Kenneth Peters: All right. Thanks, Alan. And thanks for the invite to speak about this topic, which as you know, is not an easy topic. But as you stated, we were at a consensus meeting. Dr. Badlani had developed this meeting. We all met at Wake Forest in Winston-Salem, and he had people from all over the world there, which was great. There were clinicians, there were researchers, there were support group members. And what was really nice about it is they invited our trainees, our fellows. So, they were part of this, and helped initiate the initial publications that came out of this. They had created several different working groups or subcommittees around phenotyping and biomarkers and patient-reported outcomes. My group was assigned to therapeutics. I wish I could tell you we found all the answers, but I can't say that, but it was an interesting discussion. And we just published that here in Neurourology and Urodynamics. So, you feel free to look up the article. But in the end, my overall impression was there's very little new, unfortunately. I think probably the most important thing in this disease state is phenotyping is incredibly important. And easy things are easy, and everything else is more challenging. And so, my personal feeling is, and we'll talk more about this in a sec, is that Hunner's lesion IC, I mean, that's what I call real interstitial cystitis. It's how it was first described. It's a true bladder disease for certain. It's pretty straightforward now, in my practice at least. And I think we do a really good job with it. Patients that have pelvic pain with voiding dysfunction, it's not so easy.
And I think that there's still... We have to keep harping on our clinicians and our trainees about evaluating the pelvic floor because I think the pelvic floor is involved in much of this kind of syndrome of pain urgency frequency. I don't think there's really any new medications to say, "Oh, you should do this." I think there's a lot of hesitancy about using pentosan polysulfate anymore for several reasons. One is the data was never that strong, and there's some long-term side effects that have come forward. And I think one thing that I've learned in my practice is we have to get out of our silos. We have to evaluate the whole patient, the whole mind, body, and spirit. And at my institution, we're fortunate we have a multidisciplinary clinic where we have urologists and gynecologists and pelvic floor physical therapists and pain psychiatrists and integrative medicine and colorectal under one roof. So, we look at the entire person to try to understand where triggers are, and see how we can make a difference. I always go back to this study from the National Institute of Health, the NIDDK. We were part of this consortium for many, many years. There was the interstitial cystitis database, treatment group, research network. We did a lot of clinical trials over the years, looking at many different treatments. And the only clinical trial that was statistically significant over a sham or a placebo was when we enrolled patients with interstitial cystitis. And we also had an arm of men with chronic prostatitis to either a therapeutic massage, like you're just going to get a full-body massage, or directed pelvic floor physical therapy in women intravaginal or men intrarectal myofascial release. And when we did this study, what we found is that the group who actually got the intrarectal/intravaginal massage, that group had a much greater improvement in their symptoms than the group who just got a spa-type massage.
We repeated that study in a larger cohort of women and found very similar outcomes. So, that really screamed to us that you could be away from the bladder and make people better. And I think the problem is once somebody is labeled with the term interstitial cystitis, people tend to keep focusing on the bladder. And I think that's why we've failed at finding new therapies, because if you have a therapy that only is supposed to work on the bladder, and you're enrolling patients who have other triggers, and the bladder is really just an innocent bystander in this whole pelvic process, then we're not going to be successful in managing patients. So, like in our hands, we do a lot for pelvic floor dysfunction. I mean, number one's evaluating it, actually doing an exam and feeling the levator muscles and seeing, "Are there triggers?" And if there are triggers, then addressing those. Some easy things to address is we use a lot of vaginal or rectal Valium. So, we'll prescribe Valium to be inserted there. We work with our pelvic floor physical therapists who are doing intravaginal or intrarectal myofascial release. They're teaching them how to use dilators or pelvic wands, where patients can do their own therapy at home to get those muscles to relax because those muscles are important in everything we do. They're how we urinate, how we defecate, our sexual function. And if they're tense and tight, it can lead to voiding dysfunction and chronic pain. We do a lot of transvaginal, and in men, transrectal, trigger-point injections into these muscles, using like ropivacaine and Kenalog, is what I use.
