When it comes to treating Inflammatory Bowel Disease, the way a patient’s clinicians work together can lead to more effective care, according to Walter A. Koltun, M.D., Chief, Professor of Surgery and Peter and Marsha Carlino Chair in IBD, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA.
Dr. Koltun and his colleagues have made the commitment to treat patients with IBD in special fashion at the Inflammatory Bowel Disease Center
at Hershey Medical Center. The unit consists of a team of gastroenterologists, surgeons, nurses, and support staff, who work collaboratively to provide better, coordinated care between the medical and surgical aspects in disease management.
Since IBD can be so varied, the center provides patient symposiums to help patients provide meaningful input into the direction of his or her treatment, Koltun said. When patients have a basic understanding of the various levels of medications, some treatment concepts, potential complications, and the way that his or her disease affects them personally, their feedback can provide very relevant direction to the team.
The Surgical Approach to IBD
The medications that gastroenterologists recommend frequently target the organ of inflammation
, according to Koltun. Since Crohn’s Disease can be located in so many different places throughout the digestive tract, medications are often prescribed to specifically target the areas of inflammation. In the case of Ulcerative Colitis
, inflammation is always found in the colon. While both Ulcerative Colitis and Crohn’s Disease are considered Inflammatory Bowel Disease, surgeons approach these two diseases very differently.
The most significant difference between the two diseases is that, theoretically, the surgeon can cure Ulcerative Colitis by taking out the colon. The inflammation does not return for UC patients when they no longer have a colon, he added. In a Crohn’s Disease patient, however, the colon can be surgically removed and the disease can return in other parts of the bowel. This changes the surgeon’s aim in Crohn’s cases to treat the complications of the disease, rather than the disease itself.
If a patient with Crohn’s Disease experiences bleeding, an abscess, or a perforation, for example, the surgeon treats those specific complications. “Obviously, there are subtleties in the way you manage patients with Inflammatory Bowel Disease, as opposed to bleeding or perforation from other causes,” Koltun said. “I am not trying to minimize the sophistication needed in trying to figure out what to do for each patient, but the fundamental difference is that [a surgeon] can cure Ulcerative Colitis, and cannot cure Crohn’s. That is the fundamental difference from a surgical perspective.”
Ulcerative Colitis: The Ileal Pouch Anal Anastomosis Procedure
Twenty to 30 years ago, a breakthrough procedure called the Ileal Pouch Anal Anastomosis, or IPAA, changed the way that Ulcerative Colitis patients were typically managed in a surgical setting. Koltun explained that surgeons are able to create a reservoir of sorts that is able to store stool in a way that allows patients the ability to defecate through his or her anus, nearly eliminating the need to have a permanent ostomy bag.
In large part, the colon’s function is to act as a large reservoir, so a person can go to the bathroom once or twice a day, as opposed to continuously, he said. In cases where patients have Ulcerative Colitis, and have the colon removed, an IBD surgeon can fashion a new reservoir out of the healthy small intestine. The end of the small bowel is folded over in the shape of the capital letter “J,” the sides of the intestine are cut, it is sutured to itself to keep its shape, and then it is stitched to the anus. The function of the old, and now removed, colon as a reservoir has been restored by this new reservoir.
One of the other functions of the colon is to dry the stool out, Koltun added. Since the stool that comes out of the small bowel is comparatively less solid, the way the colon used to dry the stool is not perfectly replaced by this procedure. Patients usually have four to five bowel movements per day after the IPAA, and while not solid, the stools are paste-like and manageable. Patients are normally able to wait for a good time to go to the restroom and are usually very thankful after the IPAA procedure, he added.
“This is the operation where we shoot for the cure of Ulcerative Colitis, because we can get rid of the colon, and recreate a new colon, as it were, and patient no longer has the disease,” Dr. Koltun said. “In Crohn’s patients, the disease tends to come back, and that is the dilemma of the patient that has [this] kind of surgery.”
The IPAA is sometimes performed in three stages, but more often, it can be done in two stages, according to the surgeon. In a typical two-stage procedure, the patient receives his or her J Pouch and a temporary ostomy bag, via a stoma that is on the surface of the skin. The surgeon diverts the stool to the stoma to allow the pouch to heal. The pouch has veins and blood flow going to it, but it is not connected to the rest of the digestive tract, so to give it time to heal.
There is a lot of suturing involved in the first procedure, and “you don’t want an infection, so you divert the stool by bringing it to the surface of the belly, you wear a bag for two months, [the pouch] heals up, and then you stitch it back together two months later,” he said. “It gives the patient very good function. Ninety percent of patients will be very, very happy with this operation.”
