Intestinal metaplasia at the gastroesophageal junction
2004; Elsevier BV; Volume: 126; Issue: 2 Linguagem: Inglês
10.1053/j.gastro.2003.11.061
ISSN1528-0012
Autores Tópico(s)Gastric Cancer Management and Outcomes
ResumoLoren Laine, M.D. Clinical Management Editor University of Southern California Los Angeles, CaliforniaClinical caseA 52-year-old man has a 10-year history of typical heartburn several times a week. His heartburn responds well to antacids and over-the-counter H2-receptor antagonists. Recently, he read a newspaper article warning of an association between heartburn and cancer of the esophagus, and he became concerned. He called his primary care physician, who referred him to a gastroenterologist. The patient had no weight loss, dysphagia, or gastrointestinal bleeding. Physical examination and routine laboratory tests were unremarkable. An endoscopic examination was normal except for a slightly irregular squamocolumnar junction (Z-line) at the end of the esophagus. Two biopsy specimens were taken at the Z-line: one showed gastric cardiac-type epithelium with mild inflammation and Helicobacter pylori organisms, and the other showed moderately inflamed squamous epithelium abutting specialized intestinal metaplasia, typical of Barrett’s esophagus, with prominent goblet cells.BackgroundWhen discussing the management of the patient described in this report, physicians often focus on the semantic issue of what to call the condition. Does this patient have short-segment Barrett’s esophagus, intestinal metaplasia at the gastroesophageal junction (GEJ), or intestinal metaplasia of the gastric cardia? The debate over terminology often obscures the key clinical issues, which are: (1) Does this patient have a condition that predisposes to malignancy and, (2) If so, what can the clinician do to prevent cancer?The squamo-columnar and gastroesophageal junctions: what is normal?Stratified squamous epithelium normally lines the body of the esophagus, whereas the normal gastric body is lined by an oxyntic (acid-producing) columnar mucosa whose glands contain numerous parietal and chief cells. There is normally an abrupt transition from squamous to columnar epithelium in the distal esophagus that can be identified both grossly and histologically.1Spechler S.J. The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction.Gastroenterology. 1999; 117: 218-228Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar This squamo-columnar mucosal junction (the Z-line) may or may not coincide with the GEJ, the anatomical level at which the esophagus ends and the stomach begins. Endoscopically, the GEJ is recognized as the level of the most proximal extent of the gastric folds when the stomach is partially inflated with air (overinflation can obscure this landmark) (Figure 1). 2McClave S.A. Boyce Jr, H.W. Gottfried M.R. Early diagnosis of columnar-lined esophagus a new endoscopic criterion.Gastrointest Endosc. 1987; 33: 413-416Abstract Full Text PDF PubMed Scopus (219) Google Scholar, 3Sharma P. Morales T.G. Sampliner R.E. Short segment Barrett’s esophagus-the need for standardization of the definition and of endoscopic criteria.Am J Gastroenterol. 1998; 93: 1033-1036PubMed Google Scholar When the squamo-columnar junction (SCJ) is located proximal to the GEJ, there is a columnar-lined segment of esophagus.Both the histological type and the precise anatomical location of the columnar epithelium at the normal Z-line are disputed. Traditional teaching holds that the normal Z-line is a junction between squamous epithelium and cardiac epithelium, a columnar lining characterized by tortuous, tubular glands comprised almost exclusively of mucus-secreting cells.4Fawcett D.W. The esophagus and stomach.in: Fawcett D.W. Bloom A textbook of histology. 11th ed. Saunders, Philadelphia1986: 619-640Google Scholar Authorities have claimed that cardiac epithelium can line up to 2 cm of the most distal esophagus, and may extend several centimeters below the GEJ to line the most proximal stomach (the gastric cardia).4Fawcett D.W. The esophagus and stomach.in: Fawcett D.W. Bloom A textbook of histology. 