August 23 – August 27, 2010

New ICHelp YouTube videos
from the conference

Toronto, Canada

In August the ICA and the Pelvic and Sexual Health Institute (PSHI) presented the findings of the ICA Complementary and Alternative Medicine survey at the joint meeting of the International Continence Society and the International Urogynecological Association in Toronto.

IC studies at this meeting were numerous but many were available only as abstracts to be read. That is likely a reflection of urogynecology practice today, which is focused mainly on surgery for incontinence and prolapse, so we need to work hard to educate urogynecologists about IC and its treatment.

Many of the IC studies here were on research we've already reported on for you about sacral neuromodulation, botulinum toxin (Botox) injection in the bladder, steroid injections into Hunner's lesions, and oral dextroamphetamine. Nevertheless, there was also new and intriguing IC research.

CAM Use Among IC Patients

The ICA/PSHI poster was based on the results of the ICA’s 2009 Complementary and Alternative Medicine (CAM) Survey and statistical analysis and perspective from ICA Medical Advisory Board member Kristene Whitmore, MD, nurse practitioner Amy Rejba Hoffmann, CRNP, and statistician Anand Bhattacharya from Drexel University in Philadelphia.

The survey proved to be the largest ever of IC patients presented in a scientific study. You read about the overall survey results in the Summer 2009 issue of ICA Update. But for this poster session, we analyzed only the answers from the 1,982 respondents who said they had a definite IC diagnosis to help us zero in on therapies that might really have an effect on IC. Then, we applied statistics to determine which therapies a statistically significant number of IC patients thought were helpful and which weren’t. What’s more, statistics helped us look at the differences in what helped IC patients who had been diagnosed a short time ago compared with those who had had IC for a long time.

That analysis confirmed some things you already know but also produced some surprises. The CAM therapies that you said work best include heat or cold, diet, many mind-body techniques that are now used in pain management, and a few supplements.

Surprisingly, those supplements included only one we knew to be popular among IC patients, Prelief, and also included probiotics, fish oil, and vitamin D. None of the herbal therapies made it to the significantly helpful list. Some of the supplements that fell into the statistical gray area for all the respondents worked better for those who had had IC for a relatively short time.

Another surprise the statistics showed us is that, although many of the CAM therapies work better for those who have not had IC for a long time, many patients diagnosed a year or less ago have not tried them. Somewhat more than a quarter have not tried diet or physical therapy, which are recommended in the American Urological Association’s preliminary IC clinical guidelines, and nearly half have not tried any other type of CAM therapy.

Half the patients said they had a doctor recommend a therapy, showing that doctors are interested in CAM, too, but apparently, not enough of them are making the recommendations early, when CAM therapies, such as diet, seem more likely to help their patients.

Interestingly, there were therapies that came up unhelpful - that is, a significant number of patients who tried them thought they didn’t work. That runs counter to the idea that the placebo effect is so strong that just about anything patients put their faith in will do something for them.

These results show that there is some wisdom of the crowd. You’re not usually swayed by the hope that something will work, and the most popular “CAM” therapies are now becoming accepted mainstream treatments. Dietary modification, for example, has long been popular among IC patients but was not accepted by some of the medical community until just recently. Of course, this survey can’t prove what works, but it can help clinicians give patients some helpful pointers, and it can show which CAM therapies might deserve some more formal study.

Many doctors, physical therapists, nurse practitioners, and patient advocates stopped by the poster to study it, ask questions, and give their feedback. In fact, one physician in the Multidisciplinary Approach to Pelvic Pain research network remarked, “This is a good study!” Go to the ICHelp YouTube channel to view coauthor Hoffmann’s presentation talking about the ICA/PSHI study and how she is using the findings in her practice.

Missed the published report about the survey? Order a back issue of the Summer 2009 ICA Update.

