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BARRETT’S ESOPHAGUS

NOAH CARPENTER, MD

Dr. Noah Carpenter is a Thoracic and Peripheral Vascular Surgeon. He completed his Bachelor of Science in chemistry and medical school and training at the University of Manitoba. Dr. Carpenter completed surgical residency and fellowship at the University of Edmonton and Affiliated Hospitals in Edmonton, Alberta, and an additional Adult Cardiovascular and Thoracic Surgery fellowship at the University of Edinburgh, Scotland. He has specialized in microsurgical techniques, vascular endoscopy, laser and laparoscopic surgery in Brandon, Manitoba and Vancouver, British Columbia, Canada and in Colorado, Texas, and California. Dr. Carpenter has an Honorary Doctorate of Law from the University of Calgary, and was appointed a Citizen Ambassador to China, and has served as a member of the Indigenous Physicians Association of Canada, the Canadian College of Health Service Executives, the Science Institute of the Northwest Territories, Canada Science Council, and the International Society of Endovascular Surgeons, among others. He has been an inspiration to youth, motivating them to understand the importance of achieving higher education.

Abstract Barrett's esophagus is acquired over time due to severe injury to the esophageal lining. It may occur as a result of gastroesophageal reflux disease (GERD) or without the occurrence of GERD. It can exist as a benign condition or it may develop into cancer of the esophagus. Patient survival depends on correct diagnosis, screening/surveillance and treatment. Treatment options, such as acid suppression, chemoprevention, ablation therapy and surgery are discussed.

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Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. Continuing Education Credit Designation This educational activity is credited for 2.5 hours at completion of the activity. Pharmacology content is 0.5 hours (30 minutes). Statement of Learning Need Barrett’s esophagus in the adult, the current trends in the diagnosis of and treatment, are evolving in the medical literature. Endoscopic imaging and interventional treatments have significantly improved. Some patients are at risk to develop Barrett’s esophagus without symptoms, therefore, it is imperative that patient history and appropriate diagnosis and screening be initiated to avoid further complications and possible serious outcomes, such as esophageal cancer. Course Purpose To provide health clinicians with knowledge of Barrett’s esophagus, including its diagnosis, surveillance, treatment and prevention of future complications. Target Audience Advanced Practice Registered Nurses, Registered Nurses, and other Interdisciplinary Health Team Members. Disclosures Noah Carpenter, MD, William Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

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Self-Assessment of Knowledge Pre-Test: 1. Barrett's esophagus occurs when squamous cells, which normally

line the lower part of the esophagus, are replaced by

a. intestinal epithelium. b. cancer cells. c. congenital, dysplastic cells. d. adenocarcinoma cells.

2. There is a higher prevalence of Barrett’s esophagus in individuals

with

a. subcutaneous fat. b. abdominal obesity as measured by a high waist to hip ratio. c. a body mass index (BMI) < 30 kg/m2. d. brown fat.

3. A typical symptom associated with gastroesophageal reflux

disease (GERD) is

a. a hiatal hernia. b. peptic stricture. c. esophageal ulceration. d. frequent heartburn.

4. Which of the following persons is more likely to have

gastroesophageal reflux disease (GERD)?

a. An African American in his thirties b. An Asian female over 50 years old c. An adolescent d. White male 60 years old or older

5. True or False: Some people diagnosed with Barrett's esophagus

were not aware of the condition because they had no noticeable symptoms.

a. True b. False

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Introduction

Barrett’s esophagus is a complication of gastroesophageal reflux disease, which involves reflux of gastric contents that damages the normal lining of the lower esophagus. A different type of lining (intestinal metaplasia with goblet cells) replaces the normal esophageal lining and is known as Barrett’s esophagus. A serious, potential complication of Barrett's esophagus is the abnormal esophageal lining, which develops over time and can develop early precancerous changes. The early changes may progress to advanced precancerous cellular changes, and finally to esophageal cancer, although this final stage is uncommon. When it does progress to cancer, adenocarcinoma of the esophagus is the form of esophageal cancer typically seen in Barrett’s esophagus. Updated screening guidelines to identify the presence of Barrett’s esophagus are needed because relying on symptoms such as heartburn or gastroesophageal reflux are inadequate.

Epidemiology Barrett’s esophagus, or Barrett's, is defined as “a premalignant

condition, where the esophageal squamous epithelium is replaced by intestinal epithelium. This intestinal epithelium, also called specialized intestinal metaplasia (SIM) (with caliciform cells) forms the essence of the concept of Barrett’s esophagus.”1 Barrett's esophagus is associated with an increased risk of developing esophageal cancer.2

Most patients with Barrett’s esophagus are diagnosed with the condition when they seek medical help for symptoms associated with GERD. These symptoms include heartburn, regurgitation and dysphagia.1 However, this does not mean that these patients also had GERD since only a small percentage of people with GERD will develop Barrett's esophagus.1

Barrett’s esophagus is generally identified during an upper endoscopy

procedure in individuals that are middle-aged or older, and the mean age of diagnosis has been reported at age 55.2 Individuals who are diagnosed with Barrett’s esophagus should have regular medical follow ups, including

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surveillance through upper endoscopy to identify the presence of precancerous cells.2

Adults diagnosed with Barrett’s esophagus in the United States are

estimated at 5.6 percent; however, the vast majority of cases are underrecognized.2 This is concerning due to the risk of adenocarcinoma in Barrett’s esophagus cases. In one large population based study in Ireland between 1993 and 2010, subjects linked to the Northern Ireland Cancer registry were identified with esophageal adenocarcinoma or high grade dysplasia of the esophagus diagnoses within 3-12 months rather than > 1 year after Barrett’s esophagus was discovered.3 The authors of this study reported that an estimated one in 10 high grade dysplasia and esophageal cancer cases were identified as missed at the time of Barrett’s esophagus diagnosis.3 Esophageal cancer cases that were missed (0.26%) of all Barrett’s cases involved a significant number of study participants although this rate was lower when compared to prior studies.3

Barrett's esophagus is rare in the pediatric population, especially in children < 5 years of age. This incidence rate in children supports the belief among medical providers that Barrett’s esophagus is an acquired condition and is not congenital.2 The prevalence of Barrett's esophagus in the United States covers a wide range between 0.4 to > 20% based upon the population studied.2 Current prevalence rates for Barrett’s esophagus include the following statistics. ● Barrett’s esophagus is 2-3 times more common in men than in women.1,2

The American College of Gastroenterology (ACG) recommendations suggest screening only in men with weekly GERD symptoms or symptoms > five years, with 2 or more known risk factors.3 Routine screening of Barrett’s esophagus in women is not recommended unless multiple risk factors exist and the patient has a documented family history (first-degree relative) of Barrett’s esophagus or esophageal adenocarcinoma.3

● Among a large cohort of patients diagnosed with Barrett’s esophagus there

were no symptoms of heartburn, and the prevalence was 5.6 percent.2

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Rex, et al. (2003) studied 961 individuals who underwent screening endoscopy, and reported an overall Barrett's esophagus prevalence of 6.8%; and in patients who reported heartburn, there was an estimated 8.3% prevalence where the majority (54%) of patients with Barrett's esophagus did not report reflux symptoms.4

