Epidemiology and significance of Barrett's esophagus

Barrett's esophagus (BE) is of interest because of its recognized association with esophageal adenocarcinoma. While BE develops in a minority of patients with gastroesophageal reflux disease, its diagnosis has markedly increased over the last 30 years. Although a concurrent increase in the number of endoscopies performed annually has improved the ability to diagnose BE, the increase in prevalence appears to be a true finding. Conflicting data in the literature confound an accurate assessment of the risk for adenocarcinoma in patients with BE. Certain factors associated with BE also hold for esophageal adenocarcinoma: greater severity of reflux symptoms, specific pattern of symptoms (particularly nocturnal), longer duration of symptoms, white race, and male gender. One report has suggested a 45-fold increase in cancer risk for patients with frequent, severe and long-standing heartburn symptoms. New cases of esophageal adenocarcinoma are also increasing, especially in white males, with over 6,000 new cases diagnosed in 1995. BE can progress to esophageal dysplasia and adenocarcinoma; hence, early diagnosis and surveillance of BE and treatment of high-grade dysplasia leads to improved survival. The reported risk of developing cancer in BE ranges from 0.4 to 1.9%/year of follow-up. Most recent studies have tended to report rates of 0.5%/year or lower. Despite these data and concerns, at least two actuarial studies have suggested that the risk of death in patients with BE does not differ from that of a control population. This review of the literature focuses on the epidemiology of BE and the associated incidence of its sequelae.     

Barrett's esophagus: incidence and prevalence estimates in a rural Mid-Western population

BACKGROUND AND AIMS: Barrett's esophagus (BE) predisposes to adenocarcinoma of the esophagus and survival in esophageal adenocarcinoma is low. We studied patients diagnosed with BE in the Marshfield Epidemiologic Study Area (MESA). Our objectives were to estimate the prevalence of diagnosed BE, estimate the annual incidence of initial diagnosis of BE, and characterize the demographics of patients diagnosed with BE. METHODS: We retrospectively reviewed medical records of patients diagnosed with BE until December 31, 2002. The esophagogastroduodenoscopy (EGD) reports were reviewed to establish the presence of columnar epithelium. All slides were retrieved and reviewed by a gastrointestinal pathologist to establish the presence of intestinal metaplasia and dysplasia. Chart abstraction was conducted using a standardized form. RESULTS: BE was histologically confirmed in 216 patients. All were white, 165 (76%) were male, and 81% had a hiatal hernia. Median age at diagnosis was 65.5 yr (range 17-94). Long-segment BE (LSBE) was present in 112 (51.9%) patients. The prevalence of histologically confirmed BE in MESA was 261.8 (95% CI 222.5-301.1) per 100,000 people. The incidence of an initial diagnosis of BE between 1996 and 2002 was 32.7 per 100,000 person-years (95% CI 27.1-38.2) and did not change significantly over the study period despite an increase in EGD rates. At the initial diagnosis, 41.7% of the patients were on proton pump inhibitors. Dysplasia was present in 24.5% of patients. CONCLUSION: The incidence of initial diagnosis of BE in a stable white population did not change significantly over a 7-yr period, despite an increase in EGD rates.     

Chapter 2: Role of pathologic confirmation for Barrett′s esophagus and dysplasia

Barrett′s esophagus (BE) is a premalignant condition defined by the replacement of squamous epithelium by columnar epithelium in the distal part of the esophagus. Patients with BE have an increased risk of progression to esophageal adenocarcinoma (EAC). Advanced EAC has a poor 5-year survival rate. However, if EAC is diagnosed at an early stage, endoscopic treatment has proven to be a safe and effective treatment, with excellent long-term survival rates. Currently it is not possible to accurately predict which patients with BE will develop EAC. Despite promising developments in genetic and molecular biomarker research, grade of dysplasia is still the best predictor for progression to EAC. Present guidelines advise surveillance endoscopies with biopsies for BE patients to detect early neoplasia at a treatable stage. Surveillance intervals are determined by length of the BE segment and on the histopathologic diagnosis of the biopsies. Accurate histopathologic assessment of biopsies to define surveillance intervals or to decide on a treatment strategy, is therefore of the utmost importance.     

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high‐grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low‐grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open‐label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2–3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE‐D) and complete eradication of all intestinal metaplasia (CE‐IM). Ninety‐six subjects with Barrett's dysplasia (67% HGD; 65% long‐segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow‐up endoscopy (mean duration 21 months). In patients with LGD, rate of CE‐D was 91% (21/23) and rate of CE‐IM was 61% (14/23). In HGD, CE‐D rate was 81% (46/57) and CE‐IM was 65% (37/57). In patients with short‐segment BE (SSBE) with any dysplasia, CE‐D was achieved in 97% (30/31) and CE‐IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non‐steroidal anti‐inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.     

Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus

Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long‐segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P‐value 0.205). The rate of dysplasia detection in short‐segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high‐grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.     

A Barrett's esophagus registry of over 1000 patients from a specialist center highlights greater risk of progression than population‐based registries and high risk of low grade dysplasia

Barrett's esophagus (BE) arising from chronic gastro‐oesophageal reflux (GERD) is the main pathologic precursor of esophageal adenocarcinoma (EAC). The risk of progression to high‐grade dysplasia (HGD) and EAC is unclear, and recent population studies from Denmark and Northern Ireland suggest that this has been overestimated in the past. No data exist from the Republic of Ireland. A detailed clinical, endoscopic, and pathologic database was established in one center as a proposed pilot for a national registry, and initial and follow‐up data were abstracted by a data manager. One thousand ninety‐three patients were registered, 60 patients with HGD were excluded, leaving 1033, with a median age of 59 and 2 : 1 male to female ratio, and 3599 person‐years of follow‐up. The overall incidence of HGD/EAC was 1.33% per year overall, 0.85% if the first year is excluded. Within the first year after index endoscopy, 18 cases of HGD or EAC were identified, and 30 following the first year. Low‐grade dysplasia (LGD) on index endoscopy was associated with an incidence of progression of 6.5% per year, and 3.1% when tertiary referrals were excluded. These data provide important demographic and clinical information on the population of Irish patients with BE, with incidence rates of progression higher than recently published population‐based registry series, perhaps relating to sampling and pathological assessment. Low‐grade dysplasia on initial biopsy is a significant proxy marker of risk of progression.     

Prevalence of Barrett's esophagus in systemic sclerosis

OBJECTIVE: The esophagus is the most commonly affected gastrointestinal area in systemic sclerosis (SSc). Patients with SSc frequently develop gastroesophageal reflux, esophageal injury, and sometimes, intestinal metaplasia, or Barrett's esophagus (BE), which may increase the risk of esophageal adenocarcinoma. This study sought to determine the prevalence of BE and esophageal adenocarcinoma in a cohort of SSc patients. METHODS: One hundred ten SSc patients who were receiving long-term treatment with proton-pump inhibitors (PPIs) were assessed systematically by esophageal manometry and endoscopy. Esophageal biopsies were performed when macroscopic abnormalities were detected, and BE was diagnosed histologically. RESULTS: Among the 110 patients, 14 had BE (12.7%). None of the patients with BE had adenocarcinoma, but 3 of the 14 patients (21%) had dysplasia on esophageal biopsy. Similar proportions of patients with and without BE had abnormal peristalsis and decreased lower esophageal sphincter pressure. No association between BE and other disease characteristics was demonstrated. CONCLUSION: In this study, 12.7% of SSc patients who had been treated with PPIs for long periods had BE, similar to the prevalence in patients with gastroesophageal reflux disease. Although none of the patients had esophageal adenocarcinoma, patients with BE should be followed up closely, particularly patients with dysplasic BE. Long-term prospective studies are warranted to determine the phenotype of SSc patients at high risk of developing dysplasia or esophageal adenocarcinoma.     

Surveillance history of endoscopically treated patients with early Barrett's neoplasia: nonadherence to the Seattle biopsy protocol leads to sampling error

SUMMARY. The study's aim was to retrospectively evaluate the surveillance history of Barrett's esophagus (BE) patients with endoscopically treated early neoplasia. All BE patients endoscopically treated for early cancer (EC) or high‐grade intraepithelial neoplasia (HGIN) in a lesion or mass between 1998 and 2005 were included. Endoscopy and histology records were reviewed. Ninety‐four patients (78 males, mean age 67 years, 24 HGIN, 70 EC) were included. In 36 (38%) patients, HGIN/EC was diagnosed at (or within 6 months after) initial endoscopy. The remaining 58 (62%) patients had a surveillance history (median duration 7 years, mean 6.7 endoscopies). Seventy‐nine percent of these had low‐grade intraepithelial neoplasia (LGIN) diagnosed at least once during their surveillance period with a median of seven endoscopies and a median number of biopsies that was 50% of what should have been taken according to the Seattle protocol. Patients without any dysplasia during earlier surveillance (n = 12, 21%) had undergone significantly less endoscopies (median four endoscopies, P = 0.02) and had a median biopsy percentage that was 23% of the Seattle protocol (P < 0.001 versus 50% in LGIN). In this selected cohort of patients with early Barrett's neoplasia, 38% of patients were diagnosed at initial endoscopy. Of the patients with a surveillance history, 79% had shown LGIN prior to HGIN/EC diagnosis. Only 21% of patients had a surveillance history without any dysplasia, which in general encompassed endoscopies with an insufficient number of biopsies, suggesting sampling error. This underlines the importance of obtaining an adequate number of biopsies during surveillance endoscopies.     

Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study

OBJECTIVE: Barrett's esophagus (BE) is a premalignant condition for which regular endoscopic follow-up is usually advised. We evaluated the incidence of esophageal adenocarcinoma (AC) in patients with BE and the impact of endoscopic surveillance on mortality from AC. METHODS: A cohort of newly diagnosed BE patients was studied prospectively. Endoscopic and histological surveillance was recommended every 2 yr. Follow-up status was determined from hospital and registry office records and telephone calls to the patients. RESULTS: From 1987 to 1997, BE was diagnosed in 177 patients. We excluded three with high-grade dysplasia (HGD) at the time of enrollment. Follow-up was complete in 166 patients (135 male, 31 female). The mean length of endoscopic follow-up was 5.5 yr (range 0.5-13.3). Low-grade dysplasia (LGD) was present initially in 16 patients (9.6%) and found during follow-up in another 24 patients. However, in 75% of cases, LGD was not confirmed on later biopsies. HGD was found during surveillance in three patients (1.8%), one with simultaneous AC; two with HGD developed AC later. AC was detected in five male patients during surveillance. The incidence of AC was 1/220 (5/1100) patient-years of total follow-up, or 1/183.6 (5/918) patient-years in subjects undergoing endoscopy. Four AC patients died, and one was alive with advanced-stage tumor. The mean number of endoscopies performed for surveillance, rather than for symptoms, was 2.4 (range 1-10) per patient. During the follow-up years the cohort had a total of 528 examinations and more than 4000 biopsies. CONCLUSIONS: The incidence of AC in BE is low, confirming recent data from the literature reporting an overestimation of cancer risk in these patients. In our patient cohort, surveillance involved a large expenditure of effort but did not prevent any cancer deaths. The benefit of surveillance remains uncertain.     

Risk of progression of Barrett's esophagus in patients with cirrhosis

AIM To study Barrett's esophagus(BE) in cirrhosis and assess progression to esophageal adenocarcinoma(EAC) compared to non-cirrhotic BE controls.METHODS Cirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh(CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia(HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups. RESULTS A total of 57 patients with cirrhosis and BE were matched with 228 controls(BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls weresimilar with 8.8% vs 12% with low grade dysplasia(LGD) and 12.3 % vs 19.7% with HGD or EAC(P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls(1.4 vs 1.1 per 100 person-years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance(13.7 vs 8.1 per 100 personyears, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients(HR =7.9, 95%CI: 2.0-30.9, P = 0.003). CONCLUSION Cirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients.     

Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus.

BACKGROUND & AIMS: The exact incidence of adenocarcinoma in patients with Barrett's esophagus (BE) is not known and is reported to vary from 0.2%-2% per year. Published series of patients with BE have included relatively small numbers of patients with limited duration of follow-up. The goal of this study was to define the prevalence and incidence of dysplasia and cancer and evaluate the paths of progression in a large multicenter cohort of BE patients. METHODS: The BE study is a multicenter clinical and endoscopic outcomes project involving a single large database of patients with BE. Data from each of the participating centers were merged into the main study database. Cancers and HGD occurring within 12 months of the index endoscopy were regarded as prevalent cases. RESULTS: One thousand three hundred seventy-six patients met the study criteria (95% white, 14% women); 91 patients had cancer at the initial endoscopy (prevalent cases, 6.7%; 95% confidence interval [CI], 4.8%-8.7%). Six hundred eighteen patients were followed for a total of 2546 patient-years; mean follow-up was 4.12 years. Twelve patients developed cancer during follow-up, a cancer incidence of 1 in 212 patient-years of follow-up (0.5% per year; 95% CI, 0%-1.1%). The combined incidence of HGD and/or cancer was 1 in 75 patient-years of follow-up or 1.3% per year (95% CI, 0%-2.2%). Of the 34 patients developing HGD and/or cancer, 18 patients (53%) had at least 2 initial consecutive endoscopies with biopsies revealing nondysplastic mucosa. The incidence of LGD was 4.3% per year (95% CI, 2.8%-6.0%). In the 156 patients with LGD, regression to no dysplasia occurred in 66%, persistent LGD in 21%, and progression to HGD/cancer in 13%. The incidence of cancer in patients with LGD was 1 in 156 patient-years of follow-up or 0.6% per year (95% CI, 0%-1.3%). CONCLUSIONS: Preliminary results from this trial define the prevalence and incidence of dysplasia and cancer in a multicenter cohort of patients with BE. At least half the patients who developed HGD and/or cancer had 2 consecutive initial endoscopies with biopsies revealing nondysplastic mucosa. The majority of patients with LGD regressed and had a cancer incidence similar to all BE patients.     

