Barrett’s Esophagus

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

Photodynamic therapy (PDT) is another way to treat Barrett’s esophagus with high grade dysplasia or early cancer.  PDT was one of the first successful alternatives to surgery for Barrett’s with HGD.

Photodynamic therapy has a few steps:

1. A photosensitizing chemical is given.  The two commonly used chemicals are intravenous porfimer sodium (Photofrin), which is most commonly used in the US and oral 5-aminolevulinic acid, which is used in Europe.  The photosensitizer spreads throughout the body and locates in rapidly dividing cells, like cells in the esophagus with Barrett’s and dysplasia
2. Upper endoscopy is performed, often 2 days after the photosensitizer is given.  A special laser fiber is passed through the channel in the endoscope and the laser light causes a photochemical reaction in the cells containing the photosensitizing chemical.  This destroys the BE and dysplasia.
3. 2 days later, upper endoscopy is often repeated, to look for areas that weren’t completely treated by session #1.  Any areas that were missed are retreated during this endoscopy

A large randomized multicenter controlled trial of photodynamic therapy was published in 2005.  208 patients with Barrett’s esophagus and high grade dysplasia were randomized either to porphyrin PDT plus a proton pump inhibitor (PPI -acid suppression medication) or to PPI alone. 

Study results:

• For the patients randomized to PDT, 77% had complete ablation of their HGD and 52% had complete ablation of all their BE.
• 39% of the PPI-only patients had resolution of their HGD, but only 7% had regression of their BE. 
• 28% of the patients in the PPI-only group developed cancer while 13% of patients receiving PDT eventually developed cancer. 
• 5-year follow up of the patients showed that the cancer rates were not different than listed above (29% of the PPI- only patients vs. 15% of the PDT patients).  The patients treated with PDT who did eventually get cancer didn’t develop cancer as soon as the PPI-only patients.

There are some complications of photodynamic therapy that are typically discussed with patients before beginning treatment.  Everyone getting PDT is at risk for severe sunburn – the photosensitizing chemical also collects in the skin, so avoiding sunlight is very important. The photosensitivity typically lasts about 8 weeks. About 1/3 of patients getting PDT may develop a stricture, or narrowing of the esophagus, in the area that was treated. These can be treated with esophageal dilation, although more than one dilation session is usually needed. Chest pain and difficulty swallowing are not uncommon right after the procedure.  And like other ablation techniques, there is always a concern about ‘buried Barrett’s’, or left-over BE tissues that gets buried under the new squamous (normal) esophageal mucosa. 

This study was a large, well-designed study that shows PDT is effective for treating BE with high grade dysplasia. There are other studies that show it is an effective option for treating Barrett’s with dysplasia and early cancer.  As with any treatment, it’s important to discuss options with your doctor to determine which treatment would be best for you.

Here are a few references for the studies mentioned:

Overholt BF, et al. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial. Gastrointestinal Endoscopy 2005;62(4):488-98.

Overholt BF, et al.  Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett’s high-grade dysplasia. Gastrointestinal Endoscopy. 2007 Sep;66(3):460-8.

posted by Kerry Dunbar, MD

Just as a reminder to all our readers:  This website is for education and information, and is not intended to be individualized medical advice. The information here is not a substitute for consulting with a doctor.  You should always discuss your questions, concerns, and health issues with your own doctor.  We may not always be able to address individual comments, but will try to address as many as possible with blog posts that cover the questions. The internet is never a substitution for seeking advice and care from your own physician.

posted by Kerry Dunbar, MD

Another option for ablation of Barrett’s esophagus with dysplasia is cryotherapy. 

Cryotherapy works by spraying freezing liquid or gas onto the lining of the esophagus.  The depth of the freezing effect is 1-2 mm.  Cryotherapy has been used in other parts of the gastrointestinal tract, such as the stomach in patients with gastric antral vascular ectasia (watermelon stomach), or in the rectum to treat radiation proctitis.  

