Esophageal Columnar Metaplasia Research Articles

Distinct clinicopathological differences between early gastric cardiac and non-cardiac carcinomas: a single-center retrospective study of 329 radical resection cases

BackgroundEarly gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus–corpus and antrum–angularis–pylorus subgroups, especially between EGCC with and without oesophageal invasion.MethodsIn this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs.ResultsCompared to the EGNCC antrum–angularis–pylorus (n = 181), but not fundus–corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum–angularis–pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation.ConclusionsThere exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.

Esophageal Columnar Metaplasia in Childhood: A Population-Based Case Series Analysis

Adults with Barrett's esophagus (BE) are often entered into surveillance for esophageal adenocarcinoma (EAC), although cancer risk is relatively low. BE can be detected in children (< 16years). Little is known about the epidemiology of pediatric BE, and it is unclear what the optimal surveillance regimes are in children. To evaluate the demographic and clinical characteristics, and future neoplastic progression risk in all pediatric BE patients diagnosed in Northern Ireland between 1993 and 2010. Data from the population-based Northern Ireland BE register were matched to the Northern Ireland Cancer Registry for EAC outcomes until end 2013. Age-adjusted incidence of pediatric BE was calculated, and characteristics between pediatric and adult BE patients compared using Chi-square tests. Over 18years, 42 pediatric BE patients (< 16years) were identified, equivalent to an age-adjusted incidence of < 2 per 100,000 children. There was a clear age differential, with BE incidence increasing with age within the pediatric population. The majority (85.7%) of patients were male, a significantly higher male/female ratio than adult BE patients (p < 0.001). No pediatric BE patients progressed to high-grade dysplasia (HGD) or EAC, although the eldest patient was aged 34years by the end of follow-up. This is the largest series of pediatric BE ever reported. It demonstrates that pediatric BE is rare. The male preponderance of this condition is more apparent in childhood compared with adult cases. No children developed HGD/EAC during follow-up, suggesting that regular surveillance is not required, at least until adulthood.

Клинико-морфологические и функциональные показатели гастроэзофагеальной рефлюксной болезни при наличии цилиндроклеточной метаплазии слизистой оболочки пищевода

Клинико-морфологические и функциональные показатели гастроэзофагеальной рефлюксной болезни при наличии цилиндроклеточной метаплазии слизистой оболочки пищевода

Transcommitment: Paving the Way to Barrett's Metaplasia.

Barrett's esophagus is the condition in which metaplastic columnar epithelium that predisposes to cancer development replaces stratified squamous epithelium in the distal esophagus. Potential sources for the cell or tissue of origin for metaplastic Barrett's epithelium are reviewed including native esophageal differentiated squamous cells, progenitor cells native to the esophagus located within the squamous epithelium or in the submucosal glands or ducts, circulating bone marrow-derived stem cells, and columnar progenitor cells from the squamocolumnar junction or the gastric cardia that proximally shift into the esophagus to fill voids left by damaged squamous epithelium. Wherever its source the original cell must undergo molecular reprogramming (i.e., either transdifferentiation or transcommitment) to give rise to specialized intestinal metaplasia. Transcription factors that specify squamous, columnar, intestinal, and mucus-secreting epithelial differentiation are discussed. An improved understanding of how esophageal columnar metaplasia forms could lead to development of effective treatment or prevention strategies for Barrett's esophagus. It could also more broadly inform upon normal tissue development and differentiation, wound healing, and stem cell biology.

Issue Highlights

Issue Highlights

Associations of Serum Adiponectin and Leptin With Barrett’s Esophagus

Central adiposity is a risk factor for Barrett's esophagus (BE). Serum levels of adiponectin and leptin are deregulated in obese states and are implicated as putative mediators in the pathophysiology of esophageal columnar metaplasia. We describe associations between serum adiponectin and leptin levels with BE. Patients were recruited prospectively for a case-control study. Fasting serum levels of adiponectin and leptin were measured in 135 patients with BE and compared with 2 separate control groups: 133 subjects with gastroesophageal reflux disease (GERD) and 1157 colon screening controls. Multivariate analyses adjusted for age, race, and waist-to-hip ratio showed that patients within the highest tertile of serum adiponectin level had decreased odds of BE compared with screening colonoscopy controls (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.22-0.80). This effect was more pronounced in men (OR, 0.35; 95% CI, 0.17-0.74) compared with women (OR, 0.71; 95% CI, 0.17-3.03). In comparisons of BE cases with GERD controls, subjects within the highest tertile of serum adiponectin level showed decreased odds of BE (OR, 0.65; 95% CI, 0.31-1.36), however, this was not statistically significant. Patients in the highest tertile of serum leptin level did not have a significantly increased risk of BE in comparison with GERD (OR, 1.32; 95% CI, 0.61-2.88) or screening colonoscopy controls (OR, 1.57; 95% CI, 0.82-3.04) in analyses including both sexes. Based on sex-specific analyses, sex did not significantly alter the association of leptin with odds of BE. Serum adiponectin was associated inversely with BE and this effect was more pronounced in men, whereas serum leptin showed no evidence of association with BE in comparisons with multiple control groups. The exact mechanism, if any, by which these adipokines promote metaplasia in the esophagus needs to be explored further.