● Most cases of Barrett’s esophagus involve a short-segment of the

esophagus, and long-segment Barrett's is uncommon in patients not reporting heartburn.1,2 (Long-segment Barrett's is where the metaplastic segment is 3 cm or more.2)

● In 3-5% of patients reporting chronic GERD symptoms, long-segment

Barrett's has been reported; however, in 10-15%, short-segment Barrett's esophagus exists.2 (Short-segment Barrett's is where the metaplastic segment is < 3 cm.2) Prevalence of intestinal metaplasia has been reported to be 13.2% with long-segment Barrett's reported at 1.6%, short-segment Barrett's at 6.4%, and the gastroesophageal junction (GEJ) at 5.6%.2

● Barrett’s esophagus is rare in African American people.5 Alkaddour and

colleagues (2018) reported on the risk difference between African Americans and non-Hispanic White people, and noted “a large disparity in histologic [Barrett's esophagus] prevalence.”5 The authors reported the risk difference between both ethnic groups to be 3.6–4 times higher in non-Hispanic Whites than in African Americans.5 There is insufficient and contradictory data on prevalence in Hispanics.

● Previous studies revealed a lower prevalence of Barrett's esophagus in

Asians and a recent meta-analysis of 51 studies that included 453,157 individuals in Asian countries confirmed Barrett's esophagus (1.3 percent) with short-segment in 82 percent of cases.2

There are varied reports of a slightly higher prevalence of Barrett’s in

individuals with a body mass index (BMI) > 30 kg/m2 as compared with patients with a BMI < 30 kg/m2 (OR 1.4, 95% CI 1.1-1.6); however, other

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research points to abdominal obesity as measured by a high waist to hip ratio (≥ 0.9 in males and ≥ 0.85 in females) rather than BMI as placing individuals at higher risk of developing the condition.2 In one study of 1239 patients (average BMI: 29.8 ± 6 kg/m(2), the individuals with a lower BMI corresponded with a lower prevalence of dysplasia as compared to those with higher BMI with a higher prevalence of dysplasia.6 Fourteen cases of high grade dysplasia/esophageal adenocarcinoma in Barrett's individuals with no dysplasia was reported as compared to 29 cases of high grade dysplasia/esophageal adenocarcinoma in those with low-grade dysplasia.6

Aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use has been studied in patients with documented Barrett's esophagus. One single-institution, case-control study of 434 patients using aspirin, not other NSAIDs, suggested a decreased risk of Barrett's esophagus with aspirin use.1 Another large-population based, case-control study of subjects with current aspirin use and Barrett's esophagus did not support the hypothesis that there was any protective value of Barrett’s prevention with aspirin use. The research on NSAID use relative to decreased risk of Barrett’s esophagus remains varied and inconclusive.1 Galipeau, et al. (2018) reported that NSAID use “either reduces the frequency and diversity of somatic mutations and chromosomal alterations and/or increases the likelihood that mutated cells will be removed from cell populations.”7 The authors suggested that further studies are needed that focus on esophageal cancer prevention and the effect of NSAID use upon gene mutations in cancer-associated pathways.

There is more evidence of familial association of Barrett's esophagus and the development of esophageal adenocarcinoma. The risk of developing Barrett’s esophagus has been found in up to 28% of first-degree relatives of patients with esophageal adenocarcinoma.2 Whether this is due to common environmental exposures or an inherited predisposition is not completely clear; however, cancer risk is believed to involve a complex combination of varied genetic and environmental factors.8 Larger cohort studies will be required in the future to confirm this.

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Complications of Barrett’s Esophagus

Complications associated with Barrett’s esophagus range from symptoms associated with GERD to esophageal cancer. The primary complication of Barrett’s esophagus pertains to a reduced quality of life and the suffering that GERD and complications from long-term acid reflux and damage to the esophagus may cause. Complications may include difficulty swallowing. In addition, the patient may need to restrict his or her diet, consider medications, and make lifestyle changes in order to avoid these uncomfortable symptoms.

Gastroesophageal reflux disease associated with Barrett's esophagus may be accompanied by symptoms, such as heartburn, regurgitation and dysphagia.2 In GERD patients who are asymptomatic, clinicians must bear in mind that there may be no signs or symptoms that these patients have Barrett's. This is due in part to the fact that the changes associated with Barrett’s esophagus do not cause symptoms so if a GERD patient is asymptomatic, Barrett’s esophagus may go undetected, possibly for years. The end result may be esophageal cancer.6,8 Although technology exists to diagnose and prevent high-grade dysplasia from becoming cancerous, there continues to be a significant rate of esophageal cancer missed at the time of diagnosis of Barrett’s esophagus with high-grade dysplasia.

Other complications may occur with Barrett's esophagus. These include

esophageal ulceration, stricture, and hemorrhage. Esophageal stricture has been reported as a frequent occurrence, in an estimated 15% of patients who underwent certain treatment for esophageal cancer.9 In patients with symptomatic GERD, erosive esophagitis is a risk factor for Barrett's esophagus.10 Some studies have suggested that patients with a peptic stricture have a higher prevalence of Barrett's esophagus than those without strictures. While most adult esophageal strictures (70% - 80%) result from benign peptic strictures and long-standing GERD, malignant strictures tend to occur in older individuals where the incidence of carcinoma tends to be higher.11

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A serious potential complication of Barrett's esophagus, already mentioned, is that the abnormal esophageal lining can develop early precancerous changes over time.11,12 The early changes may progress to advanced precancerous changes, and finally to esophageal adenocarcinoma, a form of esophageal cancer. Esophageal cancer has been described as one of the deadliest cancers worldwide, primarily due to its extremely aggressive nature and corresponding poor survival rate.12

Barrett’s esophagus and cancer risk, as in all abnormal cell and cancer risk, is complex and involves a variable of multiple genetic environmental and lifestyle factors.11,12 Exposure to external agents such as tobacco smoking and infectious agents such as helicobacter pylori (H. pylori) combined with host characteristics such as obesity have been cited as risk factors that combine to cause the disease to develop. Individuals differ in their inherited genetic susceptibility and environmental vulnerability impacting carcinogenesis.

Genetic research is currently considered exploratory relative to Barrett’s esophagus and inherited traits; however, clinicians should be aware that genetic testing is being considered relative to risk prediction in vulnerable populations that may impact how individualized prevention is planned.11-13

The evolution of genetic changes in Barrett's esophagus cases that lead

to adenocarcinoma is not fully known; what is clear, however, is the fact that if esophageal cancer is present and goes undetected, this cancer can spread and invade surrounding tissues, making it a deadly form of cancer.12 Esophageal cancer is reported to be the 6th leading cause of death from cancer and the 8th most common cancer in the world with a 5-year survival rate of 15%-25%.12

Risk Factors of Barrett’s Esophagus

The general risk factors that increase the risk of Barrett's esophagus

have been already raised above in the section on epidemiology and prevalence rates; however, these will be briefly reviewed in this section along with other pertinent factors and statistics.

