Interstitial Cystitis Network (http://www.ic-network.com)
Meet the IC Expert Guest Lecture Transcript
Date: October 16, 2001
Topic: An Evening with Dr. Christopher Payne, Stanford University
Moderator: Jill Osborne, ICN Founder
We would like to thank our sponsors, AKPharma (makers of Prelief), and Farr Laboratories (makers of CystaQ) for underwriting this special event.
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<icnmgrjill> It is my pleasure to introduce Dr. Christopher Payne of Stanford University Medical Center. Dr. Payne was recruited to Stanford University in August 1993 to direct the new program in Female Urology and NeuroUrology. He completed his urology residency training at The Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania and subsequently completed a fellowship in Female Urology, Urodynamics, and pelvic reconstructive surgery at UCLA in 1992-1993. Dr. Payne is nationally recognized as a leader on issues in female urology having served on NIH advisory panels on urinary incontinence and interstitial cystitis and a member of the panel which defined bladder research priorities for the 21st century at a meeting sponsored by the Office of Women's Health Research. He is a current member of the medical advisory board for the Interstitial Cystitis Association. He has published numerous articles and book chapters on urinary incontinence and surgical reconstruction of urinary tract fistulas. He has been an invited faculty member at both international and national meetings and addressed the plenary session of the American Urological Association meeting in 1998 on the non-surgical treatment of stress urinary incontinence.
Dr. Payne's practice is concentrated in three areas: 1. Surgical treatment of urinary incontinence and pelvic prolapse, 2. Clinical trials in interstitial cystitis and non-surgical treatment of urinary incontinence, and 3. Urodynamic evaluation of complex bladder dysfunction.
Dr. Payne is greatly appreciated as a physician who is truly compassionate to his IC patients here in California. He is involved in several national and local research studies and has a truly "balanced" perspective on the many treatment options of IC and will be sharing some of his thoughts.. with us tonight!
<icnmgrjill> Welcome Dr. Payne!
<drpayne> Nice to be here. Thank you!
<icnmgrjill> Let's go a head and begin Dr. Payne's first presentation.
------------------ Presentation on BCG begins ---------------------
Stanford University Center for Female Urology and Neurourology has been selected to participate in the Interstitial Cystitis Clinical Trials Group (ICCTG). The ICCTG is sponsored by the National Institutes of Health. Stanford is the only site on the West Coast; other participating centers include University of Pennsylvania, New England Medical Center, William Beaumont Hospital, University of Oklahoma, University of Maryland, and Queen's College. This group designs and conducts scientific clinical trials into new methods of treating IC.
We are very excited about joining the group as it is intended to be a long-term project to test new therapies as they develop. Our current involvement runs through February 2003 after which we will be considered for continuation based on our performance in the research. The Stanford site includes Santa Clara Valley Medical Center in San Jose.
The group's next study is currently underway. The project is investigating the use of bacillus Calmette-Guerin (BCG) instilled directly into the bladder. BCG is a relative of tuberculosis that does not typically cause infections in humans. It does stimulate an immune response. BCG is proven to be effective in reducing the risk of recurrent bladder cancers. It has not been proven effective in treating IC.
A pilot project showed a 60% response to BCG compared to 27% in the placebo group (Peters K, et.al. J Urol 157:2090-4, 1997). While encouraging, this small study did not reach statistical significance. A follow-up article reported 8/9 initial responders maintained their improvement for more than one year (mean follow-up 21months) and 8/12 patients crossing over from the placebo group responded to open-label administration (Peters K, et. al. J Urol 159:1483-7, 1998).
Based primarily on this data the ICCTG has decided that BCG is the most promising new agent on the horizon and developed a large-scale trial to determine its efficacy. If you are interested in learning more about this study please contact our research coordinator, Debbie Clay, at 650-724-1753 for more information.
--------------- Presentation Ends ------------------
<icnmgrjill> Dr. Payne, BCG is a relatively new treatment and many patients don't know about it or have it confused with elmiron. Can you tell us what BCG is??
<drpayne> Let's start with what it is. BCG is bacillus calmette guerin. It is a live organism that is related to tuberculosis.. and it does not typically cause infections in humans the way that tuberculosis does, but it can create an inflammatory or immunologic response.
<drpayne> For many years BCG has been used throughout the world as a vaccine against tuberculosis because, by injecting it into the body, it will provoke an immune response. Later, if the body is exposed to TB, the immune system is ready to fight it off and this person is less likely to become sick. This has been known for many years.
