Over the past decade, new advancements in ablation therapy have expanded treatment options for patients with Barrett’s esophagus (BE). Introduced to clinical practice in 2005, radiofrequency ablation (RFA) is one of the most recent ablation techniques available for the treatment of this disease and is widely used in the medical community.
Although studies are now emerging that provide evidence of the medium-term effectiveness of RFA, controversy exists among medical specialists about when the most appropriate time is to administer RFA in the progression of BE.
“The gastroenterologists really don’t feel like BE is a big problem—that it’s kind of an anatomic peculiarity and not something to be frightened about,” said Lee Swanstrom, MD, FACS, clinical professor of surgery, Oregon Health & Science University, Portland.
“I think surgeons tend to be a little more aggressive about it, considering it premalignant along the same lines as colon polyps,” he said. “For my patients with low-grade dysplasia, we do tend to recommend that they have an ablation. We [first] treat them intensively, medically, and repeat their biopsies, but if it comes back a second time as low-grade dysplasia, then we will recommend those patients undergo ablation.”
This philosophical difference in approach becomes one of great significance as gastroenterologists, who were previously focused more on diagnostics, have entered the realm of treating BE through RFA, which as an endoscopic procedure falls neatly into their sphere of practice.
Prateek Sharma, MD, associate professor of medicine, Division of Gastroenterology and Hepatology, University of Kansas School of Medicine, Kansas City, doesn’t tend to use RFA on all patients with low-grade dysplasia (LGD).
“With the majority of LGD, we find that it disappears after the first endoscopy is done, so we pretty much wait on those patients because the majority of the LGD disappears in the follow-up endoscopy. It is a difficult disease to define because even expert pathologists cannot agree on the diagnosis,” said Dr. Sharma.
During an RFA procedure to treat BE, a sizing balloon is inserted into the esophagus, followed by a catheter that inflates to meet the inner esophageal lining. A controlled burst of ablative energy is then administered through the catheter, burning away the abnormal cells of BE and leaving room for new cells to grow in their place.
“Some people with LGD will get cancer, but who are they?” asked Yvonne Romero, MD, esophagologist and assistant professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn. “You would need to ablate about 400 people with nondysplastic BE to help one from developing cancer,” she said.
Individuals at most risk for developing BE are white men aged 50 years and older, who are overweight and have a history of gastroesophageal reflux disease. Although the progression from BE to adenocarcinoma is uncommon, when it does develop, it has a very low survival rate. Only 15% to 20% of patients will survive at least five years after diagnosis. According to the American Cancer Society, more than 17,000 new cases are expected to be diagnosed in 2012 and more than 15,000 patients will die from adenocarcinoma, which is the most rapidly increasing cancer in the Western world.
Dr. Swanstrom believes that more attention needs to be given to the management of BE.
“I think it’s not totally settled that waiting until a patient has HGD [high-grade dysplasia] and then trying to ablate them is the best therapy,” he said. “There should be a public policy debate on whether all patients with chronic reflux disease should have an endoscopy and if they have Barrett’s esophagus, be ablated.”
Specialists differ not only in their response to the low cancer risk inherent in LGD, but in the diagnosis of BE itself. If a particular phase of the disease is misdiagnosed, then using RFA could end up either undertreating HGD and superficial cancer or overtreating LGD, positioning RFA against a moving target.
For example, histologic characteristics of LGD are similar to that of cell inflammation and therefore can lead to difficulty in pathologic interpretation. “One thing that is hard to determine is—do cells look funny because of inflammation or funny because of an actual genetic change?” Dr. Romero pointed out.
“The accuracy rate of determining what is really LGD is pretty low and that’s a problem,” Dr. Swanstrom said. “That leads some people to recommend treating it aggressively with ablation—better safe than sorry—and other people saying, ‘well, it’s a 50-50 chance of it really being LGD, so let’s just wait and see until we know for sure before you add to the cost of the patient’s treatment.’ ”
Although less ephemeral a diagnosis, determining the phase of HGD also is open to dispute, primarily because the interpretation of pathologic results of biopsies can differ widely. According to AGA guidelines, the “risk for progression from LGD to HGD or adenocarcinoma remains controversial [because of the] difficulty in distinguishing dysplasic from nondysplastic BE and determining with reproducible accuracy the degree of dysplasia.”
The standard protocol for performing biopsies in patients with BE is four-quadrant specimens taken every 2 cm and is recommended by the AGA, the American College of Gastroenterology (ACG) and the American Society for Gastrointestinal Endoscopy (ASGE). For patients with known or suspected dysplasia, the societies recommend the Seattle protocol, which requires four-quadrant specimens taken every 1 cm.
