Information about GERD Symptoms, Diagnosis, Treatment options, and GERD Medication
 
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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).

 

 

 

 

 

 

         This is an educational site created by M. Farivar, M.D. The information provided is the author's opinion based on years of clinical experience and research.  You are advised to consult your own physician about the applicability of this information to your particular needs.  Also, keep in mind that symptom response to therapy does not preclude the presence of more serious conditions. 

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