Barrett

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Barretts Esophagus
Stuart Jon Spechler, M.D. Chief of
Gastroenterology, Dallas VA Medical
Center Professor of Medicine, Berta M. and Cecil
O. Patterson Chair in Gastroenterology, UT
Southwestern Medical Center at Dallas, Texas
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• A 58 year-old, obese white man has had heartburn
  for more than 20 years.

• He read a magazine article saying that heartburn
  is a risk factor for Barretts esophagus, which
  can lead to cancer of the esophagus.

• The article went on to say that people with
  heartburn should have an endoscopy to look for
  Barretts esophagus.

• The article scared him, and he asks you what he
  should do.

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• Endoscopy reveals Barretts esophagus.

• Biopsy specimens show high-grade dysplasia.

4
Barretts Esophagus
The condition in which a metaplastic columnar
epithelium that predisposes to cancer development
replaces the stratified squamous epithelium that
normally lines the distal esophagus
Metaplastic Columnar Epithelium
Metaplastic Columnar Epithelium
Stratified Squamous Epithelium
Affects 5.6 of adult Americans
AGA Medical Position Statement. Gastroenterology
20111401084.
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Barretts Metaplasia
Esophageal Adenocarcinoma
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Metaplasia One adult cell type replaces another
type
Response to Chronic Tissue Injury
GERD
Reflux Esophagitis
Stratified Squamous Epithelium (Normal Esophagus)
Specialized Intestinal Metaplasia (Barretts
Esophagus)
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GEJ (Gastro-Esophageal Junction)
Z-Line (Squamo-Columnar Junction)
X
Columnar Lined Esophagus
Barretts Esophagus
Specialized Intestinal Metaplasia
Adapted from Spechler. Gastroenterology
1999117218.
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Risk Factors for Barretts Esophagus
and Esophageal Adenocarcinoma

• Chronic GERD
• Heartburn, hiatal hernia

• Age gt50 years
• Uncommon in children

• Male gender

• White ethnicity
• Less common in African-Americans
• Uncommon in Asians

• Obesity
• Intra-abdominal fat distribution

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Guidelines for Endoscopy in GERD

• 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.

ACP Guidelines. Shaheen. Ann Intern Med
2012157808.

• Upper endoscopy is not required in the presence
  of typical GERD symptoms.
• Endoscopy is recommended in the presence of
  alarm symptoms and for screening of patients at
  high risk for complications Barretts
  esophagus.

ACG Guidelines. Katz. Am J Gastroenterol
2013108308.
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AGA Medical Position Statement on Endoscopic
Screening for Barretts Esophagus

• We recommend against screening the general
  population with GERD for Barretts esophagus.

• In patients with multiple risk factors associated
  with esophageal adenocarcinoma, we suggest
  screening for Barretts esophagus.

Chronic GERD, hiatal hernia, age 50, male
gender, white race, elevated BMI, intra-abdominal
body fat distribution
Norman Barrett
Gastroenterology 20111401084.
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U.S. Incidence of Esophageal Adenocarcinoma Has
Been Rising
25.6 per million 2006
30
Incidence
25
Time Trend
20
Incidence per 1,000,000
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7-Fold Increase In 3 Decades
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5
3.6 per million 1973
0
1975
1980
1985
1990
1995
2000
2005
Pohl H. Cancer Epidemiol Biomarkers Prev
2010191468.
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Estimates of Cancer Risk for Individual Patients
with Non-Dysplastic Barretts Have Been Getting
Lower

• 1990s Estimate 1 per year
• 1 in 100 patients per year
• Drewitz. Am J Gastroenterol 199792212.

• 2000s Estimate 0.5 per year
• 1 in 200 patients per year
• Shaheen. Gastroenterology 2000119333.

• 2014 Estimate 0.25 per year
• 1 in 400 patients per year

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Endoscopic Surveillance Might Not Decrease
Mortality from Esophageal Adenocarcinoma
8,272 pts. with Barretts esophagus (BE)
Surveillance endoscopy within 3 years was NOT
associated with decreased risk of death from
esophageal cancer (adjusted odds ratio 0.99 95
CI 0.36-2.75)
351 pts. with esophageal adenocarcinoma (EAC)
70 EAC in pts. with prior diagnosis of BE (6
months)
Controls 101 living Barretts pts. matched for
age, sex, follow-up duration
Cases 38 pts. with confirmed death from
esophageal cancer
55 surveillance endoscopy performed within 3
years
60 surveillance endoscopy performed within 3
years
Corley DA. Gastroenterology 2013145312.
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Do Proton Pump Inhibitors (PPIs) Prevent Cancer
in Barretts Esophagus?