Reflections on esophageal columnar metaplasia (Barrett)-ANNO 2015.

Esophageal columnar metaplasia (ECM) (Barrett's esophogus) continues to generate clinical and basic attention. Yet many questions remain unanswered and global consensus on important issues is often still lacking. This article discusses a selection of certain recent findings and reflects on some remaining uncertainties of this intriguing disease.

Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell

The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro-esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side-to-side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow-derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP-marked bone marrow after the operation. Seventy-three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow-derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago-jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow-derived cells do not contribute directly to columnar metaplasia in this mouse model.

Discrepancies and pitfalls in diagnosis and therapy of esophageal columnar metaplasia/Barrett's esophagus: A personal view

Discrepancies and pitfalls in diagnosis and therapy of esophageal columnar metaplasia/<scp>B</scp>arrett's esophagus: A personal view

Recent developments in gastroesophageal reflux disease and Barrett's esophagus: ANNO 2012

The incidence of gastroesophageal reflux disease (GERD) and esophageal columnar metaplasia is rising worldwide. Both mechanical and functional factors perturb the double sphincter barrier at the esophagogastric junction (EGJ). Discovery of the acid pocket is fundamental in understanding postprandial acid reflux. Adding impedencemetry to pH measurements allows detection of non-acid or weakly acidic reflux. Histologic and endoscopic injury of the squamous mucosa rises from dilation of the intercellular spaces, papillary extension, accentuated intrapapillary looping, red streaks, erosive tissue loss, etc., graded with the Los Angeles system. Seventy percent of patients have no recognizable abnormalities (non-erosive or neGERD). Treatment of GERD mainly relates to the control of acid secretion but a revival of alginate/antacid obliterating the acid pocket is to be expected. Weaker heartburn control in neGERD is a misnomer because most studies included patients with no evidence of reflux disease. Traditional (delayed-release) proton pump inhibitors (PPIs) are powerful suppressors of acid secretion but do have limitations such as gradual build up of acid control, weak control of nocturnal acid recovery, possibility of rebound, occasional need for dose escalation, etc. Barrett's esophagus (BE) is endoscopically diagnosed also in the absence of intestinal metaplasia. A prerequisite is the precise location of the EGJ (proximal end of gastric folds, esophageal sphincter pinch, distal extent of palisade vessels). BE is graded with the Prague C & M system. Barrett's cancer develops usually via low-grade and high-grade dysplasia. Endoscopic examination may indicate suspicious areas, amenable for targeted biopsy. Otherwise, four quadrant biopsies are obtained when searching for neoplasia. Low-grade dysplasia, especially when it is multifocal and p53 positive, high-grade dysplasia and mucosal cancer should be treated with endoscopic resection of the target area, followed by radiofrequency ablation of the adjacent non-neoplastic columnar mucosa, followed with powerful acid suppressant therapy. The long-term results of the combination of resection and ablation are exiting and at least comparable to surgical resection.

A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.

