How to diagnose and manage patients with Barrett's esophagus in China

In order to prevent the development of Barrett's esophagus (BE)-related esophageal cancer in China and facilitate the communication of research results among different centers, we propose using standardized diagnostic criteria and taking a conservative approach to diagnose and manage BE patients. BE patients without dysplasia need to be treated medically. For low-grade dysplasia, an annual endoscopy with biopsies is recommended, along with medical therapy. For high-grade dysplasia and intramucosal carcinoma, an endoscopic or surgical intervention is suggested. All BE patients should be followed up closely.     

Barrett's esophagus-related diseases remain uncommon in China

Barrett's esophagus (BE)-related esophageal adenocarcinoma (EAC) has shown the fastest rise in incidence in Western countries; however, research data on BE-related diseases from China are inconclusive. We aimed to review and analyze the published results on these diseases in China. We searched PubMed and Chinese medical literature for key words: BE, EAC, Chinese and China. Relevant research papers along with the study results from our own groups were reviewed and analyzed. Using standardized criteria, columnar-lined esophagus (CLE) was found in as many as 29% of resection specimens in Chinese patients with proximal gastric cancer. However, BE with intestinal metaplasia was rare, ranging from 0.06% in the general population to <2% in referral patients. Risk factors included advancing age, hiatal hernia and probably gastroesophageal reflux disease and tobacco or alcohol abuse, but not male gender or obesity. At endoscopy, most CLE/BE were <2 cm in length, and appeared tongue-like and island-like. The long-segment BE was rare, especially in women. Population-based studies conducted in Taiwan and Hong Kong SAR, China showed that EAC was not only rare but also stable or had decreased in incidence over the past decade. By histopathology, EAC accounted for only 1% of all distal esophageal cancers and almost all gastroesophageal junction (GEJ) cancers were centered in the proximal stomach. BE-related diseases, except for CLE, are rare in China. The clinical significance and malignant potential of CLE in the Chinese population remain elusive. Further investigation on these diseases is in progress.     

Lgr5, an intestinal stem cell marker,is abnormally expressed in Barrett's esophagus and esophageal adenocarcinoma

Lgr5 (leucine‐rich‐repeat‐containing G‐protein‐coupled receptor 5), a recently discovered intestinal stem cell marker, is expressed in premalignant lesions including Barrett's esophagus (BE) and cancers including colon cancer, ovarian cancer, and hepatocellular carcinoma. It was also recently found to be expressed in tumor spheres prepared from colon cancer, suggesting that it will likely serve as a cancer stem cell marker. We sought to examine Lgr5 as a biomarker in BE‐associated neoplasia. Using standard immunohistochemistry, we performed immunostaining on 81 esophageal specimens (53 biopsy specimens and 28 surgical resections) representing BE, BE‐associated dysplasia, and esophageal adenocarcinoma (EAC). Each immunostain was scored based on intensity of immunostaining and percentage of positive cells. For 24 EAC cases, survival analysis was performed with expression scores and other clinicopathological variables. We found that Lgr5 expression was detected in 70% of BE cases and between 90 and 100% of advanced dysplastic lesions and EAC. The intensity of expression was significantly higher in high‐grade dysplasia and EAC than BE. In EAC, high Lgr5 expression scores (≥5) were associated with worse survival, independent of stage, age, and neoadjuvant/adjuvant therapy (P = 0.03). Our findings suggest that Lgr5 has potential utility as a biomarker for BE‐associated dysplasia and EAC.     

Endoscopic imaging of Barrett’s esophagus

The incidence of esophageal adenocarcinoma(EAC) has dramatically increased in the United States as well as Western European countries. The majority of esophageal adenocarcinomas arise from a backdrop of Barrett’s esophagus(BE),a premalignant lesion that can lead to dysplasia and cancer. Because of the increased risk of EAC,GI society guidelines recommend endoscopic surveillance of patients with BE. The emphasis on early detection of dysplasia in BE through surveillance endoscopy has led to the development of advanced endoscopic imaging technologies. These techniques have the potential to both improve mucosal visualization and characterization and to detect small mucosal abnormalities which are difficult to identify with standard endoscopy. This review summarizes the advanced imaging technologies used in evaluation of BE.     

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.     

