William J. Sandborn, MD, FACG
Mayo Clinic, Rochester, MN
There are a variety of new and emerging therapies that will be of interest to patients with inflammatory bowel disease. The first class of new therapies is called the selective adhesion molecule blockers. This class of drugs selectively blocks white blood cells from moving from the blood vessels into the wall of the gut, thus blocking the inflammation in the gut wall that characterizes ulcerative colitis and Crohn’s disease. The reason that the drugs are “selective” is because they block movement of white blood cells into the gut, but not other body tissues like the brain. These drugs currently are all in clinical trials for ulcerative colitis and/or Crohn’s disease. The second class of new therapies is chemokine blockers. Chemokines are proteins that help mediate inflammation. Chemokine receptor 9 is important in regulating the movement of certain groups of white blood cells to the small intestine and colon. The third class of new therapies is directed towards a group of proteins that cause inflammation called cytokines. Three cytokines that are being targeted are interleukin 12, interleukin 23, and interleukin 17. An antibody directed against both interleukin 12 and interleukin 23 is being evaluated for the treatment of Crohn’s disease. Finally, an extract from a Chinese herb called Andrographis paniculata (also called HMPL-004) has recently been shown to be effective for induction of remission in patients with ulcerative colitis. Additional trials in ulcerative colitis and Crohn’s disease are planned.
Thomas A. Ullman, MD, FACG
Mt. Sinai School of Medicine, New York, NY
Patients with longstanding colitis, whether ulcerative colitis or Crohn’s disease with involvement of the colon, are at increased risk of developing colon or rectal cancer relative to the general population. This risk is primarily shared by IBD patients with 1/3 or more of their colon involved who have had disease for more than 8 years. In addition to those who have had disease for more than 8 years and those with more than 1/3 of their colons involved with colitis (ulcerative colitis or Crohn’s colitis), additional factors that we know to increase the risk of colon and rectal cancer include patients who also carry a diagnosis of primary sclerosing cholangitis (PSC), an inflammatory condition of the bile ducts that occurs in a small percentage of IBD patients; patients with a family history of colon or rectal cancer; and patients with more inflammation noted over time. Unfortunately, patients who develop IBD at a younger age may be at an increased risk, but it is unusual for young patients with IBD to develop colon cancer while they are young.
Despite these risks, a number of items may lessen an IBD patient’s risk for colon or rectal cancer. The ACG and other societies recommend that all IBD patients who have had the disease for 8 years and who have 1/3 or more of their colon involved undergo colonscopies every 1-2 years. For patients with primary sclerosing cholangitis, these colonoscopies should begin as soon as IBD is diagnosed. During these colonoscopies, gastroenterologists will take numerous biopsies to exclude the presence of precancerous changes, called dysplasia. They will also remove any pre-cancerous polyps that might have developed. Left unchecked, these polyps could develop into colon or rectal cancer. Most patients will return in 1-2 years for a repeat colonoscopy, while a very small minority, about 0.5%, will need to undergo surgery to prevent further changes and any cancer from developing. This process, called colonoscopic dysplasia surveillance, is probably the best practical tool we have to fight against colon cancer in IBD. Medications that reduce inflammation in IBD have also been suggested to be preventive in the development of colitis-related colorectal cancer, which is good news.
Weight loss, fatigue, blood in the stool, and crampy abdominal pain can all be signs of colon cancer, but, unfortunately, they can also be signs of active ulcerative colitis or active Crohn’s disease. That’s why undergoing regular colonoscopies is an important part of cancer prevention for IBD patients.
Recent studies have refined our knowledge about the relationship between colon cancer and IBD. First, unlike in previous years, there is now evidence that surveillance colonoscopies reduce the likelihood of developing colon cancer. Second, colon cancers appear to be happening less frequently in patients with IBD than had previously been shown. This may be a function of less inflammation over time due to the effect of IBD medicines, surveillance colonoscopies, or other factors that we don’t yet understand. No matter what the reason, it’s obviously good news.
Additionally, improved optics in colonoscopies and newer endoscopic methods that allow gastroenterologists better views of the colon’s surface leading to successful removal of small precancerous polyps and plaques might be making a difference in the likelihood of IBD patients developing cancer. Obviously, this is all welcome news, and we all look forward to further developments. For now, though, the best practical advice for patients is for them to talk about cancer risk with their gastroenterologist, take medicines as prescribed, undergo periodic colonoscopies as written in the current ACG Guidelines, and shine a light on these problems with participation in events like World IBD Day and World Digestive Disease Day.
Sunanda V. Kane, MD, MSPH, FACG
Mayo Clinic, Rochester, MN
Ladies, the most dangerous thing for your pregnancy is active disease, not the medicine that treats it. Three percent of all live births in the United States results in some sort of birth defect and no study looking at the medications used to treat IBD has shown any higher rates than that. The FDA has now done away with the rating system as they have agreed it is outdated and confusing. Your gastroenterologist, not your mother, best friend, or obstetrician, should be making the recommendations about the treatment of your IBD during this time. Remember, the number one teratogen is still alcohol. Men, while the first data suggested that 6MP was harmful to your offspring, subsequent data has refuted those claims. The number one and two enemies to sperm are alcohol and tobacco.
