Treatment for Barrett’s crucial in preventing esophageal adenocarcinoma

Adenocarcinoma of the esophagus is increasing at an alarming rate. In the United States there are approximately 6,250 new cases diagnosed every year. Barrett’s esophagus (BE), which affects approximately 700,000 people in the United States, increases the risk of developing adenocarcinoma of the esophagus 30- to 125-fold. Because the development of cancer in BE takes place over time, physicians can provide patients with interventions, according to a professor of clinical medicine at Columbia University College of Physicians and Surgeons, New York City.

Understanding current and potential treatments for BE is necessary for gastroenterologists to make effective decisions in preventing the development of these cancers, experts agreed during a discussion at the annual Postgraduate Course of the New York Society of Gastrointestinal Endoscopy. Esophagectomy has been the standard of care for the treatment of high-grade dysplasia and early cancer, with cure rates in the 90 percent range. However, the procedure is associated with a mortality rate of four percent to seven percent and a morbidity rate of 35 percent.

This is partly because the risk of high-grade dysplasia and carcinoma increases with age; older age and concurrent medical conditions increase the risk of surgical complications. Esophagectomy is the most mainstream and appropriate intervention for BE, according to an assistant professor of medicine at Weill Medical College of Cornell University and director of the Endoscopic Ultrasound Center at New York-presbyterian Hospital, both in New York City. However, if the patient is interested in a non-surgical alternative or is too ill to undergo surgery, other options can be made available within clinical trials.

Because morbidity associated with esophageal surgery is high, an alternative would be welcome. Such non-surgical alternative include:

• Chemoprevention. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors have shown promise in the treatment of BE. Cox-2 is over-expressed in Barrett’s metaplasia to low-grade dysplasia, high-grade dysplasia and adenocarcinoma. NSAIDs such as aspirin, which inhibit both COX-1 and COX-2, may decrease the incidence of esophageal carcinoma. Clinical studies are under way to evaluate the role of COX-2 inhibitors in the dysplasia to carcinoma sequence in BE, including a National Cancer Institute trial of celecoxib (Celebrex, Pharmacia) in patient with dysplasia.

• Endoscopic ablation. As an early intervention, ablation of Barrett’s metaplasia without dysplasia has generated a great deal of interest within the gastroenterological community. Several endoscopic methods have been applied for thermal ablation, including multipolar electrocautery, heat probes, cryoablation, laser ablation and argon plasma coagulation. Strictures are the most common complication. Ablating tissue is an exciting technique. However, the procedure may miss potentially cancerous cells. One problem with ablation methods is that some patients experience partial regrowth of Barrett’s epithelium in ablated areas. The absence of any Barrett’s mucosal cells on biopsy may decrease the risk of cancer. However, the possibility of Barrett’s tissue hidden beneath new squamous lining remains a concern. Endoscopic ablation is inherently uneven. But in some cases you can burn away all the Barrett’s Data are very mixed.

Overall, ablation is an experimental therapy that needs to be studies further in clinical trials.

• Photodynamic therapy. Photodynamic therapy (PDT) is being studied for the treatment of high-grade dysplasia in BE. A recent study be Wang et al included 105 patients with Be who were treated with PDT and followed for a minimum of one year. Patients had an initial Barrett’s length of 7 cm including 10 patients without dysplasia, 34 patients with low-grade dysplasia, 48 with high-grade dysplasia and 13 with adenocarcinoma. After PDT, patients were treated with omeprazole 20 to 60 mg per day for maintenance therapy.

After a mean follow-up of 45 months, 42 patients (40 percent) had no histological evidence of BE, 43 patients (41 percent) had no dysplasia, 14 patients (13 percent) had low-grade dysplasia, two patients (2 percent) had high-grade dysplasia and four patients (4 percent) developed cancer. Based on current estimates of cancer incidence in high-grade and low-grade dysplasia, 20 cancers would have been anticipated in this group versus the four that did occur (P<0.001).

In addition, the length of residual BE was significantly reduced from 7 cm to 2 cm. Esophageal strictures developed in 22 percent of patients. Based on their results, the researchers concluded that PDT was an effective treatment for helping to eliminate existing cancer and reducing the incidence of anticipated cancer in BE.

• Endoscopic Mucosal resection. The advantage of endoscopic mucosal resection (EMR is that practitioners retrieve large pathological specimens that can be used to assess the completeness and success of the resection. In one study be Lee et al., 26 patients with nodular/villiform lesions within BE underwent EMR (Gastrointest Endosc 2002;55:AB204). The researchers used a cap with a rim that allows placement of a snare around the specimen. This enables the procedure to be carried out with a single endoscope pass.

Of the 26 patients in the study, four had histological evidence of submucosal invasion of cancer, and three had subsequent esophagectomy with the finding of stage 1 lesions. One patient with intramucosal cancer and negative margins had esophagectom with no evidence of residual cancer. There were no complications from EMR. The investigators concluded that EMR or nodules within (BE) provides useful diagnostic information as well as a means of therapy.

It can serve as an alternative therapy in those patients who are poor surgical candidates. Another study by Bergman et al. Used a prototype flexible large-caliber EMR cap in 22 patients with high-grade dysplasia and early cancer in BE. The flexible cap was easily introduced in all but one patient. The mean maximum and minimum diameter of the MER specimens were 22mm and 18mm, respectively, compared to the 12mm and 10mm diameters of the specimens removed with the standard cap. Six patients developed mild postprocedure bleeding, and one had mild retrosternal pain.

• Combined EMR and ablation techniques. Researchers are also investigating using a combination of MER and ablation therapy – primarily PDT and argon plasma coagulation. In one multicenter study comprising 114 patients, those with early adenocarcinoma (95 patients) in BE were treated. EMR was used in 69 patients, PDT was used in 32, both procedures were combined to treat 10 patients, and three patients underwent primary treatment with argon plasma coagulation. Complete local remission was achieved in 98 percent of patients.

During an average follow-up of 34 months, 30 percent of patients developed metachronous lesions that were successfully treated endoscopically in all but one case. The calculated five-year survival rate (80 percent) was equal to the standard population at age 65. The authors concluded that endoscopic management can replace esophageal resection in patients with high-grade dysplasia and intramucosal cancer in BE.

More research needed. Further research will help determined which of the aforementioned therapies for BE are the most beneficial for patients. We don’t really know if any of these treatments work. The concept is, if we eradicate (BE), the risk of esophageal cancer would decrease. Researchers need to study whether or not this concept is true and which techniques work. The bottom line entails a good discussion between the physician and patients, and education about the risks and benefits of conventional and new techniques.