Posts Tagged ‘treatment’

More on Buried Barrett’s Esophagus

Tuesday, April 21st, 2009

As Dr. Montgomery described in her post, ‘buried Barrett’s esophagus’ occurs when there is Barrett’s tissue underneath the normal squamous lining of the esophagus.  It is also referred to as ‘subsquamous Barrett’s’ or ‘squamous overgrowth of Barrett’s’. 

The study Dr. Montgomery mentioned followed the patients in the big photodynamic therapy study (mentioned in the blog post on PDT) for 5 years.  This new paper includes 5-year results for 138 patients who were treated with photodynamic therapy plus omeprazole and 70 patients treated with only omeprazole for 5 years.  Patients in the study were followed with upper endoscopy after treatment to look for residual BE, subsquamous BE, and dysplasia. 

Here are some details of what the study showed:

  • The researchers looked at 33,658 biopsies from patients in both study groups (PDT vs omeprazole)
  • About 5% of patients had subsquamous BE prior to treatment
  • About 1/3 of patients in each group had some subsquamous BE after treatment
  • The number of biopsies for each patient that showed subsquamous BE was very low, with only about ½ of one biopsy showing subsquamous BE for each patient (the exact numbers are 0.48 biopsies with subsquamous BE in patients treated with BE and 0.66 biopsies per patient in patients treated with omeprazole)
  • The risk of buried BE was very low for patients in the study
  • For study patients who later went on to develop dysplasia or cancer, the dysplasia/cancer was found in multiple biopsies on the surface. No dysplasia or cancer was only found in the subsquamous BE.

Another study, presented at Digestive Disease Week 2008, an international GI meeting (but not yet published as a full article), looked at subsquamous BE before treatment with RFA (Barrx) and after treatment with RFA. 

Here are details of what the study showed:

  • 127 patients participated in the study and 2,151 biopsies were examined prior to any treatment
  • Before treatment, 32 of 127 patients had some buried BE – about 25% of the patients
  • Of all 2,151 biopsies, only 67 (3%) showed buried BE, so the number of buried BE biopsies per patient is low
  • 35 patients had RFA and had completed all their follow-up biopsies. After treatment with RFA, only 1 biopsy showed subsquamous BE out of 1,223 biopsies
  • For 16 patients who received sham treatment (they didn’t get RFA), and have had follow up biopsies: 20 of 290 biopsies showed subsquamous BE (about 4% of the biopsies)
  • The final results of this study analyzing all the patients in the study haven’t been published yet, but probably will be soon

To summarize this information about subsquamous BE:

  • Subsquamous BE can be found in many patients with Barrett’s esophagus whether they are treated with ablation or not
  • The rate of buried BE/subsquamous BE is low after treatment with ablation therapy
  • For patients who have been treated with ablation therapy, surveillance endoscopy with 4 quadrant biopsies should still be performed. Biopsies of the normal-looking squamous tissue (where the BE used to be) should be taken. This is the best way to detect subsquamous BE.

References:

Bronner MP, Overhot BF, Taylor SL, et al.  Squamous Overgrowth is not a Safety Concern for Photodynamic Therapy for Barrett’s Esophagus with High-Grade Dysplasia.  Gastroenterology 2009, volume 136, issue , p. 56-64. 

Shaheen NJ, Bronner MP, Fleischer DE,  et al.  Subsquamous Intestinal Metaplasia Is a Common Finding in Ablation-Naive Patients with Dysplastic Barrett’s Esophagus, and Significantly Decreases in Prevalence After Radiofrequency Ablation. Gastrointestinal Endoscopy, Volume 67, Issue 5, April 2008, Page AB176.

– posted by Kerry Dunbar, MD

 

Radiofrequency Ablation for Nondysplastic Barrett’s Esophagus

Friday, February 20th, 2009

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 1st 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

Photodynamic Therapy (PDT)

Tuesday, February 17th, 2009

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

Cryotherapy

Thursday, January 29th, 2009

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

Barrett’s Esophagus with High Grade Dysplasia

Wednesday, November 5th, 2008

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