
This review focuses on the histopathological evaluation of
endoscopic mucosal resection (EMR) specimens in Barrett’s esophagus, and
on the histopathological, biological, and molecular properties of postablation
Barrett’s esophagus. EMR may be used for both diagnostic and therapeutic
purposes. Diagnostic accuracy regarding the grade and stage of neoplasms is
improved with the use of EMR, but the value of this technique for treatment is
more controversial because of the high prevalence rate of positive margins and
the rate of metachronous lesions found elsewhere in the esophagus during
follow-up. Ablation techniques, such as argon plasma coagulation, photodynamic
therapy, and radiofrequency ablation, are used increasingly for the treatment
of Barrett’s esophagus and related neoplasms, often in combination with
EMR. A common problem after use of these techniques is the development of
islands of neosquamous epithelium (NSE) which can overlie buried
Barrett’s (and/or dysplasia) epithelium. This is, therefore, concealed to
the endoscopist’s view and may be allowed to progress to cancer without
detection. NSE is histologically similar to normal esophageal squamous
epithelium and does not possess the molecular aberrations characteristic of
Barrett’s esophagus. In contrast, residual nonburied Barrett’s
esophagus shows persistent pathologic and molecular abnormalities and may
progress to cancer upon long term follow-up. The biological potential and rate
of progression of nonburied residual Barrett’s esophagus following
ablation is unclear, but some preliminary studies suggest that the risk may
decrease. Buried nondysplastic Barrett’s esophagus appears to show
decreased biological potential and this may be related to protection from the
contents of the lumen by the barrier function of the overlying NSE. On the
other hand, anecdotal reports have suggested that buried dysplasia may progress
to cancer in some instances.
References
-
1
Wang K, Sampliner R.
Updated guidelines 2008 for the diagnosis, surveillance, and
therapy of Barrett’s esophagus.
Am J Gastroenterol.
2008;
103
788-797
-
2 British Society of Gastroenterology Guidelines for the diagnosis and management of
Barrett’s columnar-lined oesophagus. http://www.bsg.org.uk/pdf_word_docs/Barretts_Oes.pdf; Stand: 2005
-
3
Kelty C, Gough M, Van Wyk Q.
Barrett’s oesophagus: Intestinal metaplasia is not
essential for cancer risk.
Scan J Gastroenterol.
2007;
42
1271-1274
-
4
Takubo K, Aida J, Naomoto Y. et al .
Cardiac rather than intestinal-type background in endoscopic
resection specimens of minute Barrett adenocarcinoma.
Hum Pathol.
2008;
-
5
Jones T F, Sharma P, Daaboul B. et al .
Yield of intestinal metaplasia in patients with suspected
short-segment Barrett’s esophagus (SSBE) on repeat endoscopy.
Dig Dis Sci.
2002;
47
2108-2111
-
6
Harrison R, Perry I, Haddadin W. et al .
Detection of intestinal metaplasia in Barrett’s
esophagus: an observational comparator study suggests the need for a minimum of
eight biopsies.
Am J Gastroenterol.
2007;
102
1154-1161
-
7
Oberg S, Johansson J, Wenner J. et al .
Endoscopic surveillance of columnar-line esophagus: frequency
of intestinal metaplasia detection and impact of antireflux surgery.
Ann Surg.
2001;
234
619-626
-
8
Chandrasoma P, Der R, Dalton P.
Distribution and significance of epithelial types in
columnar-lined esophagus.
Am J Surg Pathol.
2001;
25
1188-1193
-
9
Odze R D.
Update on the diagnosis and treatment of Barrett’s
esophagus and related neoplastic precursor lesions.
Arch Pathol Lab Med.
2008;
132 (10)
1577-1585
-
10
Hahn H, Shahsafaei A, Odze R D.
Vascular and lymphatic properties of the superficial and deep
lamina propria in Barrett’s esophagus.
Am J Surg Pathol.
2008;
32
1454-1461
-
11
Glickman J N, Chen Y Y, Wang H H. et al .
Phenotypic characteristics of a distinctive multilayered
epithelium suggests that it is a precursor in the development of
Barrett’s esophagus.