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Chronic Heartburn, Acid Reflux and Erosive Esophagitis

Having GERD for more than five years or having GERD that requires regular medication and being more than 50 years of age can increase the risk of Barrett's esophagus. Risk may be further increased for those thirty years old or younger when chronic GERD develops.2 Specifically, younger patients who are obese and report chronic GERD symptoms should be screened for Barrett’s esophagus.14

As mentioned above, there may be a correlation between Barrett’s esophagus and a prior history of infection with H. pylori. Gomaa and Mosaad (2017) stated that the vast majority of the upper gastrointestinal tract pathologies are related to either H. pylori infection or GERD, and that these conditions can occur independently or concomitantly.15 However, Degiovani, et al. (2019) reported that this correlation is debatable.16 “There are aspects regarding the effect of gastric colonization by it on gastroesophageal reflux disease, Barrett’s esophageal development and its correlation with esophageal adenocarcinoma. To this end, there are studies that report HP as a risk factor for Barrett’s esophagus, while others propose the unrelation between them and also those that infer its protective effect."16

Stricture of the esophagus due to scarring, caused by continuous acid

reflux and esophageal tissue erosion, tends to be higher in people who have Barrett’s esophagus.1 This relationship is expected since peptic stricture and Barrett’s esophagus are both associated with a more severe GERD.1 Barrett’s esophagus is uncommon in children, specifically in those < 5 years of age.17

In this population, the presence of peptic strictures in the mid-upper esophagus should raise concerns about Barrett’s esophagus or cancer.17

Age, Gender, Race and Geography

Barrett's esophagus can occur at any age but is more common in older adults.14 Most people with Barrett's esophagus are in their fifties at the time of diagnosis.14 It is thought that most people who are diagnosed with Barrett's have had it for many years before diagnosis.

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Aging is also associated with esophageal and esophagogastric junction mechanical dysfunction in patients with GERD. As people age, impaired esophageal peristalsis, increasing acid exposure to the esophagus, and esophagogastric junction displacement can occur.18 Not only does the incidence of GERD symptoms increase in people ≥ 50 years of age, there is also increasing hospitalization of people who develop erosive esophagitis and complications of GERD, including Barrett's esophagus.18

Johnson and Fennerty (2004) published on a study involving 11,945 patients who were diagnosed with erosive esophagitis and that were enrolled in five prospective, randomized, controlled clinical trials.19,20 They considered factors of age, severe heartburn symptoms, and severe erosive esophagitis.19,20 Patients with severe erosive esophagitis were more commonly seen in those of advancing age; patients aged < 21 years of age showed an estimated 12% incidence of severe erosive esophagitis as compared with those > 70 years of age with an estimated 37% incidence.19,20 This study demonstrated that as a person ages every year, a corresponding odds ratio of 1.7 exists for developing erosive esophagitis. Iwaya Y, Shimamura Y, Goda K, et al. (2019) expanded on this data by reporting that patients ≤ 50 years of age who were diagnosed with early-stage esophageal adenocarcinoma or high-grade dysplasia were more likely to have suffered from continuous GERD symptoms and obesity.14

In the U.S., the prevalence of GERD symptoms appears similar among varied races, but whites have been found to be at greater risk for Barrett’s esophagus and other conditions, such as erosive esophagitis, strictures, and esophageal adenocarcinoma.20 As mentioned above, men are more likely to develop Barrett's esophagus.14 Combining the risk factors for gender and race, it is not surprising that Barrett’s esophagus is predominantly found in Caucasian males.20

Geographic estimates of GERD are important to understand as Barrett’s

esophagus and esophageal adenocarcinoma are a complication of GERD worldwide. There is an estimated 13% incidence of GERD worldwide with some geographic variation.20 In the U.S., GERD symptoms are reported to occur in

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an approximate 6% to 30% of the population with > 20% experiencing at least weekly GERD symptoms.20 Annually, about 110,000 people are admitted to U.S., hospitals due to GERD symptoms.20 The highest incidence (> 25%) of GERD appears to occur in South Asia and Southeast Europe, and the lowest incidence (< 10%) exists in Southeast Asia, Canada, and France.20

In Africa, no data on GERD prevalence exists; however current research suggests that although GERD and Barrett’s esophagus in Africa is not found that it is believed to be increasing due to demographic and epidemiologic transition.20,21 One study (2020) reported that the prevalence of GERD in a Nigerian population is 7.6%.21 In an approximate 50% of all GERD cases, symptoms corresponded with dyspepsia and/or irritable bowel syndrome.21

Obesity and Smoking

Obesity and smoking increases the risk of developing GERD, erosive esophagitis and Barrett’s esophagus. Abdominal obesity in particular has been associated with complications of GERD, such as erosive esophagitis (odds ratio, 1.87), Barrett’s esophagus (odds ratio, 1.98), and esophageal adenocarcinoma (odds ratio, 2.51).20 By lowering a person’s body mass index (at least 3.5 kg/m2), there is an increased chance to resolve GERD symptoms by 1.5- to 2.4-fold.20 Richter and Rubenstein (2019) reported that randomized trials confirmed weight loss and reduced waist circumference corresponds with a decrease of esophageal acid exposure and GERD symptoms.20

Long-segment and Short-segment Barrett’s Esophagus

Long-segment Barrett's esophagus is present when the metaplastic

segment extends at least 3 cm above the esophagogastric junction. Short-segment Barrett's is when the metaplastic segment is less than 3 cm of the distal esophagus.22 In patients who are diagnosed with long-segment Barrett's esophagus, metaplasia has been initially assumed to progress as columnar epithelium replaced an increasing extent of reflux-damaged squamous epithelium in the esophagus.22 Most cases of Barrett's esophagus fully develop over a short period of time followed by little or no progression, and Barrett’s

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metaplasia itself does not cause symptoms.22 Patients with short-segment Barrett's esophagus report few or no GERD signs and symptoms and signs, and while it has been hypothesized that intestinal metaplasia in short-segment Barrett’s may be caused by tissue injury of the GEJ, the GEJ has been questioned as a reliable landmark and is not uniformly defined.22 As compared with long-segment Barrett's esophagus, short-segment Barrett’s, especially <1 cm, has low diagnostic accuracy and could be the basis of varying prevalence of Barrett’s esophagus between geographic regions.22

To avoid acidic injury to the lower esophagus, patients with short-segment Barrett’s should be advised to avoid eating meals late in the day as well as large portions, and they should not lay down after meals.23 In particular, exposure to high concentrations of nitric oxide generated from dietary nitrates in green, leafy vegetables can be offending to the esophageal tissue that should be absorbed by the small intestine and excreted unchanged in the urine.24,25 When swallowed nitrite encounters acidic gastric juice, the nitrite is converted rapidly to nitric oxide and high levels of nitric oxide at the lower esophagus, which can be genotoxic and potentially carcinogenic.24,25 When the GEJ is exposed repeatedly to acid, pepsin, nitric oxide, and other noxious agents in gastric juice, chronic inflammation and metaplasia can develop.26

Smoking is associated with the risk of Barrett’s esophagus. A pooled

analysis of five population-based case-control studies from the International BEACON (Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium), revealed that the risk of Barrett’s esophagus was 1.7 times greater in smokers than in nonsmokers without GERD, and was 1.6 times greater than in nonsmokers with GERD.27 In addition, smoking appeared to have a synergistic effect with GERD.27,28 Also, the number of cigarette packs smoked per day, the age when a person started to smoke, duration of cigarette or smoking cessation, and the types of cigarettes used were reviewed in relation to the development of cancer. Smoking history that was greater than or equal to 10 year corresponded with the risk of cancer.28,29

