Endoscopic eradication therapy in Barrett’s esophagus

Endoscopic eradication therapy (EET), the standard of care for treatment of Barrett’s esophagus with dysplasia and early neoplasia, consists of a combination of endoscopic resection and ablative modalities. Resection techniques primarily include endoscopic mucosal resection or endoscopic submucosal dissection. Resection of nodular disease is generally followed by one of multiple ablative therapies among which radiofrequency ablation has the best evidence supporting safety and efficacy. These advanced endoscopic procedures require both experience and expertise in the cognitive and procedural aspects of EET. However, very few formal programs exist that teach endoscopists the necessary skills to perform EET in a safe, standardized, and efficacious manner. Case volume at both the endoscopist and center level has been shown to affect clinical outcomes based on limited data. As a result, some recent guidelines endorse case volume as a measure of competency. Quality indicators, which can be used as benchmarks for training and as part of pay for quality initiatives, have recently been derived for EET. However, quality metrics in EET have not been widely accepted, nor are they broadly used currently. Although the efficacy of EET for BE is established, there is a need for application of quality metrics to both assure adequate training in these procedures and assess treatment outcomes. A standardized EET training curriculum during endoscopic training, with competency assessment of both new clinicians and endoscopists in practice, has the potential to improve care in EET.     

Limitations of endoscopic ablation in Barrett’s esophagus

In the last 5–10 years, endoscopic ablative therapies have been gaining ground as treatment for Barrett’s esophagus associated with high-grade dysplasia and early cancer, and they are becoming the most preferred technique over surgery as the standard of care. These therapies are associated with a lower rate of complications and mortality than surgery; studies have found them to be safe, effective and tolerable. Endoscopic ablative therapies are not, however, without their drawbacks. There is a paucity of data on long-term efficacy, and direct comparisons of the different modalities are lacking. Unlike surgery, current data suggest that endoscopic ablation treatments may not be curative in all patients, so patients require ongoing surveillance and acid suppression. Questions remain regarding durability as well as factors promoting recurrence after endoscopic therapy. The authors conducted a systematic review of the literature on ablative therapies in Barrett’s esophagus to describe the modalities currently available and to provide an understanding of their limitations.     

Endoscopic versus surgical therapy for Barrett’s esophagus neoplasia

Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal cancer. Though surgery can completely resect the cancer and the affected lymph nodes, it carries significant morbidity and mortality (often exceeds 2%). New developments in endoscopy have provided less-invasive therapies that can also be used to stage tissue invasion of cancer; they include esophageal mucosal resection (EMR) and endoscopic submucosal dissection. Additional endoscopic therapies include photodynamic therapy, radiofrequency ablation (RFA) and argon plasma coagulation. Combining EMR that targets the cancer and RFA that targets the surrounding Barrett’s esophagus offers an alternative to the operative approach when there is no lymph node metastasis. Arguments for surgical esophagectomy include concern for missed lymph node metastasis and incomplete endoscopic resection. Based on EMR’s high neoplasia eradication rate and its fewer and more manageable complications, EMR, especially when combined with RFA, appears to be a viable alternative to surgery in early submucosal cancers, that is, sm1.     

Dysplasia in Barrett’s esophagus

Opinion statement  

Risk for cancer in Barrett’s esophagus: Medical versus surgical therapy

Esophageal adenocarcinoma associated with Barrett’s esophagus has been increasing in incidence over the past three decades. Our understanding of the risks for the development of esophageal adenocarcinoma in Barrett’s esophagus is evolving. Newer treatment options for Barrett’s esophagus are being developed in all areas, including endoscopic therapy, surgery, and chemoprevention trials.     

Endoscopic eradication therapy for Barrett’s esophagus: Adverse outcomes,patient values,and cost-effectiveness

Endoscopic therapy for Barrett’s esophagus (BE) aims to replace dysplastic BE epithelium with neosquamous epithelium to prevent and reduce the risk of progression to esophageal adenocarcinoma (EAC) and treat early-stage EAC. Various modalities of endotherapy of dysplastic BE are described. Although endoscopic therapy is safe and effective in treating subjects with intramucosal carcinoma (IMCa), high-grade dysplasia (HGD), and confirmed low-grade dysplasia (LGD), challenges to successful treatment are being recognized. Though adverse outcomes of endotherapy such as bleeding, perforation, pain, and stricture formation are observed, they are not common and can usually be treated medically or endoscopically. Patient values and preferences toward endoscopic therapy and the cost-effectiveness of these endoscopic approaches also have crucial implications for the selection of appropriate treatment and subsequent outcomes in patients with BE.     

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).     

Risk factors for neoplastic progression in Barrett’s esophagus

Barrett’s esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a metaplasia-dysplasia-carcinoma (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic...     

