Esophageal Atresia and Barrett’s Esophagus

Briefly noted: FWT Vergouwe et al. Clin Gastroenterol Hepatol 2018; 16: 513-21.

In this prospective study of adult patients with esophageal atresia (EA) with 151 participants, 6.6% had Barrett’s Esophagus (BE); squamous cell cancer (SCC) was identified in 0.7% (youngest at 42 years).  The authors note that the prevalence of BE and SCC were ~4-fold and ~100-fold higher, respectively, compared to the general population.

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Creek near Chattahoochee River

Barrett’s Esophagus -New Review

An up-to-date concise review: NEJM 2014; 371: 836-45.

A few key points:

  • “Despite the lack of high-quality evidence to support the practice, medical societies currently recommend endoscopic screening for Barrett’s esophagus in patients with chronic GERD symptoms who have at least one additional risk factor…such as age of 50 years or older, male sex, white race, hiatal hernia, elevated body-mass index…or tobacco use.”
  • If nondysplastic Barrett’s is identified, then followup endoscopy is recommended at intervals of 3 to 5 years.  Though, authors note that surveillance has not been proven to reduce death from esophageal cancer.
  • The authors recommend PPIs even in asymptomatic Barrett’s esophagus.

One other reference: Gastroenterol 2014; 147: 314-23.  “Statin Use is Assciated with a Decreased Risk of Barrett’s”

Related blog posts:

Barrett’s Esophagus –refer to cardiology?

According to a study which examined cause-specific mortality, patients with Barrett’s esophagus may be better off following up with a cardiologist than a gastroenterologist (Gastroenterol 2013; 144: 1375-83).

This study derived data from UK’s Clinical Practice Research Datalink.  8448 patients with Barrett’s esophagus were matched with 155,212 controls based on age, sex and general practice.

Key findings:

  • Patients with BE had increased risk of death from esophageal cancer leading to a 10-year risk of 1.9%.  The absolute mortality rate due to esophageal cancer was 1.44 per 1000 person-years.  Compared to the general population, this was a 4.5 fold relative increase.
  • Ischemic heart disease resulted in 168 patient deaths, nearly 4-fold the number that died of esophageal cancer.
  • Overall, individuals with Barrett’s esophagus had a 21% relative increased risk of all causes of death; the majority were not due to esophageal cancer.  32% were related to circulatory disorders, 24% were due to nonesophageal cancer, and 15% were due to respiratory disease.

While this was a large study, there remain several limitations; most of these are due to reliance on electronic records for the diagnosis of Barrett’s.  Also, some individuals with Barrett’s may have been identified due to other high risk conditions such as cirrhosis (endoscopy for varicose) which could contribute to excess mortality.  In addition, many controls likely had undiagnosed Barrett’s.  Even the attribution of the cause of death can be quite difficult, especially with a database study.

Nevertheless, the population-based setting likely means that the results are likely meaningful to a broad population.

Take-home message: While Barrett’s esophagus increases the risk of death from esophageal cancer, it is possible that strategies which focus on nonesophageal causes of death may be more effective than esophageal surveillance for increasing longevity.

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RFA doesn’t always work for Barrett’s

As noted previously in a related blog (Preventing Cancer in patients with Barrett’s Esophagus), Barrett’s esophagus (BE) is not a frequent issue in pediatric gastroenterology.  However, some esophageal problems that start in childhood can predispose to this condition later in life. Certainly, BE is a frequent clinical issue in adult gastroenterology.

Three articles in this month’s Gastroenterology provide some useful information.

  • Gastroenterology 2012; 143: 564-66
  • Gastroenterology 2012; 143: 567-75
  • Gastroenterology 2012; 143: 576-81

An editorial on these three articles is available on page 524.

The first reference describes three cases of high-grade dysplasia and adenocarcinoma that developed after ‘successful’ radiofrequency ablation (RFA).  Thus, the authors advocate continued surveillance following RFA and caution in using RFA to patients with low-risk BE.

The second reference describes an elaborate model to determine if RFA is cost-effective.  Based on their assumptions, “initial RFA might not be cost-effective for patients with BE without dysplasia.”   Though, the authors indicate that one of the cost savings was that RFA was more effective and less costly than endoscopic surveillance.  The authors acknowledge that their analysis is limited by assumptions and that the only alternative would be a large multicenter randomized trial with a long followup.

The third study examined 37 RFA patients.  22 were classified as complete responders and 15 were incomplete; complete responders had no intestinal metaplasia after fewer than 3 ablation sessions.  Risks for persistent intestinal metaplasia were uncontrolled weakly acidic reflux despite twice-daily PPI therapy, longer length of BE, and larger hiatal hernias.

Preventing Cancer in patients with Barrett’s Esophagus

Though Barrett’s esophagus is rare in pediatric gastroenterology, concerns about esophageal cancer are fairly frequent.  In addition, some conditions that increase the risk of esophageal adenocarcinoma start in childhood.

One way to lessen the risk of Barrett’s esophagus in adults is through the use of medications (Gastroenterology 2012; 142: 442-52).  This study was a pooled analysis of six population-based trials with a total of 1226 esophageal adenocarcinoma (EAC) patients and 1140 esophagogastric junctional adenocarcinoma (EGJA) patients.  NSAIDs (aspirin and nonaspirin) lowered the risk of both EAC and EGJA, with OR of 0.68 and 0.83 respectively.

Although this study suggests a possible role for NSAIDs in preventing cancer in patients with Barrett’s esophagus, the risks and benefits for this intervention need to be individualized.

