PROSTATITIS

למרכ יאופר זכרמ , תיגולורוא הקלחמ , ןייטש יבא ' פורפ

תינומרע תקלד גוויס ןוחביא לופיט

  

BPH ב לופיטכ ותוליעיו (TUMT ( הכפש ךרד םומיחב לופיט

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!

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תינומרעב תקלד תחתפתמ דציכ

י " חווטמ םיאצויו תינומרע תוטולב לש תוירוניצב םילחנתמ םיקדייח ע תינוסיחה תכרעמה לש םירוטקפ וא הקיטויביטנא לש העפשהה ) BIOFILMS ( םיטגרגא תריצי ) תקקפ ( סיזובמורט עקר לע תינומרעב םד תקפסאב תוערפה לש הכומנה תוליעיל תוביסה תחא הארנכ וז .

.

םינטקה םידירוב תינורכ סיטיטטסורפ םע םילוחב יטויביטנא לופיט • • תורבטצהל םרוג תוטולבל ביבסמ קלחה רירשה לש ןיקת אל דוקפת .

לזונה אלל םהוזמ לזונ םיאלמ םיללח תינומרעה תמקרב םיעיפומ ךשמהב .

הכיפש תעב יוניפ תלוכי לכ • •

PROSTATITIS UNDER THE MICROSCOPE

םיללוחמ םזינגרואורקימ

' וכו סנומודואיספ

ךות סקולפר

, ילוק ( ENTEROBACTERIA כ " דב

םיילילש םרג

םיקדייח לש ןונגנמב ןתשה יכרדב תקלד תובקעב ) םיללוחמהמ 90%

.

יטטסורפ

) םהינימל םיקוק ( םייבויח םרג םיקדייח םייבוריאנא ??

תינומרע תקלדל רושק הכפש תקלד םאה הידימלק תוירטפ םיסוריו ????

תברתל ןתינ אלש םימרוג • • • • • • •

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 90% Asymptomatic Inflammatory Prostatitis Cat IV: (AIP)

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 anti inflammatory 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 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

degranulation Mast cells pain NGF C fibers pain

CHRONIC NON-BACTERIAL PROSTATITIS

PATHOPHSIOLOGY

Psychological Psycological stress is a more frequent in patients with chronic non bacterial prostatitis

לודג קוביח

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

הלחמה ינימסת

םייבקנה ץיח רוזיא תעבט יפ ךותב ןותחת בג ןיפה הצק ןימי ךשא ןיפה סיסב לאמש ךשא םיכשא קש ןיפה זכרמ ןימי העשפמ לאמש העשפמ תעבט יפ ביבס המישרב אל באכ אלל

םילוח תואמ ואלימש םינולאש ךותמ

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

Cat I Antibiotics Cat II Antibiotics Catheterization Alpha blockers Absess Drainage Prostate Massage Surgery Cat IIIA Antibiotic trial Alpha-blockers Cat II Antibiotics

Alpha blockers Alpha blockers

Cat IIIB Absess Drainage Alpha-blockers Analgesics/anti inflammatories Antibiotics Alpha blockers Prostate Massage Surgery Anti-inflam Muscle relaxants Phytotherapy Physical ther Other medical Supportive therapies Physical ther Surgery Cat IIIA Cat IIIB Antibiotic trial Alpha-blockers Anti-inflam Phytotherapy Other medical Physical ther Surgery Alpha-blockers Analgesics/anti inflammatories Muscle relaxants Physical ther Supportive therapies

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 with the increased urinary flow rate after TUMT consisting • 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

Heat Distribution

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 Inflate Applicator Balloon Heating Point Marker Urinate Cannel 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

הרורב אל היגולויטאב הלחמ םירדגומ אלו םיפוצר אל םידיחא אל םימוטפמיס ) תונוש תולחממ םילבוסכ םינחבואמ םילוחה תובורק םיתעל ( תעכש הווקתב אפורל אפורמ םידדונ םילפוטמה .

םתוא וליצי ףוס ףוס .

רזוע אל עודמו רזוע עודמ רורב דימת אלש לופיט םרגו לפוטמלו לפטמל בר לוכסתל איבמ הז בצמ םהיניב ידדה ןומיא רסוחל • • • • •

ןכלו

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.