Am J Surg Pathol.
2001;
25
569-578
-
12
Westerterp M, Koppert L B, Buskens C J. et al .
Outcome of surgical treatment for early adenocarcinoma of the
esophagus or gastro-esophageal junction.
Virchows Arch.
2005;
446
497-504
-
13
Reid B J, Haggitt R C, Rubin E C. et al .
Observer variation in the diagnosis of dysplasia in
Barrett’s esophagus.
Hum Pathol.
1988;
19
166-178
-
14
Schlemper R J, Riddell R H, Kato Y. et al .
The Vienna classification of gastrointestinal epithelial
neoplasia.
Gut.
2000;
47
251-255
-
15
Odze R D.
Diagnosis and grading of dysplasia in Barrett’s
oesophagus.
J Clin Pathol.
2006;
59
1029-1038
-
16
Montgomery E, Bronner M P, Goldblum J R. et al .
Reproducibility of the diagnosis of dysplasia in
Barrett’s esophagus: a reaffirmation.
Hum Pathol.
2001;
32
368-378
-
17
Lomo L, Blount P L, Sanchez C A. et al .
Crypt dysplasia with surface maturation: a clinical,
pathologic and molecular study of a Barrett’s esophagus cohort.
Am J Surg Pathol.
2006;
30
423-435
-
18
Srivastava A, Hornick J L, Li X. et al .
Extent of low-grade dysplasia is a risk factor for the
development of esophageal adenocarcinoma in Barrett’s esophagus.
Am J Gastroenterol.
2007;
102
483-493
-
19
Skacel M, Petras R E, Gramlich T L. et al .
The diagnosis of low-grade dysplasia in Barrett’s
esophagus and its implications for disease progression.
Am J Gastroenterol.
2000;
95
3383-3387
-
20
Kerkhof M, Van Dekken H, Steyerberg E W. et al .
Grading of dysplasia in Barrett’s oesophagus:
Substantial interobserver variation between general and gastrointestinal
pathologists.
Histopathology.
2007;
50
920-927
-
21
Nijhawan P K, Wang K K.
Endoscopic mucosal resection for lesions with endoscopic
features suggestive of malignancy and high-grade dysplasia within
Barrett’s esophagus.
Gastrointest Endosc.
2000;
52
328-332
-
22
Mino-Kenudson M, Brugge W R, Puricelli W P. et al .
Management of superficial Barrett’s epithelium-related
neoplasms by endoscopic mucosal resection: clinicopathologic analysis of 27
cases.
Am J Surg Pathol.
2005;
29
680-686
-
23
Peters F P, Brakenhoff K PM, Curvers W L. et al .
Histologic evaluation of resection specimens obtained at 293
endoscopic resections in Barrett’s esophagus.
Gastrointest Endosc.
2008;
67
604-609
-
24
Lauwers G Y, Ban S, Mino M. et al .
Endoscopic mucosal resection for gastric epithelial
neoplasms: a study of 39 cases with emphasis on the evaluation of specimens and
recommendations for optimal pathologic analysis.
Mod Pathol.
2004;
17
2-8
-
25
Conio M, Repici A, Cestari R. et al .
Endoscopic mucosal resection for high-grade dysplasia and
intramucosal carcinoma occurring in Barrett’s esophagus.
Gastrointest Endosc.
2004;
59
AB253 [W1549]
-
26
Larghi A, Lightdale C J, Memeo L. et al .
EUS followed by EMR for staging of high-grade dysplasia and
early cancer in Barrett’s esophagus.
Gastrointest Endosc.
2005;
62
16-23
-
27
Hull M J, Mino-Kenudson M, Nishioka N S. et al .
Endoscopic mucosal resection: an improved diagnostic
procedure for early gastroesophageal epithelial neoplasms.
Am J Surg Pathol.
2006;
30
114-118
-
28
Mino-Kenudson M, Ohana M, Ban S. et al .
Barrett esophagus associated neoplasms treated by
photodynamic therapy: determination of limiting factors
[abstract].
Lab Invest.
