Re: New Treatments for Adhesions with David Wiseman

From: Helen Dynda (olddad66@runestone.net)
Fri Aug 25 22:44:31 2000


At Fri, 25 Aug 2000, Helen Dynda wrote:

http://health.excite.com/content/article/1700.50770

New Treatments for Adhesions with David Wiseman

By David Wiseman, PhD

Event Date: 06/15/2000.

The opinions given by Dr. Wiseman are his and his alone. If you have specific questions or are concerned about your health, please consult your personal physician. This event is for informational purposes only.

Moderator: Welcome to WebMD Live's World Watch and Health News Auditorium. Today we are discussing New Treatments For Adhesions with David Wiseman, PhD, Dr. Wiseman is a recognized expert in the science and business of preventing surgical adhesions. He has worked or consulted for 20 companies in adhesion prevention, and has also played a prominent role in the development of a number of adhesion prevention products, such as Interceed Barrier and Intergel. Dr. Wiseman is the founder and president of Synechion, Inc., a consulting and development company specializing in products for preventing post-surgical adhesions. He is also working on the establishment of a support society for patients with surgical adhesions. Additionally, Dr. Wiseman was also program leader for clinical and pre-clinical programs at Surgical Adhesions, as well as one of 60 research fellows for the Johnson & Johnson family of companies. He is widely published and a co-author of the Handbook of Biodegradable Polymer.

Dr. Wiseman, welcome back to WebMD Live.

Dr. Wiseman: Thank you and thank you for inviting me.

Moderator: What are adhesions?

Dr. Wiseman: Adhesions are abnormal connections between two tissues. Two organs in your body that are not normally connected become connected by something called an adhesion. An adhesion is essentially scar tissue similar to a scar you would have in your skin, but instead of being on your skin, it's inside you.

Moderator: Why do adhesions happen?

Dr. Wiseman: Most commonly they form because you have surgery inside you, the tissues want to heal, and as they heal, they touch each other. Because they touch each other, they will form a scar connecting the two tissues. People think they are really abnormal. It's really something that occurs normally. Our body has all kinds of defense and repair mechanisms designed to help us in the event we are invaded by foreign organisms. We have built in self-repair mechanisms. Adhesions are one part of those self-repair mechanisms. In the old days before we had surgery and antibiotics, if someone got a spear wound in their belly or an animal's horn was to penetrate into their belly, they couldn't rush to the emergency room. So God invented this wonderful way to repair ourselves and cover up holes very quickly, without more problems occurring.

One of the defense mechanisms is the mechanism relating to adhesion formation. If the bowel were punctured, it would set into motion a healing motion that would cause that raw tissue to stick to another tissue. It forms a seal, and now the intestine has been patched up. That's probably why adhesions are designed to form. Nowadays, people often have elective surgery, and we have other ways of dealing with infection, so adhesions really are potentially problematic. We really don't need them. The problems they cause are bowel obstruction, infertility and pain being the main three. Those things to a person that's been attacked by a rhinoceros are things they would live with and they would much rather have than dying quickly. In that regard, adhesions -- the trade off between good and bad is a good trade-off, because you could die immediately. Now that we have other ways of dealing with immediate problems, we're only left with the bad things adhesions do.

al_pavy_webmd: Are adhesions similar to scabs? Are they related?

Dr. Wiseman: A scab is when someone has cut themselves, and if you don't put a band-aid on, there will be a little bit of bleeding. That tissue fluid will congeal. Because it's exposed to the air, it will dry up and form a scab. It's a dried piece of congealed wound fluid. Scabs really don't form as frequently if in the skin you use dressing which keep the wound moist. It eventually drops off. Inside the body, because the inside of the body is always moist, scabs don't form. A scar is different from a scab. A scar is the equivalent of putting a patch on a bicycle tube with a puncture. A scar is the body's repair patch. When you have a hole somewhere, the body will send in its troops, and it will build a scar which covers the wound or holds the wound together. It's made up of tough fibers that form a patch. A scar is usually good. A scab is not something you particularly want. You want to discourage scabs from forming and encourage the wound to heal properly. A scab is an indication that the wound is not healing properly or as well as it could.

judith20_webmd: What is the difference between dense adhesions and other adhesions?

Dr. Wiseman: "Dense" is an adjective to describe the kind of severity of adhesions. There are lots of words that doctors use to describe adhesions. It's like you went to a dense forest, there are a lot of trees packed closely together. How tightly packed they are in one place. There's a third term which is called "cohesiveness." That means that when the adhesions are so dense that you can't tell one from another, it's just one big mass of congealed tissue and there are not ways that you can't tell one tree from the next, that's what we called cohesive adhesions. It would be like taking a raveled up ball of string and pouring glue on it, then letting it set. That's how I might describe cohesive adhesions, and obviously they're dense.

al_pavy_webmd: How do adhesions cause bowel obstruction?

