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Consensus Guideline – Management of Barrett’s Esophagus

May 3, 2015 1:22 AM

Benign Barrett’s and Cancer Taskforce (BOB CAT): a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

 

Barrett’s esophagus (BE) is a premalignant lesion of metaplastic columnar epithelium of any histological subtype. Even though guidelines for the management of BE exist, its endoscopic and histopathologic classification, and management is highly variable among and within countries. Given the impact of a diagnosis of nondysplastic BE on the patient, the cost, risk of endoscopic surveillance, and the consequences of progression to invasive esophageal adenocarcinoma (EA), the international consensus group has produced an evidence-based guideline focused on the management of nondysplastic BE and low-grade dysplasia (LGD). The consensus group agreed on a new international definition of Barrett’s esophagus. A number of other clinical recommendations were made such as:
  • Population screening with endoscopy is not recommended
  • Endoscopic resection is recommended for visible, nodular disease
  • Surveillance is not needed when life expectancy is <5 years
The Benign Barrett’s and Cancer Taskforce (BOB CAT) has established a definition of BE:
  • BE is defined by the presence of columnar mucosa in the esophagus;
    • It should be stated whether intestinal metaplasia (IM) is present above the gastroesophageal junction.
    • This definition combines the divergent European (non-IM allowed) and the US (IM only allowed) systems.
Consensus exists on a new bidirectional pathway to de-escalate or escalate the management of patients with lower-risk BE compared with those with potentially higher-risk BE such as indefinite for dysplasia (IND), or LGD with persistence over two endoscopies, multifocality, and long-segment BE. In the case of LGD found on a single occasion (if not treated), follow-up should be close (a more intensive 6–12-month surveillance interval) with strict biopsy protocols, as many may also have or go on to develop high-grade dysplasia (HGD). The diagnosis of IND should be considered a temporary diagnosis only and should prompt further close follow-up with adequate biopsy sampling.
Patients with persistent and confirmed LGD should be treated with ablative therapy, which decreases progression to neoplasia, and not just followed up.

 

Recommendations for the management of nondysplastic Barrett’s esophagus (BE) and/or low-grade dysplasia (LGD)

 

Risk factors
  • Population screening: The Benign Barrett’s and Cancer Taskforce suggests against screening the general population for BE endoscopically or with non-endoscopic methods.
  • High-risk individuals: The Benign Barrett’s and Cancer Taskforce suggests screening in men over 60 years old with GERD symptoms for 10 years, to detect BE and for the investigation of dyspepsia.
  • Accepted risk factors for cancer: men, length of BE, central obesity (waist to hip ratio), smoking, aberrant p16 and p53
Diagnosis
  • Adoption of internationally accepted pathology criteria for both benign and dysplastic BE.
  • Consensus pathology reporting for any grade of dysplasia LGD and Indefinite for dysplasia in BE (at least 2 upper GI specialist pathologists).
  • A single specialist histopathologist report is acceptable for non-dysplastic BE.
  • A proforma to report non-dysplastic BE is good practice,
  • Number of biopsies: The Benign Barrett’s and Cancer Taskforce suggests research to determine the optimum number of biopsies for surveillance.
  • Endoscopic criteria: using a proforma is good practice.
  • Measure the length of BE by reference to the proximal margin of the gastric folds.
  • High-resolution endoscopy with targeted biopsy.
  • Advanced endoscopic imaging techniques is not recommended for routine use.
  • Biomarkers: The Benign Barrett’s and Cancer Taskforce suggests research to test their utility in the histological assessment of dysplasia, and as methods of risk stratification
Management
  • The Benign Barrett’s and Cancer Taskforce suggests research into the optimal pathways of management in, and setting for, BE surveillance.
  • Surveillance in non-dysplastic BE, if undertaken, should be targeted at high risk groups with factors including but not limited to: age 50 years or older, white race, male sex, obesity, and symptoms.
  • Surveillance in non-dysplastic BE in low-risk groups to decrease mortality rates and differential management for short and long segment BE is not recommended. Surveillance intervals are unproven for non-dysplastic BE.
  • Surveillance cycle should stop if life expectancy is less than 5 years.
  • IND is an interim diagnosis only and should be intensively followed up.
  • LGD on a single occasion is to be managed with continued more frequent (6 to 12 months) surveillance (providing the patient is fit for endoscopy and not already undergoing therapy).
  • Absence of LGD after 2 consecutive endoscopic evaluations is to be managed with routine BE surveillance.
  • Chemoprevention with aspirin, statins or diet is not recommended. Current evidence does not support modification of standard guidelines for the management of Helicobacter pylori in patients with BE. In patients with BE, the Benign Barrett’s and Cancer Taskforce suggests against using aspirin.
Surgery, endoscopic, and ablative therapies
  • PPI over surgery is recommended for symptom control.
  • Surgery generally is not superior to PPIs in prevention of progression of BE.
  • ER (endoscopic resection) or ablation is not recommended in benign BE.
  • LGD and higher-risk features (multifocality, segment length, persistence) should be offered treatment options including ablative therapies. Ablative therapy with follow-up decreases the progression to neoplasia.
  • ER: in patients with non-dysplastic BE, LGD, and IND, and a visible lesion, the Benign Barrett’s and Cancer Taskforce suggests ER (followed by ablation if HGD or cancer detected) over simple biopsies.
  • Expertise level for competency in ER unknown
Consensus Guideline Statement Summary

