCT,-dimensional optical coherence tomography; PDT, photodynamic ther-py; RFA, radiofrequency ablation.

EFERENCES

1. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarci-noma among patients with Barrett’s esophagus. N Engl J Med 2011;365:1375-83.

2. Manner H, May A, Miehlke S, et al. Ablation of nonneoplastic Barrett’smucosa using argon plasma coagulation with concomitant esomepra-zole therapy (APBANEX): a prospective multicenter evaluation. Am JGastroenterol 2006;101:1762-9.

3. Gray NA, Odze RD, Spechler SJ. Buried metaplasia after endoscopic ab-lation of Barrett’s esophagus: a systematic review. Am J Gastroenterol2011;106:1899-908.

4. Ganz RA, Overholt BF, Sharma VK, et al. Circumferential ablation of Bar-rett’s esophagus that contains high-grade dysplasia: a U.S. MulticenterRegistry. Gastrointest Endosc 2008;68:35-40.

5. Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in

Barrett’s esophagus with dysplasia. N Engl J Med 2009;360:2277-88.

www.giejournal.org

1

1

1

1

May Editorial

6. Tsai TH, Zhou C, Tao YK, et al. Structural markers observed with endo-scopic three-dimensional optical coherence tomography correlatingwith Barrett’s esophagus radiofrequency ablation treatment response.Gastrointest Endosc 2012;76:1104-12.

7. Zhou C, Tsai TH, Lee HC, et al. Characterization of buried glands beforeand after radiofrequency ablation by using 3-dimensional optical co-herence tomography. Gastrointest Endosc 2012;76:32-40.

8. Titi M, Overhiser A, Ulusarac O, et al. Development of subsquamous high-grade dysplasia and adenocarcinoma after successful radiofrequency abla-tion of Barrett’s esophagus. Gastroenterology 2012;143:564-6.

9. Pech O, May A, Manner H, et al. Endoscopic resection in 953 patientswith mucosal Barrett’s cancer [abstract]. Gastrointest Endosc 2011;73(4Suppl):AB146.

10. Alvarez Herrero L, Pouw RE, van Vilsteren FG, et al. Safety and efficacy ofmultiband mucosectomy in 1060 resections in Barrett’s esophagus. En-

doscopy 2011;43:177-83.

www.giejournal.org Vo

1. Pech O, Behrens A, May A, et al. Long-term results and risk factor analysisfor recurrence after curative endoscopic therapy in 349 patients withhigh-grade intraepithelial neoplasia and mucosal adenocarcinoma inBarrett’s oesophagus. Gut 2008;57:1200-6.

2. Manner H, Rabenstein T, Braun K, et al. Final results of a prospectiverandomized trial on thermal ablation of Barrett’s mucosa with concom-itant esomeprazole treatment versus surveillance plus PPI in patientscured from early Barrett’s cancer by endoscopic resection (APE study)[abstract]. Gastrointest Endosc 2011;73(4 Suppl):AB197.

3. Pouw RE, Wirths K, Eisendrath P, et al. Efficacy of radiofrequency abla-tion combined with endoscopic resection for Barrett’s esophagus withearly neoplasia. Clin Gastroenterol Hepatol 2010;8:23-9.

4. May A, Gossner L, Pech O, et al. Local endoscopic therapy for intraepi-thelial high grade neoplasia and early adenocarcinoma in Barrett’s oe-sophagus: acute-phase and intermediate results of a new treatment

approach. Eur J Gastroenterol Hepatol 2002;14:1085-91.

lume 76, No. 6 : 2012 GASTROINTESTINAL ENDOSCOPY 1115