Evaluation of the updated confocal laser endomicroscopy criteria for Barrett's esophagus among gastrointestinal pathologists

Previously developed novel probe‐based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high‐grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low‐grade dysplasia/high‐grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4–82.3). The accuracy was higher when pathologists had ‘high confidence’ in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53–0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1–90.7) and the specificity was 70% (95% CI: 61.91–77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.     

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self‐administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e‐mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1–0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low‐grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice‐daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low‐grade dysplasia, and 52% for high‐grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence‐based guidance is required to enhance clinical practice.     

Barrett's esophagus at a tertiary care center: association of age on incidence and prevalence of dysplasia and adenocarcinoma

OBJECTIVES: Barrett's esophagus (BE) is traditionally thought of as a disease of middle-aged Caucasian men. Little is known about BE in younger patients. We sought to assess the effect of age on features of BE including the prevalence and incidence of dysplasia and carcinoma. METHODS: All patients enrolled into the Cleveland Clinic BE registry from 1979 to 2002 were studied. Age, ethnicity, number of endoscopies, hiatal hernia size, length of Barrett's segment, prevalence and incidence of dysplasia, and cancer were compared between patients > or = 50 yr old and < 50 yr old. RESULTS: There were 837 patients in the registry (638 > or = 50 yr, 199 < 50 yr). Hiatal hernia size was larger in patients > or = 50 yr than in those < 50 yr (median 4.0 cm, interquartile range 2.0-5.0 cm vs 3.0, 2.0-4.0 cm; p < 0.01). Otherwise, there were no significant differences among other features in the patient population. There were 225 patients with dysplasia or cancer (195 > or = 50 yr and 30 < 50 yr; p < 0.01). Of this group, 176 were prevalent cases (159 > or = 50 yr and 17 < 50 yr) and 49 were incident cases (36 > or = 50 yr and 13 < 50 yr). The odds of those > or = 50 yr being a prevalent case of high-grade dysplasia or cancer was five times the odds of those < 50 yr (p < 0.01). The incidence of dysplasia or cancer was similar in both age groups. CONCLUSIONS: Our study supports emerging data that approximately 25% of BE patients are less than 50 yr of age. While older patients had a higher prevalence of dysplasia or adenocarcinoma, the incidence of dysplasia and adenocarcinoma is similar in both age groups. Future screening strategies for BE should recognize these important findings.     

Esophagitis: incidence and risk of esophageal adenocarcinoma--a population-based cohort study

OBJECTIVES: Although symptoms of reflux are common, our knowledge of the epidemiology and natural history of gastroesophageal reflux disease is sparse. The risk of esophageal adenocarcinoma is increased among patients with acid reflux, but the contribution of Barrett's lesions is unknown. METHODS: With the aim to estimate the incidence of diagnosed endoscopic esophagitis lesions and the risk of esophageal adenocarcinoma among patients with previously diagnosed esophagitis, we extracted data on endoscopies, esophagitis diagnoses, and gastroesophageal cancer diagnoses from five population-based databases covering the period from 1974 to 2002, and covering all citizens in Funen County (population 470,000). RESULTS: In 2002, the incidence of esophagitis lesions was 2.4 per 1,000 person-years (95% confidence interval 2.3-2.6), 18.3 per 1,000 persons (17.9-18.7) had previously diagnosed esophagitis. Incidence increased by calendar year and age, was higher among males than among females, and was closely related to rate of endoscopy. Among 11,129 patients with previously diagnosed esophagitis, 15 had esophageal adenocarcinoma during 58,322 person-years of follow-up (26 per 100,000 person-years). The expected number was 2.79 and the standardized incidence ratio was 5.38 (3.01-8.87). Ten of the 15 patients with esophageal adenocarcinoma had previously diagnosed Barrett's esophagus. CONCLUSION: The risk of esophageal adenocarcinoma is increased fivefold in patients with previously diagnosed esophagitis, but most of the adenocarcinomas occurred among patients with Barrett's esophagus.     

c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus

We aim to determine the expression of the proto-oncogene c-Myc in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the prevalence of such expression in relation to the metaplasia-dysplasia-adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa injury from gastroesophageal reflux. BE is a premalignant lesion and plays an important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the process that transforms a normal cell into a tumorous one. In the development of human tumors, one of the most important genes is the proto-oncogene c-Myc. The c-Myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsies or the dissection of patient esophagectomy specimens. Demographic and endoscopic data (sex, age, race and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and 73% of adenocarcinoma samples, with significant statistical difference among these groups. No correlation was identified when the c-Myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-Myc overexpression along the metaplasia-dysplasia-adenocarcinoma sequence was observed. This study demonstrates a significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results point out the importance of this marker in the development of esophageal adenocarcinoma from BE.     

