Review Article
Prostatitis: Recent Update on Etiopathogenesis, Molecular Diagnosis and Role in the Genesis of Benign Prostatic Hyperplasis (BPH) & Prostatic Carcinoma (PCa)
Tahminur Rahman*
Anwer Khan Modern Medical College, India
*Corresponding author: Tahminur Rahman, Anwer Khan Modern medical College, House No17, Road No 8, Dhanmondi R/A, Dhaka 1205, Bangladesh, India
Published: 02 Dec, 2016
Cite this article as: Rahman T. Prostatitis: Recent Update
on Etiopathogenesis, Molecular
Diagnosis and Role in the Genesis of
Benign Prostatic Hyperplasis (BPH) &
Prostatic Carcinoma (Pca). Clin Oncol.
2016; 1: 1155.
Abstract
Prostatitis is a common problem in elderly. Prostatitis is causd by implantation of gram negative
organism by direct route or lymphohematogenous route, instrumentation, inoculation of BCG for
bladder cancer & occasionally as a part of military tuberculosis involving genitourinary system.
Prostatitis can lead to different clinical symptoms like fever, chill, UTI, low back pain, erectile
dysfunction and sometimes in long standing cases can lead to BPH & Pca. Diagnosis of prostatitis
specially that of chronic abacterial prostatitis may be sometimes difficult and this can create a
problem for the patient &the physician. So there is need to identify early molecular markers apart
from routine microscopical, culture & sensitivity on prostatic smear and radiology & imaging and
biopsy tests. The present review article is based on search on different web site, Pubmed, online
journals describe recent update on different types of prostatitis,its etiopathogenesis, role in the
development of BPH & Pca and early molecular makers. These will lead to a better understanding
on prostatitis,open some more research avenues and help in defining better management strategies.
Keywords: Prostaitits; Etiopathegenesis; Role in BPH & Pca; Molecular markers
Introduction
Prostatic lesions are common problem for males of increasing age. Only three pathologic
processes affect the prostate gland with sufficient frequency to merit discussion: inflammation,
benign nodular enlargement, and tumors. Prostatitis may be divided into several categories; acute
and chronic bacterial prostatitis, chronic abacterial prostatiitis, and granulomatous prostatitis [1].
Although prostatitis is much less than that of BPH and Pca but still is important for its varied clinical
presentation, increased morbidity, difficulty in exact early diagnosis and sometimes treatment failure
leading to longterm management. Prostatitis is also important for its longterm complications like
development of BPH and Pca in some cases. Different types of prostatitis, their etiopathogenesis,
molecular mechanisms and genesis in the development of BPH and Pca are discussed below on the
basis of search on different online portals and some text books.
Acute prostatitis
Acute bacterial prostatitis usually results from bacteria similar to those that cause urinary
tract infections. Thus, most cases are caused by various strains of E. coli, other gram-negative
rods, enterococci, and staphylococci. The organisms become implanted in the prostate usually
by intraprostatic reflux of urine from the posterior urethra or from the urinary bladder, but
occasionally they seed the prostate by lymphohematogenous routes from distant foci of infection.
Prostatitis sometimes follows surgical manipulation of the urethra or prostate gland itself, such as
catherterization, cystoscopy, urethral dilation, or resection procedures on the prostate. Clinically,
acute bacterial prostatitis is associated with fever, chills, and dysuria. On rectal examination the
prostate is exquisitely tender and boggy. The diagnosis can be established by urine culture and
clinical features [1].
The symptoms, investigation & treatment modalities are varied among acute prostatitis
admitted in urology, infectious disease, internal medicine & geriatric departments. Those who are
admitted in urology department presented with bladder outlet obstruction, received α blockers &
anti-inflammatory drugs. Those who are admitted in infectious disease department presented with
fever & received longer & more appropriate antibiotic. In geriatric department patients presented
with cognitive disorder and post voidal urine volume measurements. In internal medicine patients presented with wide range of symptoms and had very diverge
investigations and antibiotic regimen. Overall 3:1 ratio of community
acquired acute prostatitis to nosocomial acute prostatitis. Culture
yielded E.coli in (58% of acute prostatititis 68% community acquired
α acute prostititis) [2].
Sometimes acute bacterial prostatitis may occar due to rare
human pathogen like raultella planticola [3], Listeria monocylosenes
[4], Pseudomonas aeniginosa [5]. One study compared the clinical
and microbiological characteristics between bacterial prostatitis and
transrectal biopsy related acute prostatitis. The researchers reviewed
the record of 135 patients admitted in hospitals for acute prostatitis
in 2013. They concluded a higher incidence of septacaemia and
autibiotic resistance bacteria in transrectal biopsy related patients
then spoutaneous acute bacterial prostatitis patients [6].
