Archive for the ‘research’ Category

Risk of cancer in Barrett’s esophagus

Saturday, January 8th, 2011
Dear Ms. Atwater,
Don’t let your weekend be ruined.  If you have Barrett’s esophagus, your risk of cancer is still low – it is just higher than your risk if you did not have Barrett’s esophagus. There are about 16,000 new cases of esophagus cancer in the US whereas, for example there are over 200,000 new cases per year of lung and prostate cancer.   In a way you are lucky since you know you are at risk so you can be monitored.  There ARE ways to have the Barrett cells removed but the reason your doctor will probably not suggest them is because these methods (called radiofrequency abblation – the trade name is BARRX) are not without complications and the risk of troubles from the treatment is higher than the risk of developing cancer. 
 
Elizabeth Montgomery, MD

Letter from Vincent

Tuesday, June 29th, 2010

 

letter from Vincent

Dear Vincent D’Amato, Jr.,

Thank you so much for your wonderful letter and wonderful ideas.  I wish I were smart enough to figure out how to make the special pill that you have thought of that will make esophagus cancer go into the stomach and be destroyed.  It may not be until you become a scientist that this happens since this pill will be hard to make.  However, in the interim, I will be the next D’Amato Research Fellow and I will work in Dr.  Anirban Maitra’s laboratory.  I am coming all the way from the Netherlands (Holland) to do this.  There is a picture of me here.  My name is Mirte Stippel.  I will work as hard as I can to learn as much as I can about how esophagus cancer kills wonderful people like your grandfather and I hope to be able to report advances as I do my laboratory work.  Thanks again for your ideas.

Mirte Stippel, PhD

Mirte Mayke Streppel

 

Can in vivo endomicroscopy help physicians detect precancerous changes and early cancers in Barrett’s esophagus?

Monday, April 19th, 2010

In Vivo Confocal Endomicroscopy for Improved Diagnosis of Barrett’s Esophagus and Associated Neoplasia: A Multicenter Randomized Controlled Trial of Diagnostic Yield and Clinical Impact

The Johns Hopkins Hospital is leading a multicenter research study to determine the best way to identify cancer in people with Barrett’s esophagus.  Gastroenterologists will compare 2 different techniques   (high resolution endoscopy (HRE) and confocal laser endomicroscopy (EM) to examine the esophagus. Endomicroscopy is a relatively new advance in endoscopic imaging, to see highly magnified pictures of the esophageal lining and better guide the places to take biopsies. .  The research study will evaluate what EM adds to high definition video endoscopy in patients undergoing routine evaluation or those with suspected pre-cancer (dysplasia) or early cancers.

Adult patients aged 18- 80 years with known Barrett’s esophagus may be eligible for this research study.  Eligible patients will be studied with HRE or HRE plus EM.  A standard of care systematic biopsy protocol will be performed in all patients, in addition to targeted sampling of suspicious areas after careful endoscopic evaluation.

This international, multicenter, double-blind randomized controlled trial will recruit a total of 200 patients over 1 year at 5 sites (Johns Hopkins in Baltimore, The Cleveland Clinic Foundation in Cleveland, Mt. Sinai Hospital in New York, Massachusetts General Hospital in Boston, and University of Mainz Germany).

Interested individuals can contact the study team at Johns Hopkins (call 410-502-9795 or 410-502-2893, or email cebe@jhmi.edu).

JHM IRB study number NA_00025471

Principal investigator: Marcia Irene Canto, MD., MHS

Support Our Research

Tuesday, December 15th, 2009

As the end of the year approaches we wanted to sincerely express our deepest gratitude to those of you who have supported our research.  Thanks to private giving this has been one of the most productive years ever for our Barrett’s Esophagus research team. Many of our discoveries happen through research funded by your generosity.

Importantly, we have also used your support to hire summer students and fellows (trainees who have completed an advanced degree).  These young scientists are our future and, simply put, your generosity has had a significant impact on their careers.  We believe they are the future of the war against Barrett’s Esophagus.

As January 1st approaches many of you are considering year-end donations for tax purposes.  We sincerely thank you for your past support and ask you to consider Barrett’s Esophagus research at Johns Hopkins.  For more information visit:

http://pathology2.jhu.edu/beweb/support.cfm

RFA of Squamous Dysplasia

Tuesday, June 23rd, 2009

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.

 

 


 

Integrative Epigenomics

Thursday, May 28th, 2009

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)

Is Surveillance (Rather Than Esophagectomy) Safe For High-Grade Dysplasia?

Sunday, May 24th, 2009

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.

 

 

Buried Barrett’s

Friday, April 3rd, 2009

On the top of the image there is a pink layer of squamous (normal) esophageal epithelium.  The glands (circular structures) below are dysplastic Barrett\'s mucosa.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 Have Barrett’s

Tuesday, March 24th, 2009

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

More Issues in BE Research – When is a Treatment Experimental?

Friday, March 13th, 2009

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