There are currently two different types of cryotherapy available for treatment of Barrett’s esophagus.  Each system uses a regular upper endoscope and has a thin tube that is passed through the endoscope and out the tip.  Then cryospray, either liquid nitrogen or freezing carbon dioxide, is sprayed onto the lining of the esophagus.  When cryotherapy is used, the cells lining the esophagus are frozen, which damages them.  The body then makes an inflammatory reaction, gets rid of the damaged cells, and new (normal) esophageal mucosa covers the area where the Barrett’s used to be. 

There are a few papers describing how cryotherapy works. More recently, several research abstracts were presented at Digestive Disease Week 2008, an international gastroenterology research meeting.  One study used the carbon dioxide cryotherapy system and the other used the liquid nitrogen based system.  Both studies looked at patients with high grade dysplasia or tiny (intramucosal) cancers. 

In the liquid nitrogen cryotherapy study, 32 patients participated. For the 20 patients with HGD, 16 had at least a partial response (improvement) after cryotherapy and 50% had complete resolution of their HGD.  For the patients with intramucosal cancer, 6 of 9 had at least a partial response, and 1/3 had complete resolution of their intramucosal cancer. The average number of cryotherapy sessions in the study was 4. The complications included 3 esophageal strictures, 1 lip ulcer, and 1 stomach perforation. 

In the carbon dioxide cryotherapy study, 33 patients participated. The average number of treatments for each patient was 3. 79% of patients had a reduction in the amount of dysplasia and BE.  21% had a complete response, with complete elimination of dysplasia and BE.  3 patients in the study with intramucosal cancer had complete resolution of their cancer after cryotherapy treatment.  One patient had transient mild heartburn after cryotherapy, but no strictures or perforations occurred.

So what’s the take home message about cryotherapy?  It seems to be effective for treating Barrett’s esophagus with dysplasia, but there aren’t as many papers published about it yet.  The two studies mentioned above are ongoing and the final results haven’t been published, so the final outcome of the studies might be better (or possibly worse).  At this point, there are more studies published about photodynamic therapy and radiofrequency ablation for treating Barrett’s esophagus with dysplasia.  So cryotherapy one of the choices for treatment of Barrett’s with dysplasia and worth discussing with your own gastroenterologist.

If you think you may be interested in cryotherapy treatment, there are several ongoing research studies that can be found on clinicaltrials.gov and by searching the internet. 

Here are the references for the 2 cryotherapy studies mentioned above. 

Dumot JA, et al. Results of Cryospray Ablation for Esophageal High Grade Dysplasia (HGD) and Intramucosal Cancer (Imca) in High Risk Non-Surgical Patients.  Gastrointestinal Endoscopy, Volume 67, Issue 5, April 2008, Page AB176

Canto MI, et al. Low Flow CO2-Cryotherapy for High Risk Barrett’s Esophagus (BE) Patients with High Grade Dysplasia and Early Adenocarcinoma: A Pilot Trial of Feasibility and Safety a Pilot Trial of Feasibility and Safety.  Gastrointestinal Endoscopy, Volume 67, Issue 5, April 2008, Pages AB179-AB180

 -posted by Kerry Dunbar, MD

One of the newer treatments for Barrett’s esophagus with dysplasia is radiofrequency ablation, also sometimes referred to as Barrx (the name of the company), or Halo (the name of the specific treatment).  Several people have asked questions about Barrx, so here’s some information.

How it works

Halo 360 – Upper endoscopy is performed and the length of the Barrett’s esophagus is measured. A special ‘sizing balloon’ is used to figure out the width of the esophagus where the BE is located.  Once the diameter of the esophagus is known, a special catheter with the ablation balloon on it is passed into the esophagus. There are 3 cm of electrodes on the balloon which are placed in the area of the BE to be treated. When the balloon is inflated, the electrodes touch the wall of the esophagus and energy is released.  The release of the energy creates a shallow burn, which destroys the Barrett’s esophagus without harming the tissue underneath. The treated area is then gently cleaned with a plastic cap on the end of the endoscope to remove any loose tissue. Then the BE is treated a second time with the RFA balloon. 

Circumferential RFA is most often performed with longer BE, particularly when the BE is present on all the walls of the esophagus. 

