Barrett’s Esophagus

We had a question about squamous cell dysplasia, which is related to squamous cell cancer of the esophagus.  Squamous dysplasia and squamous cell cancer of the esophagus have different causes than esophageal adenocarcinoma, which is the type of cancer related to Barrett’s esophagus.  Diagnosis is often made with upper endoscopy (EGD) and Lugol’s iodine may be sprayed onto the lining of the esophagus to help locate areas of dysplasia.  Treatment of squamous cell cancer of the esophagus can include surgery to remove the esophagus, radiation, and chemotherapy. 

One reader asked about radiofrequency ablation (RFA) for squamous cell dysplasia.  Most of the research using RFA has been performed in patients with Barrett’s esophagus.  There are a few very small reports of RFA being used in squamous dysplasia. 

One abstract at Digestive Disease Week (international GI meeting) this year looked at 7 patients with squamous dysplasia of the esophagus. 

• - The patients in the study were not eligible for surgery, most likely due to other health problems.
• - The patients were treated with circumferential RFA (balloon) and had biopsies taken every few months. Some patients had repeat treatment and one patient also had an endoscopic mucosal resection (EMR).
• - One patient hadn’t completed the therapy yet, so his/her results weren’t available
• - 4/6 patients had complete resolution of their high grade squamous dysplasia
• - 2/6 patients were found to have squamous cell cancer at follow up and began chemoradiotherapy
• - One patient developed a stricture, which required several esophageal dilations and one patient had minor bleeding

So, this is a small pilot study that shows that RFA can be used to treat squamous dysplasia in patients who cannot be treated with surgery. 

One other case report discussed use of RFA for early squamous cell cancer and high grade squamous dysplasia of the esophagus. One patient with an early (shallow) 3.5 cm squamous cell cancer of the esophagus was treated using the circumferential RFA balloon. The patient could not have surgery for treatment due to other medical issues. Follow up endoscopy with biopsies a few months later showed no evidence of cancer or squamous dysplasia. The patient did well and this may be an option for other patients in the future.

To summarize, at this time, RFA is not being used routinely for patients with squamous dysplasia or early squamous cell cancers of the esophagus. Early reports show some success, and there will likely be other research studies looking at this disease.

References:  

JM Dunn, S Thorpe, M Novelli, SG Bown, L Lovat Radiofrequency Ablation for the Treatment of Squamous High Grade Dysplasia of the Oesophagus- First Reported Series. Gastrointestinal Endoscopy, Volume 69, Issue 5, April 2009, Page AB255.

RE Pouw, JJ Gondrie, WL Curvers, CM Sondermeijer, FJ ten Kate, JJ Bergman Successful balloon-based radiofrequency ablation of a widespread early squamous cell carcinoma and high-grade dysplasia of the esophagus: a case report. Gastrointestinal Endoscopy, Volume 68, Issue 3, September 2008, Pages 537-541.

By Dr. Anirban Maitra

In conjunction with our outstanding gastroenterology team (Drs. Canto and Dunbar) and expert pathologist (Dr. Montgomery), my laboratory has been investigating molecular events that drive the progression of Barrett’s esophagus to esophageal cancer.

There are two very important issues that need to be addressed by the Barrett esophagus/ esophageal cancer research community:

a.    First, we need better molecularly targeted treatment options for patients who already have established esophageal cancer.  As we know, the vast majority of presents with advanced malignancy that is often amenable to surgery.  For these patients, we need all the resources (”all hands on deck”) approach for cure.

b.    Second, we need better molecular predictors for identifying those individuals with Barrett esophagus who will progress to cancer.  Fortunately, the vast majority of patients with Barrett esophagus will never develop cancer in their lifetime – but a small minority will do so.  If we can identify this subset right at the outset using genetic tools, we can focus most of our resources on this subset of patients.

In the past year, funded almost entirely by philanthropic monies received through this website and the D’Amato Foundation, we have achieved considerable progress in identifying new targets in Barrett esophagus using cutting edge gene chip and other molecular profiling technologies.  One technique, that we call Serial Analysis of Gene Expression or SAGE, was first discovered right here at Hopkins in the laboratory of Dr. Bert Vogelstein, the most cited scientist in all of medicine.  SAGE allows us to identify all of the abnormally expressed genes in a particular tumor type compared to normal tissues from that same organ.  We have performed SAGE on endoscopic biopsies of Barrett esophagus and esophageal cancer, and have identified several new predictive and therapeutic targets (Figure 1).