And when appropriate, we use Botox to force those muscles to relax. And probably, the newest thing in our practice we've been doing a lot of, and I was a skeptic when we got it a couple years ago, is something called SoftWave or a shock-pulse system. This is the equivalent of like lithotripsy of a kidney stone. And when you think back of the 1980s, when lithotripsy was being developed, the FDA appropriately said, "Well, if you could put something to somebody's skin, and send a shockwave, and break a stone, what happens to the rib? What happens to the kidney, the bowel, or any other organ it touches?" And really, what was found over the years, and there's lots of published data, and a lot of it is animal data, but there's human data too, is that if you hit tissue with a shockwave at the cell level, it activates genes that can improve blood flow, nerve function, and actually release stem cell attractants. So, it's used for joint pain. It's used to heal diabetic ulcers. And we have one that we're using more for the pelvic floor, the pudendal nerve. And this is something that we deliver, either as part of our physical therapy, or standalone treatments. And really, now, I feel like it's a very important part of what we do. We've been presenting papers on it, and we're just getting in front of the IRB to do a sham-controlled trial, but something that can really give people some prolonged benefit when it really works. When I mentioned at the beginning, like Hunner's lesion IC, I think it's very straightforward. I mean, these are the patients that have a visible lesion in the bladder.
And you wouldn't know this wasn't cancer, so you'd have to do at least a biopsy of that lesion. But Hunner's lesion IC is really how IC was first described. It's usually an older patient population, usually over the age of 45 or 50. It's rapid onset. It's not like somebody who was 20 all of a sudden now develops ulcers when they're 50. They get a marked reduction in bladder capacity. If you hydrodistend the bladder in these patients, the average capacity is like 350 cc under an anesthetic where normal's over 1000. There's very less systemic symptoms, all the fibromyalgia, the irritable bowel, chronic fatigue that we see in our other non-Hunner's lesions patients, less pelvic floor dysfunction. But for many years, I mean, my treatment for this has been cautery of these lesions, sometimes resection of them, and almost always patients felt better, but almost always the symptoms came back again, and so did the Hunner's lesions. And so, I found myself doing a lot of these, and the definitive treatment was a cystectomy in my hands. But I have to say, about 10 years ago, started using cyclosporine. There's a number of papers published now, and it's totally changed my practice. The patients that were miserable are so happy now. And I have had patients on cyclosporine for many years because what almost always consistently happens, probably 90% of patients, is you never get a Hunner's lesion back again, their pain goes to zero, and their functional bladder capacity will double or triple in the first couple years. And so, it's just low-dose cyclosporine.
We start at 100 milligrams twice a day for a month. We check renal function because that's one thing you got to watch for, and we monitor blood pressure because about 10% of the time, you could get an increase in either of those with cyclosporine. And then, after that month, after cleaning up the ulcers and doing that, we cut it down to just 100 milligrams a day. And if I had somebody on it for more than three years, I usually go down to 50 milligrams a day, and we can maintain benefit. So, for me, my worst patients I've ever had in my practice, in general, these are my happiest patients now, and rarely ever do a cystectomy. So, I just wanted to give that brief overview because I think it'd be great to have a discussion with you, Alan, about where we're at and where we should go. But these are my takeaways, I can't say, "Rock my world," from the meeting, but it was great to get all these experts together and have these conversations again.
Alan Wein: Great. That was a terrific summary. One thing that I noticed in going through the slides was that you, and I think it's a more appropriate term, call those changes in the bladder a Hunner lesion rather than a Hunner ulcer because really, it doesn't have to be an ulcer. And I think there's a lot of confusion. Can you go back to that slide that shows the cystoscopic picture? Yeah, that one. Now, does that bleed when you further distend the bladder, and then release the distension or not?
Kenneth Peters: Yeah, 100%. So, a Hunner's lesion, you should be able to see without hydrodistending. I could see it in the office. When you hydrodistend, what happens is often, that will split and tear. And what it does for me is it defines the area of the disease. So, if I'm cauterizing that area, I'm eradicating where you see that lesion right now, and anything that's shown itself after the hydrodistension of being kind of friable tissue.