Red Meat Intake is Associated With Increased Risk of Barrett's Esophagus

Background: GEJ biopsies that contain inflamed squamous and columnar epithelium may represent distal esophageal columnar metaplasia or proximal gastritis (“carditis”). Pathologically, differentiation of these two disorders is difficult regardless of the presence or absence of goblet cells (GC). The aim of this study was to evaluate a wide variety of histologic features in GEJ biopsies, from a large prospective cohort of GERD patients, in order to determine their utility in predicting the presence of columnar-lined esophagus (CLE). Design: 2208 mucosal biopsies of the GEJ, from 552 GERD patients (M/F ratio: 305/247, mean age: 51 years), all of whom were endoscoped and interviewed prospectively as part of a large community clinic-based study of GERD patients in Washington state, were evaluated blindly for a wide variety of histologic features, such as mucosal and submucosal glands/ducts, multilayered epithelium (ME), type of glands (mucous, oxyntic, mixed), squamous islands, and buried columnar epithelium and correlated with the endoscopic evidence of, and length, of CLE, and with the presence of GC. The findings were also correlated with patient's clinical risk factors for BE, such as gender, race, waist:hip ratio, smoking history, and body mass index (BMI). Results: Overall, 56% of patients revealed CLE. The prevalence rates of relevant histologic features in GEJ biopsies were as follows: submucosal glands (0.6%), ducts (4%), ME (17%), GC (26%), mucous glands only (20%), oxyntic glands only (25%), mixed mucous/oxyntic glands (52%), squamous islands (15%), buried columnar epithelium (19%). The presence of ME (p=0.03), GC (p=0.001), pure mucous glands (p= 25, at least weekly heartburn, and increased waist:hip ratio (male≥0.9, female≥0.8) were all associated with CLE. Conclusion: Certain histologic features, such as submucosal glands and/or ducts, ME, pure mucous glands, squamous islands, and buried columnar epithelium, when detected in GEJ biopsies of GERD patients, are indicative of the presence of CLE at endoscopy. Any of these findings, even in the absence of GC, should warrant clinical suspicion for CLE in endoscopically ambiguous cases.

Is Cellular Senescence Commonly Found in Barrett's Esophagus?

Background: GEJ biopsies that contain inflamed squamous and columnar epithelium may represent distal esophageal columnar metaplasia or proximal gastritis (“carditis”). Pathologically, differentiation of these two disorders is difficult regardless of the presence or absence of goblet cells (GC). The aim of this study was to evaluate a wide variety of histologic features in GEJ biopsies, from a large prospective cohort of GERD patients, in order to determine their utility in predicting the presence of columnar-lined esophagus (CLE). Design: 2208 mucosal biopsies of the GEJ, from 552 GERD patients (M/F ratio: 305/247, mean age: 51 years), all of whom were endoscoped and interviewed prospectively as part of a large community clinic-based study of GERD patients in Washington state, were evaluated blindly for a wide variety of histologic features, such as mucosal and submucosal glands/ducts, multilayered epithelium (ME), type of glands (mucous, oxyntic, mixed), squamous islands, and buried columnar epithelium and correlated with the endoscopic evidence of, and length, of CLE, and with the presence of GC. The findings were also correlated with patient's clinical risk factors for BE, such as gender, race, waist:hip ratio, smoking history, and body mass index (BMI). Results: Overall, 56% of patients revealed CLE. The prevalence rates of relevant histologic features in GEJ biopsies were as follows: submucosal glands (0.6%), ducts (4%), ME (17%), GC (26%), mucous glands only (20%), oxyntic glands only (25%), mixed mucous/oxyntic glands (52%), squamous islands (15%), buried columnar epithelium (19%). The presence of ME (p=0.03), GC (p=0.001), pure mucous glands (p= 25, at least weekly heartburn, and increased waist:hip ratio (male≥0.9, female≥0.8) were all associated with CLE. Conclusion: Certain histologic features, such as submucosal glands and/or ducts, ME, pure mucous glands, squamous islands, and buried columnar epithelium, when detected in GEJ biopsies of GERD patients, are indicative of the presence of CLE at endoscopy. Any of these findings, even in the absence of GC, should warrant clinical suspicion for CLE in endoscopically ambiguous cases.

Barrett's esophagus: A historical perspective, an update on core practicalities and predictions on future evolutions of management

Interpretation of exploding knowledge about Barrett's esophagus is impaired by use of several conflicting definitions. Because any histological type of esophageal columnar metaplasia carries risk for esophageal adenocarcinoma, the diagnosis of Barrett's esophagus should no longer require demonstration of intestinal-type metaplasia. Endoscopic recognition and grading of Barrett's esophagus remains a significant source of ambiguity. Reflux disease is a key factor for development of Barrett's esophagus, but other factors must underlie its development, since it occurs in only a minority of reflux disease patients. Neither antireflux surgery nor proton pump inhibitor (PPI) therapy has major impacts on cancer risk. Within a year, a major trial should indicate whether low-dose aspirin usefully reduces cancer risk. The best referral centers have transformed the accuracy of screening and surveillance for early curable esophageal adenocarcinoma by use of enhanced and novel endoscopic imaging, visually-guided, rather than blind biopsies and by partnership with expert pathologists. General endoscopists now need to upgrade their skills and equipment so that they can rely mainly on visual targeting of biopsies on mucosal areas of concern in their surveillance practice. General pathologists need to greatly improve their interpretation of biopsies. Endoscopic therapy now achieves very high rates of cure of high-grade dysplasia and esophageal adenocarcinoma with minimal morbidity and risk. Such results will only be achieved by skilled interventional endoscopists. Esophagectomy should now be mainly restricted to patients whose cancer has extended into and beyond the submucosa. Weighing risks and benefits in the management of Barrett's esophagus is difficult, as is the process of adequately informing patients about their specific cancer risk.