Figure 1: A new molecular marker for Barrett progression identified by SAGE.  Expression of this marker is progressively increased during the transformation of Barrett esophagus to high grade dysplasia and cancer.  Moreover, cancers that express this molecule in the malignant cells have a worse prognosis than those that do not, suggesting it could have identify those patients who would need most aggressive therapy.

We have also developed a new technique of data integration in the laboratory called “Integrative Epigenomics” that uses a powerful computer algorithm to identify molecular abnormalities during Barrett progression (Figure 2).  This program was built by a very talented scientist, Dr. Hector Alvarez, who has been funded by philanthropic resources to perform esophageal cancer research.  Using this algorithm, we have also identified several promising new biomarkers for Barrett progression, including a particularly promising “blood test” for esophageal cancer.

Figure 2: Integrative epigenomics of Barrett esophagus progression.  An algorithm to integrate gene chip data that looks at DNA and RNA abnormalities in Barrett esophagus and adenocarcinoma, and helps “zoom in” on those most likely to be a major player in cancer formation.  This method can also help identify new biomarkers (for example, a new “blood test” that we are evaluating)

At Johns Hopkins, most of our patients elect to have endoscopic treatment such as endoscopic mucosal resection and something else and do not have an esophagectomy.  Drs. Canto and Dunbar very carefully screen people with numerous biopsies (the “Seattle protocol”, so-named because it was first used at the University of Washington).  Occasionally, some people will decide that they would rather have an esophagectomy than continue to deal with their high-grade dysplasia. We found out what happened to these people and the data suggest that the protocol is indeed safe for those who opt for it.  Dr. Jean Wang compiled our data and has reported them as a preliminary report (called an abstract) and has a full report in progress. 

No Occult Cancer At Esophagectomy in Patients with Barrett’s Esophagus with High-Grade Dysplasia Who Have Undergone Surveillance with the Seattle Biopsy Protocol

Jean S. Wang, Hilary Cosby, Lisa Hicks, Elizabeth A. Montgomery, Malcolm Brock, Marcia I. Canto. Gastroenterology 2007; 132(4): A64. Digestive Disease Week, Washington, DC; May 2007.

Introduction: Historical studies in the surgical literature have reported the prevalence of occult cancer in patients undergoing prophylactic esophagectomy for Barrett’s esophagus with high grade dysplasia to be as high as 30-43%. However, it is unclear what type of endoscopic surveillance biopsy protocol was performed in these patients prior to surgery.

Aim: To determine whether use of the Seattle endoscopic biopsy protocol in patients with high grade dysplasia significantly reduces the prevalence of occult cancer at the time of esophagectomy.

Methods: We reviewed medical records of patients who underwent prophylactic esophagectomy for Barrett’s esophagus with high-grade dysplasia at Johns Hopkins Hospital from 1994-2006. Clinical records were examined to determine whether the Seattle endoscopic biopsy protocol was followed during endoscopy performed prior to surgery. Pathology reports were examined to determine whether occult adenocarcinoma was detected during surgery.

Results: A total of 39 patients underwent prophylactic esophagectomy for Barrett’s esophagus with high grade dysplasia during the study period. Among patients who had undergone endoscopic surveillance with the Seattle biopsy protocol, there were no (0/15) invasive adenocarcinomas detected within their resected surgical specimens. In contrast, among patients who had not undergone endoscopic surveillance with the Seattle biopsy protocol, 33% (8/24) had invasive adenocarcinoma detected in their resected surgical specimens.

Conclusions: The prevalence of occult adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia is very low if the Seattle biopsy protocol is followed during endoscopic surveillance. Therefore, the standard care of esophagectomy for Barrett’s esophagus with high-grade dysplasia should be reconsidered.

We have all been reading a lot about “buried Barrett’s” mucosa lately.  This image is at high magnification and shows a microscopic view of what a pathologist (a  specialized medical doctor who reviews biopsies under the microscope) sees in “buried Barrett’s”.  The top part of the image has a pink layer of normal squamous epithelium.  The glands underneath (the circular structures) are Barrett’s epithelium with dysplasia.  The concern among some is that an endoscopist might not see such areas since they are covered with normal lining epithelium.  This is more of a theoretical concern than a real problem since usually such areas are accompanied by areas that are easy for the endoscopist to see.  The other concern is that some types of treatments will fail to reach this buried layer.  There is a recent publication that shows that this is not a concern for patients treated with photodynamic therapy.  The reference for that study is below.  We are still learning the answer to this question for BARRx.