Squamous cell carcinoma in Barrett's esophagus: field effect versus metastasis

Barrett's esophagus (BE) is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). Risk factors for EAC overlap with those for esophageal squamous cell carcinoma (ESCC), but ESCC is surprisingly rare in BE. We report two cases of ESCC directly surrounded by BE. Both patients had a previous medical history of cancers, i.e., head and neck squamous cell carcinomas, and were using alcohol and smoking tobacco. Using immunohistochemistry for p63, CK5, CK7, and CDX2, it was confirmed that these carcinomas were pure squamous cell carcinomas, and not EACs or esophageal adenosquamous carcinomas arising from BE. Using TP53 mutation and loss of heterozygosity analysis, we established that the ESCCs in BE were not metastases of the previously diagnosed head and neck squamous cell carcinomas but de novo primary ESCCs. This study shows the strength of molecular analysis as an adjunct to the histopathologic diagnosis for distinguishing between metastases of prior cancers and primary cancers. Furthermore, these cases imply that presence of BE is not protective with regards to developing ESCC in the lower one third of the esophagus. We suggest that their ESCCs arose from islets of squamous epithelium in BE.     

Current status of Barrett's esophagus research in Asia

In Western countries, the epidemiology of esophageal cancer has changed considerably over the past decades with a rise in the ratio of adenocarcinoma to squamous cell carcinoma. Although the prevalence of gastroesophageal reflux is increasing in Asia, the prevalences of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have remained low in most Asian countries. The Asian Barrett's Consortium recently conducted a review of published studies on BE from Asia to assess the current status of BE research in Asia, and to recommend potential areas for future BE research in the region. Differences in study design, enrolled population, and endoscopic biopsy protocols used have led to substantial variability in the reported BE prevalence (0.06% to 19.9%) across Asia. In particular, some Japanese studies used diagnostic criteria that differed considerably from what was used in most Asian studies. As in Western countries, increased age, male sex, tobacco smoking, reflux symptoms, and erosive esophagitis have been found to be risk factors for BE in several case-control studies from Asia. The Prague C and M criteria, developed to provide better interobserver reliability in diagnosis and grading of BE, are currently under extensive evaluation in the Asian population. There is a need for standardized protocols for endoscopic and histopathologic diagnosis before initiating collaborative projects to identify etiologic determinants of BE and its ensuing malignant transformation. At present, data regarding the management and long-term outcome of BE are extremely limited in Asia. More studies of BE in this geographic area are warranted.     

Chronology of the Barrett's metaplasia-dysplasia-carcinoma sequence.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.     

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.     

Advances in endoscopic diagnosis and treatment of Barrett's esophagus

Barrett's esophagus (BE) is defined as abnormal specialized columnar metaplasia with intestinalization in place of the normal squamous esophageal epithelium. Gastroesophageal reflux disease is a known risk factor for BE; nonetheless BE is also detected in asymptomatic individuals. Other risk factors for BE include smoking, male gender, age over 50 and obesity. Patients diagnosed with BE (without dysplasia) are recommended to undergo endoscopic surveillance every 3-5 years. Advances in imaging techniques (such as narrow band imaging, autofluorescence imaging and confocal laser endomicroscopy) have the potential to improve the detection of dysplasia and early cancer, thus making surveillance a more cost-effective endeavor. Patients with high grade dysplasia (HGD) and early cancer have a high rate of progression to invasive adenocarcinoma and traditionally these patients were treated with esophagectomy. The rapid advancement of endoscopic therapeutic techniques along with a low risk of complications have made endoscopic therapy an acceptable alternative to an esophagectomy in patients with HGD and early cancer. Several endoscopic treatment techniques such as endoscopic mucosal resection, multipolar electrocoagulation, photodynamic therapy, argon plasma coagulation, cryotherapy, and radiofrequency ablation have been studied for endoscopic treatment.     

Clinical significance and management of Barrett&rsquo;s esophagus with epithelial changes indefinite for dysplasia

Barrett’s esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.     

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.     

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.     

Diagnosis and management of Barrett��s metaplasia: What��s new

Barrett’s esophagus(BE) is a complication of gastroesophageal reflux disease,and a premalignant lesion for esophageal adenocarcinoma(EAC).Observational studies suggest that endoscopic surveillance is associated with the detection of dysplasia and EAC at an early stage along with improved survival,but controversies still remain.The management of patients with BE involves endoscopic surveillance,preventive and clinical measures for cancer,and endoscopic and surgical approaches to treatment.Deciding upon the most appropriate treatment is a challenge.This study presents the results and the effectiveness of these practices.     

