PROSTATITIS פרופ' אבי שטיין, מחלקה אורולוגית, מרכז רפואי כרמל
PROSTATITIS
Dec 31, 2022
To develop a multi-center cooperative research network focusing on the urologic chronic pelvic pain syndromes, specifically Interstitial Cystitis/Painful Bladder Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome, and their major associated co-morbidities.
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To develop a multi-center cooperative research network focusing on the urologic chronic pelvic pain syndromes, specifically Interstitial Cystitis/Painful Bladder Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome, and their major associated co-morbidities.
Transcript
CHRONIC NON-BACTERIAL PROSTATITIS
Life time prevalence 14.8%
<50
??
• "
(BIOFILMS)
( ) • .
.
• .
• .
PROSTATITIS UNDER THE
- ( 90%
.
•
•
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
Cat IV:Asymptomatic Inflammatory Prostatitis
febrile illness.
• Obstructive voiding complaints including hesitancy, poor interrupted stream, strangury, and even acute urinary retention are common. Tenesmus.
• Perineal and suprapubic pain
• Significant systemic symptoms including fever, chills, malaise, nausea and vomiting, and even frank septicemia with hypotension
Approximately 5% of patients with acute bacterial prostatitis may progress to chronic bacterial prostatitis( Cho et al., 2005
Acute bacterial prostatitis
bacterial
postmassage test
Nickel JC, Shoskes D, Wang Y, et al: How does the
pre-massage and post-massage 2-glass test
compare to the Meares-Stamey 4-glass test in men
with chronic prostatitis/chronic pelvic pain syndrome?
J Urol 176(1):119-124, 2006 .
adequate screening test as an alternative that is simpler,
faster, and less expensive than the four-glass test .
CHRONIC BACTERIAL
prostatitis ranges from 5% to 15%
of prostatitis cases
Have a history of chronic UTI
CP/CPPS
Pro-inflammatory cytokines* (IFN,IL-6,IL-8, TNF)
Autoimmunity *soluble signaling molecules that are produced from leukocytes and other cell types. They serve as initiators and
modulators of immune and inflammatory responses.
There is poor correlation between these cytokines and the symptoms of
prostatitis
There may be a misinterpretation between cytokine levels obtained from seminal
fluid and levels in serum obtained in other inflammatory conditions like RA,
Sjorgen
inflammatory effect.
prostate presents with androgen insensitivity
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
Neurological
The pain of CP may also be a result of “neurogenic inflammation”
in the peripheral nervous system.
PGE-2 is a known inflammatory marker.
Inflammation decreases endorphine production. CP/CPPS patients present 4-6
times higher PGE levels and low endorphine levels compared to controls.
After antibiotic treatment, the levels of PGE decresed while endorphine level
increased.
There seems to be a role for oxidative stress in the mechanism of prostatitis
CHRONIC NON-BACTERIAL PROSTATITIS
Rat model spontaneous prostatitis:
Degranulation of mast cells
One of the products released from activated mast cells is nerve growth factor
(NGF) one of the few factors that correlates with pain in CP/CPPS. NGF regulates the sensitivity of adult sensory neurons to capsaicin, which excites c-fibers. These C-
fibers are sensory nerves associated with pain transmission and they also innervate mast cells.
NGF is also a potent stimulator of mast cells and it can cause their degranulation. Released substances
lead to “neurogenic inflammation” and then sensitize C-fibers
Mast cells NGF C fibers
pain
pain
degranulation
PATHOPHSIOLOGY
Psychological
Psycological stress is a more frequent in patients with chronic non-
bacterial prostatitis
Classification: NIH
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
(AIP)
CPPS
Chronic Prostatitis Symptom
CPPS
*Mandatory
Urinalysis and urine culture
Flow rate
Cystoscopy
Prostate carcinogenesis and
inflammation: emerging insights
Is prostatitis a premalignant lesion
Review Nature Reviews Cancer
PlatzSiobhan Sutcliffe ,Jianfeng Xu ,Henrik
Grönberg ,Charles G. Drake ,Yasutomo
Nakai ,William B. Isaacs &William G.
Nelson
BJU
Treatment of chronic prostatitis
**
**cannot be recommended as a monotherapy except perhaps in men with associated BPH.
Potential Therapies Antimicrobials (6-12 weeks in cat. II and trial of 2-4 weeks in cat. III)
Alpha blockers ??
Muscle relaxants
allopurinol, antioxidants
CPPS antibiotics???
• There is no real rationale for giving antibiotics to these patients as no bacteria were isolated.
• Antibiotic therapy may benefit CPPS patients by three different mechanisms:
– A strong placebo effect, the eradication suppression of non cultured microorganisms (Nickel
et al, 2001a),
– The independent anti-inflammatory effect of some antibiotics (Yoshimura et al, 1996; Galley
et al, 1997).