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Diagnosis of Barrett’s Esophagus

Upper endoscopy is generally used to diagnose Barrett's esophagus. It is performed through the placement of the upper endoscope through the mouth and into the esophagus to determine whether esophageal tissue changes exist.30 Normal esophagus tissue appears pink and glossy. In Barrett's esophagus, the tissue appears red and inflamed.30

The endoscopist is likely to remove a small tissue sample (biopsy). The

biopsy can be examined to determine the degree of tissue change.30 A pathologist determines the degree of dysplasia in the esophagus cells. The tissue may be classified as: 1) No dysplasia, if Barrett's esophagus is present but no precancerous changes are found in the cells, 2) Low-grade dysplasia, if cells show small signs of precancerous changes, and 3) High-grade dysplasia, if cells show many changes.31 High-grade dysplasia is thought to be the final step before cells change into esophageal cancer.31

Endoscopic techniques are still being developed and include

magnification endoscopy, chromoendoscopy, optical coherence tomography, confocal endomicroscopy, narrow-band imaging and echoendoscopy.32 Narrow-band imaging is defined as a high-resolution endoscopic technique which improves the fine structure of the mucous surface without the use of coloring agents.32 Narrow-band imaging is based on the phenomenon that the penetration depth of light depends on wavelength; the longer the wavelength, the deeper the penetration.32 Light is emitted in such a way to expose the esophageal tissue so that the endoscopist is able to visualize the pattern and vasculature of areas of the esophagus and obtain needed biopsies.32

Narrow-band imaging has a reported > 95% sensitivity to detect

superficial squamous carcinoma.32 Narrow-band imaging is also reported to have improved advantages to other techniques to visualize tissue during direct endoscopic evaluation and requires no tissue stains to better detect abnormal tissue, especially short segment Barrett’s that could go unnoticed.32

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Treatment of Barrett’s Esophagus

Treatment for Barrett's esophagus depends on the degree of dysplasia found in the esophagus cells and the patient’s overall health. Dysplasia is a precancerous condition that can only be diagnosed by examining biopsied tissue samples under a microscope. When dysplasia is seen in the tissue sample, it is usually described as being high-grade, low-grade, indefinite or negative for dysplasia.33

Individuals who have a negative test report may have some of

pronounced inflammation or loss of surface epithelium, or they may have none.33 There may be a minimal amount of atypical cytology when evaluated under the microscope and normal tissue architecture at the mucosal surface.33 Nuclei will appear regular with smooth membranes and with normal mitoses, if seen, occurring within the basal compartment. If there is inflammation, there is allowance for a degree of increased atypical cytology but without neoplastic appearance.33

In low grade dysplasia, atypical cytology is evident within the mucosal

surface and there may be minimal or absent surface maturation.33 Microscopic examination of the cellular architecture may show “mild gland crowding with decreased intervening lamina propria can be seen.”33 Atypical forms of mitoses are not usually evident although minimal inflammation is seen. An important finding in low grade dysplasia is nuclear polarity that is preserved. When there is loss of polarity (the nucleus is tilted, rounded, or horizontal to the basement membrane), high grade dysplasia is suspected. In high grade dysplasia, the “cytologic changes are severe with markedly enlarged nuclei at the surface, pronounced pleomorphism, and at least focal loss of nuclear polarity.”33 There is the frequent appearance of mild to marked architectural alteration and a loss of surface maturation, but no abnormal cell invasion beyond the epithelium. When severe and extensive cytologic changes are evident, high grade dysplasia can be diagnosed despite evidence of other esophageal tissue changes that appear to be low grade severity.33

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Other conditions, such as inflammation or swelling of the esophageal lining, can make cells appear dysplastic when they may not be and it is advisable to have a diagnosis of dysplasia confirmed by separate surveillance upper endoscopy exams. Cancer that is associated with Barrett’s esophagus develops in a progressive sequence of cellular changes that starts with “metaplasia, then progresses through various stages of dysplasia prior to development of adenocarcinoma.”34 Microscopic examination of mucosal biopsies for the grade of dysplasia is the standard method of determining the patient’s risk who has been diagnosed with Barrett’s esophagus.34

Reducing or getting rid of a person’s acid reflux often is the first line of

treatment for Barrett’s esophagus. Treatment does not usually cure Barrett's esophagus, but it keeps the condition from worsening. Medication is typically prescribed to decrease stomach acid, and specific dietary and lifestyle changes may be recommended. The typical recommendation includes avoiding caffeinated and alcoholic beverages and fatty foods.35 Chocolate and peppermint should also be limited. Other beverage and meal habits that can worsen acid reflux include the consumption of acidic juices, carbonated beverages and drinking or eating large amounts, late in the day and/or before bedtime.35 People with severe acid reflux and diagnosed injury to the esophagus should avoid laying down flat and they should elevate the head of their bed by six to eight inches.35

Surveillance Endoscopy

Periodic surveillance endoscopy should be done for monitoring of the esophagus to determine whether mucosal changes or injury and cellular changes have developed. Biopsies that do not show cytologic changes or dysplasia will allow patients to schedule out a follow-up endoscopic exam within a year. If endoscopic findings remain negative, then an every three year surveillance exam is suggested thereafter. Low-grade dysplasia found on endoscopic follow up should be followed up within 3 to 6 months.36 Falk (2017) reviewed the literature on surveillance endoscopy of patients diagnosed with esophageal dysplasia and reported that “6 of the 24 studies described expert pathologic confirmation.”36 Where expert pathology review

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was available, the diagnosis of low grade dysplasia was higher; and the ratio of low grade dysplasia to non-dysplastic Barrett’s esophagus was higher.36

The guidelines published by varied professional societies relative to low-grade dysplasia and treatment raise the critical need to first confirm low-grade dysplasia by a second pathologist who has expert training and experience in gastrointestinal pathology.36 Endoscopy should be repeated within 6 months to confirm the diagnosis of esophageal dysplasia and to determine whether there has been progression to a more severe condition.36 The American College of Gastroenterology has recommended specific treatment, such as endoscopic ablation therapy, and the British Society of Gastroenterology has recommended radiofrequency ablation following a confirmed diagnosis of low-grade dysplasia; however both professional societies also state that surveillance endoscopy is a reasonable option to interventional endoscopic treatment.36

Gastroesophageal Reflux Disease

Medication and lifestyle changes are typical initial treatment for patients who are diagnosed with gastroesophageal reflux disease (GERD). Surgery can be done to tighten the esophageal sphincter at the distal esophagus to better control stomach acid reflux into the esophagus. Treating GERD does not treat the underlying Barrett's esophagus but can assist in the detection of disease progression and stage of dysplasia.