Bronner MP, Overholt BF, Taylor SL, Haggitt RC, Wang KK, Burdick JS, Lightdale CJ, Kimmey M, Nava HR, Sivak MV, Nishioka N, Barr H, Canto MI, Marcon N, Pedrosa M, Grace M, Depot M; International Photodynamic Therapy Group for High-Grade Dysplasia in Barrett’s Esophagus. Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett’s esophagus with high-grade dysplasia. Gastroenterology. 2009 Jan;136(1):56-64

If you already have Barrett’s esophagus, you will need to talk to your doctor about surveillance but there are some factors that you have control over.  Risk factors for Barrett’s esophagus include male gender, white race, and family history. Obviously one cannot control these things.  However, things that are also associated with Barrett’s esophagus include obesity, smoking, and alcohol use.  If you are heavy, you can do something about that.  If you smoke and drink, you can reduce or eliminate those things.

Elizabeth Montgomery, MD

One of the readers (AL) asked whether the HALO 90 and 360 are considered experimental.

The HALO 90 and 360 are FDA approved for sale and use.  There are still lots of studies ongoing, which is not uncommon for new technologies in medicine – when any drug, treatment, or device is approved, studies continue to be done after approval. 

There are several types of studies that get done after approval.  Here are a few types of studies that get done after approval:

1.  Studies to confirm the initial results (yes, drug A does work)

2.  Studies too look for long term issues related to treatment – these are longitudinal studies or registry studies (what happens 10 years after drug A is given)

3. Studies of the cost of care and treatment (does drug A save money in the long run if compared to other treatments?)

4. Studies using the drug/device in a new patient population or for a new disease (are the results of treatment with drug A the same in patients over age 80?)

So defining whether a treatment is still experimental isn’t always clear as research continues for many new drugs and devices.   It’s always worth talking with your own physician to get her/his opinion about new medications and treatments.

 - posted by Kerry Dunbar, MD

One of the readers (Jack) posted a comment with some questions about how research in BE is conducted.  The answers are too long to fit in a reply box, so I’ll address the questions here.

1. Do you feel that all hospital GI departments are coordinating in an effort to preserve or save all records of patients treated for LGD and HGD, and by all available treatments? I guess that I am trying to ask you if this precious data is being collected by any one particular organization, such as the American College of Gastroenterology, or the National Institutes of Health?

Hospital GI departments do keep records of all procedures, but mainly for clinical use.  Keeping records of individual patients by diagnosis and treatment type for research is more challenging.
Depending on the type and amount of data collected, permission may need to be obtained from every patient to store their information in a database.  Databases for research need to be secure (password protected, securely backed up, etc) to protect patient privacy and prevent loss of data.  This kind of data collection and storage is expensive, so not all departments and programs are able to afford this. To my knowledge, the NIH doesn’t have a BE database.  There’s a national database of cancer patients (the SEER network), but it doesn’t include precancerous conditions like BE.  There is a national data collection project, the CORI project, which stands for Clinical Outcomes Research Initiative (www.cori.org),  that collects some data on endoscopy outcomes.  This group has published a few papers on BE, but I haven’t seen anything specifically on types of BE treatment.

2. I was diagnosed with BE without dysplasia, around 3 months ago and have read about a lot of research that has one common theme; “small studies”. This is very discouraging for myself, when cancer from BE has been around so long and is increasing.

Small studies are a problem in many areas of medical research.  As common as Barrett’s seems to be, recruiting research patients isn’t always easy.  Academic referral centers can attract more patients with BE if they have specialized diagnosis and treatment programs, but for small centers and community practices, BE is a less common diagnosis.  For anyone who’s interested in participating in research studies for BE, one place to look for studies is on www.clinicaltrials.gov. This is a searchable website sponsored by the government where clinical trials are registered.  Details are given about research studies that are available and the contact information for the researchers is on the site. 

3. There seems to be a lack of funding from the NIH for BE research. Do you agree? I believe that we need a campaign for awareness of BE and its potential.