Eosinophilic infiltration of the esophagus following endoscopic ablation of Barrett's neoplasia

To assess the incidence of esophageal intra‐epithelial eosinophilic infiltration following endoscopic ablation of Barrett's esophagus (BE), a retrospective study of consecutive cases of endoscopic ablation of BE with dysplasia or cancer using radiofrequency ablation (RFA) and spray cryotherapy at two centers in the United States was performed. Post‐ablation eosinophilia was defined as ≥5 eosinophils per high power field during post‐treatment surveillance. Twenty of 122 patients (16%) undergoing ablation developed esophageal eosinophilia after ablation, including 8/77 (10%) treated with RFA and 12/44 (27%) treated with cryotherapy. No patient had clinical or endoscopic findings of or risk factors for eosinophilic esophagitis. Esophageal eosinophilia persisted in 30% over a median of 20.2 months. On multivariate analysis, post‐ablation eosinophilia was independently associated with increasing BE segment length (adjusted odds ratio 1.46 for every 2‐cm increase, 95% confidence interval 1.24–1.71) and cryotherapy as the ablation modality (adjusted odds ratio 5.23, 95% confidence interval 1.67–16.39). Esophageal eosinophilic infiltration after endoscopic ablation with RFA and cryotherapy is common and is associated with the BE segment length and treatment modality. The clinical significance of post‐ablation eosinophilia is unclear.     

Natural History of Barrett’s Esophagus

Barrett’s esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years.     

Time trends of endoscopic and pathological diagnoses related to gastroesophageal reflux disease in a Chinese population: eight years single institution experience

The discrepancy between Eastern and Western countries exists regarding the time trends of Barrett's esophagus (BE)/adenocarcinoma. We aimed to elucidate this issue through a retrospective review of the endoscopic and pathological diagnoses of gastroesophageal reflux disease (GERD) over time in a Chinese population. All records were analyzed from 2000 to 2007. Records included demographic data, clinical indication for endoscopy, and endoscopic findings. The total number of endoscopic procedures increased over time. The indications for referral endoscopy secondary to GERD increased from 366 cases (4.9%) in the beginning of the study to 1439 cases (14.1%) at the end. Concomitant GERD symptoms did not significantly change (range, 13–15.1%) in screening endoscopic studies. Endoscopic detection of erosive esophagitis increased in referral populations from 1546 (20.7%) to 5207 cases (51%) and by screening endoscopy from 791 (14.5%) to 1983 cases (23.5%). The prevalence of nonerosive reflux disease and BE did not change over time. BE‐associated dysplasia and adenocarcinoma were rare. The detection of Los Angeles class A disease increased with time in referral endoscopy cases with a focus on erosive esophagitis composition. The endoscopic demand for GERD investigation and the GERD endoscopic diagnosis increased in our population. The results were related to a higher prevalence of low‐grade erosive disease diagnosed. The incidence of BE‐associated dysplasia and adenocarcinoma has been the same and the increased screening did not detect more cancers.     

洛阳地区Barrett''''s食管的发病情况、内镜和病理学特点

目的探讨洛阳地区一组Barrett’s食管(BE)的发病情况、内镜和病理学特点及其与幽门螺杆菌(H.pylori)感染的关系。方法采用普通胃镜检查结合病理检查结果,对洛阳地区有消化道症状的一组BE患者进行分析,同时采用尿素[14C]呼气试验药盒检查H.pylori感染对BE发病学的影响。结果2006年8月~2007年4月共有593例接受胃镜检查,有22例诊断为BE,BE发病率为3.71%;以短段、舌型发病率最高,分别占81.81%和77.27%;7例(31.8%)有典型反流症状;伴有低度异型性增生3例(13.64%),重度异型性增生1例(4.55%),并发腺癌1例(4.55%),其中伴有重度异型性增生的1例随访1年后并发腺癌;对其中的10例进行H.pylori检查,阳性率为90%。结论洛阳地区BE发病率较高,以短段、舌型为主,有典型反流症状者较少,伴有异型性增生、腺癌者及并发H.pylori感染者常见。