 

Definition of BE 
  • BE is a combined endoscopic and pathological diagnosis; BE is defined by the endoscopic presence of columnar mucosa of the esophagus, and the pathology report should state whether IM is present or absent in the tissue samples taken from the above gastroesophageal junction.
  • Good practice includes the adoption of internationally accepted pathology criteria for both benign and dysplastic BE.
    • Three caveats should be considered to ensure that this new global definition of BE is clinically meaningful:
      • The gastroesophageal junction is irregular and tongues of ≤1 cm may be a natural phenomenon (even if IM is present, it can occur in the cardia of the stomach).
      • In >80–90% of cases of BE a hiatal hernia (HH) also coexists.
      • The diagnosis must be an agreed clinicopathological definition.
      • There are cases in which either the pathologist or the endoscopist may be able to overrule the other (i.e. long segments of BE >3 cm (most HH are ≤3 cm) or micrometaplasia, missed endoscopically but picked up by the pathologist).
  • The optimal definition of LGD in BE includes the use of an agreed upon internationally recognized criteria including increased nuclear/cytoplasmic ratio and hyperchromatic and heterochromic nuclei.
    • The criteria for unequivocal low-grade intraepithelial neoplasia typically include preserved nuclear polarity, nuclear heterogeneity and margination, few mitoses, no atypical mitoses, and decreased numbers of transition to adjacent glandular epithelium. Architectural changes are absent or minimal in LGD but may include irregular growth patterns, parallel tubules, minimal gland distortions, no single cell budding, no significant branching of glands, no solid or cribriform patterns, and normal lamina propria. There are intraobserver variations in the diagnosis and grading of LGD and in differentiating it from reactive changes.
Diagnosis
  • The evaluation of routine biopsies by a single specialist (in BE) histopathologist, i.e. single reporting, for the diagnosis of BE is satisfactory.
  • In BE, the diagnosis of IND can be used for a variety of histopathological appearances and requires consensus agreement between at least two specialist GI pathologists.
    • When there are features of the epithelium and glands which are suspicious for dysplasia the term ‘indefinite for dysplasia’ may be useful.
      • The epithelium may possesse cytological features of dysplasia (nuclear pleomorphism, hyperchromasia, loss of polarity), but the features are present only in the base of crypts and not in the surface epithelium.
      • Lack of surface maturation has been required for the diagnosis of dysplasia.
      • Regenerative changes may mimic dysplasia, whereby there is a constellation of cytological atypical features, evidenced by an often marked increase in mitotic figures, nuclear pleomorphism, and loss of cell polarity, associated with inflammation, but a retained architecture and no sharp cutoff between normal and abnormal epithelium.
      • Technical factors may make a definitive assessment of the tissue impossible.
      • Reproducibility of a diagnosis of IND is poor and there is no evidence pointing to an optimal number of pathologists required for an IND diagnosis, but all cases of dysplasia require consensus review by at least 2 specialist GI pathologists.
  • A consensus between at least two specialist gastrointestinal (GI) pathologists is required for the diagnosis of any dysplasia (IND, LGD, HGD).
  • A proforma (standardized reporting form) should be used to report BE.
    • The use of a proforma report is strongly recommended in the setting of BE, at least for the reporting of biopsies from the index endoscopy to improve completeness, accuracy, and reproducibly of recording and reporting the morphological features of BE.
    • Proposed data set/data items that could be included in a draft proforma may include the following:
      • the number of biopsies per cm (including levels)
      • mucosal subtypes—e.g., squamous, columnar, mosaic, presence or absence of reflux esophagitis
      • IM presence or absence
      • active or chronic inflammation, with grading into mild/moderate/severe