More on CAM – Acupuncture, Honey Instillations, Hydrogen-Rich Water

Another intriguing CAM study showed that acupuncture at the sacrum eased symptoms in rats with irritated bladders. The new study looked into how it might work. Acupuncture eased bladder muscle spasms and also reduced inflammation in bladder tissue. Another animal study looked at the potential of honey instillation (don’t try this at home!) to reduce bladder inflammation and mast cell activity. Honey seemed to have some protective effect on bladder lining cells, and it inhibited mast cell degranulation (the process of spilling their contents, which can result in allergy symptoms, inflammation, and pain). A controlled, randomized trial tested the effects of “hydrogen-rich” water on IC patients and found no significant effect, although some patients improved.

IC in Men

Diagnosis of IC in men got some research attention at this meeting. One group of clinicians reviewed the records of 147 men who underwent cystoscopy and hydrodistention. Fifty-six percent got an IC diagnosis by “NIDDK criteria.” The mean lead time to diagnosis was 2.5 years. Although IC is not being diagnosed today by those old criteria, which treated glomerulations as diagnostic, men are indeed underdiagnosed. The symptoms that were common in the men when they came for treatment certainly fit the IC picture: 84 percent had urinary frequency, 63 percent had pain in the bladder area, 61 percent had urgency, 49 percent had bothersome nocturia, and 41 percent had pelvic floor pain. In addition, 74 percent had painful urination, 51 percent had testicular or penile pain, 26 percent had “chronic pelvic pain syndrome,” 24 percent had benign prostate enlargement, and 41 percent had urinary tract infections. Like women with IC, most of the men (81 percent) had conditions often associated with IC. Forty-one percent had gastrointestinal complaints, 37 percent had anxiety or depression, 34 percent had chronic back pain, 23 percent had chronic joint pain or neuropathy, and 9 percent had migraines.

What Might Cause IC, New Diagnostic Tests

A number of studies were aimed at uncovering what might cause IC and new ways of diagnosing it. One used a very new technique to look in urine for tiny amounts of the genetic material RNA related to genes that are more active in IC patients than in healthy people. The team found RNA markers of distinctive gene expression in IC patients with Hunner’s lesions but not in other IC patients. On the other hand, another team, which previously identified some 28 micro RNAs that were different in IC patients than in controls, zeroed in on one micro RNA called miR-199a-5p. This micro RNA seems to play a role in how “tight” bladder lining cells are and may be the key to the “leakiness” of the bladder lining, thought to be a characteristic of IC. Another study of the workings of the IC bladder lining linked inflammation under the lining, high rates of bladder lining cell death, and low levels of proteins that bind the cells together and help form the barrier. One protein in particular, E-cadherin, was low in IC patients, and low levels correlated with pain scores.

The concept of phenotyping has been talked about a lot lately in IC, and one study here introduced a new IC phenotyping approach. It characterized IC patients by their degree of pain, looking at the differences between those with mild to moderate pain (pain scores from 0 to 7) and those with severe pain (scores greater than 7). Patients with the lower pain scores tended not to attribute their IC to any specific cause. Those with higher pain scores could often attribute the onset of their symptoms to an acute bladder infection or to surgery or trauma to the pelvic area. Patients with severe pain were less likely to have benefitted from hydrodistention, and had more problems with voiding, rather than urine storage than those with less pain. IC also had a greater impact on the ability to work in patients with high pain scores. It may be that when some severe event kicks off IC, it stimulates local or regional pain pathways in a big way, which carries forward in the degree of chronic pain.

Sacral Neuromodulation

 One treatment study looked at sacral neuromodulation in a way that has never been done before. It analyzed how irritable bowel syndrome (IBS) occurring with IC affected the treatment’s outcome. The researchers looked at the records of 79 IC patients who tried sacral neuromodulation, 25 of whom also had IBS. The IC patients with IBS had more pain at the outset, and outcomes of treatment were not as good when patients had IBS or higher pain levels to begin with. Over the long term, patients without IBS maintained a better response to treatment than those with IBS, and more patients with IBS had the implants removed.

Steroids for Hunner’s Ulcers and Urethral Pain Syndrome

Another study revived an abandoned IC treatment, oral steroids, in a new context - just for IC with Hunner’s lesions. The patients had already had their lesions excised or fulgurated (“burned off”) from one to seven times, but their symptoms came back. They took the steroid betamethasone orally at a higher dose for one or two months, and then at lower doses for an average of nearly a year. Twelve of the 23 patients improved, and 2 were able to stop taking the steroid. Although the treatment needs further study, it could be an option for this severest form of IC, said the authors.