I searched the CRISP database, which is a list of all the NIH funded studies.  Using the search term ‘Barrett’s’, there are 25 grants that currently fund (at least in part) research into Barrett’s esophagus.  Certainly there are more NIH funds devoted to other cancers (colon, breast, etc) and for other diseases, such as heart disease, which affect more people.  There’s only so much NIH funding to go around and the budget has been stretched for the last few years for a variety of reasons.  Funding for research studies is also available through several of the gastroenterology societies, such as the American Gastroenterological Association, American Society of Gastrointestinal Endoscopy, and American College of Gastroenterology, although these grants are generally smaller in size than NIH grants. Occasionally funding from private donors is available for research and several of the pharmaceutical and device companies also have research funding programs.

An awareness campaign for Barrett’s would be great!

4. Also, all of the currently available treatments for HGD, excluding removal of the esophagus, must carry a bias by the treatment specialist, as these treatment centers invest in the different equipment, for different treatments. Do you think that any of the treatment results are skewed, or not properly reported due to rival technologies?
There are several treatment options for BE. Not all specialists get trained in every type of therapy.  Buying each type of equipment is also expensive and not feasible for every academic medical center.  These issues make head-to-head comparisons of Barrett’s therapies more difficult.  From attending gastroenterology research conferences, it does seem that there is interest in comparing RFA with cryotherapy, so hopefully some of these studies will be up and running soon. 

There are commonly accepted criteria for reporting studies in the medical literature. For clinical trials, the rules are called the CONSORT criteria and are a list of issues that must be reported in papers about clinical trials.  Most studies also go through the peer-review process, first if they’re being funded by grants, then by the local institutional review board at each hospital, and then also when the manuscript is submitted for publication. The scientific design, results, and reporting are closely inspected, which can help with the reporting process.  Clinical trials of drugs and treatments are also required to be registered with clinicaltrials.gov. These things can help make sure results are reported clearly and honestly. 

Also, most researchers have spent years training (think 8 years of college and medical school plus 3 years of internal medicine and at least 3 years of gastroenterology training), and get specific training in research ethics, so intentional misreporting shouldn’t be common.  For almost all the medical research journals, authors are required to report where all the funding for the study came from.. Authors are also required to report any potential conflict of interest related to the research, such as whether the author is on the board of directors for the company, has been paid to consult for the company, etc. The information about study funding and potential conflicts of interest is usually located at the end of a medical research article.  So, for all the reasons listed above, I don’t think there’s a lot of intentional misreporting or skewing of research results. 

Several of you have mentioned participating in Barrett’s research studies, such as clinical trials of new treatments (cryo, RFA, etc).  There are several different ways to find clinical research studies to participate in. 

If your gastroenterologist works at a university academic medical center, this is a good place to start to find studies. He/she may have suggestions for participating in trials of new therapies in your area.   You can also check the websites of nearby academic medical centers for available research studies.

In the US, one of the best sources of information is www.clinicaltrials.gov.    Many clinical trials in the US get registered with this site and they have an straightforward search function for locating studies. From the main page, select ’search for clinical trials’.  In the search box, then enter the words you’re interested in. For example, entering ‘Barrett’s esophagus’ produces a list of 60 studies, 34 of which are recruiting.  With more specific terms, such as ‘cryotherapy AND Barrett’s’, 6 studies are listed with 3 active or recruiting.  There is also a ‘refine search’ page, where you can enter more specific details, such as searching only a specific state for available studies.  You can click on individual studies to read more about them and the contact information for the researchers is listed. 

Internationally, there are other clinical trials registries, sponsored by the WHO and individual countries.  I’m not as familiar with these, but here’s a list of a few:

International clinical trials registry:  www.ISRCTN.org

Australia and New Zealand: www.anzctr.org.au

Japan:  www.umin.ac.jp/ctr/index/htm

The Netherlands: www.trialregister.nl

China: www.chictr.org/

Germany: www.germanctr.de/

India: www.ctri.in:8080/Clinicaltrials/trials_jsp/index.jsp

- posted by Kerry Dunbar, MD

One of the big controversies in gastroenterology currently is whether to ablate non-dysplastic Barrett’s esophagus.  In the past, the number of treatments needed and side effects of some of the ablative therapies kept ablation of nondysplastic BE from being used for most patients.  For example, photodynamic therapy was developed and used to treat patients with dysplasia and early cancer with good success.  However, the side effects (photosensitivity, chest pain, strictures) kept it from being a viable option for treatment of patients with no dysplasia. Other types of ablation, such as cautery and argon plasma coagulation, have also been used, but typically for patients with dysplasia.  There’s no short answer to this question, so this post will be longer than usual.

