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Unlocking the Mysteries of IBD & Colorectal Cancer

Imagine that you could have a simple blood test to determine if you are at risk for Crohn's disease, ulcerative colitis (collectively known as inflammatory bowel disease, or IBD), or colon cancer.

Now imagine that doctors could replace or repair genes to prevent the disease from occurring.

Finally, imagine that future generations of your family may never have to experience the pain and anguish that these digestive diseases wrought.

Well, you don't have to imagine because the University of Louisville Section of Colon and Rectal Surgery is involved in research that aims to make the realities of these digestive disorders a thing of the past.

"This is an exciting time in the field of digestive disease research. However, investigators face some hurdles vital to the basic understanding of these maladies. With those answers, scientists may be able to improve the quality of life for patients and their families by making these disorders preventable, more manageable, or curable," explained Susan Galandiuk, MD, professor of surgery at the University of Louisville.

Challenges In Research
So, where are we now and what lies ahead as researchers begin to unlock the mysteries of IBD and colorectal cancer? Dr. Galandiuk had the following comments:

What are the greatest challenges facing researchers of these digestive diseases?

First, physicians need to be able to accurately distinguish between Crohn's disease and ulcerative colitis. Even now, doctors often have a very difficult time in diagnosing Crohn's disease and ulcerative colitis.

Medical treatments for Crohn's disease and ulcerative colitis are similar. Yet, the surgical treatments for these two diseases are very different. Because of the difficulty that physicians have in telling the two ailments apart, patients may undergo surgery for ulcerative colitis while they, in reality, have Crohn's disease. Sadly, many patients develop complications due to this.

And the other obstacle?

Presently, there is no way to predict which patients with Crohn's disease will develop a recurrence after surgery. Identification of these patients would allow us to put them on preventative medication after surgery.

How can we detect patients at risk of developing colorectal cancer earlier?

The current method of detection and screening using colonoscopy, is invaluable as a diagnostic tool. However, it has not significantly improved the stage at which cancers have been diagnosed over the past 10 years. Many patients who are diagnosed with cancer are well past the stage for it to be cured. It is our hope that we will be able to develop a blood test to identify patients who are at risk of getting colorectal cancer years before it forms in the colon.

If we are able to predict patients at risk of getting colon cancer, can we place them on some type of medication that would prevent these cancers from occurring?

Possibly, while numerous studies have already shown an association between regular use of calcium or aspirin with a lower risk of developing colon cancer, additional studies are needed to better understand the relationship.

Can we determine which cancer patients will develop spread or recurrence of that cancer?

If we were able to predict this, only these patients would be given preventative chemotherapy and radiation treatments, which can both have a lot of side effects.

What can we expect to find out about gastrointestinal illnesses and future treatments?

I believe that, in the coming years, we will witness the dawn of new medications to treat these ailments. Just look at the progress medicine has made to date.

In the 1980s and 1990s, the 5-ASA products (i.e., Pentasa®, Asacol®, Dipentum®, Colazal®, Canasa®, and Rowasa®) were developed. They continue to help many patients with ulcerative colitis and Crohn's disease. A new 5-ASA drug—LIALDA™ (mesalamine) with MMX® technology—was approved by the U.S. Food and Drug Administration (FDA) in 2007. It is the first and only once-daily oral formulation of mesalamine and is prescribed to induce remission in patients with active, mild to moderate ulcerative colitis.

In 1998, the first breakthrough biologic drug, infliximab (Remicade®), was FDA approved specifically for the treatment of Crohn's disease. In September 2005, it was approved for the treatment of ulcerative colitis. Three other biologic drugs that also inhibit tumor necrosis factor-alpha (TNF-alpha)—a protein involved in the inflammatory process—have since been approved: adalimumab (Humira®), certolizumab pegol (Cimzia®), and golimumab (Simponi®).

Humira received FDA approval in 2007 for the induction and maintenance of remission in adults with moderately to severely active Crohn's disease who have lost their response to conventional therapies or who are intolerant of, or have stopped responding to, Remicade.

In 2012, Humira received FDA approval for the induction and maintenance of remission in adults with moderately to severely active ulcerative colitis when certain other medicines have not worked well enough. It is unknown if it is effective in people who are intolerant of, or have stopped responding to, other anti-TNF medicines.

In 2008, Cimzia—the first PEGylated anti-TNF inhibitor—received FDA approval for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have an inadequate response to conventional therapy.

In 2013, the FDA approved Simponi to treat adults with moderate to severe ulcerative colitis that is resistant (refractory) to prior treatment or requires continuous steroid therapy.

Some patients with mild to moderate active Crohn's disease may have the option of taking budesonide (Entocort-EC®). FDA approved in 2001, Entocort-EC is a steroid that acts topically in the gut. In 2013, the FDA approved budesonide extended relief tablets (UCERIS®) for patients with active, mild to moderative ulcerative colitis.

Another medication that came on the market in 2008 is natalizumab (Tysabri®). It received FDA approval for the treatment of moderate to severe Crohn's disease in patients with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional Crohn's disease therapies or TNF inhibitors. Because of one potential side effect with dangerous outcomes, patients with Crohn's disease who are using the drug must be enrolled in a special restricted distribution program called the Crohn's Disease–Tysabri Outreach Unified Commitment to Health (CD TOUCH) Prescribing Program.

Additional biologic medicines are in the pipeline for both types of inflammatory bowel disease. In the future, as genetic research progresses, it may play a major role in how we diagnose and treat these disorders.

This, of course, is only the beginning. Our ultimate goal is to find a cure for these inflammatory bowel diseases.

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