<drpayne> Later, researchers in cancer came up with the idea rather than injecting into the skin, injecting it into a tumor, the body might get a little confused and create an immune response to the tumor. Now, that was never terribly successful for most cancers but it has been tremendously successful in treating superficial bladder cancer and it is our number one treatment for treating superficial bladder cancer and for prevention of recurrence (note, it is not injected but instilled into the bladder as a liquid). Most of all, it is used for the prevention of recurrence.
<icnmgrjill> How did it first get used with IC... because we know that IC isn't cancer?
<drpayne> Good question. It was just by chance that it was used in IC initially. Those patients got better and that doctor tried it on a few other IC patients who got better. It was used in a patient that either had IC and cancer or was felt to have cancer that later didn't have bladder cancer but had IC instead.
Because of this report, a prospective randomized double blind study was performed in Detroit by Ken Peters and Diokno.
<drpayne> This is an important study mainly because of the high quality of the design in that they used very carefully described patients, all of them had cystoscopy, distention, urodynamics. They also used very careful evaluation tools. They used bladder diaries and symptoms scores... validated symptom scores.
<drpayne> The design of the study was one of the best designs ever used on IC. The only drawback was that the number of patients used was very small. My memory is that there were only 15 patients in each group. In the group treated with BCG, they had a 9 out of 15 had a very good response. In the group that was given placebo, it was only 4 out of 15. So, that was actually not statistically significant but it was certainly very promising.
<drpayne> Then, there was a subsequent report for patients who got placebo who then went on to use BCG. Twelve elected to have the drug and 8 out of the 12 had positive results. The thing that is most interesting and most different from other IC treatments was that when they did the long term follow up of 20 months, almost all of the patients who responded initially continued to response. So it seemed that this treatment was much more durable than other treatments used. Again, it's a small number of patients.
<drpayne> The ICCTG decided that a larger national study should be done and that it was worth spending your and my tax payers money on it. The study is being done at research centers across the US. Jill will have more info on the other research centers as well as one center in Canada.
<icnmgrjill> Is Stanford now accepting patients for the study?
<drpayne> Yes, that's correct. All of the centers are now open and will enroll patients.
<icnmgrjill> How should a patient contact your group if they are interested??
<drpayne> Our research coordinator is Debbie Clay and her phone number was in the presentation above.
<icnmgrjill> What should a patient expect if they choose to participate??
<drpayne> In our office, they will have a history, physical exam, blood work. If they qualify, they will then be randomized and will be one treatment a week for six weeks.
<icnmgrjill> Does it cost anything??
<drpayne> No. The taxpayer dollars are paying for all of the costs of the study. The NIH is sponsoring the study completely.
<icnmgrjill> Mel asks "What is the risk of developing infection after a BCG treatment. She says that she's talked with a few patients who seemed to have more UTI's??"
<drpayne> We are not aware of any risk of increase urinary infection from BCG treatments. Most of our experience is with cancer patients and probably hundreds of thousands of cancer patients have received BCG without that showing up in studies for cancer as a significant risk. It's always possible that IC patients may be different, but we don't see that as a risk.
<icnmgrjill> Are there any other risks that you are aware of??
<drpayne> Yes.. there are many risks of BCG and this study has gone through the FDA and through all of the institutional review boards of the institutions participating. All of them have created a very long, detailed informed consent forms because of the risk. When BCG first became commonly used, we did not think that this organism could cause infection. That is clearly wrong. It can cause infection. When I was a resident in the mid 1980s, some cancer patients died from BCG given in the bladder. Now, our feeling is that in most cases severe infections occurred for a few specific reasons. #1: The treatment was given right after the bladder tumor was removed or given traumatically when a catheter created bleeding and the BCG was allowed to get right into the bloodstream. #2: the patient was immune system compromised either because they used steroids or had another immune deficiency/disease.
<icnmgrjill> Are you aware of any IC patients who have had this problem?
<drpayne> Of the patients that I have known are here at Stanford or in this area, I have not known of any serious infections or treatment with antituberculin drugs. In the original study group, there was one patient who did drop out of treatment with persistent flu like problems. That one might reasonably account as due to the treatment and it did take a couple of months to resolve.
<icnmgrjill> Let's put this in perspective with the other IC treatments.. because I'm sure that we have some newbies here. Would you consider this a treatment for a patient who was just diagnosed.. in other words.. is BCG a first line treatment?