Alan Wein: Yeah. So, if the patient comes in the office with typical bladder-centric lesions or typical bladder-centric symptoms, and the frequency, the urgency, which is really more pain-related or something than the fear of leakage, and you cystoscope them, and you see one of these, do you go right to cyclosporine or do you fulgurate, and then give them cyclosporine?
Kenneth Peters: It's a great question. I mean, if I see this and they have the typical symptoms, they always... What I do is I'll go to the operating room under an anesthetic, I will hydrodistend them to see what their anesthetic bladder capacity is. To me, that's prognostic. And we're also looking in a handful of them that we've hydrodistended after cyclosporine, I could actually see, even operatively, does their bladder capacity change, but then, we biopsy this because I don't know this isn't carcinoma in situ, so they all deserve a biopsy. And then, I'll cauterize whatever the affected areas are. My typical practice is I'll give them one cautery and not start cyclosporine because there are some people who do really well for a year or even two years, and don't necessarily get them back. But I'd say, the majority of the people within the first 6-9 months are back in the office again. And then, what I'm going to do is I'm going to do the same thing again. I'm going to eradicate those lesions, and then start cyclosporine right after eradicating them. I find it works best if you get them lesion-free and start it, as opposed to trying to treat it when it's fully showing itself.
Alan Wein: Now, how about if that same patient, but you scoped them, and they don't have a Hunner lesion?
Kenneth Peters: Yeah, there's a good question. I mean, before I would go down that route, obviously, I've already done an evaluation, a physical exam, I've assessed their pelvic floor. Because in my mind, if I could reproduce pain on a pelvic floor exam, and its pelvic floor dysfunction until proven otherwise. And I'll maximize treatment of that. And if they still have pain with bladder filling and relief with emptying, which really is the hallmark of IC, then I'll do more bladder-directed therapy. Not saying I wouldn't add something like hydroxyzine or, rarely, amitriptyline these days to their mix. Hydroxyzine, particularly if they have some seasonal allergies. But what I would do is I would maximize their pelvic floor treatment, and then reassess their bladder. In the old days, I used to hydrodistend everybody who had these kind of symptoms, and convince yourself you're seeing some glomerulations and, "Oh, that must be IC." But there is no data that shows that that's diagnostic of it, and so... But I do have some patients in my practice that actually do well with a hydrodistension and once or twice a year, that's all they need. So, I think if the pelvic floor isn't the issue, the bladder is, I would probably take them, do a hydrodistension, see what their capacity is, see how they respond to it. And then, I do have some patients I put on cyclosporine without Hunner's lesions, but that's the rare patient of having truly bladder-centric disease and a smaller bladder capacity under an anesthetic.
Alan Wein: And someone comes in with non-bladder-centric symptoms, but they do have the pain with filling and relieve by emptying, etc. They do have increased frequency. So, it's not just bladder-centric, but it's their entire pelvic floor. So, the first thing that you look for on the exam is basically tenderness on a vaginal and a rectal exam. So, if a patient comes in with non-bladder-centric symptoms, pelvic symptomatology, but also has the urgency, frequency, pain with filling, etc., what do you do with those people? Do you do the same routine, you cystoscope them to make sure they don't have a Hunner's lesion, which most of the time they don't, and then you go right to pelvic physiotherapy?
Kenneth Peters: I would say it depends, which I hate that, but it does. If somebody is 20 years old in my practice and has that, I'm not necessarily scoping them. I mean, seeing a Hunner's lesion in somebody who's younger than 45 or 50 is extraordinarily rare, unless there's some other indication, blood in their urine, or concern beyond just the bladder symptoms they're having. So, what I would do is I would do my pelvic exam, and if I can... And we were all taught, "You're doing a pelvic exam to look for prolapse, you're looking for cystoceles, rectoceles," but no one taught us to swing our fingers laterally and the pelvic floor muscles over the pudendal nerve. But that's what I would do and see, "Are there actually triggers?" So, my chart has very well documented, the four different quadrants and what the pain levels are, and what's it feel like over the pudendal nerve. Are there actual trigger points? And if there are, I would focus most of my treatment right off the bat on that, and tell them that I believe it's more pelvic floor dysfunction than interstitial cystitis. But most of the patients come to me, somebody already told them they had IC. So, sometimes, they're very protective of it, right? They're just like, "Well, I went to five other doctors who told me I had IC." I'm like, "But you're not any better." And I think reproducing their pain on an exam is really important because that way, they...
