Endoscopy Surveillance in Patients with Barrett’s
Esophagus
In a preliminary study presented
at the 2002 Digestive Disease week in San Francisco, Cleveland Clinic researchers
have shown that
telomerase activity
is upregulated in the area of intestinal metaplasia up to 10 years prior to
development of high grade dysplasia and adenocarcinoma by using a telomerase
enzyme immunostaining technique. Patients with Barrett’s that do not
express telomerase activity in their nuclei do not develop dysplasia.
Telomeres are DNA protein complexes essential for the maintenance of chromosomes.
They have a role in natural aging and cancer. Normally most human cells do
not express telomerase, thus each time a cell divides, chromosomes lose a fraction
of their telomeres. With aging telomeres eventually becomes too short to maintain
chromosome it is attached to, and the parent cell can no longer divide. In
cancer cells, however, the production of telomerase is upregulated so that
the cell division can continue indefinitely. These cell lines become immortal
and eventually kill their host.
No Dysplasia: Presently surveillance
endoscopy is recommended every two to three years. One study showed that
the interval
between surveillance endoscopy
could be safely extended to five years in patients with Barrett’s esophagus who have no dysplasia on baseline histology and flow cytometry analysis of
DNA cell content (Am J Gastroenterology 95: 1,669-76, 2000)
Low Grade Dysplasia: Guidelines from the American College of Gastroenterology
(ACG) now recommend that patients with low-grade dysplasia undergo endoscopy
every six months. If two subsequent endoscopies are negative, since two-thirds
of low grade dysplasia is transient, annual follow up endoscopy is adequate.
High Grade Dysplasia: Progression
of high grade dysplasia to cancer may take several years and may occur in
some patients.
At this time it is difficult
to predict with some degree of certainty which patients and how many years.
Furthermore to find high grade dysplasia and cancer in a flat Barrett’s
mucosa is like looking for a “needle in a hay stack”. Mayo study
of resected esophageal specimens finds that in an average of 37 cm2 Barrett’s
mucosa only 1.3 cm was HGD and 1.1 cm was cancer pointing to difficulty in
finding them during surveillance and the need for multiple biopsy samples.
My own practice is to confirm presence
of high-grade dysplasia by repeating endoscopy, obtain more biopsy samples
and make sure
that at least two pathologists,
one experienced in Barrett’s and dysplasia agree with diagnosis. If confirmed
and the patient is a good surgical candidate, or if I believe the patient will
be lost in follow-up, I’ll refer the patient for surgery and resection
to centers with high volume esophagectomy. Surgical mortality is 3-20% depending
on the institution and reported morbidity is 20-50%. However, this rate may
be significantly less in specialized centers.
Studies have shown that close to a third of these patients have carcinomas
on the resected specimen. Loss of p53 gene on biopsy specimens also indicates
a 16 folds increase in progression to cancer compared to those who have not
lost their p53 gene. If p53 staining is available, such patients should be
strongly considered for surgery as well. In patients who are poor surgical
risks, or if they refuse surgery, then extensive medical therapy with PPIs,
NSAID and, every three months, endoscopy surveillance is another option. Surveillance
problem is sampling error and patient compliance.
In recent years different modalities are developed for ablation of High grade
dysplasia by applying heat, Photochemicals or mechanical resection.
Thermal techniques are: Multipolar Electrocoagulation (MPEC), Argon Plasma
Coagulation (APC), LASERS (Nd-YAG, Argon, KTP), and Heater Probe.
Photodynamic Therapy (PDT) using combination of porfimer sodium injection
and fibers emitting red light.
Mechanical ablation includes: Endoscopic Mucosal Resection (EMR), and removing
the area by biopsying it.
In centers with experienced endoscopists
and endosonographers (EUS), with raised or nodular lesions, EMR appears to
be a reasonable option
to esophagectomy
in patients with high grade dysplasia or adenocarcinoma limited to the mucosal
especially in patients who are poor surgical risk. It appears logical to start
the evaluation of a person with Barrett’s esophagus with a suspicious
lesion (polyp, nodule, erosion and so on) or an already diagnosed adenocarcinoma
with endoscopic ultrasound (EUS). This can help better define the target lesion
and confirm that malignancy is limited to the mucosa. The next step would be
to remove the target lesion by EMR (strip or suck methods).
After EMR has eliminated the area of invasive cancer, the remainder of the
dysplastic mucosa can be managed by less invasive ablative techniques like
photodynamic therapy (PDT), argon plasma coagulation (APC) or multipolar electrocoagulation
(MPEC).
It must be noted that in one study 13% of patients with HGD who had ablation
by PDT developed carcinoma during follow up.
Chemoprevention: Aspirin and Non-Steroidal Anti-inflammatory Drugs (NSAID)
reduce relative risk for esophageal and gastric adenocarcinomas by 40-50% through
cox2 inhibition.
In Practical Terms: Roughly 20 million
Americans aged 35 or older have reflux that occurs at least weekly. 2 million
of them
are likely to have Barrett’s
esophagus. Of the two million, however, only 8,000 would develop adenocarcinomas.
As such, a little less than one in every 200 Barrett’s esophagus patients
will develop cancer. Furthermore, most patients with Barrett’s die of
other causes (Gut, 39:5-8. 1996).
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