11th ed. Saunders, Philadelphia1986: 619-640Google Scholar, 5Hayward J. The lower end of the oesophagus.Thorax. 1961; 16: 36-41Crossref PubMed Scopus (175) Google Scholar However, the evidence on which these claims are based is scanty and dubious. Endoscopically, the gastric folds that delimit the stomach are dynamic structures whose proximal extent may vary with respiration and gagging, and with the degree of gastric distention. Surgical and autopsy specimens of the esophagus and stomach can be manipulated mechanically so that the landmarks used to identify the GEJ (e.g., the proximal extent of gastric folds, the angle of His) vary considerably in location. Without a fixed and precise marker for the GEJ, it is difficult to establish whether the Z-line normally is located precisely at or slightly proximal to the junction of esophagus and stomach. Thus, it is not clear whether it is normal to have a short segment of columnar-lined esophagus.Pathologists also dispute fundamental histological characteristics of the cardiac epithelium. Some feel that the presence of any parietal cells in the glands precludes a histological diagnosis of cardiac epithelium,6Chandrasoma P. Pathophysiology of Barrett’s esophagus.Semin Thorac Cardiovasc Surg. 1997; 9: 270-278PubMed Google Scholar whereas others contend that cardiac epithelium can have occasional parietal cells provided that other architectural features are typical of cardiac mucosa.7Goldblum J.R. Vicari J.J. Falk G.W. Rice T.W. Peek R.M. Easley K. Richter J.E. Inflammation and intestinal metaplasia of the gastric cardia the role of gastroesophageal reflux and H. pylori infection.Gastroenterology. 1998; 114: 633-639Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar Some pathologists recommend the terms “oxyntocardiac mucosa” or “transitional mucosa” to describe a cardiac-type epithelium that has occasional parietal cells.6Chandrasoma P. Pathophysiology of Barrett’s esophagus.Semin Thorac Cardiovasc Surg. 1997; 9: 270-278PubMed Google Scholar Finally, authorities dispute whether cardiac epithelium is even a normal structure.6Chandrasoma P. Pathophysiology of Barrett’s esophagus.Semin Thorac Cardiovasc Surg. 1997; 9: 270-278PubMed Google Scholar, 8Oberg S. Peters J.H. DeMeester T.R. Chandrasoma P. Hagen J.A. Ireland A.P. Ritter M.P. Mason R.J. Crookes P. Bremner C.G. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.Ann Surg. 1997; 226: 522-532Crossref PubMed Scopus (293) Google ScholarTissues exposed chronically to agents that induce injury and inflammation may change into other types of tissue that are less susceptible to damage by those agents.1Spechler S.J. The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction.Gastroenterology. 1999; 117: 218-228Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar This process is called metaplasia. Recent studies have shown that both the squamous and columnar epithelia at the GEJ are exposed repeatedly to noxious agents capable of inducing injury and inflammation including acid, pepsin, bile, and nitric oxide.9Spechler S.J. Are we underestimating acid reflux?.Gut. 2004; (In press)PubMed Google Scholar Furthermore, many individuals, like the patient described at the beginning of this report, are infected with H. pylori, an organism that causes chronic gastritis, which also predisposes to metaplasia of columnar mucosa at the GEJ.10Watanabe T. Tada M. Nagai H. Sasaki S. Nakao M. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils.Gastroenterology. 1998; 115: 642-648Abstract Full Text Full Text PDF PubMed Scopus (921) Google Scholar It has been proposed that cardiac epithelium is a metaplastic mucosa acquired as a consequence of the chronic inflammation induced by repeated exposure to noxious agents.6Chandrasoma P. Pathophysiology of Barrett’s esophagus.Semin Thorac Cardiovasc Surg. 1997; 9: 270-278PubMed Google Scholar, 8Oberg S. Peters J.H. DeMeester T.R. Chandrasoma P. Hagen J.A. Ireland A.P. Ritter M.P. Mason R.J. Crookes P. Bremner C.G. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.Ann Surg. 1997; 226: 522-532Crossref PubMed Scopus (293) Google ScholarA recent study of 40 patients who had subtotal esophagectomy with esophagogastrostomy, an operation frequently complicated by severe reflux esophagitis in the esophageal remnant, supports the notion that cardiac epithelium is metaplastic.11Dresner S.M. Griffin S.M. Wayman J. Bennett M.K. Hayes N. Raimes S.A. Human model of duodenogastro-oesophageal reflux in the development of Barrett’s metaplasia.Br J Surg. 2003; 90: 1120-1128Crossref PubMed Scopus (106) Google Scholar Endoscopic examinations performed at a median of 36 months postoperatively showed that 19 of the 40 patients had developed columnar metaplasia in the esophageal remnant (10 cardiac epithelium, 9 intestinal metaplasia). Seven patients who had serial endoscopic examinations showed progression from cardiac epithelium on the initial postoperative endoscopy to specialized intestinal metaplasia (typical of Barrett’s esophagus) on subsequent studies. The median time to the development of cardiac epithelium was 14 months, whereas specialized intestinal metaplasia was found at a median of 27 months postoperatively. These findings suggest that cardiac epithelium is not only metaplastic, but also the precursor of intestinal metaplasia in the esophagus.Although it might seem that the issue of whether cardiac epithelium is a normal structure could be settled by a careful study of autopsy and surgical specimens of the GEJ (especially specimens from fetuses and children), such studies have yielded contradictory results. Table 1 summarizes the results of 5 recent studies on the histology of the GEJ that have focused on the prevalence of cardiac epithelium.12Kilgore S.P. Ormsby A.H. Gramlich T.L. Rice T.W. Richter J.E. Falk G.W. Goldblum J.R. The gastric cardia fact or fiction?.Am J Gastroenterol. 2000; 95: 921-924Crossref PubMed Google Scholar, 13Sarbia M. Donner A. Gabbert H.E. Histopathology of the gastroesophageal junction. A study on 36 operation specimens.Am J Surg Pathol. 2002; 26: 1207-1212Crossref PubMed Scopus (82) Google Scholar, 14Chandrasoma P.T. Der R. Ma Y. Dalton P. Taira M. Histology of the gastroesophageal junction. An autopsy study.Am J Surg Pathol. 2000; 24: 402-409Crossref PubMed Scopus (196) Google Scholar, 15Zhou H. Greco A. Daum F. Kahn E. Origin of cardiac mucosa ontogenic consideration.Pediatr Dev Pathol. 2001; 4: 358-363Crossref PubMed Scopus (49) Google Scholar, 16Park Y.S. Park H.J. Kang G.H. Kim C.J. Chi J.G. Histology of the gastroesophageal junction in fetal and pediatric autopsy.Arch Pathol Lab Med. 2003; 127: 451-455PubMed Google Scholar The explanation for the enormous disparity among these studies in the frequency of finding “pure” cardiac mucosa (with no parietal cells) at the Z-line is not clear. All 3 studies that found a low frequency of pure cardiac mucosa did describe a high frequency of oxyntocardiac mucosa at the Z-line.14Chandrasoma P.T. Der R. Ma Y. Dalton P. Taira M. Histology of the gastroesophageal junction. An autopsy study.Am J Surg Pathol. 2000; 24: 402-409Crossref PubMed Scopus (196) Google Scholar, 15Zhou H. Greco A. Daum F. Kahn E. Origin of cardiac mucosa ontogenic consideration.Pediatr Dev Pathol. 2001; 4: 358-363Crossref PubMed Scopus (49) Google Scholar, 16Park Y.S. Park H.J. Kang G.H. Kim C.J. Chi J.G. Histology of the gastroesophageal junction in fetal and pediatric autopsy.Arch Pathol Lab Med. 2003; 127: 451-455PubMed Google Scholar Despite the disparate results, it is clear that the extent of cardiac epithelium is considerably shorter than that suggested by traditional texts. Cardiac epithelium, if present at all, rarely extends more than a few millimeters below the Z-line. One group reported that cardiac mucosa always was located on the gastric side of the GEJ,12Kilgore S.P. Ormsby A.H. Gramlich T.L. Rice T.W. Richter J.E. Falk G.W. Goldblum J.R. The gastric cardia fact or fiction?.Am J Gastroenterol. 