Dr. Wiseman: Imagine you have your garden hose, and everyone should have one of those nice things that you wind up your hose with. Sometimes when the hose has been unraveled and it's not as taught as it should be, the hose sometimes kinks and bends so much that the water can't go through. If you imagine the bowel is like a hose pipe and it can get kinked -- if it gets kinked, it's going to be blocked. The contents of the bowel, food and waste products, will not be able to pass through. The reason it gets kinked is because adhesions are holding the loops of the kinks together. Imagine you deliberately kinked your hose. If you let go, the hose would un-kink itself. If you tied a string around it so it would remain kinked, the hose would remain blocked. That's exactly what adhesions do. They hold the bowel in their kinked configuration.

judith20_webmd: I have dense adhesions on my bowel, observed during my TAH/BSO (total abdominal hysterectomy / bilateral salpingo-oophorectomy) for endometriosis. I have had severe abdominal pain and constipation since the operation. Could this be from the dense adhesions?

Dr. Wiseman: I have a PhD and am not a medical doctor. I don't want anyone to construe what I'm saying as being medical advice. She had adhesions already, and then she had this TAH/BSO, which means she had the uterus removed via an abdominal incision and had both tubes and both ovaries removed. By itself, that operation is well known to produce adhesions that could be problematic. It's well known that these kind of operations could lead to pelvic pain or bowel obstruction, which could mean total bowel obstruction or in milder form, constipation. The simple answer is yes. I would caution you because there are many other causes of pain and many other causes of obstruction, so you mustn't jump to a conclusion that these are adhesions. But you have to have a proper examination by a doctor.

al_pavy_webmd: And infertility? How does this happen?

Dr. Wiseman: Infertility -- there are several things that could happen. You have to understand how people get pregnant. Most understand the main part, but the inside part is like this. The ovary is a woman's store of eggs. Every month the ovary, or one of the two ovaries, releases an egg and it is caught by this catcher's mitt, called fimbria. The ovary sits in the abdominal cavity and is not connected to anything. It releases this egg, the egg jumps out, and the fimbria, which is the open end of the fallopian tube, kind of catches the egg and traps it within the tube. The egg goes into tube down towards uterus, where it is fertilized by the sperm. Several things could happen. This fimbria can only work if it's free to move around. Imagine in a baseball game that you only allowed the fielding team to stand still, and they could only hold their hand out in one position. They couldn't move it around to catch the ball if it came their way. There would be quite a few runs scored in such a game. Because the fimbria is tethered, is held down, is prevented from moving by adhesions, when the egg is released it can't be caught easily by the fimbria. If egg can't get into fimbria, then the egg can't get to the sperm, and you're not going to get pregnant. That's one way. Secondly, the adhesions could be so dense that they actually form a kind of barrier between the ovary and the fimbria. Even if the fimbria could move around, there's a barrier that the egg can't penetrate. That's the main way that adhesions cause infertility. The third way is that the fallopian tube can become kinked in a way similar to what we described for the bowel. If it's kinked, the egg can't go down in a normal way.

judith20_webmd: What is the latest treatment for adhesions?

Dr. Wiseman: I am sorry to tell you that there aren't really any latest treatments. Everything that exists has been around for a while. Really the things we have are only good to prevent adhesions or reduce them if you're going to have surgery. They all work in basically the same way but in different methods. The two products on the market in the U.S. for use in the abdomen and pelvis are Interceed (oxidized, regenerated cellulose) and Seprafilm (hyaluronic acid-carboxymethylcellulose film), and both are barriers. They are either fabric or a kind of a membrane which is placed at time of surgery over the place where adhesions are expected to form. What they do is stop one organ (the ovary) from sticking to another organ (fallopian tube), and the body takes a certain time to heal, between about three to seven days. And if we can protect the healing surfaces for about four to five days, then once it's healed, then they will no longer have a tendency to stick to one another. These adhesion barriers prevent adhesions between one surface and another. There's a third product in the U.S. used in spinal surgery. That product acts differently in that it affects the way cells stick to tissues, and it acts as a barrier to cells at a cellular level. It's as if you sprayed oil on a surface, and nothing could stick to it. It's as if you Teflon-coated the surface on a molecular level. That product is called Adcon (anti-adhesion barrier gel) and is being developed in slightly different format for use in abdominal and pelvic surgery. If the early results that we saw carry, I think this could be very nice. It's a little early to tell. That's close on the horizon.