      • presence of native structures
      • Vienna neoplasia category (1: no dysplasia, 2: IND, 3: LGD, 4: HGD, 5: invasive EA)
      • p53 immunostaining.
Screening to detect BE
  • Endoscopic screening for BE is not justified in the general population.
  • Endoscopic screening for BE is recommended to decrease the risk of death from esophageal adenocarcinoma in men >60 years old with GERD symptoms for 10 years.
Risk factors for progression to EA
  • The risk of progression of BE metaplasia to HGD or EA is related to central obesity (measured by waist circumference, waist–hip ratio, or visceral abdominal fat area).
  • The risk of nondysplastic BE progressing to dysplasia or EA is greater among men than among women.
  • The risk of progression of BE metaplasia is related to the (longer) length of BE.
Endoscopic methods in confirmed BE
  • Endoscopic reporting should be carried out using a minimum data set including a record of the length using the Prague criteria, and the presence and size of a HH below and esophagitis above the BE segment.
    • The Prague criteria provide a uniform set of criteria for describing BE. Objective landmarks should be formally recorded during BE surveillance. It is vital to identify the size of the HH in order to avoid false classification of the BE where no BE or a much smaller BE segment exists.
  • Surveillance and biopsy of BE should be performed by experienced endoscopists, with the availability of and training in appropriate techniques and tools, used according to standard protocols and with sufficient time allowed for careful inspection.
    • Further studies are needed on the optimal pathways of management in BE using risk factors and biomarkers to test systematic protocols for biopsy collection, in particular the optimum number and the optimal setting for BE surveillance (e.g., dedicated lists, specialist centers).
    • Use of high-definition endoscopy and narrow band imaging is recommended.
    • It is not clear whether examination time has an influence on findings.
    • Surveillance of BE should be done in a careful and systematic manner, although there is no clear evidence to recommend specialized referral units or clinics for BE.
  • High-resolution endoscopy with targeted biopsies in experienced hands is an effective tool for the diagnosis of BE neoplasia.
    • Endoscopic surveillance of BE should be performed using high-resolution white-light endoscopy. High-resolution endoscopes (HREs) – 1,000,000 pixel resolution – have greatly improved the ability to visualize subtle mucosal abnormalities in BE and appear to have higher sensitivity for detecting progression to early neoplastic lesions in BE.
    • The use of high-resolution endoscopy with targeted biopsies is only suggested in expert centers.

Surveillance and surveillance intervals

  • For the purposes of reducing mortality from EA in nondysplastic BE patients, routine surveillance (vs. no surveillance) is not supported.
    • In the absence of agreement on surveillance vs. no surveillance for reduction of mortality from EA, consensus on statements examining intervals for surveillance was not achieved
  • If surveillance of nondysplastic BE is undertaken, it should be targeted at high-risk groups (defined using composite risk factors including, but not limited to, age ≥50 years, white race, male sex, obesity, and symptoms).
    • There are currently no tightly defined and accepted criteria to differentiate those with nondysplastic BE and a higher risk of progression from those at lower risk.
    • The decision to carry out surveillance should be based on risk of progression of BE and include evaluation of factors known to place patients at higher risk of progression.
      • Age
      • Sex
      • Length of the segment
      • Central obesity
      • Symptom duration, frequency, and severity
    • Due to the lack of definitive evidence conclusive surveillance strategies can not be made.
  • Among patients with nondysplastic BE who have <5-year life expectancy, endoscopic surveillance is not recommended.
  • There are almost no data on different surveillance intervals or its effects among individuals with only LGD. There was no agreement for surveillance intervals in LGD in BE.