Endoscopic imaging in Barrett’s esophagus

Barrett’s esophagus is the only known precursor that predisposes patients to the development of esophageal adenocarcinoma. The current recommended surveillance method is targeted biopsies of any abnormalities followed by random four-quadrant biopsies every 2 cm using standard white light endoscopy. Compliance with this and sampling error are two of the biggest problems. Several novel imaging technologies have been developed to aid the diagnosis of early neoplasia in Barrett’s esophagus. There are emerging data that some of these new modalities can increase the yield of detecting dysplasia. This review will discuss some of the present available techniques and technologies including chromoendoscopy, narrow-band imaging, autofluorescence imaging, optical coherence tomography, confocal endomicroscopy and endocytoscopy. Based on the current evidence, these imaging modalities appear to be promising as adjunctive tools to white light endoscopy. A few of them, nevertheless, remain experimental due to expense, lack of expertise, generalizability as well as reproducibility of results.     

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.     

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.     

Meta-analysis of Barrett’s esophagus in China

AIM:To investigate the epidemiology and characteristics of Barrett’s esophagus(BE)in China and compare with cases in the west.METHODS:Studies were retrieved from the China National Knowledge Infrastructure and PubMed databases using the terms"Barrett"and"Barrett AND China",respectively,as well as published studies about BE in China from 2000 to 2011.The researchers reviewed the titles and abstracts of all search results to determine whether or not the literature was relevant to the current topic of this research.The references listed in the studies were also searched.Inclusion and exclusion criteria for the literature were appropriately established,and the data reported in the selected studies were analyzed.Finally,a meta-analysis was performed.RESULTS:The current research included 3873 cases of BE from 69 studies.The endoscopic detection rate of BE in China was 1%.The ratio of male to female cases was 1.781 to 1,and the average age of BE patients was 49.07±5.09 years.Island-type and shortsegment BE were the most common endoscopic manifestations,accounting for 4.48%and 80.3%,respectively,of all cases studied.Cardiac-type BE was observed in 40.0%of the cases,representing the most common histological characteristic of the condition.Cancer incidence was 1.418 per 1000 person-years.CONCLUSION:Average age of BE patients in China is lower than in Western countries.Endoscopic detection and cancer incidence were also lower in China.     

Narrow band imaging in Barrett’s esophagus

Barrett’s esophagus is a well-recognized premalignant condition for the development of esophageal adenocarcinoma, the most rapidly rising cancer in the USA and Western Europe. Detection of intestinal metaplasia and neoplasia arising in Barrett’s esophagus patients continues to be a challenge. Limitations of conventional endoscopy with random biopsies provide the necessary impetus for the development of new approaches aimed at improving current screening and surveillance strategies. Narrow band imaging is a novel endoscopic technique that uses a higher intensity of blue light with narrow band filters, which allows a detailed inspection of mucosal and vascular surface patterns with high-level resolution and contrast. Preliminary studies have provided encouraging results for Narrow band imaging alone or in combination with other advanced endoscopic techniques in the screening and surveillance of Barrett’s esophagus patients.     

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.     

Adherence to clinical guidelines for Barrett’s esophagus

Abstract

Background and aim: Clinical guidelines recommend endoscopy surveillance at given intervals or endoscopic therapy for Barrett’s esophagus with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Whether these guidelines are followed in clinical practice is unknown and was assessed in this study.

Methods: This nationwide Swedish cohort study included patients with Barrett’s esophagus with histologically verified LGD or HGD from 50 centers in 2006–2013. These patients were followed up using nationwide registers. Adherence to clinical guidelines was explored. Eight potential risk factors for deviation from guidelines were assessed using multivariable logistic regression, providing adjusted odds ratios (OR) with 95% confidence intervals (95%CI).

Results: Among 211 patients with Barrett’s esophagus (mean age 67.0 years, standard deviation 9.7 years, 81% male), 71% had LGD and 29% had HGD. During median 3.9 years of follow-up, 84% underwent a follow-up endoscopy, 17% received endoscopic therapy and 8% underwent esophagectomy. The clinical management deviated from guidelines in 60% of all patients (69% in LGD and 39% in HGD), which was mainly due to under-surveillance (86%). Risk factors for deviation from guidelines were LGD compared to HGD (OR 3.4, 95%CI 1.7–6.8), longer Barrett’s segment length (OR 2.0, 95%CI 1.0–3.9, comparing ≥3?cm with <3?cm), and treatment at gastroenterology compared to surgery departments (OR 2.3, 95%CI 1.2–4.4). Age, sex, calendar period and university hospital status were not associated with deviation from surveillance guidelines.

Conclusions: Adherence to guidelines for dysplastic Barrett’s esophagus is poor, particularly for LGD. Efforts to implement clinical guideline recommendations are needed.