However, the AGA notes in its medical position statement on the management of BE that “many practicing gastroenterologists do not adhere to those guidelines.”
Dr. Romero said that increasing the sampling surface area from 2 cm to 1 cm is still an insufficient sample. “There is error in the system because we only sample a small amount of mucosa. Even if you double from 1% to 2%, it’s not like you capture 50% of the mucosa,” she said.
A recent study (Clin Gastroenterol Hepatol 2009;7:653-658) supports the view that in patients with HGD, surveillance using the Seattle protocol may not be adequate for cancer detection and recommends that patients be evaluated by endoscopic mucosal resection (EMR). A distinct advantage of EMR is that the abnormal tissue removed can be sent to the lab for analysis, whereas with RFA, biopsies cannot be done at the same time as ablation due to the risk for perforation and strictures, so in effect, ablation burns the evidence.
“Ablation is a welcome technology in the right person with the right amount of disease and who is willing to live with risk,” said Dr. Romero. “I’m one of the people who isn’t terribly enthusiastic about ablating. Endoscopic mucosal resection is the key. No one argues against it. EMR is a slam-dunk advance in our field.”
Prior to the advent of ablation, the standard of care for HGD was an esophagectomy, a major surgical procedure and a potentially traumatic one for BE patients who tend to be older and have comorbid conditions that make surgery of this magnitude very difficult.
RFA (combined with EMR) has given patients an alternative to such an invasive procedure, yet it poses its own dilemma: It does not guarantee the complete elimination of precancerous cells in the long term, nor can it address the risk for submucosal abnormalities, therefore committing the patient to a lifetime of follow-up endoscopies. In contrast, esophagectomy, for obvious reasons, can provide this peace of mind.
Although both gastroenterologists and surgeons perform RFA, an esophagectomy is solely in the domain of surgeons, which leads to the question of who is best positioned to advise on the range of treatment options for BE: One particular study shows that specialists tend to more frequently recommend treatments that fall within their own field of practice (Dis Esophagus 2008;21:241-250).
“Different specialties will likely converge more,” said Steven DeMeester, MD, associate professor, University of Southern California, Los Angeles. “As we’re moving to a point where we’re doing more and more things through the endoscope—both gastroenterologists and surgeons—you can see the natural tendency would be for the blending of those two fields into people who are considered experts in endoscopic surgery.” A thoracic surgeon, Dr. DeMeester performs “the A to Z on the esophagus,” including endoscopic resection, ablation and esophagectomies. “But I’m rare, very rare,” he said.
Gary M. Hochheiser, MD, chief, thoracic surgery, Baystate Medical Center and assistant professor of surgery, Tufts University School of Medicine, Boston, said, “Unfortunately, we have specialized in such a way that we specialize to procedure rather than specializing to disease. And so a gastroenterologist is specialized to do endoscopy, a surgeon is specialized to operate, but is there someone who is specialized to treat esophageal disease from top to bottom? I don’t think our training programs are set up that way. If you can develop a program that has a multidisciplinary team and you all treat the patient together, then that is just as good, if not better, because having more minds involved is better than having one person try to do all of this themselves.”
Various surgeon and gastroenterologist societies have created guidelines in an effort to streamline procedures like RFA, but differences in their recommendations exist. Guidelines are of no great value, Dr. DeMeester said, as they cannot keep up with the pace of medical research and technology.
“Medicine is constantly moving forward. The day [the guidelines] are published, there could be a brand new article that comes out in the literature that completely revolutionizes the way you think about things and it will take years before the guidelines catch up.”
One of the co-authors of a recent international paper on the management of HGD (Gastroenterology 2012;143:336-346), Dr. Romero said, “We accept that guidelines will change with medical advancements, but the question is can we hammer down a process where we are all involved in the conversation?”
According to Dr. Romero, research already is under way to find a more definitive way to pinpoint the various stages of BE. Biomarkers such as stool, urine and blood samples are being studied as possible alternatives to biopsies. “My question is how can we get endoscopists and pathologists out of the equation?”
New RFA medical devices are being launched by companies like Barrx Medical (recently acquired by Covidien) that broaden the scope of patients who qualify for ablation therapy, including those with strictures or other esophageal conditions.
“All these [new devices] open up new doors to treat patients who, a year ago, you would struggle to treat because of the limitations in the technology and the catheter design,” Dr. DeMeester said. However, although medium-term results of RFA are encouraging, the long-term effects remain to be seen.
“I think [RFA] is a fantastic technology,” said Dr. Swanstrom. “It works amazingly well to get rid of BE. But there are a lot of questions we don’t know about it. Like, do you need to do something else to make sure it doesn’t just come back in seven or 10 years? In which case, it’s a waste of money.”