Original article: The prevalence of Barrett's esophagus in the US: estimates from a simulation model confirmed by SEER data

Barrett's esophagus (BE) is the precursor and the biggest risk factor for esophageal adenocarcinoma (EAC), the solid cancer with the fastest rising incidence in the US and western world. Current strategies to decrease morbidity and mortality from EAC have focused on identifying and surveying patients with BE using upper endoscopy. An accurate estimate of the number of patients with BE in the population is important to inform public health policy and to prioritize resources for potential screening and management programs. However, the true prevalence of BE is difficult to ascertain because the condition frequently is symptomatically silent, and the numerous clinical studies that have analyzed BE prevalence have produced a wide range of estimates. The aim of this study was to use a computer simulation disease model of EAC to determine the estimates for BE prevalence that best align with US Surveillance Epidemiology and End Results (SEER) cancer registry data. A previously developed mathematical model of EAC was modified to perform this analysis. The model consists of six health states: normal, gastroesophageal reflux disease (GERD), BE, undetected cancer, detected cancer, and death. Published literature regarding the transition rates between these states were used to provide boundaries. During the one million computer simulations that were performed, these transition rates were systematically varied, producing differing prevalences for the numerous health states. Two filters were sequentially applied to select out superior simulations that were most consistent with clinical data. First, among these million simulations, the 1000 that best reproduced SEER cancer incidence data were selected. Next, of those 1000 best simulations, the 100 with an overall calculated BE to Detected Cancer rates closest to published estimates were selected. Finally, the prevalence of BE in the final set of best 100 simulations was analyzed. We present histogram data depicting BE prevalences for all one million simulations, the 1000 simulations that best approximate SEER data, and the final set of 100 simulations. Using the best 100 simulations, we estimate the prevalence of BE to be 5.6% (5.49–5.70%). Using our model, an estimated prevalence for BE in the general population of 5.6% (5.49–5.70%) accurately predicts incidence rates for EAC reported to the US SEER cancer registry. Future clinical studies are needed to confirm our estimate.     

肠型巴雷特食管危险因素临床分析

目的探讨肠型化生巴雷特食管（BE）的相关危险因素。 方法收集2017年1月至2020年1月在新疆维吾尔自治区人民医院诊治的55例肠型BE和性别、居住情况匹配的110例非肠型BE患者的临床资料，对两组患者基本状况、生活习惯以及临床病理参数进行回顾性分析，对比分析两组患者临床资料差异性，利用Logistic回归分析筛选肠型BE发生、发展相关的危险因素。 结果本院肠型BE患者检出率为3.7%（55例），其中男性占56.4%（31例），女性占43.6%（24例），平均年龄为57.73±6.54岁。肠型和非肠型BE患者在年龄、体重指数（BMI）、是否伴有胃食管反流病（GERD）症状和食管裂空疝、是否有食管癌家族史、血清幽门螺旋菌（HP）感染状态以及按化生的柱状上皮长度分型差异有统计学意义（P＜0.05）；在吸烟、饮酒、咖啡因摄入、饮茶习惯、结肠腺瘤诊断史及BE和结直肠癌家族史等上均无统计学意义（P＞0.05）。年龄≥50岁（P=0.031，OR=3.027，95%CI：1.107-8.278）、BMI＞25 kg/m²（P=0.029，OR=2.300，95%CI：1.089-4.856）和食管癌家族史（P=0.020，OR=2.420，95%CI：1.152-5.084）是肠型BE的危险因素。 结论年龄≥50岁、高BMI以及食管癌家族史是BE，尤其是肠型BE的危险因素，应加强具有上述危险因素的高危人群的健康宣传和管理，注重消化系统内镜监测，防止其发展为恶性肿瘤。     

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.     

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.     

Endoscopic diagnosis of early Barrett's neoplasia: Perspectives for advanced endoscopic technology

Barrett's esophagus (BE) is a metaplastic condition that occurs secondary to gastroesophageal reflux disease. BE is also a precursor to esophageal adenocarcinoma, which, although still rare in Japan, is one of the most rapidly increasing cancers in Western countries. However, the prevalence of gastroesophageal reflux disease has increased significantly over the past few decades in Japan, possibly leading to an incremental rise in BE and the associated inherent risk of adenocarcinoma. Given the poor prognosis of advanced‐stage Barrett's adenocarcinoma, endoscopic surveillance is recommended for subjects with BE to detect early neoplasias including dysplasia. However, endoscopic identification of dysplastic lesions is still not sufficiently reliable or subjective, making targeted therapy extremely difficult. Over the past few years, improvements in image resolution, image processing software, and optical filter technology have enabled identification of dysplasia and early cancer in BE patients. We retrieved as many studies on advanced endoscopic technologies in BE as possible from MEDLINE and PubMed. The present review focuses on the emergent clinically available technologies to provide an overview of the technologies, their practical applicability, current status, and future challenges.