2000; 95: 921-924Crossref PubMed Google Scholar but it is not clear that the gross landmarks used to identify the GEJ have the precision necessary to localize a structure whose extent is measured in millimeters. Thus, it remains unclear whether this tiny band of cardiac mucosa is a normal structure, and whether it lines the esophagus, the proximal stomach, or both.Table 1Results of Studies on Frequency of Cardiac Mucosa at the Gastroesophageal JunctionStudy AuthorNumber (type) of specimensAge of subjects% of Subjects with “pure” cardiac mucosaaOnly mucus cells, no parietal cells.Length of cardiac mucosa (range)Kilgore12Kilgore S.P. Ormsby A.H. Gramlich T.L. Rice T.W. Richter J.E. Falk G.W. Goldblum J.R. The gastric cardia fact or fiction?.Am J Gastroenterol. 2000; 95: 921-924Crossref PubMed Google Scholar33 (autopsy)6.3 yearsbMean.100%1.8 mmbMean. (1.0–4.0 mm)Sarbia13Sarbia M. Donner A. Gabbert H.E. Histopathology of the gastroesophageal junction. A study on 36 operation specimens.Am J Surg Pathol. 2002; 26: 1207-1212Crossref PubMed Scopus (82) Google Scholar36 (surgical)55 yearscMedian.97%5.0 mmcMedian., dLength of maximal extent of cardiac mucosa. (1–15 mm)Chandrasoma14Chandrasoma P.T. Der R. Ma Y. Dalton P. Taira M. Histology of the gastroesophageal junction. An autopsy study.Am J Surg Pathol. 2000; 24: 402-409Crossref PubMed Scopus (196) Google Scholar18 (autopsy)24 yearsbMean.44%1.3 mmbMean., dLength of maximal extent of cardiac mucosa. (0.25–2.75 mm)Zhou15Zhou H. Greco A. Daum F. Kahn E. Origin of cardiac mucosa ontogenic consideration.Pediatr Dev Pathol. 2001; 4: 358-363Crossref PubMed Scopus (49) Google Scholar31 (autopsy)fetal6%NS46 (autopsy)children 1 wk–17 yrs48%NSPark16Park Y.S. Park H.J. Kang G.H. Kim C.J. Chi J.G. Histology of the gastroesophageal junction in fetal and pediatric autopsy.Arch Pathol Lab Med. 2003; 127: 451-455PubMed Google Scholar23 (autopsy)fetal and children0%-NS, Not stated.a Only mucus cells, no parietal cells.b Mean.c Median.d Length of maximal extent of cardiac mucosa. Open table in a new tab Intestinal metaplasia at the GEJAlthough authorities dispute the normal features of the GEJ, all seem to agree that it is abnormal to find intestinal metaplasia in this region.1Spechler S.J. The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction.Gastroenterology. 1999; 117: 218-228Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar If biopsy specimens from a columnar-lined esophagus show specialized intestinal metaplasia, then the patient has Barrrett’s esophagus (Figure 1). If the distance between the Z-line and the GEJ is ≥3 cm then the patient has long-segment Barrett’s esophagus, whereas the condition is deemed short-segment Barrett’s esophagus if that distance is <3 cm.3Sharma P. Morales T.G. Sampliner R.E. Short segment Barrett’s esophagus-the need for standardization of the definition and of endoscopic criteria.Am J Gastroenterol. 1998; 93: 1033-1036PubMed Google Scholar Substantial diagnostic difficulties result when there are very short segments of intestinal metaplasia (spanning millimeters rather than centimeters) in the region of the GEJ, however, as there were in our patient.Intestinal metaplasia can develop in the stomach, the esophagus, or both. Histologically, intestinal metaplasia in the stomach can be indistinguishable from intestinal metaplasia in the esophagus. Since the GEJ cannot be identified with great precision, it can be difficult to determine whether short segments of intestinal metaplasia found in the GEJ region are lining the esophagus (short-segment Barrett’s esophagus) or the proximal stomach (intestinal metaplasia of the gastric cardia).3Sharma P. Morales T.G. Sampliner R.E. Short segment Barrett’s esophagus-the need for standardization of the definition and of endoscopic criteria.Am J Gastroenterol. 1998; 93: 1033-1036PubMed Google Scholar The term “intestinal metaplasia at the GEJ” has been used to describe the condition in which intestinal metaplasia is found at a Z-line that appears to coincide precisely with the GEJ (Figure 2). Rather than constituting an independent condition, however, intestinal metaplasia at the GEJ almost certainly represents either short-segment Barrett’s esophagus or intestinal metaplasia of the cardia.Figure 2The SCJ and GEJ coincide. If biopsy specimens at the Z-line reveal intestinal metaplasia, the condition is called intestinal metaplasia at the GEJ. Intestinal metaplasia at the GEJ represents either short-segment Barrett’s esophagus or