Structures of the normal esophagus and Barrett’s esophagus

This article reviews and discusses several topics, mainly relating to the histology of the normal esophagus and of Barretts esophagus, in order to facilitate the understanding of Barretts esophagus. The border between the esophagus and stomach is considered in Japan to be the lower limit of longitudinal vessels which are visible in the lower segment of the esophagus at endoscopy. This definition has been authorized by the Japanese Society for Esophageal Diseases. The longitudinal vessels are also visible through the metaplastic columnar epithelium of Barretts esophagus. Identification of the esophageal glands proper in biopsy specimens can assist in the histologic diagnosis of Barretts esophagus. The histologic diagnosis of Barretts esophagus in biopsy specimens, in relation to the presence of esophageal glands proper, is discussed. Ciliated pseudostratified epithelium is discussed in detail, including the fact that it is thought to be an intermediate stage between squamous and columnar epithelium at the esophagogastric junction and at ectopic gastric mucosa in the upper esophagus. The differences in the histopathologic criteria for a diagnosis of Barretts adenocarcinoma between Western countries and Japan are also discussed. The four editions of the Comprehensive Registry of Esophageal Cancer in Japan, and the Long Term Results of Esophagectomy in Japan (1988–2000), published by the Japanese Society for Esophageal Diseases and available on its website (http://jsed.umin.ac.jp), are introduced. These editions give detailed information on the pathology, endoscopic features, radiation treatment, and surgery of esophageal cancer in Japan.The contents of this paper were presented at the 57th Annual Meeting of the Japan Esophageal Society as an educational lecture on June 27, 2003.     

Crohn’s disease of the esophagus

Opinion statement Esophageal damage is an uncommon manifestation of Crohn’s disease. The diagnosis should be considered in patients who have other intestinal manifestations of Crohn’s disease and present with esophageal symptoms. Diagnosis should be based on history, known extraesophageal Crohn’s disease, endoscopic evaluation with biopsy, and exclusion of gastroesophageal reflux disease. Mild disease should be treated with acid suppression and a short course of steroids. 5-amino-salicylates are not likely to be effective due to drug release characteristics. Patients who have moderate to severe disease should be treated aggressively with acid suppression, a longer course of steroids, and consideration of immunosuppressive therapy with 6-mercaptopurine or azathioprine. Infliximab or other anti-tumor necrosis factor therapy also can be considered in refractory patients to try to prevent the complications of stricturing and fistula formation. In those patients who develop strictures of the esophagus, treatment with balloon dilatation of the stricture followed by injection of a long-acting steroid such as triamcinolone will help to alleviate symptoms. Surgery may be required for severe, refractory symptoms, but it has a high morbidity in this population.     

Gallstones increase the prevalence of Barrett’s esophagus

Purpose  

Bile and acid exposures are thought to be major risk factors for Barrett’s esophagus in Western countries. The association of gallstones with Barrett’s esophagus has not been fully evaluated. The present study was designed as a case-control study for determining the possible factors associated with endoscopically suspected esophageal metaplasia (ESEM), defined as an endoscopic finding suggestive of Barrett’s esophagus, in Japanese patients.     

Does this patient have Barrett's esophagus? The utility of predicting Barrett's esophagus at the index endoscopy

OBJECTIVES: Few studies have evaluated the ability of the endoscopist to predict the presence of Barrett's esophagus (BE) at index endoscopy. The goals of this study were to determine the operating characteristics of endoscopy in diagnosing BE, and to determine the clinical and endoscopic predictors of BE in suspected BE patients at the index endoscopy. METHODS: From September 1993 to October 1997, endoscopic reports were examined to identify patients with suspected BE. All esophageal pathology reports during the same period were evaluated for the presence of specialized intestinal metaplasia. RESULTS: During the study period, 4053 endoscopies were performed on 2393 patients. Eight percent of all procedures were performed for suspected or confirmed BE. Fifty-three patients were known to have BE and thus their reports were excluded from this analysis. Five hundred seventy of the remaining patients had esophageal biopsies performed, and were included in this analysis. Among these 570 patients, 146 were suspected to have BE on endoscopy, while 424 were not suspected to have BE at the time of endoscopy. There were no differences among the two groups in terms of gender, race, and dyspepsia as an indication for the endoscopy. However, suspected BE patients were slightly younger and were more likely to have heartburn, but were less likely to have dysphagia as an indication for the endoscopy. The sensitivity and specificity of the endoscopists' assessments were 82% (95% confidence interval [CI], 72-92) and 81% (95% CI, 78-84), respectively. The positive predictive value and the negative predictive value were 34% and 97%, respectively. The positive likelihood ratio was 4.32 (95% CI, 3.49-5.31) and the negative likelihood ratio was 0.22 (95% CI, 0.13-0.38). Univariate analysis showed that endoscopists diagnosed BE in those with long-segment BE (LSBE) more accurately than in those with short-segment BE (SSBE) (55% vs 25% p = 0.001; odds ratio [OR] = 3.63, 95% CI, 1.71-7.70). Barrett's esophagus was correctly diagnosed in 38.5% of white patients but in only 14.7% of black patients (p = 0.01; OR = 3.63, 95% CI, 1.31-10.13). Multivariable logistic regression identified only the length of the columnar-appearing segment (p = 0.002; OR = 3.33, 95% CI, 1.54-7.17) and race (p = 0.08; OR = 2.31, 95% CI, 0.88-6.03) to be associated with the presence of BE on biopsy. CONCLUSIONS: Barrett's esophagus is frequently suspected at endoscopy; SSBE was more frequently suspected than LSBE, but was correctly diagnosed only 25% of the time, versus 55% for LSBE. Endoscopists diagnosed BE with a sensitivity of 82% and a specificity of 81%. However, the positive predictive value was only 34%, whereas the negative predictive value was 97%. The length of the columnar-appearing segment is the strongest predictor of BE at endoscopy. Alternative methods are needed to better identify BE patients endoscopically, especially those with SSBE.     