Crohn’s Disease: Ileocolectomy
The most common cases of Crohn’s Disease involve the end of the small intestine, said Koltun, and these patients will frequently present with bowel that is either strictured or fistulized. A stricture, or a narrowing in the caliber of the intestine caused by scarring, inflammation, or both, can cause intestinal contents to have difficulty passing the area. A fistula is a communication, or tunnel, between the bowel and another organ or the surface of the skin.
In a Crohn’s Disease patient that has indolent, chronic, worsening disease over many years, the ileum will often become strictured and they will begin to have difficulty eating, Koltun explained. The ileocolectomy procedure removes damaged tissue at the small intestine and reconnects it to the healthy portion of the colon.
“This operation now typically allows patients to be out of the hospital in three days, and back at work, usually, in a couple of weeks,” the surgeon said. “That usually works very well for patients, presuming that they are not in dire straits with their disease.”
Roughly 60% of patients that might be a candidate for the ileocolectomy present in a fashion that reflects good, continuing, ongoing care by their physicians and a certain amount of compliance by the patient, Dr. Koltun said. Forty percent are admitted through the emergency room, however, possibly because they have been ignoring symptoms, pain, and have a perforation of the bowel. Stricturing can cause the bowel to perforate and create an abdominal abscess. This is an emergency situation, he said, and the patient will need a hospital setting to begin a multi-step process reserved for patients who present urgently.
Laparoscopic Surgery Techniques for IBD
“The big thing in surgery for Inflammatory Bowel Disease is that we’re doing this with a laparoscopic technique,” Koltun said. “We are not making big incisions anymore. We’re making small incisions, and doing this all laparoscopically and in minimally invasive fashion.”
Laparoscopy is a surgical technique that uses tools that grasp, close, and burns, or cauterizes, tissue to cut it, Koltun explained. This is done through small incisions in the abdomen, where the largest is usually hidden mostly inside the patient’s belly button. The two small “port site” incisions allow the surgical team to use the grasping tools in conjunction with the cutting tool. The three incisions are triangulated over the surgical site, while a camera in the abdomen projects the images onto monitors placed throughout the operating room. These monitors allow the members of the surgical team to work together and to see the surgical site without a large incision.
During the ileocolectomy procedure for Crohn’s Disease patients, surgeons “wiggle the bowel out through the incision at the belly button, cut off the bowel, stitch it back together, tuck it back in the hole, and that’s the way it works these days,” said Koltun. “We’ve been doing [laparoscopic procedures] about ten years now, commonly. It gets patients out of the hospital fast, and gets patients back to work and doing their things. It has good cosmesis too.”
Many patients view surgery as sort of a last resort, according to the doctor, but surgery should be considered just another tool in the toolbox of the IBD clinician. Often, patients view surgery as the last thing to do, when it sometimes is the best thing to do, based on the patient’s circumstances. This is an instance where it is advantageous to have a gastroenterologist and a surgeon with a good working relationship.
“It’s great to have a very smart surgeon, but make no mistake about it, most people need a technically competent surgeon,” Koltun said. “If you want smart, you can find a lot of people who are smart, but if you want a surgeon, you want someone who knows how to operate. It’s a technical thing. Like anything else in life, you are good at what you do a lot of. And when it comes to Inflammatory Bowel Disease, it really is different than a lot of other surgery.”
Surgical Management for Abscesses
Seventy-five percent of Crohn’s Disease patients will have surgery within ten years, according to Dr. Koltun. That surgery may be abdominal surgery, as in the case of the aforementioned ileocolectomy, or it may include anal surgery. A relatively common complication of Crohn’s Disease involves abscesses and/or fistulae at the backside, he added, and that three-quarters statistic includes patients who need less-involved anal surgery.
Similar to an abdominal abscess, a perianal abscess is a collection of pus and infection, but is frequently much more easily accessible to a surgeon for drainage purposes. Fistulae may also be present, which in this area, is the tracking or tunneling, of infection to the bladder or to surface of the skin.
“Some patients will have almost no intestinal disease and this will be the major difficulty they have,” Dr. Koltun said. “It can be quite disabling. It can be quite embarrassing and painful for them.”
In some regards, perianal and recto-vaginal abscesses and fistulae are similar to their abdominal counterparts because they both reflect activity of the disease, the doctor said. If a patient has anal complications or activity of his or her anal disease, that usually is paralleled by the patient’s intestinal disease activity.