A clinician may prescribe medications that reduce the amount of acid produced by the stomach, such as proton pump inhibitors (PPIs). There is variation in patient response to PPI dosing, however empiric PPI treatment is typically started ahead of endoscopic and other testing, such as manometry and ambulatory because they are less costly than such diagnostic testing and has been approved by professional societal guidelines.37 Five different formulations (some of which are available as a generic) are currently available: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex) and pantoprazole (Protonix).38-42

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Gyawali and Kahrilas (2018) stated that although a “pragmatic, symptomatic response to PPI therapy does not equate to a GERD diagnosis, exhibiting an imperfect correspondence with objectively defined disease.”37 They cited an estimated 69% of esophagitis cases, 49% of non-erosive reflux disease (NERD) and 35% of normal endoscopy and pH-metry (a test of esophageal pH levels over a 24-48 hour period) will experience a reduction of GERD symptoms following a trial of PPI medication.37 Empiric use of PPI is reported to have a sensitivity of 71% and specificity of only 44% when compared to combination endoscopy and pH-metry testing.37 Atypical symptoms of GERD, such as chest pain, chronic cough, laryngitis, corresponds with a lower rate of symptom relief with PPI use, which is significantly lower than symptoms of heartburn. 37

Data suggesting protective benefit of aspirin and other nonsteroidal

anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX) against the development of Barrett's esophagus or the development of cancer in patients with established Barrett's esophagus exists.7 However, given the potential for adverse effects and the overall low absolute risk of developing esophageal adenocarcinoma, it is not currently routinely recommended for patients with Barrett's esophagus to take NSAIDs solely for the purpose of chemoprevention. In cases where esophageal cancer has developed, the prognosis is poor, and the inclusion of such adjuvant therapies with standard treatment has received conflicting results in the current studies with failure to show significant survival benefits.44 Some researchers have suggested that the protective effect of NSAID use may be greater if combined with a statin.45

The ASPECT trial being conducted in the United Kingdom is evaluating the efficacy and safety of aspirin along with other treatment for the prevention of cancer in Barrett's esophagus.46 The general recommendations to prevent malignant progression of Barrett’s included: ● Pharmacological: The most important studied drugs included proton pump

inhibitors (PPI) (for symptom control only).46 ● Aspirin and NSAID: Aspirin combined with high-dose PPI as compared to

low-dose PPI without aspirin, has shown the highest positive effect on

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overall mortality, esophageal adenocarcinoma, and high-grade dysplasia). The numbers needed to treat for PPI and aspirin were 34 and 43, respectively.46

● Statins: Lipid-lowering statins may also reduce cancer cell proliferation and lead to apoptosis.

Pech (2019) reported that the data on the prevention of neoplastic

progression with PPI use for the diagnosis of Barrett’s esophagus is based on acid suppression with corresponding inflammatory and carcinogenesis reduction.46 He cited a meta-analysis of 7 observational studies that showed a significant reduction of cancer risk in patients diagnosed with Barrett’s and a second Danish population study that suggested there was no effect from PPI treatment.46 Pech stated that the “AspECT trial, a large multicenter prospective randomized trial comparing either low- or high-dose PPI with or without aspirin, … included 2,557 patients in 84 centers and the median follow-up was almost 9 years. That study showed only a delay of cancer development but aspirin did not reduce death.”46

Aspirin and NSAID COX2 inhibitors can reportedly lower inflammation and neoplastic progression seen in Barrett’s, thereby potentially reducing neoplastic progression.46 Cancer risk has been shown to be reduced by an approximate 30% in observational and population-based studies, and aspirin and other NSAID use has been associated with a 32% cancer risk reduction.46 One meta-analysis of 9 studies with more than 5,000 patients by Zhang, et al. (2014) revealed a similar risk reduction, and the AspECT trial confirmed data from a prospective randomized controlled trial on the use of anti-inflammatory agents to lower the cancer risk in Barrett’s patients.46

More could be said about the effect of statins to lower cancer risk; however, these agents are currently said to have chemopreventive effects shown in multiple observational studies. A risk reduction of esophageal adenocarcinoma progression (43% - 74%) has been reported for patients diagnosed with Barrett’s esophagus.46 Further prospective randomized controlled studies remain to be done to confirm such findings.

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High-grade Dysplasia and Treatment

The management of high grade dysplasia has evolved in recent years but remains based upon multifactorial findings and patient choice to pursue a type of treatment. The optimal treatment depends upon the person's age and health, the patient and their physician's preference. The options include removal of the esophagus (esophagectomy) and removing or destroying the abnormal tissue using endoscopic techniques. Removal of abnormal tissue may involve an endoscopic mucosal resection. Destruction of abnormal tissue may involve radiofrequency ablation, photodynamic or other ablation therapies. The most recent 2020 AGA guidelines included the following recommendations for Barrett’s endoscopic therapy (BET) for the treatment of high grade dysplasia:47

● BET is the preferred treatment and is preferred over esophagectomy for

Barrett’s patients with intramucosal esophageal adenocarcinoma. ● Patient consent for BET should include an explanation of risk, including the

more common occurrence of post-procedural stricture formation (6% of cases) and bleeding and perforation (< 1% occurrence rate).

● In patients with submucosal esophageal adenocarcinoma with low-risk features (i.e., < 500-µm invasion in the submucosa), good to moderate differentiation, and no lymphatic invasion, BET is a reasonable alternative to esophagectomy.

● BET should be considered for patients at high surgical risk. ● BET procedure: “mucosal ablation should be applied to 1) all visible

esophageal columnar mucosa; 2) 5–10 mm proximal to the squamocolumnar junction and 3) 5–10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (i.e., gastric cardia) using focal ablation in a circumferential fashion.”47

● Mucosal ablation therapy: should be limited to endoscopic findings of flat Barrett’s esophagus without inflammation and visible abnormalities.

● Only experts in high-volume centers (minimum of 10 new cases annually) who are trained to perform BET should be performing the procedure.

● BET should continue with an treatment goal of the “absence of columnar epithelium in the tubular esophagus on high-definition white-light

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endoscopy and preferably optical chromoendoscopy.”47 A follow-up endoscopic procedure with 4-quadrant biopsies should be done to confirm eradication of abnormal tissue.47 Random biopsies revealing intestinal metaplasia/dysplasia or sub-squamous intestinal metaplasia, should be followed up with a repeat endoscopy and targeted focal ablation.

● Added ablation therapy is not warranted in cases where Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) is found.

● Endoscopic surveillance following BET should be performed with a high-definition white-light endoscope for enhanced and careful monitoring of the esophageal mucosa, including in the retroflexed view (endoscope tip is flexed backward) to evaluate the gastric cardia.