Now that RFA (Barrx) is available, there has been renewed interest in ablating nondysplastic BE.  Here’s some of the research that’s been published on ablation of BE with no dysplasia and BE with low grade dysplasia (LGD):

AIM-1 and AIM-2 Studies

This set of studies looked at 102 patients with Barrett’s esophagus, but no dysplasia. This is the largest study looking at RFA ablation in patients with BE and no dysplasia. All patients were treated with circumferential RFA.

AIM-1:    32 patients were treated with RFA. The purpose of this study was to choose the right dose of energy needed to ablate the Barrett’s esophagus.  All the patients were treated with RFA, but at different doses (from 6 J/cm² to 12 J/cm²).  Repeat EGD with biopsy was performed at 1 month and 3 months after the initial treatment.

Results: 26 of 32 patients had some BE left after the first RFA treatment and were retreated with an RFA dose of 10 J/cm².

At 12 month follow up, EGD results were available for 31 of the 32 patients.

• 19 patients (59% of the whole group) had no BE left.
• 8 patients (25%) had a partial response, so had some BE left.
• 5 patients (16%) had no response, so their BE was still present after treatment.

Adverse events/complications: 1 patient with scarring that resolved in a few months, 3 patients with chest pain, and 1 patient with a shallow mucosal tear that resolved. For the patients who were treated with a second ablation, 3 had fever, 1 had scarring that resolved, 1 had abdominal pain, and 2 had problems with sedation.

AIM-2: This study was done to see how effective RFA was in completely ablating nondysplastic BE.  Using the dose of RFA that worked best from AIM-1 (10 J/cm²), 70 patients were treated with RFA.

Results:  Of the 70 patients, 36 had a second RFA procedure to treat residual BE. 12 month EGD results were available for 69 of the 70 patients.

• 48 patients (69%) had a complete response to treatment, so had no Barrett’s esophagus left.
• 17 patients (24%) had a partial response, so had some BE left after treatment.
• 5 patients (7%) had no response to treatment.

Adverse events/complications: 24 adverse events were reported (out of 106 treatments).  2 patients had fever and 9 had sore throat/chest pain. There was also 1 superficial mucosal injury, 1 minor bleed, 1 scarred area that resolved in time, 2 sedation problems, and 8 episodes of nausea.  There were no strictures or buried Barrett’s glands.

Summary of AIM-1 and AIM-2:  About 2/3 of patients treated with RFA had complete eradication of their BE.  Some patients (7-15%) didn’t have any improvement at all.  The rest of the patients had partial improvement of their BE, with some BE left after treatment with RFA. Patients tolerated the procedures well.

Prospective Pilot Trial of HALO in BE with LGD

This small study (10 patients) looked at patients with 2-6 cm of BE with LGD who were treated with circumferential and focal RFA.

Results: 10 patients were treated with circumferential RFA. EGD with biopsy was repeated 1 and 3 months after the procedure to look for BE.

• 6 of the patients had some BE left after the 1^st treatment. Of these 6, 2 still had LGD and 1 had HGD.  These 6 patients had a second circumferential RFA procedure.
• At 1 year, EGD with biopsy showed that 9 of the patients had a small amount of BE left.  9 of 10 patients (90%) had no dysplasia, 1 patient had a nodule removed by EMR that showed HGD and a tiny intramucosal cancer.
• At 1 year, 7 of 10 patients (70%) had a complete response to treatment, meaning they had no BE left.  3/10 still had some BE.
• The 9 patients were treated with focal RFA after their 1 year EGD with biopsy.
• At 2 years, no patients had dysplasia on biopsy (100% response).
• At 2 years, 90% had complete eradication of BE.

Adverse events: 1 patient taking aspirin had bleeding that resolved.  There were no strictures and no buried Barrett’s.