<drpayne> No. I think that all of the investigators who designed the study feel like the patients who will be recruited will be heavily skewed towards severe, chronic patients who have tried just about everything. It will be a difficult patient group. We don't anticipate having anyone who is early on in the onset of IC. This is a negative... because this may put some bias into the study. But most of the group feel that BCG should not be offered until patients have tried some of the other standard treatments. The inclusion criteria specifically says that patient must have tried another therapy for three months before trying this.
<drpayne> If this study has a tremendous result and patients did great and tolerated it well, then you might envision a second study where you give it to patients early on. But, right now, we're not anticipating enrolling early patients.
<icnmgrjill> Let's move on to the second topic.. which is hormones and IC. I understand that you'll be beginning another research study.. but can't comment in depth about that just yet. But, can give us some ideas of what you'll be doing??
<drpayne> What we have is a pilot project grant from the ICA to try to investigate whether female sex hormones influence IC symptoms. We're trying to study the younger patients who are not on hormones but who have ovaries.. etc. and who are experiencing changes in their symptoms and whether or not those symptoms correlate with hormone levels.
<icnmgrjill> Are you recruiting for that study?
<drpayne> Yes, the same number above for patients who would like more info.
<icnmgrjill> I understand you can't say much more at this time on that study but this does bring up a very important topic about hormone replacement. Some patients who are on hormone replacement seem to struggle. One woman from England submitted a question asking if you have ever encountered estrogen patches causing IC symptoms or bladder flares. Any comment??
<drpayne> I would say that I have not noticed anything consistent in what different patients tell me about the various methods of hormone replacement and how they effect their symptoms. For the individual patient, the type may make a difference but we're not seeing a consistent response. That's the problem when you talk with patients one on one versus doing a large study where you can pick up a pattern. So what we're trying to do with individual patients is to try to see if bladder symptoms are related to hormone levels in the blood.
<drpayne> An example in a disease where it has been studied better - migraine headaches. You can identify patients who get pre-menstrual migraines and they have very abnormal estrogen levels during that time so we know that estrogen levels go up and down but these people have the bottom drop out. So, if we do a study that shows that patients flare before their period but their estrogen levels are normal, then it's something else about the menstrual cycle that is provoking symptoms. But, if the estrogen or progesterone levels vary, then we might have a clue as to what is happening.
<drpayne> So we have to measure the level to see if it's abnormal. This has never been done before and that's what we're going to do, courtesy of the ICA pilot study. Patients near us can participate... but for patients who are farther away, we can give their physician advice on when to have the blood drawn, the methods to use, etc. etc.
<drpayne> It's kind of interesting that here is something that effects mostly women. We know that one of the things that makes women different than men is hormones. We have ways of measuring hormones and yet we don't do it. Usually doctors like to measure things because it makes us feel all comfortable that we know what is going on. For some reason, we don't do that in IC even if the patient says it gets worse during their cycle.
<drpayne> If our results are positive it means all kinds of interesting things about new research, new treatments. If results are negative, we can say that it's not related to hormones and we can stop thinking about that.
<drpayne> The point is that in every aspect of IC, we have to do good quality studies with adequate numbers of people so that we can say this is important, or not important, so that we can move on to more productive research. Let's answer this question now. The only way this will happen is if more groups get together to do studies and more patients participate. You have to have BIG numbers. We can't have studies with 10 or 15 patients in them. We need larger studies that have hundreds of patients.
<drpayne> A good example was the Elmiron Dose Ranging Study completed last year that had more than 300 patients participate in that study. It researched a clear conclusion and ended one point of discussion that we don't have to think about anymore.. that high dose of Elmiron didn't work better than lower doses. The BCG study is supposed to have 250 patients and should give us an answer, yes or no. I think these are really important. It is frustrating for me as much as it is for patients to say "I don't know.. I don't know." We want to be able to tell you what we do know.
<icnmgrjill> Ruth had a question.. What's your current view of hydrodistention as a diagnostic tool?
<drpayne> We just submitted an abstract to the American Urological Association (AUA) as hydrodistention as a treatment. I see three roles for hydro: (1) diagnosis, (2) prognosis and (3) treatment. The questioner wants to know about diagnosis and for diagnosis, I think that it is fair.
