‫‪PROSTATITIS‬‬
‫פרופ' אבי שטיין‪ ,‬מחלקה אורולוגית‪ ,‬מרכז רפואי כרמל‬
‫דלקת ערמונית‬
‫‪‬סיווג‬
‫‪‬איבחון‬
‫‪‬טיפול‬
‫טיפול בחימום דרך שפכה ( ‪ (TUMT‬ויעילותו כטיפול ב ‪BPH‬‬
Prostatitis: A Major Clinical
Problem
Incidence/prevalence: 4% -11%
8-12% of urologist office visits
Life time prevalence 14.8%
most common urological diagnosis in men
<50
Quality of Life is dismal!
‫כיצד מתפתחת דלקת בערמונית??‬
‫• חיידקים מתנחלים בצינוריות של בלוטות ערמונית ויוצאים מטווח‬
‫ההשפעה של אנטיביוטיקה או פקטורים של המערכת החיסונית ע"י‬
‫יצירת אגרגטים (‪)BIOFILMS‬‬
‫• הפרעות באספקת דם בערמונית על רקע טרומבוזיס (פקקת)‬
‫בורידים הקטנים‪ .‬זו כנראה אחת הסיבות ליעילות הנמוכה של‬
‫טיפול אנטיביוטי בחולים עם פרוסטטיטיס כרונית‪.‬‬
‫• תפקוד לא תקין של השריר החלק מסביב לבלוטות גורם להצטברות‬
‫הנוזל‪.‬‬
‫• בהמשך מופיעים ברקמת הערמונית חללים מלאים נוזל מזוהם ללא‬
‫כל יכולת פינוי בעת שפיכה‪.‬‬
PROSTATITIS UNDER THE
MICROSCOPE
‫מיקרואורגניזם מחוללים‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫חיידקים גרם שליליים בד"כ ‪( ENTEROBACTERIA‬קולי‪ ,‬פסיאודומונס וכו'‪-‬‬
‫‪ 90%‬מהמחוללים) בעקבות דלקת בדרכי השתן במנגנון של רפלוקס תוך‪-‬‬
‫פרוסטטי‪.‬‬
‫חיידקים גרם חיוביים (קוקים למיניהם)‬
‫אנאירוביים‬
‫קלמידיה ‪ -‬האם דלקת שפכה קשור לדלקת ערמונית??‬
‫פטריות‬
‫וירוסים‬
‫גורמים שלא ניתן לתרבת????‬
Classification: NIH
Cat I: Acute Bacterial Prostatitis
Cat II: Chronic Bacterial Prostatitis
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
Asymptomatic Inflammatory Prostatitis Cat IV:
(AIP)
90%
ACUTE PROSTATITIS
SYMPTOMS
Acute onset
pain
irritative and obstructive voiding symptoms
febrile illness.
The patient typically complains of :
•
Urinary frequency, urgency, and dysuria.
•
Obstructive voiding complaints including hesitancy, poor interrupted stream,
strangury, and even acute urinary retention are common. Tenesmus.
•
Perineal and suprapubic pain
•
Associated pain or discomfort of the external genitalia.
•
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
Supportive treatment
Broad
spectrum
penicillins
Aminoglycosides
quinolones
Transperineal approach?
CHRONIC PROSTATITIS
DIAGNOSIS
CLASSIC STAMEY 4 GLASS TEST
bacterial
Non- bacterial
PRE-M
Prostate massage
POST-M
PROSTATITIS DIAGNOSIS
Donna R. Coffman, MD
Comparison of four-glass and two-glass premassage and
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 .
The Premassage postmassage test (PPMT) may offer an
adequate screening test as an alternative that is simpler,
faster, and less expensive than the four-glass test .
CHRONIC BACTERIAL
PROSTATITIS
The prevalence of chronic bacterial
prostatitis ranges from 5% to 15%
of prostatitis cases
25-43 % of patients with a
diagnostic glass test of prostatitis
Have a history of chronic UTI
CP/CPPS
CHRONIC NON BACTERIAL
PROSTATITIS cat III
Asymptomatic
WBC- positive postmassage
urine
Symptomatic
WBC- negative postmassage
urine
CP/CPPS catIIIB
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
• Inflammatory /
Immunological
•
•
•
•
Endocrine
Neurological
Psychological
Role of normal prostate
bacterial flora
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
Inflammatory / Immunological
WBC in EPS or VB-3
Pro-inflammatory cytokines* (IFN,IL-6,IL-8, TNF)
Anti-inflammatory cytokines* (IL-10)
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
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
Endocrine
Testosterone seems to have a protective antiinflammatory effect.