Summary of the pilot trial:  At 2 years, none of the 10 patients had LGD. 9 of the 10 patients were BE-free.  1 patient was diagnosed with HGD and intramucosal cancer during the study (in a nodule) and was treated. Patients tolerated the procedures well. The authors point out that patients undergoing ablation need frequent biopsies to make sure that the dysplasia and BE are completely treated. They also suggest that surveillance biopsies should be continued after ablation is complete.

Pilot Series of RFA for BE With or Without Neoplasia

40 patients with BE were studied and treated with circumferential and focal RFA. Of the 40 patients, 5 had dysplasia and the other 35 had nondysplastic BE.  All patients had follow up EGD 3 months and 12 months after the first (circumferential) RFA treatment. Patients with residual BE were retreated with focal RFA.

Results:  The paper presents the results of the 10 patients who completed 12 months of follow-up after treatment.  28 patients had repeat EGD 3 months after RFA treatment, but hadn’t completed 12 month follow-up at the time the paper was published.

• For the 10 patients who have completed the study and have had their 12 month EGD
  • 7 (70%) have no BE left on EGD with biopsy (complete response)
  • 3 (30%) had a partial response with only a few islands of BE left
• For the 28 patients who have completed 3 months of follow up after treatment
  • 12 (43%) had a complete response (no residual BE)
  • 14 (50%) had a partial response (some BE left)
  • 2 (7%) have no improvement in their BE after RFA

Adverse events/complications: Mild throat and chest pain in some patients, there were no perforations or strictures. There was one case of ‘buried Barrett’s, or BE glands under new squamous epithelium, treated with repeat ablation.

Summary of the pilot series:  3 months after treatment with circumferential RFA, 43% of patients had no residual Barrett’s esophagus. For the 10 patients with 1 year follow up, 70% of patients had no BE left.  The final results of the study are pending.  The procedures were well tolerated.

So the big question – what do these studies mean for patients with nondysplastic BE?  The RFA procedures seem fairly safe, with the main adverse events and complications being chest discomfort and sore throat. There were no perforations and the bleeding rate was low.  For patients with nondysplastic BE and LGD, 60-70% of patients had complete eradication of their BE, but 1/3 still had some BE left.  These studies aren’t particularly large, but larger studies are likely ongoing around the US and Europe.

Questions that are unanswered:

• What we don’t know yet is whether ‘a little bit’ of BE is as dangerous as longer BE.  Cancer is more common in patients with long-segment BE, but cancers do occur in short lengths of BE. Are the few tongues and islands left after RFA still a risk for future cancer? No one knows.  Long term studies would be needed.
• How many treatments is the right number? Most of these studies used 2 treatments, but RFA sessions can be repeated more if needed.
• After treatment, what is the risk of the BE re-growing? No one can answer this question yet because there isn’t data to answer the question. Several of the RFA studies are following patients long term, so more data on this topic will be available in a few years.
• Do patients with complete ablation still need surveillance EGDs?  For now, the answer is yes because no one knows if the BE will return.  EGD with biopsy should still be performed with biopsies of anything that looks like BE, plus biopsies of the areas that were treated with RFA to look for buried BE glands.
• Is RFA for ablation of nondysplastic BE cost-effective?  Unclear. Treatments are relatively expensive. Because RFA is a new technology, not much has been done to study this yet.
• The risk of esophageal cancer in non-dysplastic BE is low (0.5%/yr).  Do the potential risks of RFA outweigh the potential benefit?  Most of the studies use 1-2 treatments for BE. What happens to the risk if a patient needs to have 3 or 4 treatments?  The answer to this isn’t clear and is definitely worth discussing with your own gastroenterologist.
• 1/3 of patients with LGD will have regression to nondysplastic BE. Should all patients with LGD be treated with RFA?  Unclear.  The published studies of LGD are small and more data is needed.

In summary, there is still much debate in the GI community about ablation of nondysplastic BE.  Some gastroenterologists do use RFA to ablate nondysplastic Barrett’s.  But other gastroenterologists don’t and are waiting for more study results.  Hopefully soon there will be more published research on the subject. At this point, there’s no a clear right answer, so definitely talk with your own GI physician about her/his opinion about treating nondysplastic BE with RFA.  You can also consider seeing another gastroenterologist for a second opinion to get a second perspective on treatment.

References for the studies mentioned above:

Sharma VK, et al. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus: 1-year follow-up of 100 patients. Gastrointestinal Endoscopy 2007, vol 65, number 2, pp.185-195.