● Surveillance endoscopy with biopsies (following the complete eradication of intestinal metaplasia with BET) is recommended at the following intervals: - At 3, 6, and 12 months and annually thereafter for baseline diagnosis of

high grade dysplasia or esophageal adenocarcinoma - At 1 and 3 years for baseline diagnosis of low-grade dysplasia

Patients considering BET should be counseled that the approach to

recurrent Barrett’s disease is similar to initial therapy where endoscopic resection of visible recurrent nodular lesions should be done while any flat lesions appearing in the esophagus can be treated with BET. The cancer risk in the absence of BET and following BET should also be discussed.47 Patients and their families should be given appropriate time to reflect on options for treatment and to make an informed decision. Esophagectomy

Esophagectomy involves the removal of the portion of the esophagus with all of the precancerous tissue and some of the lymph nodes near the esophagus; however, there is an increased risk of long-term complications and death that is associated with esophagectomy compared with endoscopic treatments for dysplasia.48,49

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Most patients who are diagnosed with dysplasia in a case of Barrett’s esophagus will require esophagectomy. Where it is impossible to destroy all of the abnormal tissue by endoscopic treatments, esophagectomy may be recommended. Herbella and Patti (2020) reported that while esophagectomy is a morbid procedure, in patients diagnosed with high grade dysplasia, esophagectomy is the option for 5% to 8% of Barrett's cases.49 They reported that a study (2015) showed major surgical complication rates of 4% to 59% for endoscopic therapy and esophagectomy, respectively; and the mortality rates were 0–1% (endoscopy) and 0–2% (esophagectomy).49 Mortality, however may still occur at 2–5%, with morbidity as high as 63% according to current findings in the literature.49

Esophagectomy for HGD typically does not add malnutrition typically associated with cases of advanced cancer or lower esophageal stricture or narrowing. The surgical procedure itself was described by Herbella and Patti (2020) as technically not demanding.49 In combination with chemoradiation, the survival advantage of esophagectomy in individuals with esophageal cancer can be effective.50 Esophagectomy and definitive chemotherapy treatment (CRT) has been described as equally effective in the long-term outcome of patients who are diagnosed with stage I squamous cell carcinoma.50 Watanabe and colleagues (2020) stated that “Minimally invasive esophagectomy may improve the outcomes of patients and CRT is a curative-intent alternative to esophagectomy. CRT with 50.4 Gy radiotherapy combined with salvage surgery is a promising option to preserve the esophagus.”50

Definitive chemoradiation appears to be not as effective according to some studies. Despite the fact that one recent Cochrane meta-analysis suggested that chemoradiation might be equal to surgery patients with esophageal cancer there were other studies that indicated a surgical resection for esophageal cancer had been overlooked possibly because of factors such as limited access to high-volume centers and patient reluctance to have surgery.51 Patients who receive surgery combined with CRT appear to show improved survival benefits.51,52

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One study (2018) focused specifically on cancer survival rates in African Americans in the U.S., who were diagnosed with esophageal cancer. the authors identified that African Americans showed a poorer survival rate and recommended that esophagectomy be offered more aggressively to this patient population as a way to overcome socioeconomic barriers and as a potentially curative procedure.51 Endoscopic Mucosal Resection

Endoscopic mucosal resection (EMR) involves the removal of esophageal tissue through an endoscope that can be examined by a pathologist to determine tissue abnormality.53 Endoscopic mucosal resection helps to confirm a person’s diagnosis if the abnormal tissue is removed; however, this technique is generally performed only in specialized centers where an endoscopist is able to view the section of Barrett’s esophagus. Endoscopic mucosal resection is commonly followed by ablation of the remaining Barrett’s esophagus, usually with radiofrequency ablation.53

The available evidence suggests that endoscopic mucosal resection has

an initial success rate comparable to surgical treatment, but with fewer complications.53 EMR has been described by Shah and Gerdes (2015) as “safe and effective.”53 They stated that EMR was able to achieve eradication of all dysplastic and neoplastic in 96.3% of patients studied, and the recurrence of high grade dysplasia occurred in 14.5% of patients.53 Additionally, in 85% of patients, repeat endoscopic intervention was successful.53 In 1.5% of patients, major endoscopic procedural complications, such as perforation of the esophagus and bleeding as well as minor complications, such as esophageal stricture (1.3%) were reported.53

Multiple factors have been associated with the recurrence of esophageal

dysplasia. Risk factors for recurrence that were described by Dam and Klapman (2020) included age and Barrett’s esophagus length based upon findings from an earlier meta-analysis by Krishnamoorthi R, Singh S, Ragunathan K, et al. (2016).54 Other predictors associated with the recurrence

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of high grade dysplasia include history of intramucosal cancer, hiatal hernia, and GERD.54

In most cases, recurrences of esophageal dysplasia in Barrett’s cases can be successfully managed endoscopically. Surveillance of the original Barrett’s segment to determine the location of recurrence tends to be found in the distal esophagus at 2 cm from the GEJ although recurrences have also been reported at the GEJ, tubular esophagus, within 5 cm of the GEJ.54 The recurrence of dysplasia is treated similarly to the initial EMR treatment or ablative methods. Also, adjunctive anti-reflux therapy has been recommended to help alleviate GERD symptoms and to avoid erosive esophagitis.54 Radiofrequency Ablation

Radiofrequency ablation (RFA) is an endoscopic procedure that uses radiofrequency energy (microwaves) to destroy Barrett's cells.55 Patients with flat high grade dysplasia treated RFA monotherapy should have at least two high-resolution endoscopies with four-quadrant biopsies (every 1 to 2 cm) within two months prior to RFA to ensure there is no cancer.55

In short-term studies, RFA has been shown to prevent high-grade dysplasia from progressing to cancer and to prevent low-grade dysplasia from developing more advanced features. A meta-analysis by Qumseya and colleagues (2017) compared RFA to surveillance of patients diagnosed with Barrett’s esophagus and low grade dysplasia and the risk of progression to high grade dysplasia and esophageal cancer was found to be lower in study participants who received RFA.56 Observational studies of patients with Barrett’s esophagus and low grade dysplasia who underwent either RFA or surveillance also showed that the rate of progression to high grade dysplasia or esophageal cancer was lower in the RFA group.56

A concern with RFA is that, in a small minority of patients with high-

grade dysplasia (less than two percent), there may be cancer in the lymph nodes adjacent to the esophagus. Radiofrequency ablation cannot cure cancer in the lymph nodes. Prior to RFA, EMR may be done to flatten the mucosa

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first, to ensure that ablation treats the muscularis mucosae.55 Patients diagnosed with cancerous lesions invading the submucosa tissue have a 15% to 30% risk of local lymph node involvement and a surgical consult should be arranged.55 In all cases, the patient and family should discuss the risks and benefits of possible treatments with a healthcare provider. Photodynamic Therapy

Photodynamic therapy (PDT) is a treatment that uses chemical agents, known as photosensitizers, to kill certain types of cells (such as Barrett's cells) when the cells are exposed to laser light.57 Patients are given the photosensitizer medication into a vein and then undergo endoscopy; the PDT procedure involves multiple steps:57,58

● Administration of a light-sensitizing agent that accumulates within the

abnormal mucosa ● A light-diffusing fiber is placed in the esophagus ● A monochromatic laser light is applied to induce free oxygen radical

formation, tissue ischemia, and tissue destruction.