Although not about IC specifically, a study of treatment for “urethral pain syndrome” may be helpful for the IC patients who do have urethral pain with urination. The clinicians put a combination of a potent steroid (clobetasol) cream and lidocaine gel in patients’ urethras once or twice a week for the first week and then once a week thereafter. Some patients got as many as 16 treatments, but the average was 2. The authors said that 60 percent of the patients were cured and the rest were improved.

Basic Research Points to New Treatments

Basic research pointed to some potential new treatments. In one study, researchers who have been working with a virus to inject helpful genes into bladder tissue are now looking at that possibility with an immune system signaling protein IL-4, which has anti-inflammatory effects. IL-4 has too many side effects to be a systemic (whole-body) drug, but it could help if it were targeted to the bladder. The researchers found that, in rats with irritated bladders, treating the bladder with the IL-4-gene containing virus eased bladder overactivity and pain. Another study tested a potential drug that blocks a purinergic receptor, that is, receptors that ATP attaches to. ATP is important in transmitting bladder pain signals, as our readers have been hearing about for some time. Now, a small-molecule compound, AF-742, which targets this receptor, is showing potential. It blocked activation of these receptors in nerves and calmed spasms in irritated rat bladders.

Pudendal Neuropathy and Pelvic Floor Dysfunction and Pain

Two workshops at the meeting helped clinicians lean to understand and treat IC and some of its associated conditions. Sometimes, contend some pelvic pain experts, pudendal neuropathy or damage to the pudendal nerve can be mistaken for IC and chronic prostatitis/chronic pelvic pain syndrome, and sometimes, it may coexist with these conditions. The workshop “Pudendal Neuropathy and Its Pivotal Role in Pelvic Floor Dysfunction and Pain” helped clinicians learn how to diagnose and treat this condition. Treatments range from self care to physical therapy, nerve blocks, and surgery in severe cases. Learn more about this topic:

    • Watch the meeting webcast. Click on “Workshops” and then “Workshop 12.”
    • View interview with physical therapist Stephanie Prendergast, MPT on the ICHelp YouTube channel, who is known for her work in treating pudendal neuropathy with physical therapy. Also check out our interview with Prendergast in the Summer 2009 ICA Update.

Is it Mind? Is it Bladder?

The faculty for the workshop, “Is it mind? Is it body? Is it bladder? Is it real?” included ICA Medical Advisory Board members Ragi Doggweiler, MD, Dr. Whitmore, and Fred Howard, MD, as well as gastroenterologist Alan Watier, MD. Both mind and body play important roles in pelvic pain, according to workshop leader Dr. Doggweiler. For IBS, the most effective therapy is a mind-body therapy, hypnosis, according to Dr. Watier.

But for IC patients, who in the past were often only referred for psychiatric therapy because so many physicians saw IC as just a psychologic problem, Dr. Howard’s perspective was helpful. He discussed a telling study of treatment for another pelvic pain condition, pelvic congestion syndrome. In this study, patients got a progestin as medical therapy, progestin plus psychiatric treatment, placebo, and placebo plus psychiatric treatment. Placebo and placebo plus psychiatric treatment had little effect. It took medical therapy for patients to get better. After four months, medical treatment and medical treatment plus psychiatric treatment had the same effect. But interestingly, after 13 months of treatment, those who got psychiatric support along with the medical therapy did better than those who got medical treatment alone.

Dr. Whitmore emphasized the importance of multimodal therapy in IC, aimed at treating all the sources of pain. One of the new ideas in the field, phenotyping, should help guide clinicians to do that, since it takes the associated conditions into account and helps clinicians identify the pain and symptom generators. Dr. Whitmore also discussed some of the newest approaches to treatment, including injections of botulinum toxin (Botox) into the pelvic floor, and her take on how to treat the worst cases of IC. You can hear what she has to say about that, how IC therapy has progressed in the last 10 years, and what she sees on the horizon for IC on the ICHelp YouTube channel.

Posted September 13, 2010