And you say, "All I'm doing is touching your muscle." And then, my next step, basically, is pelvic floor physical therapy, intravaginal Valium, maybe plus or minus SoftWave, if they can do it. And as an initial thing, and see how they do with that. And many people just get markedly better doing that, and getting them engaged in doing daily exercises and stretching and all that stuff. If they're not better, then I would consider things like trigger-point injections, pudendal nerve blocks, other things to help treat that. And if those muscles, if they get temporary benefit from that, but they feel good while we do it, then I'll try to move the Botox into the pelvic floor. And we've created this template that we use to inject the Botox and do Botox injections. And for some of those, it works really well, and others, it doesn't. So, a lot of it, unfortunately, still becomes trial and error. But you also got to think about the bowel and the uterus. I mean, could they have endometriosis? Do they have irritable bowel? Do they have any other pain triggers like fibromyalgia? This is where we're looking at the whole person and trying to figure out... It's usually not just straightforward one thing. It is if it's a Hunner's lesion. Everything else, it could be multiple things, including their life stressors. I mean, stress drives pain. And when I ask every patient, what makes your pain better or worse? And I say, "There's lying, sitting, standing, stress, make it worse." They always stop at stress, so-
Alan Wein: Yeah, stress.
Kenneth Peters: It is and it's for me too. I get back pain. If I get stressed out, I can feel myself tensing up my back. So, I think that it is really looking at that whole person, and trying to give them the tools in their toolbox they need to manage this. But as you know, I'm also a big neuromodulation fan, and we, just yesterday, enrolled our first patient. We have an NIH-sponsored trial on, basically, sacral InterStim for chronic pelvic pain. So-
Alan Wein: Good.
Kenneth Peters: .. pain is a primary outcome measure, as opposed to all the publications, including our own, that show pain can improve secondarily when you do it for OAB. We're doing it, enrolling patients just for pain. So, we have about 10 patients coming up that we're going to be enrolling and continue to enroll into trial. So, I'm excited to just see over time, and it's a sham-controlled trial. There's on versus off. We're trying different settings to see the impact. So, we'll see the impact of neuromodulation in that regard too.
Alan Wein: Yeah. The intravaginal Valium is a nice touch. I've never used that. It comes as a suppository? Or you go to manufacturing, or-
Kenneth Peters: So, you can get it compounded as a suppository. But then, it's compounded, so it's out-of-pocket expense. So, years ago, we actually measured diazepam levels in the blood, and we did a compounded suppository, or we took just the Valium pill you would swallow. We had them put a little KY Jelly on it and push it into the vagina or the rectum. And both of them got absorbed at a very similar thing. And just the prescribed pill is so much cheaper. It's like pennies. So, we usually will use that. Some people will tell me it doesn't dissolve, and then it comes out, and then we'll use a cream or a suppository, but probably 80% of the time, I just try to use what you would prescribe from the pharmacy.
Alan Wein: So, you just use a 10-milligram tablet-
Kenneth Peters: Yup. Yeah, but it can make them drowsy. So, tell them to make sure they take it when they're home, and see how the impact is for them, but it is something that is really a good adjunct, and again, it gives them one more thing at home to help manage their symptoms.
Alan Wein: Right. The miniaturized, I guess, it's really a miniaturized ESW machine that you use. Is that commercially available or did you have to jury-rig a machine that already existed?
