PROSTATE DISEASE BEGS UNDERSTANDING
Anonymous User
JAMA Vol. 286 No. 4, July 25, 2001
PROSTATE DISEASE BEGS UNDERSTANDING
Brian Vastag
Washington -- Sometimes a diagnosis is a dead end, a label with little
guidance. So it goes with chronic prostatitis, also called chronic pelvic pain
syndrome, the newer term which prompts some 2 million office visits in the
United States each year (J Urol. 1998;159:1224-1228).
A catch-all term to describe an array of symptoms that include pain in various
places, urinary problems, and sexual dysfunction, "prostatitis" reflects a lack
of knowledge regarding origins and effective treatments that led urologist
Thomas Stamey, MD, to call the diagnosis a "wastebasket of clinical ignorance."
To illustrate the point, Leroy Nyberg, MD, PhD, head of urology research at the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
sketched a typical scenario: a man complains of prostate symptoms and, after
ruling out obvious bacterial infections, urethral strictures, bladder
disorders, and cancer, the physician shrugs his shoulders, calls it chronic
nonbacterial prostatitis, and prescribes an antibiotic like ciprofloxacin or an
alpha-blocker like tamsulosin although neither has ever been tested against the
disease.
That scene is slowly changing. This summer, the NIDDK will begin the first
placebo-controlled clinical trial of antibiotics and alpha-blockers, to finally
determine whether the standard treatments provide any relief.
The study comes 6 years after the Prostatitis Foundation patient group
convinced Congress to prod the National Institutes of Health to furnish some
funding. "Because it isn't a deadly disease, it required a lot of momentum from
the outside to get us going," said Nyberg. "But now we've realized the impact
of the disease." To back his words, Nyberg oversees some $2 million in annual
grants aimed at probing the most basic questions: what is prostatitis, who gets
it, and will anything treat it?
Answers are appearing, some from small treatment studies and others from the
NIDDK's Chronic Prostatitis Collaborative Research Network, six centers
tracking the natural history of the condition in a cohort of 450 patients. For
starters, researchers want to define the breadth of the problem.
A small study from Ontario reported that 10% of men in the general population
had symptoms of chronic pelvic pain syndrome (J Urol. 2001;165:842-845).
Another study from Finland reported a prevalence nearing 15% (BJU Int.
2000;86:443-448), and other reports suggest that up to half of all men will
experience some type of prostatitis during their lifetime (Eur Urol.
1992;22:14).
If those figures hold in a larger epidemiological study planned by the NIDDK,
chronic pelvic pain syndrome would be among the most common ailments in men, a
fact that makes the dearth of understanding all the more disturbing.
NEW IDEAS
Over the years, yeast, viruses, calcium deposits, stress, and psychosomatic
illness have all been proffered as causes. Desperate for relief, patients from
across the globe have journeyed to the Philippines and to Ukraine to partake in
undocumented cures, mail-ordered powerful magnets to sit on, and drunk gallons
of carrot juice, all in hope of lessening pain and restoring a normal sex life.
Frustrated by not having much to offer, urologists and primary care physicians
often advise symptomatic treatments like anti-inflammatory drugs, hot baths,
frequent ejaculation, and regular prostate massages.
After surveying this sorry state, the NIDDK brought together prostatitis
researchers - there were only a handful at the time at a 1995 conference. The
participants immediately realized that de facto clinical definitions held
little meaning and proposed a new system of nomenclature. They settled on three
categories: acute and chronic bacterial prostatitis (with documented
infections) and chronic pelvic pain syndrome. While the first two generally
respond to antibiotics, they account for just 5% to 10% of cases.
Since then, a handful of new ideas have been getting attention and, finally,
the scrutiny of rigorous testing. While some researchers maintain that
difficult-to-find bacterial infections are to blame, others document evidence
of autoimmune activity. A third camp holds that chronic tension in the pelvic
floor muscles, not the prostate itself, accounts for the problem. And some
think that all three processes could be at play.
A BACTERIAL CONNECTION?
Daniel Shoskes, MD, a transplant surgeon and urologist at the Cleveland Clinic
Florida in Fort Lauderdale, said that many physicians are missing a bacterial
connection by failing to culture prostate secretions. "It's the reasoning that
if the culture is positive, they'll treat with antibiotics, and if it's
negative, all they have to offer is antibiotics, so why culture?"
But he said that culturing is important because he's seen patients with
infections resistant to standard antibiotics improve after switching drugs. He
added that even if physicians do culture, current techniques are a problem
growing bacteria from prostate secretions (collected after a digital rectal
exam) takes as long as 5 days, said Shoskes, whereas many laboratories grow
samples for only 48 hours. "Some people with negative cultures have true
infections," he said.
Shoskes and other researchers also report evidence of chronic inflammation or
autoimmunity in patients with no evidence of infection. Shoskes became
intrigued with the idea when he noticed parallels between kidney transplant
rejection and chronic prostatitis. "In both cases you have some type of initial
injury or event . . . and then weeks or months later you still have this
progressive inflammatory condition."