• PPIs are the most effective medical treatment for
  reflux esophagitis
• Decrease gastric acid production
• Decrease acid reflux
• Heal reflux esophagitis

• Evidence that PPIs prevent carcinogenesis in
  Barretts esophagus is indirect and not proven in
  controlled trials.

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PPIs Reduce the Risk of NeoplasticProgression in
Barretts Esophagus
540 Barretts patients, median follow-up 5.2 years
PPI Nonusers
PPI use associated with 75 reduction in risk of
neoplastic progression
PPI Users
Kastelein F. Clin Gastroenterol Hepatol 201311
382-8.
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AGA Medical Position Statement on the Treatment
of GERD in Barretts Esophagus

• GERD therapy with medication effective to treat
  GERD symptoms and to heal reflux esophagitis is
  clearly indicated.

• Antireflux surgery is not more effective than
  medical therapy for prevention of cancer in
  Barretts esophagus.

• We recommend against attempts to eliminate
  esophageal acid exposure (PPIs in doses gtonce
  daily or antireflux surgery) for cancer
  prevention.

Norman Barrett Age 13
Gastroenterology 20111401084.
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AGA Medical Position Statement on Endoscopic
Surveillance for Barretts Esophagus

• We suggest that endoscopic surveillance with
  biopsy be performed in patients with Barretts
  esophagus.

• We suggest the following surveillance intervals

? No dysplasia 3-5 years
? Low-grade dysplasia 6-12 months
? High-grade dysplasia in the absence of
eradication therapy 3 months
Norman Barrett
Gastroenterology 20111401084.
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The Cancer Risk for High-Grade Dysplasia in
Barretts is Sufficient to Warrant Intervention
6 per year
High Grade Dysplasia
Cancer
Rastogi . Gastrointest Endosc 200867394.
Spechler. Am J Gastroenterol 2005100927.
AGA Medical Position Statement.
Gastroenterology 20111401084.
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Management Options for High-Grade Dysplasia in
Barretts Esophagus
Intensive endoscopic surveillance (every 3
months)
Endoscopic ablation
Endoscopic mucosal resection
Esophagectomy
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AGA Medical Position Statement on the Management
of Barretts Esophagus

• We recommend endoscopic eradication therapy
  rather than surveillance for treatment of
  patients with confirmed high-grade dysplasia in
  Barretts esophagus.

Norman Barrett
Gastroenterology 20111401084.
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HGD
T2
T1
Basement membrane
Muscularis mucosae
Epithelium
Mucosa
Lamina propria
Submucosa
Drawing courtesy of Tom Rice
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T Staging of Esophageal Cancer
Muscularis mucosae
Mucosa
T1
Mucosa
Submucosa
Submucosa
T2
Muscularis propria
T3
T4
None considered curable by endoscopic therapy.
Drawing courtesy of Tom Rice
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HGD
T2
T1
Intramucosal Carcinoma
High Grade Dysplasia
Muscularis mucosae
Mucosa
T1a
T1b LN mets gt10
T1b
Submucosa
Potentially curable with endoscopic therapy
Potentially metastatic
Drawing courtesy of Tom Rice
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Systematic Review Risk of Lymph Node Metastases
for High Grade Dysplasia (HGD) or Intramucosal
Carcinoma (IMC) in Barretts Esophagus

• Reviewed studies that included
• - Patients who had esophagectomy for HGD or IMC
  and
• - Final surgical pathology results (lymph node
  status)

• Identified 70 relevant articles
• 1,874 patients who had esophagectomy for HGD (524
  patients) or IMC (1,350 patients)

• Lymph node metastases in 26 of 1,874 patients
• (1.39, 95 CI .86 - 1.92)

Dunbar K, Spechler S. Am J Gastroenterol
2012107850.
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Accurate T Staging Crucial to Determine if
Curative Endoscopic Therapy Feasible