2006;
86
114A (Abstract 517)
-
29
Mandal R V, Forcione D G, Brugge W R. et al .
Effect of tumor characteristics and duplication of the
muscularis mucosae on the endoscopic staging of superficial Barrett
esophagus-related neoplasia.
Am J Surg Pathol.
2008;
In press
-
30
Ell C, May A, Pech O. et al .
Curative endoscopic resection of early esophageal
adenocarcinomas (Barrett’s cancer).
Gastrointest Endosc.
2007;
65
3-10
-
31
Vieth M, Ell C, Gossner L. et al .
Histological analysis of endoscopic resection specimens from
326 patients with Barrett’s esophagus and early neoplasia.
Endoscopy.
2004;
36
776-781
-
32
Pacifico R J, Wang K K, Wongkeesong L M. et al .
Combined endoscopic mucosal resection and photodynamic
therapy versus esophagectomy for management of early adenocarcinoma in
Barrett’s esophagus.
Clin Gastroenterol Hepatol.
2003;
1
252-257
-
33
Prasad G A, Buttar N S, Wongkeesong L M. et al .
Significance of neoplastic involvement of margins obtained by
endoscopic mucosal resection in Barrett’s esophagus.
Am J Gastroenterol.
2007;
102
2380-2386
-
34
May A, Gossner L, Behrens A. et al .
A prospective randomized trial of two different endoscopic
resection techniques for early stage cancer of the esophagus.
Gastrointest Endosc.
2003;
58
167-175
-
35
Berenson M M, Johnson T D, Markowitz N R. et al .
Restoration of squamous mucosa after ablation of
Barrett’s esophageal epithelium.
Gastroenterology.
1993;
104
1686-1691
-
36
Hornick J L, Blount P L, Sanchez C A. et al .
Biologic properties of columnar epithelium underneath
reepithelialized squamous mucosa in Barrett’s esophagus.
Am J Surg Pathol.
2005;
29
372-380
-
37
Ban S, Mino M, Nishioka N. et al .
Histopathologic aspects of photodynamic therapy for dysplasia
and early adenocarcinoma arising in Barrett’s esophagus.
Am J Surg Pathol.
2004;
28
1466-1473
-
38
Sampliner R, Fass R.
Partial regression of Barrett’s esophagus – an
inadequate endpoint.
Am J Gastroenterol.
1993;
88
2092-2094
-
39
Biddlestone L, Barham C, Wilkinson S. et al .
The histopathology of treated Barrett’s esophagus:
squamous reepithelialization after acid suppression and laser and photodynamic
therapy.
Am J Surg Pathol.
1998;
22
239-245
-
40
Sharma V K, Wang K K, Overhold B F. et al .
Balloon-based, circumferential, endoscopic radiofrequency
ablation of Barrett’s esophagus: 1-year follow-up of 100 patients.
Gastrointest Endosc.
2007;
65
185-195
-
41
Sharma V K, Kim H J, Das A. et al .
A prospective pilot trial of ablation of Barrett’s
esophagus with low-grade dysplasia using stepwise circumferential and focal
ablation (HALO system).
Endoscopy.
2008;
40
380-387
-
42
Gondrie J J, Pouw R E, Sondermeijer C M. et al .
Stepwise circumferential and focal ablation of
Barrett’s esophagus with high-grade dysplasia: results of the first
prospective series of 11 patients.
Endoscopy.
2008;
40
359-369
-
43
Gondrie J J, Pouw R E, Sondermeijer C M. et al .
Effective treatment of early Barrett neoplasia with stepwise
circumferential and focal ablation using the HALO system.
Endoscopy.
2008;
40
370-379
-
44
Gossner L, Stolte M, Sroka R. et al .
Photodynamic ablation of high-grade dysplasia and early
cancer in Barrett’s esophagus by means of 5-amino-levulinic acid.
Gastroenterology.
1998;
114
448-455
-
45
Barham C P, Jones R L, Biddlestone L R. et al .
Photothermal laser ablation of Barrett’s oesophagus:
endoscopic and histological evidence of squamous re-epithelialisation.
Gut.
1997;
41
281-284
-
46
Van Laethem J L, Peny M O, Salmon I. et al .