Related previous blog post: More bad news for smokers

Additional references:

  • -Gastroenterology 2011; 141: 2000. Lower risk of Barrett’s in pts taking NSAIDs & statins. n=570.
  • -Gastroenterology 2011; 141: 1179. Overall, patients with BE and LGD have a low annual incidence of EAC, similar to nondysplastic BE. There are no risk factors for progression and there is significant interobserver variation in diagnosis, even among expert pathologists.
  • -NEJM 2011; 365: 1375. Large Danish study, n=11028. Lower incidence of Barrett’s than previous estimates. Relative risk of 11.3 compared to general population for adenoca of Esophagus with absolute annual risk of 0.12%. Barrett’s patients have the same life expectancy as general population (ed. pg 1437). Detecting cancer only ~1 in 1460 scopes with screening whereas Barrett’s detected in 10% of pts.
  • -Gastroenterology 2011; 141: 417, 460. Durable effects of ablation, n=127..
  • -Gastroenterology 2011; 140: 1084. AGA statement on Barrett’s . Recs screening only in those with multiple risk factors (age 50, male, chronic GERD, white, incr BMI)
  • -Clin Gastro & Hep 2010; 8: 565. Guidelines suggest that screening for Barrett’s is not justified w/o alarm symptoms (dysphagia, odynophagia, wt loss, anemia, hematemesis)
  • -Gastroenterology 2010; 138: 2260. n=11,823. Decrease risk of esophageal adenoCa in patients taking NSAIDs & statins.
  • -Gastroenterology 2010; 138: 854. Nice review.
  • -Gastroenterology 2010; 138: 5. Survival equivalent to general population according to Mayo study, n=366. In Barrett’s patients, leading cause of death was cardiovascular (28%). Esophageal cancer resulted in 7% of deaths. Study presented at ACG Oct 26, 2009.
  • -Clin Gastro & Hepatology 2009; 7: 1266. no benefit from surgery for Barrett’s & unclear if chemoprevention works.
  • -Gastroenterology 2009; 137: 763. Suggests surveillance with Barrett’s is not beneficial.
  • -NEJM 2009; 360: 2277, 2353.. Radiofrequency ablation can be effective.
  • -Gut 2008; 57: 1200-06. Utility of endoscopic Rx.
  • -Clin Gastro & Hep 2008; 6: 1206; editorials: 1180, 1181, 1183.. n=2107 with Barrett’s. 79 w surgery and 80 w endoscopic Rx.
  • -Gastro & Hep 2006; 2: 468. 2-8% of pts in general population have Barrett’s. >90% of ptsc Barretts will never develop cancer. Screening has not been proven to be effective in lowering rate of death from cancer. ~40% of US population has heartburn; only 8000-9000/yr develop esoph adenoCa. Also, the presence of Barrett esophagus does not decrease life expectancy.
  • -Gastroenterology 2005; 129: 1825-31. 1.6% incidence of BE in adult Swedish population. Alcohol, smoking increase risk.

More bad news for smokers

Add two more cancer risks for tobacco smoke (Gastroenterology 2012: 142: 233-40, 242-47).  There is now evidence linking tobacco smoke to 18 different cancers and tobacco smoke is probably the most preventable cause of death in the world.

In the first study, the investigators examined 3167 patients with Barrett’s esophagus.  This retrospective study followed patients for 7.5 years.  Patients who were current smokers (any form of tobacco) had double the risk of developing high-grade dysplasia or cancer compared to those who had never smoked.  Former cigarette smokers had a hazard ratio of 1.53.

In the second study, 386 patients with Lynch syndrome were analyzed during a 10 month period.  The hazard ratio for developing colorectal adenomas was 6.13 for current smokers and 3.03 for former smokers compared with patients who never smoked.  In addition, the authors identified a trend for developing adenomas based on pack-years.

Two more reasons to quit smoking.  On a side note, my grandmother said quitting smoking was the easiest thing that she ever did.  So easy, she did it a thousand times.

Additional references:

  • -Gastroenterolgy 2005; 129: 1825-31.  1.6% incidence of BE in adult Swedish population. Alcohol & smoking increase risk.
  • -NEJM 2011; 365: 1222. Treating smokers -useful review.
  • -NEJM 2011; 365: 1193. Cytisine -inexpensive- helps with smoking cessation (8.4% success vs 2.4%in placebo)
  • -NEJM 2008 358; 2249. Smoking and role of social networks.
  • -Gastroenterology 2011; 141: 2000. Lower risk of Barrett’s in pts taking NSAIDs & statins. n=570.
  • -Gastroenterology 2011; 141: 1179. Lower risk of Barrett’s in pts with low-grade dysplasia than previously noted -similar to non-dysplastic Barrett’s.
  • -NEJM 2011; 365: 1375. Large Danish study, n=11028. Lower incidence of Barrett’s than previous estimates. Relative risk of 11.3 compared to general population for adenoca of Esophagus with absolute annual risk of 0.12%. Barrett’s patients have the same life expectancy as general population (ed. pg 1437). Detecting cancer only ~1 in 1460 scopes with screening whereas Barrett’s detected in 10% of pts.
  • -Gastroenterology 2011; 140: 1084. AGA statement on Barrett’s . Recs screening only in those with multiple risk factors (age 50, male, chronic GERD, white, incr BMI)
  • -NEJM 2005; 352: 1851. Cases of Lynch can be missed when following screening guidelines.
  • -Gastroenterology 2010; 138: 207-2177 (entire issue) Colon cancer, Lynch syndrome
  • -Gastroenterology 2008; 135: 380.  Review of colon cancer screening and prevention -2008 up-to-date- literature review
  • -Gastroenterology 1967; 53: 517-27.  Seminal article.  Lynch HT showed gene-related cancer in family cancer syndrome -different than polyposis syndromes.