Another study by Ludwig M [7] concluded acute prostatits does
not seem to represent a major diagnostic therapeutic problem as long
as prostatitic abscess formation is present. Acute bacterial prostatitis
is common in patient population who are at high risk include those
with diabetes, cirrhosis, suppressed immune system [8]. Depending
on history of previous antibiotic use, clinical pictures, Microbiological
features, resistance pattern of the isolate it is advocated that prompt
initiation of effective treatment is essential to decrease morbidity and
mortality in hospital admitted patients of acute bacterial prostatitis
specially after transurethral ultrasound guided biopsy of prostate [9].
Another form of acute bacterial prostatitis is caused by Extended
Spectrum Beta Lactamase (ESBL) Producing E. coli: A study of 1339
hospital admitted patient who reached imipenem finally after not
responding to usual treatment with ciprofloxacin 500 mg BD for 5
days. It emphasises promt initiation of effective antimicrobial therapy
especially with ESBL producing E-coli based on knowledge of local
distribution of pathogen & their susceptibility [10]. Since 2006 ESBL
strain is increasing and presence of ESBL showed more determental
effects on clinical course of the patients resulting in higher rate of
progression rate to chronic prostatitis [11] for early diagnosis of acute
prostatitis. Diagnostic & pronostic value of acute prostatitis depend
on blood culture was evaluated blood culture was positive in 21% of
patients [12]. Other diagnostic tests like urinary leukocyte esterase
and Nitrite dip test for acute prostatitis maybe tried [13] for early
diagnosis of acute prostatitis.
Chronic bacterial prostatitis
Chronic bacterial prostatitis is difficult to diagnose and treat. It
may present with low back pain, dysuria, and perineal and suprapubic
discomfort. Aternatively, it may be virtually asymptomatic. Patients
often have a history of recurrent urinary tract infections (cystitis,
urethritis) caused by the same organism. Because most antibiotics
penetrate the prostate poorly, bacteria find safe heaven in the
parenchyma and constantly seed the urinary tract. Diagnosis of
chronic bacterial prostatittis depends on the demonstration of
leukocytosis in the expressed prostatic secretions, along with positive
bacterial cultures. In most cases, there is no antecedent acute attack,
and the disease appears insidiously and without obvious provocation.
The implicated organisms are the same as those cited as causes of
acute prostatitis.
Chronic abacterial prostatitis
Chronic abacterial prostatitis is the most common form of
prostatitis seen today. Clinically, it is indistinguishable from chronic
bacterial prostatitis. There is no history, however, of recurrent urinary
tract infection. Expressed prostatic secretions contain more than 10
leukocytes per high power field, but bacterial cultures are uniformly
negative. The etiology and pathogenesis of nonbacterial prostatitis
which accounts for 90-95% of cases is largely unknown. Protein
biomarkers like SOD3 and CA1 are identified as potential diagnostic,
marker for non bacterial prostatitis. In a study by (Yan x etal 2015)
they have validated more than 160 samples from various categories of
non bacterial prostatitis (III, a, II b, IV) and matched healthy controls
found two zinc binding protein superoxide dismutase 3 (SOD3) and
carbonic anhydrase 1 (CA1) were significantly higher in all types of
prostatitis than control.
Granulomatous prostatitis
Extra Pulmonary Tuberculosis constitutes 20-25% of all System.
Only 27% of Extra Pulmonary Tuberculosis Causes genitourinary
system [14]. Prostate gland is affected in 2.6% [15] characterized by
the presence of tuberculous granuloma with Langhans giant cell in
the prostate. Although TB seems to be a rare disease 77% of men who
died of tuberculosis of all conditions had prostate TB mostly contacted
during their life time [16]. Some studies suggests that prostate TB like
any other chronic inflammation may predisposeprostate cancer [17].
Granulomatous prostatis may be specific, where an etiologic
infectious agent may be identified or non specific. The most common
cause is related to installation of BCG within the bladder for treatment
of superficial bladder cancer. BCG is an attenuated mycobacterium
strain that gives rise to a histologic picture indistinguishable from that
seen with systemic tuberculosis. However, in this setting the finding of
granulomas in the prostate is of no clinical significance, and requires
no treatment. Fungal granulomatous prostatitis is typically seen
only in immunocompromised hosts. Nonspecific granulomatous
prostatitis is relatively common and represents a reaction to secretions
from ruptured prosatic ducts and acini. Although some of these men
have arecent history of urinary tract infection, bactereia are not seen
within the tissue in nonspecific granulomatous prostatitis.