Halo 90 – A small device that looks like a paddle (about 2 cm by 1 cm in size) is placed on the end of a regular endoscope.  An upper endoscopy is then performed and the paddle is placed on areas of BE that to be treated.  The endoscopist then steps on a pedal, and energy is released, making a shallow burn in the area.  Each area of BE is treated twice, then the mucosa is cleaned with the paddle. The same areas are then treated 2 more times with the Halo90 during the same procedure. 

Halo90 is typically used in patients with small amounts of BE, such as tongues or islands of Barrett’s.  

Complications

Chest discomfort may occur after the procedure. Other possible complications include lacerations of the esophageal mucosa, which is like a shallow tear or cut which may bleed.  Some patients have had difficulty swallowing after the procedure and rarely patients will develop a stricture that needs dilation with a special balloon.  Perforation, or tearing the wall of the esophagus, is a risk, but so far no studies have been published showing a perforation during RFA.

What’s published?

There is alot of interest in ablation of Barrett’s esophagus and several ongoing research studies.  Here are a few of the published studies using RFA in dysplasia:

At Digestive Disease Week 2008, an international gastroenterology meeting, the interim results for a randomized, multicenter, sham-controlled trial of RFA were presented.  All the patients in the study had BE with HGD or LGD.  The patients were randomized (randomly assigned) to either RFA or a sham (fake) RFA.  Halo 360 and Halo 90 were performed to treat the BE and dysplasia. 

At the time of the presentation in May 2008, 127 patients had been treated.  The average number of sessions needed to treat BE with dysplasia was 3.5.  67% of patients with HGD had complete eradication of dysplasia compared to no patients who received the sham treatment.  96% of patients with LGD had complete eradication of dysplasia with RFA.  Looking at complete eradication of the BE, 60% of patients with HGD and 83% of patients with LGD had no BE left after treatment with RFA.  1 patient had a stricture treated with dilation and there were no esophageal perforations.  The study’s expected completion date was summer 2008, so complete results should be available soon. (1) 

A US Multicenter registry study of RFA was published in July 2008, which looked back at the records of 142 patients with BE-HGD at 16 different academic hospitals.  RFA was performed in all the patients using the Halo360.  In this study, patients had 1 to 2 ablation sessions.  2 patients had HGD after ablation.  Of the patients in the study who had follow up biopsies, complete eradication of HGD was seen in 90% of patient.  Complete eradication of all dysplasia (including LGD) was seen in 81%. Complete eradication of all Barrett’s esophagus occurred in 54% of patients.  One patient in the study developed an esophageal stricture (narrowing) which was treated with esophageal dilation. (2)

Another study looked at RFA in patients with early cancer, high grade dysplasia (HGD), or low grade dysplasia (LGD).  44 patients were in the study and 31 patients had endoscopic mucosal resection (EMR) of nodular BE.  The patients then had ablation of the remaining BE using the Halo360 or Halo90 system.  At the end of the study, the BE and dysplasia was completely gone in 98% of the patients (43 of 44).  Follow up at 21 months showed no recurrence of dysplasia in the patients. (3)

Who Should Consider RFA?

Most of the research done with RFA has been targeted to patients with Barrett’s esophagus and dysplasia. The response to treatment is very good in most of the studies, and is a reasonable option to consider for treatment.  For patients without dysplasia, the use of RFA is not as clear, which will be addressed in a separate post. 

Here are the references for the 3 studies discussed above:

1. Shaheen NJ, Sharma P, Overholt BF, et al.  A randomized, multicenter, sham-controlled trial of radiofrequency ablation for subjects with Barrett’s esophagus containing dysplasia: interim results of the AIM dysplasia trial.  Gastroenterology, Volume 134, Issue 4, Supplement 1, April 2008, Pages A-37
2. Ganz RA, Overholt BF, Sharma VK, et al.  Circumferential ablation of Barrett’s esophagus, that contains high-grade dysplasia: a U.S. multicenter registry. Gastrointestinal Endoscopy 2008, vol 68(1), pp 35-40. 
3. Pouw RE, Gondrie JJ, et al. Eradication of Barrett’s esophagus with early neoplasia by radiofrequency ablation, with or without endoscopic resection. J Gastrointest Surg 2008, vol 12, pp 1627-37.