<drpayne> Cystoscopy is a good test in that it allows us to rule out other diseases but that, for many patients, can be performed in the office IF you don't do a hydrodistention. Some IC patients would even use anesthesia for a simple cystoscopy but many can have an office cystoscopy and not be distended. I think that cystoscopy is important but that hydrodistention is not particularly important. Why? Because we don't have good objective data about what glomerulations mean. Papers have been written that criticize hydrodistention for being falsely negative and falsely positive. I treat many of my patients without ever doing a hydrodistention. They tend to be patients who have milder disease and respond to one of the treatments that we offer. But I also do hydrodistentions frequently in patients who have a confusing picture and where it doesn't seem like typical IC. I'll do it when patients have hematuria (blood in the urine) or patients who don't respond to a few courses of treatment and patients who have fairly severe symptoms.
<icnmgrjill> So.. how do you diagnose IC?
<drpayne> History and physical exam. I think that an initial patient needs a good history, a good physical exam and a urinalysis. And, for some patients, if you have a good history then there's almost nothing else it could be. I also insist on a bladder diary so that we can really see the volume that they urinate when they go to the bathroom. For these patients, if everything falls into place, I may offer them treatments right there at the first visit.
<drpayne> The other two tests that we consider useful are urodynamics and potassium sensitivity. I often combine the two at one time. The urodynamics helps us understand what's happening in the bladder and the urethra when the patient is complaining that they are having pain or that the bladder is full. Then we can manipulate the bladder to see if we can change that. That's when we do a KCL test and a lidocaine test. We do the lidocaine after the KCL so that if they had pain from the KCL, the lidocaine will get rid of that. This will also help us to see if the bladder will improve with an anesthetic agent.
<drpayne> One of the things that I would like to say is that I get really frustrated to see a referred patient who has had symptoms for five or ten years and has never had a hydrodistention. I don't think that people should be strict and say that a test is worthless. They all have some value. We don't have one test that is a gold standard for IC so we have to gleam information from several tests. My philosophy is that each step of the way, I need to gather useful information on my patients condition until I feel that I have enough information to treat that patient. Initially that may just be the history and physical exam. If I treat them and they don't get better, I may do another test and then treat some more and then do another test, etc. I think that you have to treat each patient individually and try to do the best for that patient.
<icnmgrjill> Sheila asks if you have any thoughts on the use of pre sacral neurectomy for IC?
<drpayne> #1.. no personal experience, #2. I'm not aware of any literature that suggests that it would be an effective or safe treatment. So, if someone would propose a study and outline why it would be a good idea then fine. But I'm not aware of any literature supporting that.
<icnmgrjill> Do you believe that many years of urethral dilation can cause damage to the urethra???
<drpayne> Well, it probably depends upon to what degree the urethra is dilated. Under anesthesia, there was a protocol to dilate to 40 French. That's about 13-14 mm.. or 1/2" in diameter. I would certainly say that would at least cause inflammation and possible damage but I don't think that there is any data about this. Most people dilated in the office aren't dilated that much and I doubt that it's likely to cause damage.
<icnmgrjill> Under what circumstance is a dilation appropriate. Twenty years ago many patients were given dozens of dilations as an answer to their frequency/urgency. We now know that it's not a treatment for IC but is it appropriate in some circumstances???
<drpayne> Most of the people that I do dilations on are people who have difficulty emptying their bladder and some of them have that after having surgery and some just have it. We'll usually try at least one dilation to see if they feel an improvement and if we can measure that they empty better after being dilated, then we may do this further. The other group are those with isolated urethral symptoms. They have only urethral burning with urination and usually need anesthesia for that. I don't like to do that in the office.. because that is too much for them.
<icnmgrjill> Ruth asks.. "Do you have any experience with alternative therapies.. such as aloe or quercetin??"
<drpayne> I don't have any experience with those. If patients say they want to do something like this, I tell them to do the same thing with any of the meds I prescribe which is not to do anything else while they are doing the new thing. Do one thing at a time! I also ask that they keep a bladder diary to measure if their frequency and bladder symptoms are getting better. This way, we can evaluate if it is really working for them. I'll also ask them about side effects.
<drpayne> It is important to consider an alternative with the same seriousness that we do other prescriptions. I don't think we should exclude alternatives. Given our relative lack of good treatments, there is no reason not to try some of these alternatives also. I would say that acupuncture, for instance, has helped a lot of people but that very few patients can go off the acupuncture. In other words, they are having success while doing the treatments but as soon as they stop their symptoms may come back.