Management strategies

  • Endoscopic ablation therapy should not be offered routinely to patients with nondysplastic BE.
    • Studies indicate that no ablation technique can achieve 100% BE ablation and neosquamous epithelium after ablative treatment may still contain buried glands  that could be associated with progression to cancer. Prophylactic BE ablation does not appear to be cost effective.
  • Patients with BE with LGD on a single occasion (confirmed by at least two specialist GI pathologists), without higher risk features (including multifocality, long segment), should be managed with continued more frequent (6–12 months) surveillance (provided the patient is fit for endoscopy and is not already undergoing therapy).
    • The majority of patients diagnosed with LGD do not progress to HGD/EA.
    • The rate of progression from LGD to EA was reported as 0.44% per year; 1.83% per year progression from LGD  to HGD or EA combined.
    • LGD is subject to a high degree of inter observer variability and may be overcalled.
  • Absence of dysplasia in two subsequent consecutive endoscopic evaluations, after an initial diagnosis of LGD in BE, identifies a cohort of patients who are at low risk to progress to dysplasia or EA and can continue routine surveillance rather than intensive surveillance.
    • If patients are diagnosed with dysplasia (confirmed by at least 2 specialist GI pathologists), they should have a repeat endoscopy to confirm the findings (i.e., 8 weeks to 12 months). If the repeat endoscopy shows that dysplasia is absent after two further endoscopies (at 6–12-month intervals), the patients appear to be at lower risk of developing EA comparable to patients who have not been diagnosed with LGD. Intervention in these patients can be de-escalated to continued routine surveillance rather than intensive BE surveillance.
  • Patients with BE with multifocal LGD (confirmed by at least two specialist GI pathologists) have an increased risk for progression of neoplasia compared with those with focal LGD.
  • Patients with BE with LGD (confirmed by at least two specialist GI pathologists) that persists have an increased risk for progression of neoplasia compared with those with LGD at a single endoscopy.
    • The absolute risk of neoplastic progression (to HGD or EA) in BE patients with LGD has been controversial.
    • Phenotypic characteristics of LGD in BE (e.g., focal vs. multifocal, short segment vs. long segment, persistent over time vs. intermittent (i.e., found at a second confirmatory endoscopy at a surveillance interval of 6–12 months), consensus pathological agreement, have variably been described as important in predicting progression.
    • Patients with persistent, multifocal LGD in a longer segment of BE are more likely to progress to EA.
  • Patients with BE with LGD (confirmed by at least two specialist GI pathologists) and higher-risk features (multifocality, segment length, persistence) should be offered treatment options including ablative therapies.
  • Ablative therapy (with scheduled follow-up) decreases the progression of neoplasia in BE with LGD (confirmed by at least two specialist GI pathologists) and with risk factors (persistence, long BE segment, multifocality).
    • Ablation of BE in patients with LGD remains controversial due to the lack of reproducible data on cancer risk or clarity as to the clinical features that confer increased risk in BE patients with LGD. However, ablation therapy has improved outcomes by reducing neoplastic progression (to EA). Indirect evidence would suggest that in high-risk patients with LGD (multifocality, segment length, persistence) escalating intervention to ablative therapy to decrease the risk of progression to EA should be considered. There is evidence from RCTs and case studies that the durability of LGD eradication is long lasting.
  • Management of IND in BE should require an agreed consensus diagnosis by at least 2 specialist GI pathologists. Follow up with intense sampling by endoscopic biopsies within 12 months should be undertaken, after increased acid suppressive therapy, to downgrade or upgrade the lesion.
    • Note that the diagnosis of IND should be considered as an interim diagnosis only. Further endoscopic surveillance (after acid-suppressive therapy and within 1 year or sooner) is required to up- or downgrade the dysplasia after careful biopsy sampling/endoscopic resection (ER) (endoscopic mucosal resection).
    • Follow-up is recommended because of uncertainty about the nature of the lesions classified as IND. Some follow-up studies have shown increased likelihood of progression to higher grades of neoplasia. The risk appears higher in patients with multifocal IND.
    • It has been suggested that patients with “regenerative” changes and inflammatory infiltration require increased acid suppression with PPI therapy before rebiopsy
  • ER should not be offered routinely to patients with nondysplastic BE and no visible lesion (harms outweigh benefits).
  • BE patients with visible lesions in the BE segment should undergo ER to stage the lesion.
  • ER of visible endoscopic lesions in diagnosed LGD should be carried out to enable accurate histological assessment.
    • Patients with a visible lesion in nondysplastic BE (as well as visible lesions in BE with LGD or IND) should undergo ER (followed by ablation if HGD or intramucosal cancer is detected) over simple biopsies.
    • A biopsy finding of LGD in BE, especially if multifocal, carries a higher risk of progression to HGD or cancer compared with benign BE. Hence, the finding of endoscopically visible lesions is especially significant in the setting of biopsy-detected LGD as they may contain HGD or invasive cancer. ER of visible lesions (nodules and irregularities visualized by conventional endoscopy, without obvious signs of invasion) in previously confirmed LGD with the diagnosis confirmed by at least two specialist GI pathologists should be carried out to enable accurate histological assessment, as ER may result in a change in the diagnosis of LGD.