Recent animal studies demonstrate that inflammatory
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
PATHOPHSIOLOGY
Neurological (continued)
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 Cfibers 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
degranulation
pain
Mast cells
NGF
C fibers
pain
CHRONIC NON-BACTERIAL PROSTATITIS
PATHOPHSIOLOGY
Psychological
Psycological stress is a more frequent in patients with chronic nonbacterial prostatitis
‫חיבוק גדול‬
Classification: NIH
Cat I: Acute Bacterial Prostatitis
Cat II: Chronic Bacterial Prostatitis
Cat III: Chronic Pelvic Pain Syndrome (CPPS)
Cat IIIA: Inflammatory CPPS
Cat IIIB: Non-inflammatory CPPS
Cat IV: Asymptomatic Inflammatory Prostatitis
(AIP)
CPPS
‫תסמיני המחלה‬
‫איזור חיץ הנקביים‬
‫בתוך פי טבעת‬
‫גב תחתון‬
‫קצה הפין‬
‫אשך ימין‬
‫בסיס הפין‬
‫אשך שמאל‬
‫שק אשכים‬
‫מרכז הפין‬
‫מפשעה ימין‬
‫מפשעה שמאל‬
‫סביב פי טבעת‬
‫לא ברשימה‬
‫ללא כאב‬
‫מתוך שאלונים שמילאו מאות חולים‬
Chronic Prostatitis Symptom
Index (NIH-CPSI)
Validation Process
Pain
Locations
Severity
Frequency
Voiding
Irritative
Obstructive
Quality of Life/Impact
NIH - CPSI
Suggested Evaluation of a Man with
CPPS
*Mandatory
History Physical examination, including digital rectal examination
Urinalysis and urine culture
Recommended
Lower urinary tract localization test
Symptom inventory or index (NIH-CPSI)
Flow rate
Residual urine determination
Urine cytology
Optional
Semen analysis and cultureUrethral swab for culture
Pressure flow studiesVideo urodynamics (including flow electromyography(
Cystoscopy
Transrectal ultrasound Pelvic imaging (ultrasound, CT, MRI)Prostate-specific antigen)
Nickel, 2002
Is prostatitis a premalignant lesion
Prostate carcinogenesis and
inflammation: emerging insights
Patrick j. et al.,
Carcinogenesis 2005 26(7):1170-1181
Is prostatitis a premalignant lesion
Review
Nature Reviews Cancer
)2007( 269-256
Inflammation in prostate carcinogenesis
Elizabeth A. ,Angelo M. De Marzo
Henrik ,Jianfeng Xu ,PlatzSiobhan Sutcliffe
Yasutomo ,Charles G. Drake ,Grönberg
William G. & William B. Isaacs ,Nakai
Nelson
Is prostatitis a premalignant lesion
Is prostatitis a premalignant lesion
BJU
Is prostatitis a premalignant lesion
Treatment of chronic prostatitis
**
**cannot be recommended as a monotherapy except perhaps in men with associated BPH.
Campbell’s urology
Potential Therapies
Antimicrobials
(6-12 weeks in cat. II and trial of 2-4 weeks in cat. III)
Alpha blockers ??
Muscle relaxants
Anti-inflammatories
Anti-depressants
Phytotherapy, Other- finasteride, pentosan polysulfate,
allopurinol, antioxidants
Repetitive prostatic massage
Biofeedback
Heat treatment
Intra-prostatic injections
Transrectal shock waves
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.