898 Title: Insulin Like Growth Factor (IGF) Signaling Pathway in Barrett's Esophagus (BE)

Background: Little is known regarding the role of mucosal and submucosal glands in the development of Barrett's esophagus (BE). Some studies have suggested that mucosal and/ or submucosal glands, and their ducts, may contain precursor stem cells for BE. Unfortunately, previous studies that have evaluated glands in BE did not always specify the type or location of these structures. The aim of this study was to evaluate the pathologic features of mucosal and submucosal glands in BE in order to gain insight into their role in the pathogenesis of this condition. Design: Routinely processed tissue sections from 112 patients with BE (64 patients with biopsies only, 48 with resection specimens) and 32 non-BE controls (9 esophageal resections, 23 autopsies) were evaluated for the number and location of glands, and for their association with the type of overlying epithelium. BE patients with biopsies were separated into no (i.e. esophageal columnar metaplasia without goblet cells), low, high, and very high density goblet cell groups based on predetermined criteria. Immunostaining for p63, a peptide known to be present in basal squamous cells, including stem cells, was performed on a subset of BE biopsies. Results: Submucosal glands were nearly significantly increased in prevalence in non-BE controls (resections and autopsies) versus BE resection specimens (mean # glands per tissue section: 2.5 vs. 1.4, p=0.08). Mucosal glands were present in 86% of BE resections, but in none of the control esophageal resections or autopsies without BE, except at the distal GEJ. In BE biopsies, mucosal glands were present in 66% of cases, but showed a highly significant decrease in number from no (89%), to low (44%), to high (21%), and very high (7%) goblet cell density BE subgroups (p<0.001). P63 was positive in 43 % of glands overall, and it was significantly more common in glands of “BE” cases without goblet cells (p<0.01). Finally, a strong significant association was also noted between the presence of non-goblet columnar epithelium including multilayered epithelium overlying mucosal glands in all patients, regardless of the patients' goblet cell density (p<0.001). Conclusions: Increased submucosal glands may play a protective role in the prevention of BE. Our data also suggests that mucosal glands are metaplastic in origin, may be derived from the adjacent basal cell layer of squamous epithelium, and probably give rise to early non-goblet columnar metaplasia in patients developing BE.

W1879 Esophageal Columnar Metaplasia is Common in the Distal Esophagus of Chinese Patients

W1879 Esophageal Columnar Metaplasia is Common in the Distal Esophagus of Chinese Patients

Definition of Barrett's Esophagus: Time for a Rethink—Is Intestinal Metaplasia Dead?

The definition of Barrett's esophagus (BE) varies worldwide, particularly with regard to the need to identify goblet cells in esophageal biopsies in order to diagnose this condition. Problems related to the need to identify goblet cells to diagnose BE include the facts that goblet cells are uncommon in pediatric patients with BE, a small percentage of adults with columnar metaplasia of the esophagus do not contain goblet cells, the chances of detecting goblet cells are proportional to the length of columnar metaplasia, sampling error is common, and interpretation and differentiation of goblet cells vs. pseudogoblet cells may be difficult in some circumstances. In addition, goblet cells have been shown to wax and wane over the natural history of BE. Recent studies suggest that the background nongoblet epithelium in BE is biologically intestinalized, and shows a variety of molecular abnormalities similar to the goblet cell-containing epithelium. In addition, several retrospective and outcome studies suggest a well-defined risk of neoplasia in patients with esophageal columnar metaplasia, but without goblet cells. There are important clinical and economic implications to these findings and also with regard to the definition of BE. This review provides evidence to suggest that a diagnosis of BE should not require demonstration of goblet cells in mucosal biopsies, and offers considerable data to support the notion that a nongoblet epithelium is also at risk of malignancy. Guidelines for the diagnosis of BE need to consider revisions that take into account new data regarding nongoblet cell epithelium in BE, and the difficulties in recognizing columnar metaplasia that measures less than 1 cm in length.