POSSIBLE AUTOIMMUNITY
Richard Alexander, MD, a urologist at the University of Maryland Medical
Center, Baltimore, has published several articles supporting the idea. He
reports abnormal T-cell activity and high levels of inflammatory cytokines in
patients with chronic prostatitis compared with controls. Most recently, his
laboratory identified T cells from patients with prostatitis that switch on in
response to prostate-specific antigen (Prostate. 2000;44:49-54). Earlier, he
found that the semen of prostatitis patients held large amounts of tumor
necrosis factor and interleukin 1-; both promote inflammation (Urology.
1998;52:744-749).
"This is all consistent with the idea of autoimmunity directed toward the
prostate," said Alexander, whose laboratory is now looking for similar patterns
in samples from all of the men in the NIDDK network. But he emphasized that he
does not believe that autoimmunity will explain the majority of cases.
Given the evidence of chronic inflammation, both Shoskes and Alexander are
testing novel agents directed at the process. In 1999, Shoskes published a
small study with the dietary supplement quercetin, a bioflavonoid antioxidant
and anti-inflammatory agent. After taking 500 mg of the supplement twice daily
for a month, two thirds of men in the treatment group (and only 20% in the
control group) reported a 25% or greater improvement in symptoms (Urology.
1999;54:960-963). But the study was small (30 patients) and remains to be
replicated.
While quercetin can be bought off the shelf, the agent under study by Alexander
and other urologists costs more than $10 000 per year. Called etanercept
(Enbrel, Immunex Corp, Seattle), the drug binds to and sops up excess molecules
of tumor necrosis factor . Approved by the US Food and Drug Administration in
1998 for treatment of rheumatoid arthritis the most common autoimmune disease
in the country the drug reduces joint pain in most patients with that disease.
Data from the etanercept prostatitis trial should be available next year.
MUSCLE TENSION STUDIED
In the meantime, David Wise, PhD, of Stanford University Medical Center's
urology department, believes that chronic pelvic muscle tension explains many
cases of prostatitis. He presented data at last fall's third international
prostatitis meeting in Arlington, Va, that showed men with prostatitis have
more muscle tension than controls. Wise is testing a months-long regimen of
intense pelvic muscle massage and relaxation training.
Ultimately, all or none of these ideas may lead to proven, effective
treatments. "Right now, the evidence for any etiology is minimal," said the
NIDDK's Nyberg. "It's a level playing field, and there are a lot of ideas
around."
While the new ideas shake out, some of the old, especially that antibiotics
and -blockers are helpful may fall into disfavor after the NIDDK clinical
trial. Maryland's Alexander, for one, thinks that the results will pick
prostatitis out of the clinical trash bin. "In the next year or two, the data
from the [NIDDK] cohort study are going to debunk a lot of the myths about this
problem," he said. "And it's going to be clear that the assumptions are wrong
and that we need to start all over again."
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Prostatitis Supermall: http://www.chronicprostatitis.com
Rhemium
>Alexander
I was worried that it might be expensive. What a relief.
Derek
> Daniel Shoskes, MD, a transplant surgeon and urologist at the Cleveland
Clinic
> Florida in Fort Lauderdale, said that many physicians are missing a
bacterial
> connection by failing to culture prostate secretions. "It's the reasoning
that
> if the culture is positive, they'll treat with antibiotics, and if it's
> negative, all they have to offer is antibiotics, so why culture?"
>
> But he said that culturing is important because he's seen patients with
> infections resistant to standard antibiotics improve after switching
drugs. He
> added that even if physicians do culture, current techniques are a problem
> growing bacteria from prostate secretions (collected after a digital
rectal
> exam) takes as long as 5 days, said Shoskes, whereas many laboratories
grow
> samples for only 48 hours. "Some people with negative cultures have true
> infections," he said.
I like this......I'm glad to see someone point this out! Very good :-)
Rhemium
This doesn't mean you're included in this group, though, Derek.
Lost in all this anti-bacterial crusading is the fact that, indeed, some cases
are true infections.
That being said....do these people with positive cultures truly have "CP/CPPS"?
Or do they have a true "prostatitis" caused by infection?
CP/CPPS seems like a different creature all together. I think you have
CP/CPPS. Derek.
Derek
"Rhemium" wrote....
> This doesn't mean you're included in this group, though, Derek.
I'm not excluded either. One thing I know is that I've only had one culture
of my semen, and it was only a 2 day culture. My sample was left over the
weekend in a heating chamber before the pee-brain that was in charge ever
even looked at under a microscope! Something else I'm aware of is that the
"majority" of infectious disease clinics in North America culture for 2 days
only. Have you ever asked exactly what they're looking for? I don't usually
see any GP write "screen all", or "test for everything." Another thing I
know.....my balls started to hurt within a week of having unprotected sex.
> CP/CPPS seems like a different creature all together. I think you have
> CP/CPPS. Derek.
I do.....but what causes it? Million dollar question $$$$$$$ cha-ching! :-)
Rhemium
>> CP/CPPS. Derek.
>
>I do.....but what causes it? Million dollar >question $$$$$$$ cha-ching! :-)
>
>
Genetic predisposition to autoimmune susceptibility coupled with possible
environmental factors such as antigens or trauma.
There. I've figured it out.
Email me privately so we can exchange addresses - - I really need that mill
right now!
Ciao
Derek
"Rhemium" wrote...
> Genetic predisposition to autoimmune susceptibility coupled with possible
> environmental factors such as antigens or trauma.
>
> There. I've figured it out.
Are you taking new patients? By the way.....how come you charge $700 for a
first visit?