Schaeffer's Editorial 2003

[J Dimitrakov]

The Journal of Urology 2003; 169(2):597-598

Editorial: Emerging Concepts in the Management of Prostatitis/chronic
Pelvic Pain Syndrome

Anthony J. Schaeffer
Department of Urology
Northwestern University Medical School
Chicago, Illinois


The etiology of the chronic pelvic pain syndrome remains an enigma.
Traditional thinking implicates the prostate as a primary source of
the discomfort and bacteria and/or inflammatory cells as the cause of
prostate malfunction. To this end, a lot of time and effort have been
spent using traditional culture and more sophisticated polymerase
chain reaction techniques to identify putative bacterial pathogens
that could infect the prostate and lead to the development of the
chronic pelvic pain syndrome. Previous studies using sophisticated
polymerase chain reaction technology have failed to identify evidence
of bacteria in prostatic tissue obtained from young, presumably
healthy cadaver specimens. Traditional techniques to identify bacteria
in the prostate are based on localization studies that identify
bacteria in prostatic fluid and/or post-prostatic massage voided
urine. Obviously, contamination of these specimens from urethral
organisms is a common concern and the significance of low numbers of
bacteria in expressed prostatic secretions is questionable.

To avoid this problem, Lee et al (page 584) performed transperineal
tissue biopsies of the prostate. Contamination of the skin was
negligible. Using aggressive culture techniques, they identified low
numbers of nonpathogenic bacteria in about 30% of the patients and
controls. Older men were more likely to have positive cultures, as
were those with inflammation in the prostatic fluid. None of the
counts was high enough and/or associated with recognized pathogenic
bacteria and, therefore, these bacteria are probably colonizing
bacteria rather than infecting strains. Since the patients in these
studies were older, it is likely that in time urethral bacteria
colonized the prostatic ducts. However, these bacteria apparently do
not lead to a host response and, particularly, there is no evidence
that they are associated with symptoms.

It is well recognized that even if pathogenic bacteria are present in
the prostate, as in men with established chronic bacterial
prostatitis, they do not cause chronic pelvic pain unless acute
urinary tract infection develops. Taken together, these data suggest
that bacteria do not have a significant role in the development of the
chronic pelvic pain syndrome. The clinical observation that
antimicrobial therapy reduces symptomatology in men with chronic
pelvic pain syndrome is being tested in a double-blinded NIH
controlled study. Since antimicrobials may have anti-inflammatory
activity, it is possible that these drugs may benefit the patient by
reducing inflammation rather than eradicating bacteria.

[webslave]

Since antimicrobials may have anti-inflammatory
activity, it is possible that these drugs may benefit the patient by
reducing inflammation rather than eradicating bacteria.

:happy: :cool(1): :biggrin:

[Hepcat]

Well, it seems the verdicts are in.

So where will the focus shift next do you think? Pelvic neuropathic disease? Autoimmune disorders? Do we forgo the prostate as culprit in type IIIB/CPPS and start looking at the surrounding anatomy for clues?

In my case at least, I'm betting on a neuropathic problem, possibly even at a systemic level.

I just hope it's not autoimmune

[webslave]

You are correct that a milestone seems to have been reached.

Quo Vadis? Where to now? It's a time for debate and deliberation among the scientific cognoscenti.

[Adam Boyd]

This is definitely a major turning point!

Now, perhaps, important causative factors may be found more quickly - without the bacterial distraction. I think an important first step is to critically evaluate the role of inflammation in CPPS. While it probably contributes to symptoms in some men, I don't suspect that it is the most important contributor in most cases. Unfortunately, it would take a signficant investment in research to sort this out definitively, and at the present time the NIH has made no commitment to fund any basic science research in CPPS. Certainly. the $3.2 million for clinical trials is much needed, but it amazes me that the focus would be solely on such studies, considering the fact that appropriate targets for treatment have not yet been clearly identified.

[webslave]

Adam, maybe they are trying to work backwards, i.e. first find something that works to alleviate symptoms, then deduce what must be causing the problem. It's also the shortest route to concrete help for patients. They could spend years on the basics while men are not helped. That's my take on it.

[Richard.N]

I must admit the auto-immune angle is worrying. I got numbness in my hands again last night and this morning...

[Adam Boyd]

Adam, maybe they are trying to work backwards, i.e. first find something that works to alleviate symptoms, then deduce what must be causing the problem. It's also the shortest route to concrete help for patients. They could spend years on the basics while men are not helped. That's my take on it.

I agree that finding an effective treatment is a priority, and only clinical trials can establish the efficacy of any treatment. I also believe, however, that concurrent basic science research is just as important clinical research for two reasons:
1) Finding an effective treatment can offer clues to the cause of the problem, but since all drugs have multiple effects, it's impossible to come to a definitive answer based on treatment response alone. For example, alpha blockers relax smooth muscle of the lower urinary tract, reduce central sensitization after noxious stimulation, and inhibit stretch-activated ATP release in the bladder - so, which effect is most important in CPPS? Perhaps one, perhaps all. Only basic science studies can answer this type of question.
2)Basic science research provides the foundation for rational therapy. Understanding the basic mechanisms of the disease can provide the basis for conducting clinical trials. This is by far a more efficient approach than trial and error.

That's just my opinion. Feel free to disagree.

[Hepcat]

IMHO:

Adam is correct when he suggests that both clinical and basic research must be pursued concurrently. A summary, if perhaps a bit trivializing, statement may also be presented like this:

You cannot know what basic science to pursue without clinical findings and you cannot interpret clinical findings without basic science.

Also, at some point, any problems of any complexity will require a multi-disciplinary approach. No discipline can function effectively in a vacuum.

Even the NIH whitepapers affirm these points.

I would also note that study design is a highly complex subject. To properly critique a study usually requires some specific training and at least some mentoring. Any PhD. guy can tell you this. It is, however, esoteric enough that that virtually anyone thinks themselves astute enough play amateur scientist. If any doubt exists on this point, read the discussion group transcripts printed in the Urology prostate supplement linked elsewhere. Even professional researchers, the illuminati, differ on study design and research approach. I know I've done it for 10 years and even I hesitate to offer critique on a paper. There is always more to learn.

Sadly, I've also seen a lot of scientific fraud that goes unchallenged, particularly in academic hospitals. But, thats another rant.

Clearly though, research that fails to meet even the most basic criteria for proper study design is easily spotted. A decent researcher will report his findings in this manner however, explaining that further investigation is warranted.

I would hope a foundation could help to coordinate the efforts of top researchers in a variety of fields. I would offer that at this point, an action plan be developed as soon as a functioning foundation exists which draws from the input of the major stakeholders and lays the groundwork for efficient and timely use of resources to get all identifiable obstacles addressed.

How this is done I'll leave more capable *coughAdam* others

[webslave]

Well, bottom line is that the response to the formation of a nonprofit to lobby for research funds to be channelled into scientifically acceptable research (instead being of peed into the wind through donations to private clinics) has been absolutely miserable.

Unless something drastic changes, we may be left with the status quo, in which case I'm quite pleased that the NIH saw fit to put $3.2M into clinical trials this year for CPPS, all without any lobbying at all of which I am aware.