3 November 2008

Dear Dr. Montgomery,

Thank you for your prompt reply to my inquiry regarding donations in the memory of Philippe (Phil) Ross. I know that you are responding to each donor with a thank you note; that is a wonderful gesture. I also want to express my gratitude to each of them for honoring Phil.

I know that with the relatively low numbers of cases of esophageal cancer diagnosed each year, it is considered an “orphan” disease and doesn’t get the attention that more widespread cancers do. Recently, I read that the number of cases of esophageal cancer diagnosed yearly is increasing, especially adenocarcinoma, the form of esophageal cancer that Phil had. Our hospice nurse, who has been in nursing for 30 plus years and in hospice for the last 18 years, told us that she is seeing an increase in the number of patients in the hospice system in Denver with esophageal cancer.

I hope that some of the research effort taking place in esophageal cancer is outreach and education to doctors. Phil woke me in the middle of the night in late 2003 with excruciating pain in his upper abdominal area and drove himself to the emergency room to be seen. Phil was not a person to visit the emergency room; for him to seek relief there meant it was serious. However, he was treated for an episode of acid reflux with the usual medications. There was no examination beyond an oral account of his symptoms and the monitoring of standard vital signs. I understand that triage nurses and emergency room doctors and nurses see many patients, some with gastric distress, but I can’t keep myself from thinking that if someone had taken the symptoms more seriously, he would be here now. He was a member of the population most susceptible for esophageal adenocarcinoma, a white male in his fifties. If I knew then what I do now, I would have insisted on further tests. He was diagnosed with cancer at the gastroesophageal junction in October 2005 while on a teaching and research sabbatical at a university in Aveiro, Portugal. At that time, he was in apparent excellent health; he worked out regularly at the University’s gym and ran about 30 miles per week. He consulted a doctor there when he started having difficulty swallowing. By then, the cancer was stage IV. When I read the prognosis on medical websites, my world was shattered. When Phil returned to the U.S. for follow-up and treatment, he gave me the option of not being involved in his care, knowing that it was going to be hard and that the likely outcome was a short survival time. I told him then and throughout his treatment that we were a team; I couldn’t imagine not being there to love and support him and act as his caretaker and health care advocate. Today is the four month anniversary of Phil’s death and I still can’t believe that it happened. He fought such a brave fight – a cliché – but it is true. He suffered through chemotherapy, radiation, radical surgery and visits to the emergency room with systemic infections, a suspected lung infection and bowel impactions. He lost the ability to do the things that he loved the most but never adopted a “poor me” attitude. Anything that we can do to keep other people and those who love them from going through this is an effort that deserves attention and support. I have enclosed a contribution today and will continue to contribute to your department when I am able – in recognition of ‘Team Phil’.

I hope for continued advances in detection and treatment from your department’s research.

With kind regards,
Sherry Skipper

We’ve had some questions about high grade dysplasia in Barrett’s esophagus, so here’s some information that may be helpful.

The lifetime risk of esophageal cancer from Barrett’s esophagus is low, probably on the order of 5% or less.  Surveillance programs with regular upper endoscopy seem to help detect dysplasia before it progresses to cancer. 

So what if you do have high grade dysplasia (HGD)?  HGD occurs when the Barrett’s esophagus cells accumulate mutations and lose their normal shape and pattern.  HGD isn’t cancer, but it is the step before cancer. The risk of developing esophageal cancer from HGD has been looked at in several studies and ranges from 20% to 50%.  