intestinal metaplasia of the gastric cardia, but these conditions cannot be distinguished because the gross landmarks used to identify the GEJ are imprecise. (Reprinted with permission from Spechler SJ. The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction. Gastroenterology 1999;117:218–228).View Large Image Figure ViewerDownload (PPT)Intestinal metaplasia in the stomach often develops as a consequence of chronic H. pylori gastritis, whereas intestinal metaplasia in the esophagus develops as a sequela of chronic gastroesophageal reflux disease (GERD).17Correa P. Helicobacter pylori and gastric carcinogenesis.Am J Surg Pathol. 1995; 19: S37-S43PubMed Google Scholar For some patients, therefore, intestinal metaplasia at the GEJ is merely part of a diffuse H. pylori gastritis whereas, for others, the condition results from GERD that causes intestinal metaplasia in segments of esophagus so short that they cannot be distinguished from the serrations of a normal Z-line. Some studies even have shown a negative association between H. pylori and complicated GERD, suggesting that the infection may protect against Barrett’s esophagus.18Vicari J.J. Peek R.M. Falk G.W. Goldblum J.R. Easley K.A. Schnell J. Perez-Perez G.I. Halter S.A. Rice T.W. Blaser M.J. Richter J.E. The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease.Gastroenterology. 1998; 115: 50-57Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar Unfortunately, testing for H. pylori is not a reliable way to distinguish short-segment Barrett’s esophagus from intestinal metaplasia of the gastric cardia. H. pylori gastritis is not rare in patients with Barrett’s esophagus, even though they have a lower prevalence of infection than patients without GERD complications. Furthermore, one recent study found that intestinal metaplasia at the GEJ was not clearly associated either with H. pylori infection or GERD symptoms in more than one-third of cases.19Couvelard A. Cauvin J.M. Goldfain D. Rotenberg A. Robaszkiewicz M. Flejou J.F. Groupe d’Etude de l’Oesophage de BarrettCytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology.Gut. 2001; 49: 761-766Crossref PubMed Scopus (91) Google Scholar Our patient has both classic GERD symptoms and H. pylori infection, and it is not clear whether his intestinal metaplasia at the GEJ represents short-segment Barrett’s esophagus or intestinal metaplasia of the gastric cardia.If intestinal metaplasia in the esophagus had the same malignant potential as intestinal metaplasia in the stomach, then distinguishing short-segment Barrett’s esophagus from intestinal metaplasia of the gastric cardia would have no impact on patient management and little practical importance. However, circumstantial evidence suggests that the risk of malignancy is substantially higher for intestinal metaplasia in the esophagus. Sharma et al. found dysplasia (the precursor of malignancy) in 20 of 177 patients (11.3%) with short-segment Barrett’s esophagus, but in only 1 of 76 patients (1.3%) with intestinal metaplasia in the gastric cardia.20Sharma P. Weston A.P. Morales T. Topalovski M. Mayo M.S. Sampliner R.E. Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia.Gut. 2000; 46: 9-13Crossref PubMed Scopus (172) Google Scholar Authorities recommend endoscopic cancer surveillance routinely for patients with Barrett’s esophagus, but not for patients with intestinal metaplasia in the stomach.21Sampliner R.E. The Practice Parameters Committee of the American College of GastroenterologyUpdated guidelines for the diagnosis, surveillance, and therapy of Barrett’s esophagus.Am J Gastroenterol. 2002; 97: 1888-1895Crossref PubMed Google Scholar, 22Fennerty M.B. Gastric intestinal metaplasia on routine endoscopic biopsy.Gastroenterology. 2003; 125: 586-590Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Therefore, the distinction between these 2 conditions has clear-cut clinical implications.Cytokeratin (CK) staining has been proposed as a means to differentiate intestinal metaplasia of the cardia from short-segment Barrett’s esophagus. The specialized intestinal metaplasia of Barrett’s esophagus frequently exhibits strong immunoreactivity for CK7 in its superficial and deep glands, and immunoreactivity for CK20 in superficial glands and surface epithelial cells.23Ormsby A.H. Goldblum J.R. Rice T.W. Richter J.E. Falk G.W. Vaezi M.F. Gramlich T.L. Cytokeratin subsets can reliably distinguish Barrett’s esophagus from intestinal metaplasia of the stomach.Hum Pathol. 