Molecular markers of dysplasia and progression

  • Aberrant p16, p16 methylation, or p16 loss in nondysplastic BE is associated with an increased risk of progression to LGD.
  • Aberrant p53, p53 mutation, or p53 loss in nondysplastic BE is associated with an increased risk of developing dysplasia.

Prevention of progression

  • Chemoprevention with aspirin (acetylsalicylic acid; ASA), statins, or diet was not agreed upon.
  • The use of PPIs (compared with no therapy or histamine receptor type 2 antagonists) is not associated with a decrease in progression from benign BE metaplasia to BE neoplasia (dysplasia and EA).
    • There is no evidence from high-quality prospective trials (RCTs) that PPI use prevents progression of BE to neoplasia, but there is scientific plausibility (prevention of injury leading to mutational events and neoplasia).
      • Cohort studies demonstrate that the use of PPIs decreased neoplasia development.
      • Systematic reviews have reported a strong inverse association between PPI use and the risk of EA or HGD in patients with BE.

Surgical therapies for prevention of progression

  • Antireflux surgery offers an alternative to PPIs in the treatment of GERD: it corrects lower esophageal sphincter failure and associated HH and controls abnormal gastric and duodenal reflux in 80–90% of patients.
  • Rates of progression to dysplasia or cancer in patients with BE are similar when comparing medical management with fundoplication.
    • Surgical management of reflux (fundoplication) in GERD patients, with or without BE, can provide long-term control of symptoms and esophageal pH.
    • Some cohort studies suggest that effective antireflux surgery may reduce the risk of progression.
  • The Benign Barrett’s and Cancer Taskforce suggests against antireflux surgery beyond establishing reflux control in patients with BE and suggests using medical therapies over surgical therapies for preventing progression to dysplasia or cancer in patients with BE. Patients who place a lower value on potential complications from surgery and a higher value on avoiding daily medications may opt for surgical approaches. Patients should be counselled that acid suppression medications may need to be used on a long-term basis after surgery.

 

Upper Endoscopy for Gastroesophageal Reflux Disease – ACP Guidelines

May 1, 2015 2:21 PM

Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians (ACP)

Nearly 38% of the upper endoscopies performed in outpatients with gastroesophageal reflux disease and low-risk dyspepsia do not adhere to current best-practice guidelines. The most common inappropriate uses were in patients who received an inadequate course of proton pump inhibitors (PPIs) before upper endoscopy and in those who underwent too-frequent surveillance of Barrett’s esophagus. Inappropriate use of endoscopy generates unnecessary costs and exposes patients to harms without improving outcomes.

Read the full text here and download the paper. http://annals.org/article.aspx?articleid=1470281

 

Best Practice Advice

  • Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting).
  • Upper endoscopy is indicated in men and women with:
    • Typical GERD symptoms that persist despite a therapeutic trial of 4 to 8 weeks of twice-daily proton-pump inhibitor therapy.
    • Severe erosive esophagitis after a 2-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus. Recurrent endoscopy after this follow-up examination is not indicated in the absence of Barrett esophagus.
    • History of esophageal stricture who have recurrent symptoms of dysphagia.
  • Upper endoscopy may be indicated:
    • In men older than 50 years with chronic GERD symptoms (symptoms for more than 5 years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus.
    • For surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than 3 to 5 years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia.