<icnmgrjill> Are you doing pelvic floor work in your practice??? What relationship do you see between IC and PFD, if any??
<drpayne> We treat a lot of patients with PFD. We have a therapist who comes into our clinic one day a week to do these treatments and we also have a group of therapists in our area who have an interest in pelvic pain and the ability to treat these patients.
<drpayne> Now, as to the specific relationship between PFD and IC, I think they are separate problems that sometimes occur together. But, I've seen many patients who have been diagnosed with IC who I think don't have IC. They have only PF pain. And, I see other patients who have terrible IC who have no PFD. Of course, there are also people who have both problems. I think that they should be looked at separately and treated separately.
<icnmgrjill> Have you seen long term success with PFD therapy?
<drpayne> Absolutely. There are many patients who are enormously better, and stay better, after PFD.
<icnmgrjill> Shawnda asks "How come I stay in so much pain.. all the time. I stick to my diet. I do my meds. I've had bladder distentions but nothing has worked."
<drpayne> Well, this goes back to the comments we made earlier when we were talking about diagnosis. When we start out, we try a treatment. If they don't get better, we gather more information. So, an example is PFD. Maybe I wasn't thinking about it during the first exam or maybe I missed it. So, we repeat the exam and try other tests to make sure that we are treating the right thing. And then we have to acknowledge that for some patients, they don't respond to treatments and we try to get a pain specialist involved. We might also get a second opinion with someone who can take a fresh look at the problem.
<icnmgrjill> Lisa asks about Interstim?? Do you do them??? Success rates??
<drpayne> Stanford was one of the three centers that did the pilot study that Medtronic sponsored and that has been presented at national meetings. The three centers did show a very good response but this was only a pilot study looking at test stimulation, not implants. The results were very promising. We have implanted four or five IC patients who have done very well.
<drpayne> This treatment, more than others, need careful studies with long term follow up. You can't use the standard design for a research study with a placebo because it's not ethical. You're implanting something in the body. So you're left with certain biases and other factors that are hard to control for. We really need long term follow up before we get super excited about this. I will say that this is a totally different treatment than any of the other things out there so it truly offers some hope for patients who are truly refractory. That's how I feel about BCG too. The fact that a patient may have failed other therapies doesn't mean that they will fail this because they are truly different treatment modalities.
<drpayne> The other point is that interstim has been a phenomenal treatment for other patients who are really difficult, such as patients with severe urge incontinence that years ago, we'd be doing a bladder operation on. These patients can respond dramatically to interstim. Whether it will be dramatic for IC patients is another deal. It's novel, different and testable.
<drpayne> One of the problems that I've experienced is that patients that I thought were ideal for various studies didn't respond to Interstim. So, it is hard when a patient that I had hoped it would work well with... that it didn't work. That's the nice thing about having a trial stimulation because you can test that without doing an implant.
<icnmgrjill> Lisa asks.. "Do you encounter infections of the paraurethral glands??"
<drpayne> Well I know that that is a theory but I would say that I don't recognize that in my patients. Right now, I don't think that that is a common problem but I'm open to someone proving me wrong.
<icnmgrjill> Do you do pudendal nerve blocks??
<drpayne> No, but I do use an anesthesia pain team that may do that. I don't do that as a urologist.
<icnmgrjill> Do you think that Interstim works with PFD?
<drpayne> Yes.. When myofascial therapy doesn't work, they may be a good candidate to interstim. Myofascial therapy and massage should always be a first line treatment for that.
<icnmgrjill> Last question of the night... Are you taking new patients???
<drpayne> Yes, not only am I but I have an excellent Physician Assistant (Megan Squibb) who is also taking new patients. She does many of the IC therapies. We have a really good group at Stanford. We also have a PhD in Medical anthropology interested in doing IC research who has received an ICA Pilot grant to do her work. Her name is Kathryn Azevedo and she is researching socioeconomic aspects of IC.
Interstitial Cystitis Clinical Trials Group Press Announcement - BCG Study
Dr. Payne's Contact Information:
Dr. Christopher Payne
Department of Urology
Stanford Health Services
300 Pasteur Drive, S-287
Stanford, CA 94305-5118
For Study Information - (650) 724-1753
Books & Resources That You can Purchase:
The Interstitial Cystitis Survival Guide By Dr. Robert Moldwin $13.00/$11.00 for ICN Subscribers
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