Intramucosal adenocarcinoma arising under squamous
re-epithelialisation of Barrett’s oesophagus.
Gut.
2000;
46
574-577
-
47
Ackroyd R, Brown N J, Davis M F. et al .
Photodynamic therapy for dysplastic Barrett’s
oesophagus: a prospective, double blind, randomised, placebo controlled
trial.
Gut.
2000;
47
612-617
-
48
Sampliner R E, Faigel D, Fennerty M B. et al .
Effective and safe endoscopic reversal of nondysplastic
Barrett’s esophagus with thermal electrocoagulation combined with
high-dose acid inhibition: A multicenter study.
Gastrointest Endosc.
2001;
53
554-558
-
49
Peters F TM, Ganesh S, Kuipers E J. et al .
Endoscopic regression of Barrett’s oesophagus during
omeprazole treatment; a randomised double blind study.
Gut.
1999;
45
489-494
-
50
Paulson T, Xu L J, Sanchez C. et al .
Neosquamous epithelium does not typically arise from
Barrett’s epithelium.
Clin Cancer Res.
2006;
12
1701-1706
-
51
Leedham S J, Preston S L, McDonald S AC. et al .
Individual crypt genetic heterogeneity and the origin of
metaplastic glandular epithelium in human Barrett’s oesophagus.
Gut.
2008;
57
1041-1048
-
52
Finkelstein S D, Lyday W D.
The molecular pathology of radiofrequency mucosal ablation of
Barrett’s esophagus.
Gastroenterology.
2008;
134
A437
-
53
Sarosi G, Brown G, Jaiswal K. et al .
Bone marrow progenitor cells contribute to esophageal
regeneration and metaplasia in a rat model of Barrett’s esophagus.
Dis Esoph.
2008;
21
43-50
-
54
Houghton J M, Stoicov C, Nomura S. et al .
Gastric cancer originating from bone marrow-derived
cells.
Science.
2004;
306
1568-1571
-
55
Thiery J P.
Epithelial-mesenchymal transitions in development and
pathologies.
Curr Opin Cell Biol.
2003;
15
740-746
-
56
Gillen P, Kneeling P, Byrne P J. et al .
Experimental columnar metaplasia in the canine
oesophagus.
Br J Surg.
1988;
75
113-115
-
57
Sharma P, Morales T G, Bhattacharyya A. et al .
Squamous islands in Barrett’s esophagus: what lies
underneath?.
Am J Gastroenterol.
1998;
93
332-335
-
58
Krishnadath K K, Wang K K, Taniguchi K. et al .
Persistent genetic abnormalities in Barrett’s esophagus
after photodynamic therapy.
Gastroenterology.
2000;
119
624-630
-
59
Reid B J, Blount P L, Feng Z. et al .
Optimizing endoscopic biopsy detection of early cancers in
Barrett’s high-grade dysplasia.
Am J Gastroenterol.
2000;
95
3089-3096
-
60
Hornick J L, Mino-Kenudson M, Lauwers G. et al .
Buried Barrett’s epithelium following photodynamic
therapy shows reduced crypt proliferation and absence of DNA content
abnormalities.
Am J Gastroenterol.
2008;
103
38-47
-
61
Panjehpour M, Coppola D, Overholt B. et al .
Photodynamic therapy of Barrett’s esophagus: ablation
of Barrett’s mucosa and reduction in p53 protein expression after
treatment.
AntiCancer Res.
2008;
28
485-490
-
62
Hage M, Siersema P, Vissers K. et al .
Genomic analysis of Barrett’s esophagus after ablative
therapy: Persistence of genetic alterations at tumor suppressor loci.
Int J Cancer.
2006;
118
155-160
-
63
Hage M, Siersema P, Vissers K. et al .
Molecular evaluation of ablative therapy of Barrett’s
oesophagus.
J Pathol.
2005;
205
57-64
R. D. OdzeMD
Brigham and Women’s Hospital
Gastrointestinal
Pathology
75 Francis St.
Boston, MA 02115
USA
Fax: 01-617-278-6950
Email: rodze@partners.org