CP v IC - A New Study

[alphacentauri]

I found the study below posted in the prostatitis newsgroup and I thought I'd repost here for your thoughts & comments.

This could be a very interesting finding for those who are wondering if we have CP or IC or whether CP/CPPS & IC are the same thing.

To a layperson like myself, it appears that the study shows a clear method of distiguishing CP from IC using just urine samples, which sounds like great news!

But what's not clear to me is whether an invasive procedure is involved. For instance what is meant by 'H-thymidine incorporation into primary normal adult human bladder epithelial cells'?

And most importantly, how significant is this study anyway?

Urology. 2004 Jan;63(1):22-6.

Antiproliferative factor, heparin-binding epidermal growth factor-like
growth factor, and epidermal growth factor in men with interstitial
cystitis versus chronic pelvic pain syndrome.

Keay S, Zhang CO, Chai T, Warren J, Koch K, Grkovic D, Colville H,
Alexander R.

Division of Infectious Diseases, Department of Medicine, University of
Maryland School of Medicine, Baltimore, Maryland, USA.

OBJECTIVES: To determine whether men with chronic prostatitis/chronic
pelvic pain syndrome (CP/CPPS) have urine markers previously described
for patients with interstitial cystitis (IC; presence of
antiproliferative factor [APF] activity, decreased levels of
heparin-binding epidermal growth factor-like growth factor [HB-EGF],
and increased levels of epidermal growth factor). METHODS: Clean catch
urine specimens were collected from 41 symptomatic patients with
CP/CPPS, 36 asymptomatic men without bladder disease who served as the
control group, and 24 men with IC. APF activity was determined by
(3)H-thymidine incorporation into primary normal adult human bladder
epithelial cells. HB-EGF and epidermal growth factor levels were
determined by enzyme-linked immunosorbent assay. RESULTS: Men with
CP/CPPS did not differ significantly from asymptomatic controls for
any of the three markers tested (P >0.49). In contrast, APF activity
was present significantly more often and HB-EGF levels were
significantly lower in the urine specimens from men with IC than in
the specimens from controls or patients with CP/CPPS (P <0.00001 for
all four comparisons). Although the epidermal growth factor levels
also tended to be higher in the urine from patients with IC than in
the urine from controls, the difference did not reach statistical
significance (P = 0.06). CONCLUSIONS: These findings indicate that at
least two of the urine biomarkers previously identified in women with
IC (presence of APF activity and decreased levels of HB-EGF) are also
found in men with IC, but not in men with CP/CPPS. This finding
suggests that IC and CP/CPPS may be two different disorders with
distinct pathophysiologies. It also confirms the utility of the
presence of APF activity and HB-EGF levels as markers for IC in men,
as well as in women, with this disorder.

[webslave]

1) The study comes from Susan Keay, someone who has made a career of investigating IC, at one stage finding a chemical marker that supposedly distinguishes IC pts from controls, and she probably does not want IC to fall under the chronic prostatitis / chronic pelvic pain syndrome rubric. That's just my speculation, but it does cause one to pause when considering the study.

2) The study compares clean catch urine in IC and male chronic prostatitis / chronic pelvic pain syndrome patients. I contend that this is a hopeless exercise, for this reason: the inflamed epithelial linings are physically located in different places in the two groups. In women (and men with bladder-centred inflammation), the bladder lining is open to urine, while in men with prostate-centred inflammation the prostatic ducts are not constantly shedding into the urine stream. In fact both sets of epithelia may be identically affected by mast cell degranulation without showing similar urine markers.

In conclusion: proves nothing, IMO.

[latte]

I agree, she should have tested the urine of the chronic prostatitis / chronic pelvic pain syndrome patients after prostate massage. If APF is present in the prostate it may have been detected after massage. My own speculation is that the process that happens with woman with IC may be happening to men in the prostatic membrames but harder to detect and harder to treat.

[Paso]

This is interesting. Back in June just after my chronic prostatitis / chronic pelvic pain syndrome just started I sent a urine sample for testing. It came back with low HB-EGF factors, even though APF was not tested. I had seroius "prostate" related problems at this time with "strange" looking semen and many problems. The doctor suggested I had IC in the prostate... Very very strange indeed. Now that I feel better I dont think I would have the same results on my tests.

Also what is you guys general thaught on IC? IS it caused by the muscles, nerves etc etc and can be "fixed" with PT and Relaxation? Or do you think it is a separate "bladder" problem?

/Paso

[Guest]

I was at the conference in Alexandria when this study was presented and, yes, it did catch many of us by surprise. The data was actually quite compelling. I didn't see active bias (but I don't have my notes in front of me with respect to methodology) however, I will offer the following.

Politics in the IC/prostatitis/pelvicpain/painful bladder syndrome communities have NEVER been worse than they are today. There is a faction that wants to confine IC just to the bladder.. who have the ear of the NIDDK. There is another faction that believes that IC is more than just the bladder.. that it involves the prostate and/or pelvic area, as well as other related conditions.

Nine months ago, IC was labelled a pelvic pain syndrome by an international panel of doctors, just as prostatitis was five years ago. We all sighed in relief. But then, a "secret committee" met in a "secret meeting" in Alexandria in October and determined that it should be called a "painful bladder syndrome." Clearly, this had been in the works for some time because researchers then presented power point presentations using IC/PBS. (I should say, however, that the European community clearly believes that it should only be painful bladder syndrome. )

Ultimately, I walked away from Alexandria greatly disappointed and frustrated. I don't like these secret meetings and secret committees which are making HUGE decisions without giving all an opportunity to participate. Meetings like these become more about WHO has the power and WHO keeps the power rather than what science is being presented. If you look behind the scenes, you see the same ole people who have been around for a decade and who seem to be desperate to keep their place in the power structure and force their views on others. Uggh!