The Potential Impact of Contemporary Developments in the Management of Patients with Gastroesophageal Reflux Disease Undergoing an Initial Gastroscopy

Recent developments may alter the approach to patients presenting with gastroesophageal reflux disease (GERD)-like symptoms. A newly proposed Montreal consensus definition of Barrett's esophagus includes all types of esophageal columnar metaplasia, with or without intestinal-type metaplasia. There is also increasing recognition of eosinophilic esophagitis (EE) in patients with GERD-like symptoms. To quantify the impact of these developments on a multiphysician general gastroenterology practice in a tertiary care medical centre. Medical charts of all patients having an initial gastroscopy for GERD-like symptoms over a one-year period were reviewed retrospectively, and audits of their endoscopic images and esophageal biopsies were performed. Of the 353 study participants, typical symptoms of heartburn and acid reflux were present in 87.7% and 23.2%, respectively. Less commonly, patients presented with atypical symptoms (eg, dysphagia in 9.4%). At endoscopy, 26% were found to have erosive esophagitis and 12% had endoscopically suspected esophageal metaplasia. Histological evaluation was available for 65 patients. Ten of the 65 biopsied patients (15%) met traditional criteria for Barrett's esophagus (ie, exhibiting intestinal-type metaplasia), whereas 49 (75%) fulfilled the newly proposed consensus definition of Barrett's esophagus. Five patients (7.7%) met the study criteria for EE (more than 20 eosinophils per high-power field), four of whom had not been previously recognized. Among patients presenting with GERD-like symptoms, the prevalence of Barrett's esophagus may increase markedly if the Montreal definition is adopted. In addition, growing awareness of EE may lead to an increase in the prevalence of this diagnosis. Prospective studies of the management implications of these findings are warranted.

The evaluation of esophageal motility in patients with esophageal columnar metaplasia (ECM)

Patients with specialized intestinal metaplasia (SIM) of the esophagus were shown to have more acidic and biliary reflux than patients with oxynthic or cardia type metaplasia (OM), which was further increased in patients with dysplasia. Although this led to the hypothesis that the esophageal motility disorder may be severe in this patient group, detailed prospective evaluation of this question has not been carried out. Aim: To evaluate the esophageal motility by manometry, in patients with different histological types of ECM with or without dysplasia. Patients, methods: Esophageal motility was prospectively evaluated by standard water perfusion esophageal manometry in 132 patients [M/F 79/53, mean age 55.5(26–81) ys] with endoscopic and histological evidence for ECM. Parameters studied: pressure and relaxation time of the lower esophageal sphincter (LES); peristaltic wave amplitude, duration and propagation velocity in the esophageal body (EB). The type of metaplasia and the presence of dysplasia were established by immunohistochemistry and cytometry. Results: Patients with SIM had decreased EB peristaltic amplitudes in the distal esophagus (3cm-s above the LES, p<0.01) compared to patients with OM. Other parameters were similar. On the other hand patients with IM with dysplasia had significantly lower LES pressure (p<0.05), EB peristaltic amplitude and duration (3 and 8cm-s above the LES, p<0.05) compared to those without dysplasia. Conclusions: Our results provided data that both LES and EB motility is impaired in patients with ECM. Furthermore, they support the hypothesis that esophageal motility abnormalities are more pronounced in patients with more severe histopathological stage of the disease.

Prevalence of Barrett's esophagus in Japan

Norman Barrett originally described two special conditions, namely, a congenital short esophagus with an intrathoracic gastric columnar lining and congenital gastric heterotropia in the esophagus with ulceration. Thereafter, these conditions began to be known as “Barrett's esophagus.” It is an acquired condition of esophageal columnar metaplasia following chronic gastroesophageal reflux, and the classical Barrett's esophagus has been defined as having a circumferential columnar metaplasia spreading minimally 3 cm or more upward from the esophagogastric junction, because the esophagogastric junction still tends to be difficult to recognize precisely. Recently, from the point of view of adenocarcinogenesis of the esophagus, the term and concept of short-segment Barrett's esophagus (SSBE) as a developing condition of the classical Barrett's esophagus and the confirmation of intestinal metaplasia has been required; however, the definition of Barrett's esophagus still remains controversial. In Japan, although the prevalence of short-segment Barrett's esophagus has been reported to vary considerably, from 1% to 52%, the prevalence of long-segment Barrett's esophagus (LSBE) tends to range from 0% to 2%, which is a quite lower rate than that observed in Western countries. The great difference in the prevalence of SSBE is caused by the differences in the criteria of the esophagogastric junction and the definition concerning the necessity of intestinal metaplasia. A universally accepted definition of Barrett's esophagus is thus needed to accurately determine its actual prevalence.