From a surgical perspective, the key difference between these complications is the kind and severity of the surgical options available. If a patient presents with an abdominal abscess, the team of doctors must first remove the infection and pus. It is treated with antibiotics and drainage, but if the doctor can only choose one of the two options, Koltun said drainage is preferable. Antibiotics cannot permeate or infiltrate that kind of pus, so drainage is the best way to treat an abscess.
To drain an abdominal abscess, a surgeon will open the skin and will either insert a tube or use a knife to open the collection and evacuate the infection. The incision, however, essentially creates a fistula because the infection came from the bowel, and now the incision has created a communication from the bowel to the outside world. This requires the surgeon to fix the hole in the bowel, he added.
On the other hand, for a patient with a perianal abscess, a surgeon can create an incision – sometimes even in a clinic setting – and drain the pus out immediately, said Dr. Koltun. The consequences are more significant for a patient with an abdominal abscess.
A patient’s management with perianal disease is a multidisciplinary process, Koltun said. Close collaboration between a gastroenterologist and the IBD surgeon is imperative. Commonly used medications like infliximab (Remicade), azathioprine (Imuran), prednisone, and others, are contra-indicated in an active infection because they have immunosuppressive properties, according to the doctor.
“There is a complex paradigm of care for a patient with perianal Crohn’s Disease,” he said. “It is not a straightforward process and it is another reason why a center concept is important, so that everyone coordinates well with the various treatments.”
In perianal disease cases, the surgeon typically first sees the patient to get the infection under control. A common way to achieve this, surgically, is to use a seton, which is a string, or piece of rubber, that is placed through the fistula and clasped outside the body to allow the infection to properly drain. Then, the surgeon usually works with the patient’s gastroenterologist to utilize medications that suppress the immune response, so to facilitate healing the process that caused these complications to originate.
These patients will visit the surgeon again to decide when to have the seton removed, or whether measures like a fistula plug, fibrin glue, or the LIFT procedure might be considered. The recto-vaginal fistula is notoriously the most difficult to treat, he added, and these cases often require a “flap” procedure that essentially allows the surgeon to use surrounding tissue to “shingle,” or “flap shut” the hole.
“It won’t heal if the disease is not under control,” said Koltun. “So you have to get the disease under control, and then the body wants to help it heal, but the body is creating this erosive, fistulizing process in the first place, so you can’t expect it to heal by doing any of those surgical manipulations alone. The anal complications of Inflammatory Bowel Disease are a whole subject unto itself, and we are pretty good these days at saving peoples’ backsides, using a coordinated approach between surgeon and gastroenterologist.”
There is a much higher incidence of patients preserving their long-term continence, in large part because of some of the medications helpful to the process. Undoubtedly, he added, the medical treatment must be well-coordinated with the surgical involvement.
Perianal disease can reoccur and be rather disconcerting to patients, especially ones with very active disease that cause fistulas and abscesses to return, the doctor said. Infliximab, and some of the other biologic therapies, have been shown to be of great benefit in the treatment of perianal fistulas; however, if the surgeon carefully examines the area with MRI or ultrasound imaging after the fistula has “gone away,” the fistula tract itself can still be seen most of the time. It is often collapsed shut and quiescent, he said, but fistulas have a tendency to come back because they are still present to a degree.
If medication controls the situation, without infection or pain, further surgery is not usually elected at this time, Dr. Koltun explained. “Chasing it” frequently with surgery can cause collateral injury, because any time a surgeon makes an incision, other tissues are cut in the process. If the patient’s medications have the situation under control, the gastroenterologist and surgeon will often suggest a passive approach in such a circumstance. If an abscess or fistula returns, however, the process begins again.
“[Patients with perianal Crohn’s] have Crohn’s Disease giving them anatomic problems, but then you get a superposition of the infection. The Crohn’s patient has a ‘double whammy’ in that the fistula was created by the disease, and now they have the superposition of the secondary effects of the infection,” Koltun said. “That makes the medical management with the gastroenterologist so important to coordinate.”
Surgical Research in IBD
There are probably a half a dozen surgeons that do IBD research in the United States, according to Dr. Koltun, who is also former president of the American Society of Colon and Rectal Surgeons Research Foundation. One of the key research areas he believes will provide significant results is to find ways to better help doctors determine which patients will respond well to medications and surgical procedures. Many of IBD’s medications come with high costs, diminishing results, and in some case, potential undesirable side effects. He feels that further research will help doctors better pair patients with effective medications and will help them pair patients with effective surgery.