• High Grade Dysplasia and Intramucosal Carcinoma
• Lymph node metastases in 1-2
• Curative endoscopic therapy feasible

• Submucosal invasion
• Lymph node metastases in gt10
• Failure rate for endoscopic therapy unacceptable

• Endoscopic mucosal resection (EMR) the best
  procedure for T staging

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EMR is as much a staging procedure as it is a
therapeutic procedure.
If EMR shows submucosal invasion, then endoscopic
therapy is not advised.
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Radiofrequency Ablation (RFA)
Radiofrequency Energy Generator
Closely spaced electrodes
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Radiofrequency Ablation of Barretts Esophagus
Ablated Barretts Metaplasia
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Randomized, Sham-Controlled Trial of
Radio-frequency Ablation for Dysplasia in
Barretts
Shaheen. N Engl J Med 20093602277-88.
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Radiofrequency Ablation of Dysplasia Prevents
Neoplastic Progression at One Year
Radiofrequency ablation
Sham ablation
16.3
with Progression
9.3
3.6
1.2
Progression of Neoplasia
Progression to Cancer
Shaheen. N Engl J Med 20093602277-88.
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Complications of Radiofrequency Ablation in 84
Patients
5 esophageal strictures (6)
1 UGI Bleed (1)
2 hospitalizations for chest pain (2)
Shaheen. N Engl J Med 20093602277-88.
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Endoscopic Therapy for Mucosal Neoplasia In
Barretts Esophagus 2014

• EMR of mucosal irregularities for staging and
  therapy

• Ablate the remaining Barretts metaplasia to
  minimize metachronous neoplasia

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PROPOSAL Routine Polypectomy for Colon Polyps
and RFA for Non-Dysplastic Barretts Esophagus
Are Intellectually the Same

• Non-dysplastic Barretts esophagus is like a
  small colon polyp

• RFA, like colonoscopy, is safe and effective

• Limiting RFA only to Barretts with dysplasia is
  like limiting polypectomy only to polyps that are
  large or clearly malignant.

El-Serag HB, Graham DY. Gastroenterology
2011140386.
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U.K. Experience with EMR and RFA for Treatment of
Mucosal Neoplasia in Barretts Esophagus
335 pts with HGD (72), IMC (24) or LGD (4)
One year protocol
Mean 2.5 RFA treatments
270 (81) complete eradication of dysplasia
208 (62) complete eradication of Barretts
metaplasia
10 (3) progressed to invasive cancer
30 (9) strictures requiring dilation, 1
perforation
Haidry. Gastroenterology 2013. 14587-95.
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RFA for Non-Dysplastic Barretts Esophagus?

• Generally requires several endoscopies for
  complete eradication

• Complication rate low, but not trivial

• Substantial rate of recurrence of metaplasia

• Frequency and importance of subsquamous
  intestinal metaplasia not clear

• Efficacy in preventing cancer not established

• Does not obviate surveillance

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Chronic GERD symptoms and 1 risk factor(s) for
adenocarcinoma (Agegt50, male, white, hiatal
hernia, obesity, intra-abdominal body fat,
smoking)
No Barretts
No more screening
Consider screening endoscopy
on screening
Barretts esophagus
No dysplasia
Low-grade dysplasia
High-grade dysplasia or intramucosal Ca
Surveillance endoscopy every 3-5 yrs
Have diagnosis confirmed by expert pathologist
Low-grade dysplasia
High-grade dysplasia or intramucosal Ca
Surveillance endoscopy every 6-12 months
or endoscopic eradication
Endoscopic eradication
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AGA Medical Position Statement on the Management
of Barretts Esophagus

• Endoscopic eradication therapy is not suggested
  for the general population of patients with
  Barretts esophagus in the absence of dysplasia.

• RFA should be a therapeutic option for select
  individuals with non-dysplastic Barretts
  esophagus who are judged to be at increased risk
  for progression to HGD or cancer.

Specific criteria that identify this population
have not been fully defined.
Norman Barrett
Gastroenterology 20111401084.
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• Knowledge is knowing a tomato is a fruit.

• Wisdom is knowing not to put it in a fruit salad.