1999; 30: 288-294Abstract Full Text PDF PubMed Scopus (205) Google Scholar In contrast, intestinal metaplasia in the gastric body infrequently shows this so-called “Barrett’s CK7/20 pattern.” In one recent study of 34 patients with biopsy specimens showing intestinal metaplasia at the GEJ, immunostaining revealed a Barrett’s CK7/20 pattern in 16.19Couvelard A. Cauvin J.M. Goldfain D. Rotenberg A. Robaszkiewicz M. Flejou J.F. Groupe d’Etude de l’Oesophage de BarrettCytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology.Gut. 2001; 49: 761-766Crossref PubMed Scopus (91) Google Scholar These patients had a low prevalence of H. pylori infection and frequent symptoms of GERD, whereas the 18 patients with a CK7/20 pattern typical of gastric intestinal metaplasia usually had H. pylori gastritis. The sensitivity and specificity of the CK7/20 immunoreactivity pattern as a marker for Barrett’s esophagus remains disputed, however,24Jovanovic I. Tzardi M. Mouzas I.A. Micev M. Pesko P. Milosavljevic T. Zois M. Sganzos M. Delides G. Kanavaros P. Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction.Histol Histopathol. 2002; 17: 445-454PubMed Google Scholar, 25Glickman J.N. Wang H. Das K.M. Goyal R.K. Spechler S.J. Antonioli D. Odze R.D. Phenotype of Barrett’s esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction. An immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI.Am J Surg Pathol. 2001; 25: 87-94Crossref PubMed Scopus (131) Google Scholar, 26El-Zimaity H.M.T. Graham D.Y. Cytokeratin subsets for distinguishing Barrett’s esophagus from intestinal metaplasia in the cardia using endoscopic biopsy specimens.Am J Gastroenterol. 2001; 96: 1378-1382Crossref PubMed Google Scholar and it is not clear that immunostaining for cytokeratins has advantages over other proposed biomarkers for Barrett’s esophagus such as reactivity with mAb Das-1 (a monoclonal antibody raised against colonic epithelial cells) and expression of colonic-type sulfomucins.25Glickman J.N. Wang H. Das K.M. Goyal R.K. Spechler S.J. Antonioli D. Odze R.D. Phenotype of Barrett’s esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction. An immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI.Am J Surg Pathol. 2001; 25: 87-94Crossref PubMed Scopus (131) Google Scholar, 27Das K.M. Prasad I. Garla S. Amenta P.S. Detection of a shared colon epithelial epitope on Barrett epithelium by a novel monoclonal antibody.Ann Intern Med. 1994; 120: 753-756Crossref PubMed Scopus (82) Google Scholar A recent review has concluded that the utility of biomarkers in distinguishing short-segment Barrett’s esophagus from intestinal metaplasia of the gastric cardia has not been established, and the authors advised against basing clinical decisions on the presence of these biomarkers.28Morales C.P. Spechler S.J. Intestinal metaplasia at the gastroesophageal junction Barrett’s, bacteria, and biomarkers.Am J Gastroenterol. 2003; 98: 759-762Crossref PubMed Scopus (26) Google ScholarCancer risk for intestinal metaplasia at the GEJThere are few prospective data on the incidence of adenocarcinoma for patients with intestinal metaplasia at the GEJ and, consequently, their risk of malignancy is not known. As discussed above, intestinal metaplasia at the GEJ likely represents either intestinal metaplasia of the stomach, which has a low risk of progression to malignancy, or short-segment Barrett’s esophagus, which is more worrisome. Therefore, the risk of cancer for intestinal metaplasia at the GEJ should be less than or equal to that for Barrett’s esophagus. Published estimates on the annual incidence of cancer in patients with long-segment Barrett’s esophagus have ranged from 0.2% to 2.9%, but modern studies suggest that that their cancer risk is approximately 0.5% per year.29Shaheen N.J. Crosby M.A. Bozymski E.M. Sandler R.S. Is there publication bias in the reporting of cancer risk in Barrett’s esophagus?.Gastroenterology. 