“A lot of people view IBD as a medical illness, but the problem with that is all Ulcerative Colitic patients can be cured by surgery, and like I said, 75% of patients within ten years with Crohn’s Disease will need surgery,” said Dr. Koltun. “So I believe it is very much a surgical illness as well, but nonetheless, the research that is being done is more frequently being done on the medical side [rather] than on the surgical side.”
Research funded by the ASCRS is primarily focused on colorectal cancer; however Inflammatory Bowel Disease is a part of the foundation’s work. Over the past fifteen years, the ASCRS research foundation has provided IBD funding to study intestinal inflammation, bowel permeability in Crohn’s Disease, several studies concerning the Ileal Pouch Anal Anastomosis for Ulcerative Colitis patients, and many that focus on the genetics that affect IBD.
“There are all these new medicines coming out and we are finding that they help with certain patients and certain problems, but they have to be fit into a coordinated effort,” Koltun said. “For example, we have shown that certain patients don’t do well with surgery if they have been heavily treated with all these other drugs, so you have to time the surgery correctly. You might have to let the drugs wear off, so you do not have complications from them at the time of surgery, or in fact, you treat them very immediately right after surgery so they get immediate suppression of possible disease recurrence.”
Research: The Lock and Key of IBD
Inflammatory Bowel Disease has a genetic component that can be further broken down into immune issues and epithelial barrier functions. Your gut is a barrier to the outside world, the surgeon explained. Bacteria “in your gut,” are not really inside your body. When you eat food, it gets passed along to the various parts of your digestive tract, but at no point is that a part of your body. That food is inside your gut and your gut is a tube that is essentially outside your body – a long passage that begins at your mouth and goes all the way to the other end.
Since the contents of your bowel are not inside your body, the surface of the bowel represents a barrier to anything you digest. Studying the genetic problems that predispose Inflammatory Bowel Disease is focused around immune response problems, or difficulty with immune regulation, and epithelial barrier dysfunction, according to Dr. Koltun. When you combine either an immunological or barrier genetic fault with just the right kind of environmental trigger, this is when immune system disregulation takes place.
One person might have immune disregulation as their predisposition, but they will only get Inflammatory Bowel Disease if they interact with a certain kind of gut organism, he said. If they are not exposed to that environmental trigger, they won’t get IBD. On the other hand, someone else who does not have the immune problem may be exposed to that same organism and will not get IBD because their immune system does not have the defect.
“It is a lock and key phenomenon to some degree,” he said. “You have a lock that is your genetic predisposition, but it is only going to be opened if a certain key (the environmental part) fits in just right.”
The different forms of IBD are a consequence of numerous possible genetic predispositions that then have to interact in the exact unfortunate way with something in the environment that gives a person that particular variation of the disease.
“Cystic fibrosis has one gene,” Koltun explained. “There can be two or three variations, but there is one gene. That’s one mutation in one gene and you have the disease, and in [IBD], there are now about 150 genes that can [contribute to Inflammatory Bowel Disease].”
Genetic Analysis Will Lead to More Effective IBD Treatment
The gene mutation that was first discovered to affect IBD was NOD2, and has been found to be present in somewhere between 20 and 40% of patients with Crohn’s Disease. DNA contains two copies of genes, and in a person with double copies of the abnormal gene NOD2, his or her absolute risk of getting Inflammatory Bowel Disease is only 2.5 percent, Koltun said. That person’s risk of getting IBD, relative to someone who does not have that mutation, is 30 times higher, but even thirty times as high is only about one in 50 odds.
There are a lot of new biologic medications on the horizon, but when it comes to those medications, Dr. Koltun believes the key to their success will be in better using this genetic research to find the subcategories of patients where it will be most effective. Some drug companies are already testing to see if patients are NOD2 positive or not to see if they respond differently to medications.
Genetic research will soon let medical doctors tell a patient that he or she has Crohn’s Disease, listed with the genes that are found to be abnormal, he said. Since Inflammatory Bowel Disease has so many different variations, customized patient treatments will become more commonplace. This kind of personalized approach will be especially relevant because of the variations from one IBD patient to the next.
“It is exciting in many ways,” said Koltun. “We have been looking at drugs forever and drugs fall by the wayside all the time. Everybody has their disease for a different reason, and in some patients, that medication might work, but when you clump together 50 different kinds of IBD and see if that medication works, it worked for three of [one group] like a magic pill, but that was not statistically significant relevant to the other group. What we have to do is to segregate those patients more carefully based upon [the genetic research] and then test these medications again, because what we’re going to find is that these medications work for a subset of these patients. And that’s where we’re going now. We’re going there both medically and we’re going there surgically.”