Sharma VK, et al. A prospective pilot trial of ablation of Barrett’s esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system). Endoscopy 2008; vol 40, pp. 380-387.

Hernandez JC, et al. Pilot series of radiofrequency ablation of Barrett’s esophagus with or without neoplasia. Endoscopy 2008l vol 40, pp 388-392.

posted by Kerry Dunbar, MD

Endoscopic mucosal resection (EMR) is another treatment for Barrett’s esophagus with dysplasia.

EMR can be used to remove small nodules and lesions or to remove flat-appearing BE. The pieces removed are 15-20 mm in size, compared to regular esophageal biopsies, which are about 3-4 mm in size. EMR can be used to take out one piece of mucosa at a time (like a single nodule). Multiple EMRs can also be done in one area to resect a larger area of mucosa (like a flat area known to have a lot of HGD). In some centers, larger areas of BE (think 3 cm or larger pieces) have been removed, also called ‘en bloc’ resection or ‘total endoscopic resection’. In the US, EMR is often used with other techniques (such as ablation) for management of BE with dysplasia.

There are several methods used to perform EMR. Here are a few:

Band mucosectomy – a small plastic cap is placed on the tip of the endoscope. The lining of the esophagus is sucked into the cap and a small rubber band is placed around the tissue. The tissue looks like a polyp after the rubber band is in place. A snare (like a lasso) can then be used to cut off the polyp, typically using some electric current to cut the tissue loose. The tissue is collected, pinned to a piece of foam to keep it flat, and sent to pathology for examination.

Cap and snare – a plastic cap is attached to the tip of the endoscope. Fluid, such as sterile saline, may be injected under the mucosa of the esophagus, raising it up. The esophageal mucosa is then sucked into the cap and a metal snare is placed around the tissue. When the snare is closed, an electric current (cautery) is used to cut the tissue. The piece is collected and sent to pathology.

En bloc resection – Multiple EMRs are performed, with the goal of resecting every bit of BE tissue in an area. Large (a few centimeters) areas of BE may be resected during one procedure. This is less commonly performed in the US, but is popular in some areas of Europe and Asia.

Endoscopic submucosal dissection (ESD) – First used in the stomach to remove small gastric cancers in Asia, ESD has also been used in the esophagus to resect areas of BE with dysplasia. The area to be resected is marked with cautery, and special tools are used to ‘dissect’ (peel up the mucosa) from the underlying submucosa of the esophagus. Much of the research on ESD has been done in Japan and some in Europe. Special tools are typically used to perform ESD and most are not available in the US at this time.

As far as risks of EMR and complications, there are several. Resection of small areas of BE and nodules is typically successful, but only treats the area of BE where it is applied. So there may be other areas of dysplasia in the esophagus that aren’t treated with the EMR. Repeat biopsy to look for other areas of dysplasia is important. Resection of larger areas of BE during one procedure is more challenging, but can be done. The potential complications of EMR include bleeding and perforation. The risk of bleeding is higher than with a standard biopsy as the pieces are larger, but can typically be treated by applying small metal clips to the bleeding areas. Perforation of the esophagus (making a hole) can also occur with EMR and the rate of perforation is about 1%. Strictures, or narrowing of the esophagus by scar tissue, can also occur. This is less common with small areas of EMR, but can occur with circumferential resection or large areas of EMR. Strictures can be treated with esophageal dilation (stretching with a balloon or rubber tube) but may take several dilations to be treated completely. For EMR of large areas, making sure that all the dysplastic BE tissue has been resected is important. Residual areas of BE between EMR sites should be re-biopsied and resected if possible. Some people will have discomfort after EMR, particularly if multiple pieces of the esophageal lining are removed during the procedure, but this typically improves in a few days.

So, EMR is one of several methods of treating BE with dysplasia. It often gets used in combination with other therapies, like ablation. As with all treatments for BE, surveillance endoscopy is needed.

References:

Seewald S, et al. Total endoscopic resection of Barrett’s esophagus. Endoscopy 2008;40:1016-1020.

Pouw et al. Endoscopic resection of early oesophageal and gastric neoplasia. Best Practice & Research Clinical Gastroenterology 2008;(22):929-943.

posted by Kerry Dunbar, MD