There's another product close on the horizon in the U.S., and already available in other parts of the world: Intergel. This is a gel, and it's similar in consistency to KY Jelly. Basically the surgeon puts it in the abdomen at the time of surgery, and it keeps all the surfaces apart and kind of lubricates them and makes them slide over one another, rather than being able to stick to one another. There are some interesting results obtained with this, and it's currently going through FDA approval process. There's a product on the market in Europe called Adept that works in a different way. It works by keeping a lot of fluid, watery fluid, in the abdomen for a period of several days, and because there's a lot of fluid in the abdomen, it's believed the organs float around. Because of that, they can't stick to one another. I haven't seen any data from this yet.

Those are the kind of treatments that are around somewhere. There are several companies that are developing different things, but all work in pretty much the same way. There are one or two companies that have drugs that may even work on existing adhesions, but those are very early stage development here. We don't expect to see those available for at least five or six years, if everything goes to plan. Those are the kind of official things.

karla10_webmd: If I suffer with major infections following surgery, should I consider the use of Intergel?

Dr. Wiseman: Good question. There's two things here. First of all, is you suffer from infections, you have to ask why. Is it because you have some problem with your immune system? That's an important thing to address. As a general principle, any time you have an infection any of these materials, Interseed or Seprafilm or anything else that might come along, you should not use foreign substances and leave them in the body in the presence of infection. The reason is because it's well known that when you do such a thing, the chances of developing a clinically important infection are much greater. I don't want to single out Intergel or anything particularly. However, the question may have arisen. There was an FDA panel meeting several months ago concerning the approval of any particular product. There was such a meeting in January where this issue came up specifically in regard to Intergel, because the company had not fully answered that question as to what likely safety would be in that situation. Even if they would have shown that it was safe, I think everyone would agree that it would be prudent to caution use anyway. There were some additional questions to which I don't know what the answer was, but I believe the company concerned was attempting to address them, and I don't know how that will be resolved. The answer is threefold: Ask why you're getting these infections, caution against the use of any kind of thing when there's infection, and watch the space or the Intergel as to how the company will answer those specific questions that were raised at the FDA panel meeting. That's my answer. Ask the company.

judith20_webmd: Can you have a laparoscopy with adhesion removal and then use Seprafilm or Interceed to prevent new adhesions from forming?

Dr. Wiseman: That's done. That's done not infrequently. The only thing is, Seprafilm itself, you cannot use it laparoscopically because the physical make-up of the product does not allow one to insert it through the laparoscope except for one thing. My company is developing instruments that will solve that problem. If everyone got up in arms about it and called, we might get it developed sooner rather than later. The Seprafilm product, in its current form, does not lend itself to be used laparoscopically. Interceed does, although it's slightly difficult to be used although it can be and is used. Curiously, it is not approved for use in laparoscopy in the U.S., and despite that, about 60% of its use is in laparoscopy. To caution the questioner, even if you do that, no one would say or promise you that you have got a 0% chance of reforming adhesions. There is some chance that it will reform. It's not a perfect solution, but might work in some cases.

karla10_webmd: When it comes to adhesions wrapping themselves around the bladder, is there any way a doctor can determine that to be the problem before doing invasive bladder surgery?

Dr. Wiseman: The question is broad, because there is really no good way to detect adhesions non-invasively other than by doing surgery. There's no X-ray method. There's no ultrasound method or MRI (magnetic resonance imaging) method that can detect adhesions reliably and accurately enough to allow a doctor to say that. Sometimes you can see certain things on X-rays, and the main thing the doctor is going to rely on is probably the history of the person. If the person has a history of either abdominal surgery, or possibly multiple C-sections or infection, then the doctor should be suspicious that there may be adhesions. If adhesions aren't the cause of the problem, they will certainly be things that can complicate the surgery, and the doctor has to take extra caution in entering the surgical space.

judith20_webmd: Based on date, what is the percentage that my adhesions will come back after a laparoscopy to remove adhesions then use Interceed?

Dr. Wiseman: You have to consider each location separately. Let's imagine adhesions on an ovary. If 100 people -- and this has been done; I've published a meta-analysis to look at this question, and do some type of surgery on them and nothing else -- then there's a 75% chance that you will have adhesions at some point afterwards, let's say two months. Seventy-five out of 100 ovaries will have formed or reformed adhesions. If Interceed is used on that ovary, instead of 75 ovaries reforming adhesions, assuming the doctor uses product correctly, then the number is about 50%. We don't actually have good numbers on laparoscopy, because there haven't been too many studies. The number basically goes from 75% recurrence without anything, to 50% recurrence with Interceed.

al_pavy_webmd: What exactly are adhesions composed of?