Management Strategies
Antibiotics
Catheterization
Alpha
blockers
Alpha
blockers
Cat I
Antibiotics
Cat II
Antibiotics
Cat IIIA
Cat IIIB
Absess
Drainage
Cat II
Cat IIIA
Cat IIIB
Antibiotics
Antibiotic trial
Alpha-blockers
Alphablockers
Alpha-blockers
Analgesics/antiinflammatories
Anti-inflam
Antibiotic trial
Alpha-blockers
Prostate
Massage
Alpha-blockers
Analgesics/antiinflammatories
Surgery
Muscle relaxants
Phytotherapy
Other medical
Physical ther
Catheterization Alphablockers
Absess
Drainage
Prostate
Massage
Anti-inflam
Muscle relaxants
Surgery
Phytotherapy
Physical ther
Surgery
Supportive therapies
Physical ther
Other medical
Supportive therapies
Physical ther
Surgery
HYPERTHERMIA
How to convey heat to the prostate:
Transrectal (microwave)
Transurethral (microwave)
Interstitial (laser, Nanoparticles)
Tuna (radiofrequency)
Hifu (ultrasound)
All treatments cause some degree of prostate tissue
denaturation and if high temperatures are achieved,
even tissue necrosis
TUMT
• Thermotherapy 40-47 c
• Cooled thermotherapy 80%
MICROWAVE - MECHANISM OF
ACTION
Microwaves produce electromagnetic radiation with
oscillating electrical and magnetic fields. The design of
the antenna seems to affect
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.
LOCAL EFFECT OF TUMT
• 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
Heat Distribution
60
Heating point center
For BPH: 55 to 60° C
For Prostatitis: 47° C
Heating Point
Balloon
Heating
Point Center
The urethral heating System
Thermaspec consists of:
Microwave energy source •
Computerized console •
Multi-use Applicator •
Applicator Assembly
Balloon Channel
Balloon
Heating Point Marker
Balloon Inflate
Urinate Cannel
Applicator
Thermocouple
THERMOTHERPAY
THERMOTHERPAY
Treatment Protocol for Prostatitis
Insertion of catheter
(containing the Applicator)
Inflation of catheter balloon
& repositioning of catheter
Temperature is raised
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
insertion is optional)
Interval between treatments: 1 month
CPPS AND THERMOTHERAPY
Transurethral Microwave Thermotherapy for Nonbacterial Prostatitis: A
Randomized Double-Blind Sham Controlled Study Using New Prostatitis
Specific Assessment Questionnaires
Nickel, J. Curtis; Sorensen, Ron
J Urol 155: 1950-54, 1996.
TUMT COMPLICATIONS
UTI (17%)
HEMATURIA (1.2%)
URINARY RETENTION (23.9%)
DYSURIA (3%)
RETROGRADE EJACULATION (22%)
ED (5.7%)
TUMT MANAGEMENT AFTER PROCEDURE
INDWELLING CATHETER FOR AT LEAST TEN DAYS
TEMPORARY CYSTOSTOMY
TEMPORARY STENT*
Reduced Voiding Symptoms and Bother Without Exacerbating Irritative Symptoms
,Martin K. Dineen etal., Urology Volume 71, Issue 5
Contraindications for TUMT
•
•
•
•
•
•
•
UTI
Penile implants
Artificial sphincter
Urethral stricture
Previous prostate surgery
Leriche syndrome
Prostates under 30 gr or over 100gr.
Injectables to the prostate
Intraprostatic injection in prostatitis
cathegory IIIa And IIIb(CPPS)
•
•
•
•
•
Antibiotics
Zinc
Periprostatic BOTOX
Antibiotics and esracain
Antibiotics and steroids
ROUTS OF INJECTION
Transrectal
Perineal
transurethral
Us guided
Intraprostatic injection chronic
bacterial prostatitis(II)
Intraprostatic injections
Possible side effects
•
•
•
•
Pain
Hematuria
Dysuria
Hemospermia
‫‪SUMMARY‬‬
‫•‬
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‫•‬
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‫•‬
‫מחלה באטיולוגיה לא ברורה‬
‫סימפטומים לא אחידים לא רצופים ולא מוגדרים‬
‫(לעתים קרובות החולים מאובחנים כסובלים ממחלות שונות)‬
‫המטופלים נודדים מרופא לרופא בתקווה שכעת‬
‫סוף סוף יצילו אותם‪.‬‬
‫טיפול שלא תמיד ברור מדוע עוזר ומדוע לא עוזר‪.‬‬
‫מצב זה מביא לתסכול רב למטפל ולמטופל וגרם‬
‫לחוסר אימון הדדי ביניהם‬
‫ולכן‬
NIH Initiative: Multi-disciplinary
Approach to the Study of Chronic
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
– (3) Basic science studies addressing the underlying pathology of
disease.