Kenneth Peters: No, it is commercially available. It's FDA-cleared, and now, there's actually a code that you could bill the insurance company. Before, it was all cash-pay stuff. Now, the code isn't getting paid so well yet, but they have a code for treatment of muscle spasm, and there are different ones on the market. This is the original kind of lithotripsy, the actual spark plug, which I think has the best data. And there's fascinating things that have been... There was, just recently, a publication for, in cardiothoracic surgeons, where at the time of open-heart surgery, they randomized patients to do that shockwave to the heart, or they just laid it on and didn't turn the machine on, and they followed them for a year. And the group that got the shockwave showed improved heart function at the end. And the thought is because of its impact on improving blood development of new blood vessels and nerves, and that's why you don't... Most patients feel better right after a treatment. I've done it to myself, but it's really, if it's going to work, it's working on a cellular level. And it's 10-12 weeks later, you're going to really get the most benefit. So, we do it for six treatments, but what we're looking for is that 12-week, 16-week follow-up. And I think doing the sham study, we're getting ready to start, put a little more signs because I'm always show-me-the-data kind of person that's what we want to prove.
Alan Wein: Now, do most physiotherapists have that in their repertoire?
Kenneth Peters: No, I mean... So, physiotherapists and podiatrists are probably the most common people out there that have those machines. We have two of them as part of our program, and we do it independently with our APPs, but then the physical therapists will also use it as part of one of their tools. And they were a little skeptical when we first got it because it felt like it was replacing them a little bit, but I think they see a great value in it too. So, having that available, I think is one more thing to be able to offer patients. I think the more data we get to support it is going to make it easier to become more mainstream.
Alan Wein: Yeah. I mean, you have this all set up for a routine. Everything is vertically integrated. What would you suggest to a person in practice, sees one of these patients, they have generalized pelvic tenderness, lower urinary tract symptoms as well? When you send them to a physiotherapist, what exactly do you tell the physiotherapist, who may not be very familiar with IC, whether it's non-bladder-centric, whatever? I mean, what do you tell them? Do you give them any specific instructions? I mean, I have that problem here in West Palm Beach.
Kenneth Peters: Yeah. So, it's so important to physical therapists, right? Because most physical therapists who consider themselves pelvic physical therapists are teaching Kegel exercises for incontinence.
Alan Wein: Right. Yeah, exactly.
Kenneth Peters: And that's the opposite of what you want to do, right? These muscles are already tense and tight. So, it's all about relaxation techniques and the physical therapists you want to seek out are ones that have actually been... I mean, there's a certification now for pelvic floor dysfunction because part of physical therapy is external, but internal work. So, much of the important physical therapy is done just as if you had a muscle out in your neck, and you went to a massage therapist, and they're untwisting the muscle. They're doing the same thing intravaginally or intrarectally, in my men with pain, and in a very therapeutic way. And then, they empower... Then obviously, they're giving them breathing exercises to relax. They're giving them stretches to do at home. And most of the patients will then, ultimately, go home with a wand that they could use vaginally, or, my guys, use rectally, where they can do their own pressure points on those internal muscles to focus on relaxing. And then, we augment that with the Valium. We do guided imagery.
We work with our integrative medicine people with acupuncture and stuff. So, again, we're trying to touch the whole person, and then having our pelvic pain psychologists, and just helping them on what kind of life stressors they are, how to manage it, how to live within the constraints they have, and we find is incredibly helpful for patients too. But we didn't always have this integrated system. It started with me and my APP just reaching out to other people in other disciplines for help and who had an interest in it, which ultimately created a little network, which then, ultimately led for us the ability to build a center with all of that under one roof. And really, it's like, "Build it and they will come." We've seen patients from 40 states and seven countries in our center. People come, they'll spend a week with us. We call it a mini retreat, where they're basically getting their whole body evaluated.
Alan Wein: Yeah. So, that's very valuable information that I'm sure that people just haven't thought about. And it is part of the whole patient philosophy that you espouse, which obviously has been very successful. But listen, thank you so much because all that is great advice. And I would encourage everybody to read actually the article because it's really well constructed and well done, so-
Kenneth Peters: All right. Well, thank you, Alan. It's always great talking to you.
Alan Wein: Thanks so much. Take care.
Kenneth Peters: Bye.