Is there a rationale to treat by antibiotics patients with cpps IIIa and IIIb who
have been previously treated by antibiotics
• Two multicenter randomized placebo-controlled studies have assessed the
efficacy of 6 weeks of levofloxacin (Nickel et al, 2003b) and ciprofloxacin
(Alexander et al, 2004) in men with CP/CPPS. In these trials the participants
had chronic symptoms for a long duration (many years) and had been
heavily treated (including treatment with antibiotics).. Antibiotics should
not be prescribed for previously treated men with CP/CPPS of long
duration.
Antibiotics
Catheterization
Absess
Drainage
Antibiotics
Alpha-
blockers
Prostate
Massage
Surgery
Antibiotics
Catheterization
Absess
Drainage
Antibiotics
Alpha-
blockers
Prostate
Massage
Surgery
Transrectal (microwave)
Transurethral (microwave)
denaturation and if high temperatures are achieved,
even tissue necrosis
the heating pattern more than the wave frequency does
Heat is produced while the microwaves are absorbed
by the tissue. It arises mainly by electrical dipoles (water
molecules) oscillating in the microwave field and electrical
charge carriers (ions) moving back and forth in the
field. These movements transfer energy to the tissue in
form of heat.
• heating in excess of 45C is followed by coagulation necrosis
• Histopathological effect of thermotherapy appears to be related to
the induction of cell death
• induced necrosis was shown to disrupt periurethral a-adrenergic
receptors reflecting denervation of smooth muscle cells consisting
with the increased urinary flow rate after TUMT
• Recently, it was demonstrated that TUMT increased the sensory
threshold (evoked by electrical stimulation) in the posterior urethra
by 30%, resulting in the reduction of irritative symptoms
60
For Prostatitis: 47° C
to 39°c (for at least 3 min) than gradually
raised to 46-47°c for additional 87 min.
Following treatment - immediate removal
of catheter (post-treatment catheter
CPPS AND THERMOTHERAPY
Randomized Double-Blind Sham Controlled Study Using New Prostatitis
Specific Assessment Questionnaires
TUMT COMPLICATIONS
UTI (17%)
HEMATURIA (1.2%)
TEMPORARY CYSTOSTOMY
TEMPORARY STENT*
Injectables to the prostate
Intraprostatic injection in prostatitis
cathegory IIIa And IIIb(CPPS)
•
.
•
Pelvic Pain (MAPP)
• To develop a multi-center cooperative research network focusing on the urologic chronic pelvic pain syndromes, specifically Interstitial Cystitis/Painful Bladder Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome, and their major associated co-morbidities.
• MAPP Network research priorities include: – (1) Studies of individual patients to identify disease phenotypes,
– (2) Targeted epidemiologic studies to examine the natural history of disease, and
Life time prevalence 14.8%
<50
??
• "
(BIOFILMS)
( ) • .
.
• .
• .
PROSTATITIS UNDER THE
- ( 90%
.
•
•
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
Cat IV:Asymptomatic Inflammatory Prostatitis
febrile illness.
• Obstructive voiding complaints including hesitancy, poor interrupted stream, strangury, and even acute urinary retention are common. Tenesmus.
• Perineal and suprapubic pain
• Significant systemic symptoms including fever, chills, malaise, nausea and vomiting, and even frank septicemia with hypotension
Approximately 5% of patients with acute bacterial prostatitis may progress to chronic bacterial prostatitis( Cho et al., 2005
Acute bacterial prostatitis
bacterial
postmassage test
Nickel JC, Shoskes D, Wang Y, et al: How does the
pre-massage and post-massage 2-glass test
compare to the Meares-Stamey 4-glass test in men
with chronic prostatitis/chronic pelvic pain syndrome?
J Urol 176(1):119-124, 2006 .
adequate screening test as an alternative that is simpler,
faster, and less expensive than the four-glass test .
CHRONIC BACTERIAL
prostatitis ranges from 5% to 15%
of prostatitis cases
Have a history of chronic UTI
CP/CPPS
Pro-inflammatory cytokines* (IFN,IL-6,IL-8, TNF)
Autoimmunity *soluble signaling molecules that are produced from leukocytes and other cell types. They serve as initiators and
modulators of immune and inflammatory responses.
There is poor correlation between these cytokines and the symptoms of
prostatitis
There may be a misinterpretation between cytokine levels obtained from seminal
fluid and levels in serum obtained in other inflammatory conditions like RA,
Sjorgen
inflammatory effect.
prostate presents with androgen insensitivity
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
Neurological
The pain of CP may also be a result of “neurogenic inflammation”
in the peripheral nervous system.
PGE-2 is a known inflammatory marker.
Inflammation decreases endorphine production. CP/CPPS patients present 4-6
times higher PGE levels and low endorphine levels compared to controls.
After antibiotic treatment, the levels of PGE decresed while endorphine level
increased.