 

GERD, Barrett Esophagus, and Esophageal Adenocarcinoma
Tissue injury is not necessary to fulfill disease criteria, as 50% to 85% of patients with GERD have nonerosive reflux disease. As many as 40% of U.S. adults report some symptoms of reflux (heartburn and regurgitation), and 10% to 20% have symptoms on a weekly or more frequent basis. Approximately 10% of patients with chronic heartburn symptoms have Barrett esophagus. GERD and Barrett esophagus are associated with an increased risk for esophageal adenocarcinoma. While the absolute risk for adenocarcinoma of the esophagus in the general population remains low (26 cases per 1 million in the U.S. population), its incidence has increased more than 5-fold in the past 40 years. Adenocarcinoma of the esophagus carries a poor prognosis with a 5-year survival rate less than 20%. Given the rising prevalence of chronic GERD, the use of upper endoscopy for GERD indications is rising in an effort to promote early detection and reduce the risk for death from adenocarcinoma of the esophagus. Since 1% to 5% of the U.S. adult population may have Barrett esophagus, the public health and financial implications of endoscopic screening and surveillance programs are substantial.

 

All 3 major U.S. gastroenterologic professional societies have released guidelines but differ in recommendations.

  • The American Society of Gastrointestinal Endoscopy (ASGE) recommends that screening upper endoscopy be considered in selected patients with chronic, longstanding GERD:
    • Frequent GERD symptoms (several times per week),
    • Chronic GERD symptoms (symptoms for >5 years)
    • Age > 50 years
    • White race
    • Male sex
    • Nocturnal reflux symptoms
  • The American Gastroenterological Association (AGA) guidelines recommend against screening the general population with GERD for Barrett esophagus and esophageal adenocarcinoma but should be considered in patients with GERD who have several risk factors associated with esophageal adenocarcinoma
    • Age 50 years or older
    • Male sex
    • White race
    • Hiatal hernia
    • Elevated body mass index
    • Intra-abdominal distribution of fat
  • The American College of Gastroenterology (ACG) guidelines note that screening for Barrett’s esophagus in the general population cannot be recommended at this time. The use of screening in selective populations at higher risk remains to be established, and therefore should be individualized.
    • GERD symptoms
    • Body mass index

Formulation of these guidelines was hampered by the generally poor quality of data about the use of endoscopic screening and surveillance programs. In many cases, expert opinion formed the basis for specific recommendations.

 

The value of endoscopy is well-substantiated in several clinical settings.

  • GERD associated with the alarm symptoms of dysphagia, bleeding, anemia, weight loss, or recurrent vomiting merits investigation with upper endoscopy because of its yield of potentially clinically actionable findings, such as cancer of the esophagus or stomach, bleeding lesions in the foregut, or stenosis of the esophagus or pylorus.
  • Patients with a documented history of severe erosive esophagitis (grade B or worse on a validated A-to-D scoring system) treated with PPIs have a substantial rate of incomplete healing with medical therapy and may have Barrett esophagus in the areas of previously denuded esophageal epithelium. For these reasons, follow-up upper endoscopy is recommended after 8 weeks of PPI therapy for severe esophagitis to ensure healing and to rule out Barrett esophagus.
  • The use of upper endoscopy in patients with esophageal stricture secondary to GERD is largely symptom-based. Because recurrence of strictures is common, repeated upper endoscopy with dilatation may be required.
  • Screening intervals for patients with Barrett esophagus without dysplasia are recommended at 3- to 5-year intervals. More frequent endoscopy is reserved for the subset of patients who develop low- or high-grade dysplasia, as they face a higher risk for progression to cancer.
  • In patients with chronic GERD whose initial endoscopic screening results were negative, no additional endoscopic screening is necessary, even if the patient continues medical therapy. Observational data show that the likelihood of development of Barrett esophagus in the 5 years after a negative result in such patients is less than 2%. Therefore, routine serial endoscopy in patients with initially negative results for Barrett esophagus is not recommended. Patient and primary caregiver expectations may promote overuse as patients may anticipate serial cancer screening and may inappropriately view no screening or a once-in-a-lifetime screening upper endoscopy for GERD symptoms as inadequate. Patients who have Barrett esophagus and no dysplasia may be dissatisfied with a 3- to 5-year interval of surveillance examinations, as patients with Barrett esophagus grossly overestimate their risk for esophageal cancer.