Photodynamic therapy may eliminate Barrett’s esophagus with high grade dysplasia and early esophageal adenocarcinoma.57,58 High level stricture formation and skin photosensitivity reduces PDT efficacy; however, to eradicate non-dysplastic Barrett’s esophagus, a safer approach in such instances is ablative techniques such as radiofrequency ablation.57,58 During the endoscopy, a laser light is used to activate the photosensitizer and destroy the Barrett's tissue. However, there is limited information on the long-term outcome of this approach.57,58 Furthermore, PDT is expensive and available in only a small number of academic medical centers. Short and long term adverse effects can include photosensitivity remaining up to 48 hours after the treatment (total sun avoidance is required during that time period) and transient, amnestic episodes.58

Pain can occur with PDT although it tends to be temporary. Tingling or burning sensation, edema, minute vesicles, or crusting, erythematous

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reaction, exfoliation and pruritus of the skin have been reported that could last as much as a week.58 Photosensitization, stricture formation, and skin sunburn (two-thirds of documented cases) are important adverse events.59 Also, acute chest pain, nausea and odynophagia can result, and symptomatic esophageal stricture formation can occur in an estimated 30% of patients who were treated with PDT.59 Endoscopic Spray Cryotherapy

Endoscopic spray cryotherapy is a technique for ablation of Barrett's mucosa. A cryotherapy system is used to apply cold nitrogen or carbon dioxide gas endoscopically to Barrett's esophagus.60,61 According to Pech and Alqahtani (2020), two cryoablation systems are available: 1) endoscopic spray cryotherapy (liquid nitrogen or rapidly expanding carbon dioxide gas), which is applied at the Barrett’s segment of the esophagus to cause cell death; and 2) cryo-balloon ablation in which a balloon is expanded by the endoscopist within the esophagus at the Barrett’s segment followed by a focal spray ablation to the target area.61 Dysplasia has been eradicated in 87% – 96% and complete ablation of Barrett’s in 57% – 96% of patients.61

Cryoablation appears to be a safe and effective treatment for Barrett’s

esophagus. In people with early Barrett’s esophagus, cryotherapy has been reported as effective with complete remission seen in 75% of patients who are diagnosed with adenocarcinoma.61 Following ablative therapy, it is critical that there be adequate acid suppression for reepithelialization and tissue healing to occur. Typically, high-dose PPI therapy with a standard dose twice daily for at least 8 weeks is prescribed.61 Sucralfate and ranitidine 150–300 mg at night may also be recommended. Without sufficient acid control, there can be failure of Barrett’s treatment and an estimated 10% of all patients will reportedly fail to regenerate with normal epithelium even while taking a high dose proton pump inhibitor.61

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Screening Guidelines

A concern about Barrett’s esophagus is that almost half of all patients diagnosed with the disease do not experience symptomatic heartburn or acid reflux prior to their diagnosis.62-64 This suggests that the current screening guidelines based on symptoms of GERD are inadequate for timely diagnosis and treatment.

To decrease mortality from esophageal adenocarcinoma, patients with GERD symptoms should be screened endoscopically for Barrett's esophagus. There is no expert consensus on who should be screened, and the American Society for Gastrointestinal Endoscopy (ASGE) has described Barrett’s esophagus as uncommon and esophageal cancer as very rare. The ASGE currently recommends screening for Barrett’s esophagus in men and women who are older than age fifty.65 The ASGE also notes that middle-aged Caucasian men who have been diagnosed with frequent heartburn for many years are at higher risk as men have a 50% higher risk of Barrett’s esophagus than women.65 People age 50 who report significant heartburn or that required regular use of medications to control heartburn for several years should be screened; if negative for Barrett’s tissue, there is no need to repeat screening.65

Patient risk factors were identified earlier and those risk factors requiring closer screening and surveillance endoscopic examinations in the literature included age, sex, body mass index (BMI), smoking history, GERD, use of proton-pump inhibitor (PPI) medications, and histopathology of specimen(s) obtained during the EGD. It is not clear that screening patients with GERD symptoms reliably identifies individuals at high risk for esophageal adenocarcinoma or has an impact on mortality. According to the ASGE, although screening helps to identify individuals who have a disease or a preclinical condition that predisposes to a disease, “the evidence to support screening and surveillance endoscopy, a practice that has been recommended by national guidelines, is highly variable and based on observational data.”65 There are no randomized controlled trials (RCTs) that have been to evaluate these screening and surveillance endoscopy.65

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Any screening program that targets only patients with heartburn can have only limited impact on cancer mortality rates and there is little evidence that these programs have prevented deaths from esophageal adenocarcinoma. According to the ASGE (2019), “The ideal study to assess the effectiveness of screening and surveillance is an RCT (randomized control trial) of individuals at risk for BE (Barrett’s esophagus) and EAC (esophageal adenocarcinoma) who are randomized to undergo screening upper endoscopy (EGD) compared with no screening.”65 In such as study, the frequency of surveillance of patients diagnosed with Barrett’s esophagus would be based on the grade of dysplasia and therapeutic procedures recommended for both low grade and high grade dysplasia. For example, individuals diagnosed with high grade dysplasia and cancer, and treated with ablation and/or endoscopic resection procedures or invasive cancer esophagectomy would undergo recommended surveillance endoscopy and compared to mortality from cancer as a critical endpoint (including secondary outcomes of all-cause mortality, the incidence of esophageal cancer, stage of diagnosis, the numbers of people undergoing esophagectomy for cancer, and the stage of diagnosis).65

The ASGE suggests that future endoscopic study designs focused on Barrett’s esophagus and esophageal cancer would need to be very large (i.e., thousands of study participants) to potentially yield the best evidence for clinical practice of screening and surveillance with the goal to lower esophageal disease mortality and morbidity. The challenge is that given the existing low incidence of Barrett’s esophagus, the length and feasibility of such a study would likely be difficult to maintain and there are no such studies underway.

The general wisdom is that adherence to quality indicators and surveillance guidelines in the evaluation and management of Barrett’s esophagus needs to be done to ensure safe and appropriate treatment and best outcomes for patients. The ASGE continuously studies and evaluates the existing criteria for screening and surveillance practices, such as Barrett’s esophagus grading and recommendations for disease assessment and treatment, as well as the certainty of the evidence. Clinicians need to continue to update their knowledge of the existing ASGE and other gastrointestinal

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literature when making patient care decisions on treatment cost-effectiveness, risk/benefits and patient preferences.65 Future directions of endoscopic practice will need to focus on high-quality evidence with regard to screening and surveillance in patients with Barrett’s esophagus and esophageal adenocarcinoma by specifically reviewing important diagnosis and treatment outcomes. Some of the topics in future studies noted by the ASGE (2019) include noninvasive genetic or blood biomarkers. The ASGE states that future studies will need to focus on improved risk stratification of patients diagnosed with Barrett’s esophagus, including high-risk populations.

Case Study: GERD Progression to Barrett’s Esophagus

The authors of this case study reported on a 40-year-old Caucasian male who reported worsening symptoms of acid reflux with onset of symptoms since in his twenties.66 The patient’s symptoms were described as acidic sour taste and upper-mid chest burning for several months, which typically occurred 30 minutes after eating that lasted for 90 minutes as well as at night. Despite elevating the head of his bed and taking daily ranitidine and over-the-counter antacids, the patient experienced only brief relief.

Risk factors for GERD included gradual weight gain. His diet included

fried food, several cups of coffee every day, orange juice with breakfast, diet sodas daily, and chocolate. There was no history of tobacco use or drug use, however he reported drinking 1 to 2 glasses of wine over the weekends only.