Current strategies in the management of Barrett’s esophagus

Barrett’s esophagus has become a very important topic in gastroenterology. Its management may vary from essentially a surveillance strategy to highly invasive esophagectomy. The variation in management strategies has occurred because of the current perceptions regarding cancer risks, which range from almost negligible to an incidence of 30% in high-grade dysplasia. Although it is clear that most patients with Barrett’s esophagus without dysplasia will not require therapy, the prospect of continued surveillance is unpleasant at best. Promising future tools and techniques for surveillance and treatment are described in this review.     

What is the optimal medical therapy for Barrett's esophagus?

The development of Barrett's esophagus (BE) in patients with gastroesophageal reflux disease (GERD) is troubling because of its known association with esophageal cancer. When evaluated clinically, patients with BE have the severest form of GERD and require aggressive therapy to control esophageal acid exposure. Both hypotension of the lower esophageal sphincter and the extent of esophageal acid exposure are major contributors to severe GERD and its complications. It is hypothesized that better control of acid will improve outcomes for BE patients. While it is clear that therapy (medical or surgical) for reflux rarely if ever results in total regression of BE, there are some limited data to support improvement in BE with control of reflux. Current medical choices include prokinetic agents, histamine type-2 receptor antagonists, and proton pump inhibitors. In the future, genetic markers may be used in identifying BE patients at the greatest risk for histologic progression, and chemoprevention with cyclooxygenase-2 inhibitors may be a therapeutic option. This paper will review the rationale for and results of medical antireflux therapy in patients with BE.     

Advanced imaging in surveillance of Barrett's esophagus: Is the juice worth the squeeze?

Esophageal cancer is on the rise. The known precursor lesion is Barrett's esophagus(BE). Patients with dysplasia are at higher risk of developing esophageal cancer. Currently the gold standard for surveillance endoscopy involves taking targeted biopsies of abnormal areas as well as random biopsies every 1-2 cm of the length of the Barrett's. Unfortunately studies have shown that this surveillance can miss dysplasia and cancer. Advanced imaging technologies have been developed that may help detect dysplasia in BE. This opinion review discusses advanced imaging in BE surveillance endoscopy and its utility in clinical practice.     

Barrett’s esophagus

Opinion Statement Patients who develop Barrett’s esophagus should be entered into an endoscopic surveillance program, including endoscopic biopsy. For patients who do not develop dysplasia, we recommend surveillance every 3 years. Patients with low-grade dysplasia should be surveyed with endoscopy and biopsy every 6 months over the next year, then at 1-year intervals if there has not been progression to a higher grade of dysplasia. The role of endoscopic ablation therapy has yet to be defined. Because of the high risk (30% to 40%) of developing esophageal cancer among patients with high-grade dysplasia, we recommend esophagectomy for those who are medically fit to undergo this surgery. However, it is important that an expert pathologist confirms the diagnosis and that the operation is performed by a surgeon experienced in esophageal resection. For those who are not candidates for surgery or refuse it, we recommend consideration of endoscopic ablative therapy. The other option available is to continue surveillance at 3- to 6-month intervals with reconsideration of surgical or experimental ablative therapy if cancer develops (see Figure 1).     

Acid suppression and adenocarcinoma of the esophagus: cause or cure?