Administration of Bacillus calmette-Guerin (BCG) has been
shown to cause granulomatous prostatitis mistaken for prostate
cancer [18,19]. Malignant diseases like mantle cell lymphoma
involving the prostate can features as granulomatous prostatitis [20].
Infectious granulomatous prostatitis is uncommon and most cases of
granulomatous prostatitis are classified as nonspecific granulomatous
prostatitis [21,22]. Apart from histopathology granulomatous
prostatitis can be diagnosed by MRI, PET Scan with increased FDG
activity (Flusine 18 flurdeoxygluese) [23-26].
Fat, impaired metabolic syndrome and prostatitis: Fat and
insulin could have a detrimental effect on prostate health boosting
inflammation. This indirect link between metabolic syndrome and
chronic inflammation fat boosts, while androgen receptor activation
counteracts BPH associated prostate inflammation [27]. One review
article focused on the role of HFD in the genesis of oxidative stress,
intra prostatic inflammation and their influences on signaling
pathways that orchestrate various prostate diseases, including cancer
and Oxidative stress in BPH [28].
Chemokine and prostatitis
A variety of chemokines are actively secreted by prostatic
microenvironment causes disruption in tissue hemostasis. The
accumulation of senescent stromal fibroblasts and possibly epithelial
cells may serve as potential driving force behind chemokine secretion
in the ageing enlarged human prostate. This is mediated by MAPK (mitogen activated protein kinase) and P13K (Phosphoinositide
3 kinase) Jignalling which is responsible for cellular proliferative
response [29]. Studies suggest that cytokine family might be associated
with BPH & Pca. Immunology showed immune staining for IL17A,
IL17RA, IL17E, IL17F was significantly elevated in prostatic tissue for
BPH and Pca compared to that of control with increased human of
inflammatory cells and CD 31+ blood vessels [30].
Zinc and prostatitis
Prostatic zinc accumulation is connected with secretory function
of prostate and zinc concentration present in prostatic of diseases
differs greatly from normal level [31]. They reviewed systemic
literature serches as pubmed, embase, CNk1 science direct/Elsevier,
and cochrane library upto March 2015 and found that the zinc
concentration in prostatic fluid and seminal plasma from chronic
prostatitis were significantly higher than normal controls.
Sexual dysfunction & prostatitis
Men with symptomatic benign prostatic hyperplasia and erectile
dysfunction had significant inflammation of the prostate to cause
spurious increase of PSA level and results in unnecessary biopsy
[32,33]. Asymptomatic prostatic inflammation in men with clinical
BPH and erectile dysfunction affects the predictive value of prostatie
specific antigen [34].
Prostatitic & BPH
Chronic prostatic inflammation seems to play a crucial role in
BPH pathogenesis & progression. Several data favors the role of
lymphocytes infiltration in the development of prostatic adenoma as
an effect of self monitoring remodeling process [35].
Chronic prostatic inflammation would lead to tissue demage
and continuous wound healing thus contributing to prostatic
enlargement. (Gandaslia G, 2013) (Kaplal SA, 2016) Several different
stimuli may induce chronic prostatic inflammation which in turn
would lead of tissue damage and continous wound healing thus
contributing to prostatic enlargement [36,37].
Prostatitis & Pca
Infection or inflammation of the prostate (prostatitits) may
increase the chance for prostate cancer while another study shows
infection may help prevent prostate cancer by increasing blood to
the area. In the particular, infection with the sexually transmitted
infections Chlamydia, gonorrhea, or syphilis seems to increase risk.
Finally, obesity and elevated blood levels of testosterone may increase
the risk of inflammation and subsequently prostate cancer [38-40].
Conclusion
From the literature reviewed it is evident that prostatitis is one of the most common urological problems interms of morbidity and its longterm complication can lead to BPH and Pca in some cases, although the evidence is not compelling. Diverse in its clinical manifestation, etiology, treatment modalities has laid the importance of early & proper diagnosis of prostatitis and its effective treatment. As most of the non bacterial prostatitis which accounts for 90-95% of the cases, the etiology is largely unknown estimation of serum protein can be a potential diagnostic marker in this setting. Serum protein SOD3 and CA1 and zinc estimation, different cytokine can also be very helpful to understand the etiopathology of prostatitis, along with radiology & imaging techniques like USG, MRI, culture & sensitivity, Histopathology of prostate & DPRE can be combinedly used for acute diagnosis & better management for prostatitis. These will lead to define better strategies for early diagnosis of different types of prostatitis and can reduce the morbidity from it & prevent progression to BPH & Pca.
Acknowledgement
We are grateful to different on line journals, search line, pubmed, text books for writing this article.
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