2000; 119: 333-338Abstract Full Text Full Text PDF PubMed Scopus (734) Google Scholar, 30Drewitz D.J. Sampliner R.E. Garewal H.S. The incidence of adenocarcinoma in Barrett’s esophagus a prospective study of 170 patients followed 4.8 years.Am J Gastroenterol. 1997; 92: 212-215PubMed Google Scholar, 31O’Connor J.B. Falk G.W. Richter J.E. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus. Report on the Cleveland Clinic Barrett’s esophagus registry.Am J Gastroenterol. 1999; 94: 2037-2042PubMed Google Scholar, 32Spechler S.J. Lee E. Ahnen D. Goyal R.K. Hirano I. Ramirez F. Raufman J.P. Sampliner R. Schnell T. Sontag S. Vlahcevic Z.R. Young R. Williford W. Long-term outcome of medical and surgical treatments for gastroesophageal reflux disease. Follow-up of a randomized controlled trial.JAMA. 2001; 285: 2331-2338Crossref PubMed Scopus (831) Google Scholar The risk for cancer in short-segment Barrett’s esophagus is disputed.Cancers in Barrett’s esophagus evolve through the accumulation of genetic mutations that endow the cells with growth advantages.33Morales C.P. Souza R.F. Spechler S.J. Hallmarks of cancer progression in Barrett’s oesophagus.Lancet. 2002; 360: 1587-1589Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Mutations are to some extent chance events, and it seems logical to assume that the risk of cancer in Barrett’s esophagus should vary with the extent of metaplastic epithelium. Patients with longer segments of metaplasia have more cells at risk for DNA damage and, therefore, should be more likely to acquire the critical mutations that cause malignancy. Although data from a number of observational studies support this hypothesis,31O’Connor J.B. Falk G.W. Richter J.E. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus. Report on the Cleveland Clinic Barrett’s esophagus registry.Am J Gastroenterol. 1999; 94: 2037-2042PubMed Google Scholar, 34Iftikhar S.Y. James P.D. Steele R.J. Hardcastle J.D. Atkinson M. Length of Barrett’s oesophagus an important factor in the development of dysplasia and adenocarcinoma.Gut. 1992; 33: 1155-1158Crossref PubMed Scopus (261) Google Scholar, 35Menke-Pluymers M.B. Hop W.C. Dees J. van Blankenstein M. Tilanus H.W. Risk factors for the development of an adenocarcinoma in columnar-lined (Barrett) esophagus. The Rotterdam Esophageal Tumor Study Group.Cancer. 1993; 72: 1155-1158Crossref PubMed Scopus (215) Google Scholar, 36Weston A.P. Krmpotich P.T. Cherian R. Dixon A. Topalosvki M. Prospective long-term endoscopic and histological follow-up of short segment Barrett’s esophagus comparison with traditional long segment Barrett’s esophagus.Am J Gastroenterol. 1997; 92: 407-413PubMed Google Scholar, 37Hirota W.K. Loughney T.M. Lazas D.J. Maydonovitch C.L. Rholl V. Wong R.K. Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction prevalence and clinical data.Gastroenterology. 1999; 116: 277-285Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar, 38Avidan B. Sonnenberg A. Schnell T.G. Chejfec G. Metz A. Sontag S.J. Hiatal hernia size, Barrett’s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma.Am J Gastroenterol. 2002; 97: 1930-1936Crossref PubMed Google Scholar there is yet no proof that the risk of cancer varies with the extent of the metaplastic lining. In one recent report of 235 patients with Barrett’s esophagus, furthermore, the cancer risk was not found to vary significantly with the extent of metaplasia.39Rudolph R.E. Vaughan T.L. Storer B.E. Haggitt R.C. Rabinovitch P.S. Levine D.S. Reid B.J. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus.Ann Intern Med. 2000; 132: 612-660Crossref PubMed Scopus (252) Google Scholar For our patient, therefore, the maximum annual risk for adenocarcinoma is approximately 0.5%, and his real risk probably is substantially lower than that.Potential management strategiesIntestinal metaplasia at the GEJ causes no symptoms. Therapies might be aimed at treating associated conditions like GERD and H. pylori gastritis, and at reducing the risk of malign
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