In this issue El-Serag et al. present a retrospective study which shows that patients with Barrett's esophagus and no dysplasia who were prescribed PPIs had a lesser rate of developing dysplasia than patients who were not prescribed PPIs. Acid suppression has been proposed both as a cause and a cure for the "epidemic" of adenocarcinoma of the esophagus, which has been noted in the United States. The article and the current evidence related to acid suppression and adenocarcinoma of the esophagus are reviewed.     

Role of goblet cells in the progression of Barrett’s esophagus

正Objective To investigate the clinical pathological features of Barrett’s esophagus in China,and to study the relationship between the number of goblet cells and the severity of Barrett’s esophageal dysplasia.Methods From January 2008 to October 2018,in the Department of Gastroenterology and Hepatology,Tianjin Medical University     

From GERD to Barrett's esophagus: Is the pattern in Asia mirroring that in the West?

Gastroesophageal reflux disease (GERD) is a known predisposing factor for Barrett's esophagus. Amongst individuals with symptomatic GERD, the prevalence of Barrett esophagus is estimated to be more than 10%, and an individual with Barrett's esophagus is more likely than the general population to develop esophageal adenocarcinoma. In Western Europe and North America, incidence of esophageal adenocarcinoma had been on the upward trend for many decades. In comparison, although the prevalence of GERD and reflux esophagitis has increased several fold in some parts of Asia, the prevalence of esophageal adenocarcinoma and Barrett's esophagus remains generally low in the region. Rising incidence of esophageal adenocarcinoma has been observed in regions witnessing increasing prevalence of GERD. If the recent increase in prevalence of GERD in parts of urbanized Asia is any indication of the beginning of an upsurge in the incidence of Barrett's esophagus and associated adenocarcinoma, would we be witnessing a pattern of epidemiological shift mirroring that in the West? Given that more than 90% of Barrett's esophagus in Asian patients is of the short‐segment type, which is reported to have lesser propensity to develop to adenocarcinoma, could the ongoing epidemiologic transition take Asia on the same trail as that which the West has taken? This article will draw on relevant findings from various parts of Asia and take an in‐depth look at prevailing disease trends to see where Asia stands now in the changing epidemiology of GERD, Barrett's esophagus and associated adenocarcinoma.     

Expression of TNF-α and VEGF in the esophagus of portal hypertensive rats

AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats. METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M7, M14, and M21) in which the rats were kiued on the seventh day, the 14^th d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C7, C14 and C21) corresponding to the models. The expression of TNF-α and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique. RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82±1.83 vs 11.61±0.86 cmH2O, 20.90±3.27 vs 11.43±1.55 cmH2O and 20.68±2.27 vs 11.87±0.79 cmH2O respectively, P<0.01), as well as the number (9.3±1.6 vs 5.1±0.8, 11.1±0.8 vs 5.4±1.3 and 11.7±1.5 vs 5.2±1.1 respectively, P<0.01) and the total vascular area (78 972.6±3 527.8 vs 12 993.5±4 994.8 um^2, 107 207.5±4 6461.4 vs 11 862.6±5 423.2 um^2 and 110 241.4±49 262.2 vs 11 973.7±3 968.5 um^2 respectively, P<0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNF-α and VEGF in M21 was significantly higher (2.23±0.30 vs 1.13±0.28 and 1.65±0.38 vs 0.56±0.30 for TNF-α and VEGF respectively, P <0.01), whereas there was no difference in M7 (1.14±0.38 vs 1.06±0.27 and 0.67±0.35 vs 0.50±0.24 for TNF-α and VEGF respectively, P>0.05) and M14 (1.20±0.25 vs 1.04±0.26 and 0.65±0.18 vs 0.53±0.25 for TNF-α and VEGF respectively, P>0.05). And the expression of TNF-α and VEGF in M21 was significantly higher than that in M7 (2.23±0.30 vs 1.14±0.38 and 1.65±0.38 vs 0.67±0.35 for TNF-α and VEGF respectively, P<0.01) and M14 (2.23±0.30 vs 1.20±0.25 and 1.65±0.38 vs 0.65±0.18 for TNF-α and VEGF respectively, P<0.01), but there was no difference between M7 and M14 (1.14±0.38 vs 1.20±0.25 and 0.67±0.35 vs 0.65±0.18 for TNF-α and VEGF respectively, P >0.05). CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-α and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.     

Circumferential and focal radiofrequency ablation for the treatment of Barrett’s esophagus

This invited profile summarizes the technical aspects and clinical trial results related to the use of circumferential and focal radiofrequency ablation in the management algorithm for Barrett’s esophagus. What makes this relatively new endoscopic intervention unique is its promising safety and efficacy profile reported in published clinical trials. This technology appears to have overcome many of the limitations of prior endoscopic ablative modalities, and is thus garnering a role in the management of this disease state.