Sunanda V. Kane, MD, MSPH, FACG
Mayo Clinic, Rochester, MN
Entire books have been written on this topic, and there are certainly a lot of them out there! That just goes to show that there really ISN’T a single diet that is right for absolutely everyone. Diets are like perfumes, they are tailored for your body chemistry and won’t fit everyone. What you want to eat, what you should eat and what you can eat are all dependent on so many factors–lifestyle, culture, and economics, not to mention other medical problems, medications and disease activity.
If you have ulcerative colitis you may have been told “it doesn’t matter what you eat.” This is because the colon is in charge of water re-absorption and not nutrition per se. Nutrients, vitamins and calories are absorbed in the small intestine which is not involved, and thus why “it doesn’t matter.” Nor do we think it was something in your diet or missing from your diet that led to your disease so again it would not matter what you ate. However, what you need to take away from “it doesn’t matter” is that you do not need to confine your diet as part of your health management plan. When you have active disease eating may trigger diarrhea, and some foods will do it more than others, like corn or fatty foods, but those are foods that have the inherent properties of giving humans diarrhea even without colitis being present.
For Crohn’s disease what you put in your mouth can matter. Since Crohn’s disease can be quite diverse, depending on its location, activity level and character, different people need different things. Surgery too plays an important role as once you are missing key parts of the gut you have to supplement the body with nutrients like vitamin B12 in other ways since the body can no longer absorb it if the terminal ileum is gone. Surgery can lead to bacterial overgrowth and certain diets will feed those bacteria and make you feel worse. Sometimes you need extra bacteria and taking probiotics is a good idea. No plan is right if you continue to lose weight abnormally or feel miserable. Very strict, all inclusive elimination diets are meant to be short-term not long-term. Diet plans that come with expensive laundry lists of required supplements, which only that practitioner sells are also suspect. The best advice is to talk to an IBD expert, a nutritionist that works with GI patients, and other patients in your area to find out what they eat. This is about living a lifetime, not for a couple of weeks to months.
Jean-Paul Achkar, MD, FACG
Cleveland Clinic Foundation, Cleveland, OH
Genetic factors have long been suspected as key contributors in the development of inflammatory bowel disease (IBD) based on early studies that showed higher rates of IBD among Caucasians and those of Jewish ethnicity; findings of families in which two or more people were affected with IBD; and higher rates of both twins developing IBD for identical twins compared to fraternal twins. However, the identification of specific genes that cause IBD had been challenging for several decades. Fortunately, recent advancements in genetic knowledge and technology have allowed an unprecedented rapid unraveling of the genetic basis of IBD over the past five years. Currently, over 30 replicated genes or areas on certain chromosomes have been found to be associated with Crohn’s disease and similar numbers will likely soon be reached for ulcerative colitis.
The overall findings of these genetics studies have built on our understanding of IBD and have highlighted the interplay of genetics, environment, intestinal bacteria, and abnormalities in the immune system in the development of IBD. For example, the identification of several genes that relate to response to bacterial challenges supports longstanding theories and animal studies demonstrating that intestinal bacteria and how they interact with intestinal cells play an important role in the development of IBD. Similarly, identification of several related immune function genes have emphasized the importance of certain parts of the immune system in IBD.
The ultimate hope of such advancements in genetic understanding is that they could lead to new and highly specific medical therapies that can target specific abnormalities that lead to IBD. In addition, defining whether genes may predispose to certain clinical outcomes should help clinicians better predict disease outcomes including risk for complications, need for surgery, and response to medical therapy.
Stephen B. Hanauer, MD
University of Chicago Medical Center, Chicago, IL
Maria T. Abreu, MD, FACG
University of Miami Miller School of Medicine, Miami, FL
Flare-ups can occur at any time, but are more likely to occur after periods or during periods of stress, following antibiotic use (ulcerative colitis), after taking non-steroidal anti-inflammatory drugs like ibuprofen, and after a cold or infection. It is hard to be able to predict when a flare-up will occur. The first thing is that it is important for the patient to recognize the early signs that they are developing a flare-up. If they have not been adhering to therapy with their mesalamine products, this is the time to make sure they are taking all of the mesalamine and all of their prescribed medications for their inflammatory bowel disease. They should have a diet that minimizes spicy foods and high sugar which can cause diarrhea and generally, I recommend a low fiber diet during periods of flare-up. The patient should call their doctor to make a follow-up appointment as soon as possible to see if any additional therapy is necessary. Rather than waiting until the last minute, it is always better to catch a flare-up in its earliest stages.