 

Summary of the ACP best practice advice:

The ACP has found evidence that upper endoscopy is indicated in patients with heartburn and alarm symptoms, such as dysphagia, bleeding, anemia, weight loss, and recurrent vomiting. However, upper endoscopy is not an appropriate first step in most patients with GERD symptoms and is indicated only when empirical PPI therapy for 4 to 8 weeks is unsuccessful. Upper endoscopy is not indicated in asymptomatic patients with a history of esophageal stricture but is appropriate in patients with recurrent symptoms of dysphagia. Screening upper endoscopy should not be routinely done in women of any age or in men younger than 50 years regardless of GERD symptoms because the incidence of cancer is very low in these populations. Screening endoscopy may be indicated in men older than 50 years with several risk factors for Barrett esophagus. This screening decision should include an assessment of the patient’s life-limiting comorbid conditions. Risk factors include chronic GERD symptoms (symptoms of >5 years’ duration), nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat. If an initial screening examination is negative for Barrett esophagus or esophageal adenocarcinoma, recurrent periodic endoscopy is not indicated. Among patients found to have Barrett esophagus on screening upper endoscopy, endoscopic surveillance may be indicated at 3- to 5-year intervals. More frequent endoscopic examinations are reserved for patients with low- or high-grade dysplasia because of their higher risk for progression to cancer.

Unnecessary endoscopy exposes patients to preventable harms, may lead to additional unnecessary interventions, and results in unnecessary costs. Patient education strategies should be used to inform patients about current and effective standards of care.

 

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Barrett’s Esophagus

April 24, 2013 11:22 PM

By Dr. Michael Sossenheimer

Barrett’s esophagus (BE) is a condition in which the normal lining of the esophagus is replaced by tissue similar to the intestinal lining. Although the histologic classification is still under debate, BE is currently defined by the presence of specialized intestinal metaplasia and is recognized as a risk factor for esophageal adenocarcinoma. Although the presence of gastric cardia-type epithelium in the esophagus may also predispose to cancer, most pathologists require the presence of intestinal metaplasia for a diagnosis of Barrett’s.

BE is likely caused by injury of the esophageal epithelium due to acid or non-acid reflux. This abnormally changed lining (metaplasia) may progress via low-grade and high-grade dysplasia to cancer. The histologic staging of progression  greatly influences surveillance and treatment decisions:

  • NDBE – non-dysplastic Barrett’s esophagus
  • IGD – indeterminate-grade dysplasia
  • LGD – low-grade dysplasia
  • HGD – high-grade dysplasia
  • IMC – intramucosal carcinoma
  • IAC – invasive adenocarcinoma

BE occurs in middle-aged or older adults with a mean age at diagnosis of 55 years. BE is diagnosed with an EGD done as part of a screening exam or done for related reflux symptoms. Although BE has a characteristic endoscopic appearance (salmon or pink colored mucosa), histology is required to confirm the diagnosis. The overall reliability of endoscopy plus biopsy for detection of BE is ~ 80-90%. Special targeted biopsies of nodules, ulcers, and mucosal irregularities increase detection rates of dysplasia or cancer. BE is further characterized by the length of Barrett’s tissue:

  • short-segment Barrett’s <3cm
  • long-segment Barrett’s >3cm

Although Barrett’s appears to be more common in white and Hispanic men, it is also found in women, Blacks and Asians. While estimates of prevalence of BE vary widely (0.4% – 20 percent), one must note that up to 44% of patients lack symptoms (i.e. GERD) as the lining of BE causes no symptoms, thereby disallowing for a meaningful screening strategy. Still, in order to optimize screening with targeted endoscopic exams, risk factors for BE must be considered such as:

  • male sex
  • white race
  • age > 50
  • family history of BE
  • smoking
  • obesity
  • longstanding history of GERD

Significant variations in the description of Barrett’s have lead to the development of endoscopic grading systems, such as the Prague C & M Criteria and the Paris Classification. The Prague C & M Criteria describe the extend of disease (C value – circumferential extent of visualized Barrett’s above the GE-junction; M value – maximum extent of visualized Barrett’s above the GE-junction) while the Paris Classification addressed findings of lesions such as raised or depressed nodules (0-Ip protruded, pedunculated; 0-Is protruded, sessile; 0-IIa superficial, elevated; 0-IIb flat; 0-IIc superficial shallow, depressed; 0-III  excavated).

To further complicate the classifications, some authorities now suggest that gastric cardia-type epithelium at the GE-junction represents abnormal metaplastic mucosa, being a precursor of intestinal metaplasia of the esophagus. The term “intestinal metaplasia at the GE-junction” has been proposed, as it can be difficult to determine whether intestinal metaplasia found at the GE-junction is involving the esophagus (short-segment Barrett’s) or the proximal stomach (intestinal metaplasia of the gastric cardia). This distinction has important implications, since medical societies currently recommend endoscopic cancer surveillance for patients with Barrett’s but not for patients with intestinal metaplasia of the stomach. Patients with intestinal metaplasia at the GE-junction should be followed similar to patients with short-segment Barrett’s, as the cancer risk appears proportional to the length of BE. Patients with short-segment Barrett’s have a lower incidence of dysplasia (6–8% vs. 15-24% in long-segment Barrett’s) and cancer. The risk of cancer has been estimated to be 2-15 times higher in patients with long-segment Barrett’s.

Screening

To decrease risk and mortality of esophageal adenocarcinoma, endoscopic screening in conducted for patients with GERD, i.e. patients with at least weekly GERD symptoms for at least five years and who have multiple risk factors for esophageal adenocarcinoma. However, it is not clear that screening patients with GERD reliably identifies all individuals at risk, since more than 40% of patients with esophageal adenocarcinoma have had no history of heartburn.

The American Gastroenterological Association (AGA) recommends screening patients for Barrett’s if they have multiple risk factors associated with esophageal adenocarcinoma. Risk factors include:

  • Age > 50
  • Male sex
  • White race
  • Chronic GERD
  • Hiatal hernia
  • Elevated body mass index
  • Intra-abdominal distribution of body fat

The American College of Physicians (ACP) suggests screening for Barrett’s in men older than 50 with GERD symptoms for more than five years and additional risk factors:

  • Nocturnal reflux symptoms
  • Hiatus hernia
  • Elevated body mass index
  • Tobacco use
  • Intra-abdominal distribution of fat

Surveillance

Once BE has been identified, a variety of endoscopic surveillance and management options are available based on histologic staging as described above. The American Society for Gastrointestinal Endoscopy  (ASGE) has proposed the following surveillance schedule as published in December 2012:

  • NDBE: For Barrett esophagus (BE) with no dysplasia, consider no endoscopic surveillance. If surveillance is done, conduct endoscopy with 4-quadrant biopsies at 2 cm intervals at a 3-5 year interval. A 1-year follow-up after initial diagnosis is not recommended.
  • LGD: For BE with low-grade dysplasia, confirm the diagnosis with an expert pathologist, repeat endoscopy in 6 months to confirm diagnosis and then annually with 4-quadrant biopsies at 1 to 2 cm intervals. Alternatively, consider endoscopic resection or ablation.
  • HGD: For BE with high-grade dysplasia, confirm the diagnosis with an expert pathologist; consider endoscopic surveillance at 3-month intervals with 4-quadrant biopsies at 1 cm intervals; and consider endoscopic resection and radio-frequency ablation (preceded by endoscopic resection in the case of focal nodular or ulcerated changes), endoscopic ultrasound for local staging, and surgical consultation.

Evans JA et al. for the ASGE Standards of Practice Committee. The role of endoscopy in Barrett’s esophagus and other premalignant conditions of the esophagus. Gastrointest Endosc 2012 Dec; 76:1087.