That said, the absolute highlight of the conference were the presentations by Susan Keay whose work, over all, is breathtaking AND Scott Hultgren, who is destined to win the Nobel prize for studying ecoli infection/pilli structures etc. in the urinary tract. I think that both of their motivations & methodologies are very pristine and above board.

Jill O.

[Paso]

Jill,

This idea on Ecoli, what is it about? They found E.coli in my unrine or semen when this started, so thats why I am curoius.

/Paso

[webslave]

Susan Keay, a very pleasant person who has communicated with me in the past, is a perfectly respectable and highly intelligent researcher, that is without doubt. But in this one instance I think the METHOD used in this study was flawed.

To Paso: stress can provoke IC in rodents, and it does so through muscle tension (how else)? Case closed, I feel.

[Guest]

Paso,

Just do a search on google for Scott Hultgren. His research page should come up. Too big or extensive to outline here. Better to just go to the source.

Jill

[MastCells]

I agree, she should have tested the urine of the chronic prostatitis / chronic pelvic pain syndrome patients after prostate massage. If APF is present in the prostate it may have been detected after massage. My own speculation is that the process that happens with woman with IC may be happening to men in the prostatic membrames but harder to detect and harder to treat.

I third that. You and Mark are absolutely right about this.

[alphacentauri]

I think the METHOD used in this study was flawed.

she should have tested the urine of the chronic prostatitis / chronic pelvic pain syndrome patients after prostate massage. If APF is present in the prostate it may have been detected after massage.

This suggests that with improved methodology, the study has the potential to have significant results.

My gut feeling tells me that IC is part of a larger pelvic pain syndrome. However if we can use a simple non-invasive procedure to see whether the main source of our inflammation is in the bladder or the prostate - or somewhere else for that matter, that should be big step forward in terms of identifying effective treatment options earlier.

That is if - as Jill pointed out so well - the politics of all this can allow that to happen.

[MS]

This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies.

While this research may support IC/CPPS are seperate or mutually exclusive conditions, other recent studies suggest otherwise:

• Etiology: where does prostatitis stop and interstitial cystitis begin?
  Evan R. Eisenberg, Robert M. Moldwin
  World Journal of Urology, 21(2), 64-69
  April 2003
  
  
  Abstract:
  
  Male chronic pelvic pain syndrome (MCPPS) and interstitial cystitis (IC) patients show striking similarities in clinical presentation, diagnostic evaluation, purported pathogenesis, and even response to therapy. This makes the distinction between them very difficult. This review aims to show just how easy it is for the clinician to miss the features of IC in the MCPPS patient (and conversely). Misdiagnosis can result in the rejection of various potentially helpful therapies while accurate early diagnosis will lead to appropriate therapies and a better quality of life for the patient.

• Similarities Between Interstitial Cystitis and Male Chronic Pelvic Pain Syndrome
  Robert M Moldwin MD
  Current Urology Reports, 2002, 3:313-318
  
  Abstract
  
  Few clinical conditions encountered by the urologist cause more patient and clinician frustration than interstitial cystitis and male chronic pelvic pain syndrome, also know as nonbacterial prostatitis. This frustration is fueled by the chronicity of often disabling urogenital (and often associated systemic) symptoms coupled with delayed care, misdiagnosis, and suboptimal clinical responses. Basic research and therapeutic trials for these syndromes have historically taken two separate paths. However, mounting evidence suggests that significant overlap may exist between them in epidemiology, pathophysiology, and even therapy. This discussion reviews some of the common features of these clinical problems and makes a case that they might in fact represent different manifestations of the same disease process.

[webslave]

Good point, MS.

[alphacentauri]

While this research may support IC/CPPS are seperate or mutually exclusive conditions, other recent studies suggest otherwise:

Abstract:

Male chronic pelvic pain syndrome (MCPPS) and interstitial cystitis (IC) patients show striking similarities in clinical presentation, diagnostic evaluation, purported pathogenesis, and even response to therapy. This makes the distinction between them very difficult. This review aims to show just how easy it is for the clinician to miss the features of IC in the MCPPS patient (and conversely). Misdiagnosis can result in the rejection of various potentially helpful therapies while accurate early diagnosis will lead to appropriate therapies and a better quality of life for the patient.

That's an important point. IC may well be a part of CPPS, but a bladder-centered inflammation may require a different therapeutic approach from a prostate-centered one. Doesn't that last line suggest exactly that - that clearly telling one from the other can result in a more effective treatment for the patient?

I'm all for studies that compare IC to CP - we should know once and for all how the two relate to each other & whether they require similar or different treatment approaches. Also a non-invasive procedure that could rule out IC early on would be a great relief for many of us!

[latte]

alphacentauri, that the whole point, no one really knows how they relate. The politics of the bladder group versus the prostate group is growing and it gets in the way of really finding out. There are a few researchers working on this very point but, as you can see by Moldwin's work versus Keay's work, there are major disagreements going on right now. It will take more bantering about before this is sorted out I am afraid.

[alphacentauri]

alphacentauri, that the whole point, no one really knows how they relate.

Yes, I'm beginning to see that

It will take more bantering about before this is sorted out I am afraid.

Well, let's hope that continuing discussions like this one are at least a tiny step closer to a solution.