Dr. Wiseman: Sugar and spice and all things nice -- really, you have to look at them at two stages of their life cycle. Step one in the early stage, when the two surfaces, let's say ovary and fimbria, stick to one another, the substance causing the sticking is made of something called "fibrin." Fibrin is really the long strands of a protein whose precursor, called fibrinogen, is found in blood. Fibrinogen is a protein which is not normally sticky. It circulates in blood, and when you bleed, everyone knows you get a clot. A clot is a network of fibrin that is formed because fibrinogen recognizes the blood vessel has been broken and it needs to be repaired. The fibrinogen is converted to fibrin which forms big networks which seal over the hole in the blood vessel. Entrapped in those networks are red blood cells, and that forms a cell. That's why blood clots are red. If you were to extract the fibrinogen, it would clot on its own and form a glob, which if you looked at it under a microscope you would see a network of what looks like tangled string. The string is sticky and sticks to itself. When you have a wound, even if there's no bleeding, you get an oozing of clear fluid. That's what happens in your body when you have surgery. This clear fluid, because it coats the wound, forms a congealed mass of fibrin, and the fibrin is the glue holding two surfaces together. That's the initial attachment. What's going to happen is that sometimes the body can come and dissolve away the fibrin, but sometimes it doesn't. When it doesn't, what happens is cells called fibroblasts, macrophages and endothelial cells come and they migrate into these fibrin clots, then start to produce blood vessels and something called collagen. Collagen, when it becomes more and more mature, becomes tougher, thicker and stronger, and now you end up with a fibrous adhesion. Collagen is the tough substance that gristle and tendon is made of. That's the similar stuff that comprises adhesions once they become mature.

One of the questions I get asked often is, if I had my choice of anything that could be done, what would I do? It all depends on the individual's circumstance. The doctor has to consider pros and cons. This is not the prescription. They can decide whether it's for you or not. If you're going to have any surgery regardless of whether you have adhesions already, if you can have laparoscopy, it probably is better, and if you're going to have a laparoscopy, make sure the doctor uses warm and humidified gases. They blow you up with gas to allow the doctor to put in a camera and surgical equipment. Sometimes it's cold and dry. The doctor should use powder-free gloves. The surgeon must make sure they get very good hemostasis. They have to control bleeding. They have to use very careful, delicate technique. They should use an adhesion barrier. I don't have any preferences, but probably I would use Interceed together with heparin. This is not approved with heparin. I would place some heparin on the Interceed. If adhesions were widespread, I might consider using Intergel. The doctor has to approve all of this. You can't go to a drugstore and do this yourself. Don't do this at home. If I knew I was going to have surgery, I would ask the doctor to put me on steroids for probably a month before surgery. There's some evidence that people who have steroids before surgery may do slightly better in terms of adhesions. I would use that in combination with other things I described. That's probably the best set of things I can think of right now. That's the best we can do at this point. You have to join the International Adhesion Society: http://www.adhesions.org

judith20_webmd: Are adhesions from endometriosis different than adhesions from surgery?

Dr. Wiseman: Good question. Really good question. The end result is the same. The substance of the adhesions is the same. The problems they can cause are the same. As with any adhesion, whatever the cause, the thing is that if someone has active endometriosis and they have adhesions, and the surgeon cuts the adhesions, not only do you have problems of adhesions, but if the endometriosis is active, still causing inflammation and so on, it increases the chance for adhesions to form. In that sense, it seems that, we believe -- we don't have good numbers -- we believe that that's the more severe case. The circumstances why they might form all may be different.

karla10_webmd: I know you covered a little on obstructions as I joined the chat, but I was wondering how we would know if we were suffering from continuing partial obstructions?

Dr. Wiseman: People know if they can pass bowel movements. You're going to have abdominal discomfort, nausea, constipation, different patterns of griping and colicky kinds of pains, and there could be fever. Doctors should know how to recognize obstruction. Because we have so few tools available to us, patients get passed from one person to another because they have to exclude other bowel diseases. There's no good answer to that. If you don't feel right, you aren't right, and we've got to figure out what the problem is and if it's possible to solve it. The doctor will know that this could represent partial obstruction. There's lots of information on http://www.adhesions.org. There's a message board there. You can write questions to me if you keep it kind of short, and don't give me three pages of medical history. We are trying to win money, so if anyone's just won the lottery, we could use some of that because we need to hire people. We have to do

Moderator: Dr. Wiseman, thank you for joining us today. WebMD members, please be sure to check the events calendar for other upcoming live events.

Dr. Wiseman: Thank you. I enjoyed it.

The opinions given by Dr. Wiseman are his and his alone. If you have specific questions or are concerned about your health, please consult your personal physician. This event is for informational purposes only.


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