With HGD, there are several options for evaluation and treatment

 Evaluation

1. Have your slides reviewed by an expert GI pathologist – to make sure the biopsies show HGD and not cancer or low grade dysplasia (LGD)
2. Have repeat endoscopy with more biopsies to determine if there’s just one area with HGD or multiple areas of HGD (multifocal HGD)
3. Some gastroenterologists like to perform an endoscopic ultrasound for any patient diagnosed with BE-HGD.  This is done to look for signs of cancer, such as enlarged lymph nodes or invasion of tissue through the wall of the esophagus.  However, experts disagree about whether this is necessary.  There have been a few studies that EUS isn’t that helpful for HGD.  But EUS is important for staging cancers in Barrett’s esophagus.

Treatment

There are several options for treatment and there’s no one right answer for every patient.  Often, patients may need a combination of the therapies below to treat their HGD.  Other health issues and patient preferences play a role in choosing the right treatment.

1. Continued surveillance – repeating an EGD every 3 months to look for cancer.  This is an option for patients who don’t want (or are too unhealthy) for other therapies.  Also, continued surveillance is important for anyone treated for HGD with any of the therapies listed below, to make sure new areas of HGD haven’t arisen. 
2. High dose proton pump inhibitor therapy – generally given twice daily.  It doesn’t cure HGD, but can help reduce inflammation and make biopsies easier to interpret.  There are some studies that show regression of low grade dysplasia with PPI therapy.
3. Esophagectomy – surgical removal of the esophagus.  This procedure gets rid of all the BE and dysplasia.  The esophagus is removed and the stomach is pulled up into the chest or a piece of large intestine is used to make a new esophagus. This is very effective for getting rid of HGD, but is a major surgery and the complication rate varies.  It’s important to choose a surgeon who does many esophagectomy procedures as they tend to have lower complication rates.
4. Endoscopic mucosal resection (EMR) – useful for removing small areas of the esophageal mucosa that contain HGD.  EMR is often used to remove bumpy areas of HGD. 
5. Photodynamic therapy – A light-sensitizing medication, porfimer sodium, is injected intravenously.  Then a special laser fiber is inserted through the endoscope to the area of BE and dysplasia. The light from the laser causes a photochemical reaction with the porfimer sodium, which destroys the mucosa.  Patients who have PDT are photosensitive for several weeks and are advised to avoid the sun. 
6. Radiofrequency ablation -  A special balloon or small paddle attached to the endoscope are used to burn away a thin layer of the esophageal mucosa, getting rid of the HGD in the Barrett’s esophagus.  This is one of the newer treatment options for BE HGD.
7. Cryotherapy – Freezing liquid nitrogen or carbon dioxide is sprayed onto the esophageal mucosa, freezing the BE and HGD.  This is another newer treatment option for BE HGD.

If you have any questions about treatment of HGD, talk with your gastroenterologist about the different options to see which treatment would be best for you. 

posted by Kerry Dunbar, MD

Dear All

As I discussed in my first post, one of the areas of research in my laboratory involves testing the use of curcumin as an anticancer and chemopreventive agent. Curcumin is derived from turmeric, which for those of you who have eaten Indian food, know as the spice that gives curry its yellow color. Curcumin is known to be a potent anti-cancer agent, but its use in cancer (as well as in many other diseases like Alzheimer disease) has been limited because the drug does not get absorbed from the GI tract. We have developed a nanoparticle (nano = very small, about 10,000 times smaller than the size of a pin-head) that can encapsulate curcumin and help deliver it into the body. This product, which we call “nanocurcumin” (or nanocurry) is being tested in the laboratory and hopefully will be in the clinic in a couple of years, ready for human use.

I am very excited by this research for several reasons:

First, curcumin has been a component of diet for many centuries, so this is relatively safe as a “drug”.

Second, nanocurcumin is able to get hundred fold higher levels of curcumin in the blood compared to the free drug, a big advancement by any strecth.

Third, in addition to being useful as an anti-cancer agent, curcumin also works in chemoprevention. Once this drug is approved for human use, we hope to perform a trial in Barrett esophagus patients in collaboration with the clinical team at Hopkins to see if nanocurcumin can help prevent progression in this disease. This study is however, a few years away.

The local CBS affiliate in Baltimore (WJZ13) did a story on nanocurcumin. You can read the story and watch the video by clicking here:

Anirban Maitra, MD