There seems to be a role for oxidative stress in the mechanism of prostatitis
CHRONIC NON-BACTERIAL PROSTATITIS
Rat model spontaneous prostatitis:
Degranulation of mast cells
One of the products released from activated mast cells is nerve growth factor
(NGF) one of the few factors that correlates with pain in CP/CPPS. NGF regulates the sensitivity of adult sensory neurons to capsaicin, which excites c-fibers. These C-
fibers are sensory nerves associated with pain transmission and they also innervate mast cells.
NGF is also a potent stimulator of mast cells and it can cause their degranulation. Released substances
lead to “neurogenic inflammation” and then sensitize C-fibers
Mast cells NGF C fibers
pain
pain
degranulation
PATHOPHSIOLOGY
Psychological
Psycological stress is a more frequent in patients with chronic non-
bacterial prostatitis
Classification: NIH
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
(AIP)
CPPS
Chronic Prostatitis Symptom
CPPS
*Mandatory
Urinalysis and urine culture
Flow rate
Cystoscopy
Prostate carcinogenesis and
inflammation: emerging insights
Is prostatitis a premalignant lesion
Review Nature Reviews Cancer
PlatzSiobhan Sutcliffe ,Jianfeng Xu ,Henrik
Grönberg ,Charles G. Drake ,Yasutomo
Nakai ,William B. Isaacs &William G.
Nelson
BJU
Treatment of chronic prostatitis
**
**cannot be recommended as a monotherapy except perhaps in men with associated BPH.
Potential Therapies Antimicrobials (6-12 weeks in cat. II and trial of 2-4 weeks in cat. III)
Alpha blockers ??
Muscle relaxants
allopurinol, antioxidants
CPPS antibiotics???
• There is no real rationale for giving antibiotics to these patients as no bacteria were isolated.
• Antibiotic therapy may benefit CPPS patients by three different mechanisms:
– A strong placebo effect, the eradication suppression of non cultured microorganisms (Nickel
et al, 2001a),
– The independent anti-inflammatory effect of some antibiotics (Yoshimura et al, 1996; Galley
et al, 1997).
Is there a rationale to treat by antibiotics patients with cpps IIIa and IIIb who
have been previously treated by antibiotics
• Two multicenter randomized placebo-controlled studies have assessed the
efficacy of 6 weeks of levofloxacin (Nickel et al, 2003b) and ciprofloxacin
(Alexander et al, 2004) in men with CP/CPPS. In these trials the participants
had chronic symptoms for a long duration (many years) and had been
heavily treated (including treatment with antibiotics).. Antibiotics should
not be prescribed for previously treated men with CP/CPPS of long
duration.
Antibiotics
Catheterization
Absess
Drainage
Antibiotics
Alpha-
blockers
Prostate
Massage
Surgery
Antibiotics
Catheterization
Absess
Drainage
Antibiotics
Alpha-
blockers
Prostate
Massage
Surgery
Transrectal (microwave)
Transurethral (microwave)
denaturation and if high temperatures are achieved,
even tissue necrosis
the heating pattern more than the wave frequency does
Heat is produced while the microwaves are absorbed
by the tissue. It arises mainly by electrical dipoles (water
molecules) oscillating in the microwave field and electrical
charge carriers (ions) moving back and forth in the
field. These movements transfer energy to the tissue in
form of heat.
• heating in excess of 45C is followed by coagulation necrosis
• Histopathological effect of thermotherapy appears to be related to
the induction of cell death
• induced necrosis was shown to disrupt periurethral a-adrenergic
receptors reflecting denervation of smooth muscle cells consisting
with the increased urinary flow rate after TUMT
• Recently, it was demonstrated that TUMT increased the sensory
threshold (evoked by electrical stimulation) in the posterior urethra
by 30%, resulting in the reduction of irritative symptoms
60
For Prostatitis: 47° C
to 39°c (for at least 3 min) than gradually
raised to 46-47°c for additional 87 min.
Following treatment - immediate removal
of catheter (post-treatment catheter
CPPS AND THERMOTHERAPY
Randomized Double-Blind Sham Controlled Study Using New Prostatitis
Specific Assessment Questionnaires
TUMT COMPLICATIONS
UTI (17%)
HEMATURIA (1.2%)
TEMPORARY CYSTOSTOMY
TEMPORARY STENT*
Injectables to the prostate
Intraprostatic injection in prostatitis
cathegory IIIa And IIIb(CPPS)
•
.
•
Pelvic Pain (MAPP)
• To develop a multi-center cooperative research network focusing on the urologic chronic pelvic pain syndromes, specifically Interstitial Cystitis/Painful Bladder Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome, and their major associated co-morbidities.
• MAPP Network research priorities include: – (1) Studies of individual patients to identify disease phenotypes,
– (2) Targeted epidemiologic studies to examine the natural history of disease, and
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