A personal health history showed no chronic illness or surgeries. A family history was negative for cancer. There were no acute symptoms reported such as abnormal vital signs, pain, unintended weight loss or dysphagia. On physical examination, the patient’s vital signs included temperature 98.4°F, blood pressure 127/76 mmHg, pulse 72 per minute, respirations 16 per minute, oxygen saturation 98% on room air, height 5 feet 10 inches. and weight 225 lbs., with a body mass index (BMI) of 32.3 kg/m2.66

Laboratory testing was done that included a complete blood count, comprehensive metabolic panel, and serum troponin level, which were all

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normal. The differential diagnoses following laboratory testing included esophagitis, esophageal webs, achalasia, esophageal motility disorder, Barrett’s esophagus, and gastritis. Esophagogastroduodenoscopy (EGD) with biopsies was performed, which showed “esophageal intestinal metaplasia characterized by intestinalized mucosa consisting of columnar and goblet cells.”66 The findings resulted in a diagnosis of glandular metaplasia (Barrett esophagus) and severe GERD. Discussion

The authors stated that GERD and its progression to Barrett esophagus have “well-established risk factors unrelated to hereditary conditions.”66 Risk factors in this case included obesity and dietary habits that aggravated GERD symptoms, which predisposed the patient to developing Barrett’s esophagus. The static risk factors for developing Barrett’s esophagus also included male sex, Caucasian ancestry, and advanced age.

Summary

Barrett’s esophagus is a condition in which the lining of the esophagus changes, becoming more like the lining of the small intestine rather than the esophagus, often occurring near the gastroesophageal junction. It is believed that the main reason that Barrett’s esophagus develops is because of chronic inflammation due to reflux. The condition is more common in people who have had GERD for a long period of time. The frequency or the severity of GERD symptoms does not necessarily affect the likelihood that Barrett’s esophagus will develop.

Despite the uncertainties surrounding the monitoring and treatment of Barrett's esophagus, there is consensus that the available options should conform to the individual patient condition. Clinicians need to understand and pursue gastrointestinal endoscopy societal guidelines for the treatment of Barrett’s esophagus, specifically, people with ongoing reflux. Also, people without evidence of precancerous changes or esophageal cancer should have surveillance endoscopy exams to assess for the development of precancerous

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changes. The American Society of Gastrointestinal Endoscopy (ASGE) provides current evidence and updated criteria for the safe and appropriate diagnosis and management of Barrett’s esophagus and esophageal cancer. The incidence of Barrett’s esophagus is low, which makes the potential for high quality, large controlled studies difficult to design and carry forward. Newer methods to diagnose and to treat individuals with low-grade and high-grade Barrett’s esophagus continue to be developed with regard to existing non-invasive and invasive procedures to manage disease progression and to improve morbidity and mortality rates.

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Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation. Completing the study questions is optional and is NOT a course requirement. 1. Barrett's esophagus occurs when squamous cells, which normally

line the lower part of the esophagus, are replaced by

a. intestinal epithelium. b. cancer cells. c. congenital dysplastic cells. d. adenocarcinoma cells.

2. There is a higher prevalence of Barrett’s in individuals with

a. subcutaneous fat. b. abdominal obesity as measured by a high waist to hip ratio. c. a body mass index (BMI) < 30 kg/m2. d. brown fat.

3. A typical symptom associated with gastroesophageal reflux

disease (GERD) is

a. a hiatal hernia. b. peptic stricture. c. esophageal ulceration. d. frequent heartburn.

4. Which of the following persons is more likely to have

gastroesophageal reflux disease (GERD)?

a. An African American in his thirties b. An Asian female over 50 years old c. An adolescent d. White male 60 years old or older

5. True or False: Some people diagnosed with Barrett's esophagus

were not aware of the condition because they had no noticeable symptoms.

a. True b. False

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6. The intestinal cells of Barrett's esophagus

a. is also one of the main signs of GERD. b. are malignant cancer cells that often spread to other tissue. c. are at risk of transforming into cancer cells. d. are only present with long-segment Barrett's.

7. Which of the following is generally used to diagnose Barrett's

esophagus?

a. A biopsy b. Upper endoscopy c. Microscopic examination of tissue samples d. Radiofrequency ablation (RFA)

8. High-grade esophageal dysplasia is determined by a pathologist if

a. *cells show many signs of precancerous changes. b. Barrett's esophagus is present without precancerous cells. c. cells show small signs of precancerous changes. d. esophageal cancer is present.

9. Short-segment Barrett's esophagus is present when the

metaplastic segment

a. has been present for less than one year. b. is less than 3 cm of the distal esophagus. c. does not show signs of precancerous cells. d. is less than one-half the length of the esophagus.

10. True or False: Patients who regularly use nonsteroidal anti-

inflammatory drug (NSAID) have a lower risk of developing Barrett’s esophagus.

a. True b. False

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11. A healthcare provider should recommend that a patient with severe acid reflux

a. lay flat when reclining. b. eat one large meal instead of smaller meals. c. raise the head of his or her bed by six to eight inches. d. All of the above

12. For persons with Barrett's esophagus, if biopsies show low-

grade dysplasia, the provider will likely recommend

a. another endoscopy in 3 to 6 months. b. an endoscopy in 2 years. c. lifestyle changes with no future endoscopy unless symptoms arise. d. an annual endoscopy.

13. A patient with high-grade dysplasia could use ______________

to help confirm the diagnosis and to remove abnormal tissue.

a. an endoscopic mucosal resection (EMR) b. an esophagectomy c. an endoscopic spray cryotherapy d. an RFA, i.e., a radiofrequency ablation

14. __________________ is an endoscopic procedure that uses

microwaves to destroy Barrett's cells.

a. Radiation therapy b. Radiofrequency ablation (RFA) c. Esophagectomy d. Photodynamic therapy

15. _________________________ is a treatment that uses

chemical agents, known as photosensitizers, to kill certain types of cells (such as Barrett's cells).

a. Radiofrequency ablation (RFA) b. Photodynamic therapy c. Endoscopic mucosal resection (EMR) d. Endoscopic spray cryotherapy

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16. A cryotherapy system is used to apply cold nitrogen or carbon dioxide gas endoscopically to Barrett's esophagus in a technique known as

a. endoscopic mucosal resection. b. radiofrequency ablation (RFA). c. photodynamic therapy. d. endoscopic spray cryotherapy.

17. A limitation of screening patients for Barrett's esophagus is that

almost half of all patients diagnosed with the disease

a. also have GERD, which is diagnosed instead. b. have a metaplastic segment less than 1 cm. c. do not experience symptomatic heartburn or acid reflux prior to their

diagnosis. d. have the same symptoms as GERD.

18. Esophageal adenocarcinoma is a form of

a. Barrett’s esophagus. b. low-grade dysplasia. c. esophageal cancer. d. GERD.

19. Radiofrequency ablation (RFA) cannot

a. treat cancer in the lymph nodes near the esophagus. b. destroy Barrett's cells but it stops the progress of dysplasia. c. be used once high-grade dysplasia forms. d. be used to treat esophageal adenocarcinoma.

20. True or False: Screening patients with GERD symptoms reliably

identifies individuals at high risk for esophageal adenocarcinoma.

a. True b. False

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