Prostate Cancer and Prostatic Diseases (2002) 5, 172–179 ß 2002 Nature Publishing Group All rights reserved 1365–7852/02 $15.00 www.nature.com/pcan Review Management of prostatitis

HS Gurunadha Rao Tunuguntla1 & CP Evans1* 1Department of Urology, University of California Davis School of Medicine and UC Davis Medical Center, Sacramento, California, USA

Prostatitis is a common clinical entity with a prevalence rate of 5 – 9% and accounts for over 2 million hospital visits annually in the USA. It is traditionally classified into acute bacterial, chronic bacterial, abacterial prostatitis and prostatodynia. The recent consensus conference of the US National Institute of Diabetes and Diges- tive and Kidney Diseases in 2000 resulted in renewed interest in the prevalence, etiology, pathogenesis and treatment of the prostatitis syndromes. In this review, we present the contemporary knowledge and experience regarding the etiology, classification, evaluation and treatment of this condition including the role of transurethral microwave hyperthermia and transurethral needle ablation. Prostate Cancer and Prostatic Diseases (2002) 5, 172–179. doi:10.1038=sj.pcan.4500604

Keywords: prostatitis; expressed prostatic secretions; pelvic pain syndrome; midstream urine; microwave thermotherapy; prostatic massage; transurethral needle ablation

Introduction 5 – 10% of patients with prostatitis (Table 1).4 Most patients do not have bacteria in the urinary tract but do Prostatitis is a disease entity that is diagnosed by suffer from urinary symptoms, perineal=suprapubic or symptoms, microscopy of expressed prostatic secretions low back pain and fatigue. Acute bacterial prostatitis is a (EPS) and culture of EPS and segmented urine samples. well recognized infectious disease of the lower urinary It is a common medical condition. The estimated preva- tract different from chronic prostatitis syndromes.5 lence of prostatitis in the US is approximately 5 – 9%.1,2 Different forms of chronic prostatitis syndrome are Between 1990 and 1994 prostatitis accounted for over 2 poorly demarcated and are believed to be caused by million hospital visits per year of which approximately both infectious=non-infectious inflammation of the one-half are to urologists and one-half to primary care prostate and non-inflammatory disease.6 physicians. Prostatitis contributes to approximately 8% of Acute bacterial prostatitis results from acute infection urology office visits and 1% of primary care physician of the prostate by recognized uropathogens (Table 1).7 office visits.1 An average American urologist sees 100 The organisms ascend along the urethra=urethral cathe- patients with prostatitis per year. The disorder severely ters or reach the urinary tract by sexual transmission and impairs the overall quality of life in the afflicted men.3 rarely bacteremia or septicemia. Acute bacterial prostatitis Currently, the etiology of prostatitis (more commonly is mainly due to aerobic Gram-negative rods, predomi- referred to as ‘prostatitis syndrome’) is mostly unknown nantly Escherichia coli and Pseudomonas spp. Obligate and the diagnostic criteria are weak. anaerobic bacteria rarely cause prostatitis. Fungi have

Table 1 = Etiology Bacteriology of acute chronic prostatitis Etiologically recognized Organisms of doubtful Acute and chronic bacterial prostatitis syndromes are the pathogens significance best understood, but least common of the prostatitis syndromes. A causative pathogen is detected in only Escherichia coli Klebsiella spp. Staphylococci Proteus mirabilis Streptococci Pseudomonas aeruginosa *Correspondence: CP Evans, MD, FACS, Department of Urology, Enterococcus fecalis University of California, Davis School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. Modified from:WeidnerWet al. Chronic prostatitis: A E-mail: [email protected] thorough search for etiologically involved microorganisms Received 7 March 2002; revised 24 April 2002; accepted 6 May 2002 in 1461 patients. Infection 1991; 19(Suppl 3): 119 – 125. Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 173 recently been implicated in prostatitis in immunosup- whether pain is the cause or the effect of other pathological pressed patients.8 If left untreated, the infection may processes. It is also difficult to attribute the pain to the result in septicemia or prostatic abscess. prostate, since nonspecific musculoskeletal abnormalities Chronic bacterial prostatitis is usually caused by can cause considerable discomfort in this region. Gram-negative bacteria such as Escherichia coli, Klebsiella and Proteus spp. and occasionally by Gram-positive bacteria such as Enterococcus fecalis, Staphylococcus and Streptococcus. Infections due to Gram-positive bacteria Classification rarely result in recurrent urinary tract infection (UTI) (Table 1). The clinical diagnosis of prostatitis depends on the history The exact etiology of chronic prostatitis=chronic pelvic and physical examination, although there is no patho- pain syndrome (CP=CPPS) is not completely understood gnomonic physical finding or laboratory test. The condi- at present. Organs other than the prostate may be respon- tion results in considerable morbidity and patients may sible for CP=CPPS symptoms. Multiple disorders that experience symptoms for many years. Prostatitis is tradi- have been proposed to be causally associated include tionally classified into four groups: acute bacterial, bladder neck obstruction, urethral stricture, detrusor chronic bacterial, chronic nonbacterial and prostatodynia sphincter dyssynergia and dysfunctional voiding.5,9 (Table 2). The National Institutes of Health (NIH) estab- CPSS may be multifactorial and part of a more lished an International Prostatitis Collaborative Network to generalized pain disorder. Microbiologic, immunologic, improve diagnosis and treatment of prostatitis. This col- neurologic, chemical, psychologic and anatomic factors laborative network has so far convened four consensus are believed to be involved in its etiopathogenesis.10 conferences (in 1995, 1998, 1999 and 2000) to define and High-pressure voiding, ‘intra-prostatic reflux’ of urine,11 classify the syndrome based on contemporary literature autoimmune process,12,13 reflux of urine and metabolites and clinical practice and thereby optimize the diagnosis (urate) into the prostatic ducts=acini14 and infection due and therapy. to coagulase negative staphylococci, chlamydia, urea- The NIH consensus classification of prostatitis syn- plasma, anaerobes, or certain non-culturable organisms dromes22 includes the following four categories: such as ‘Biofilm’ bacteria=viruses=cell-wall deficient 15 – 17 (i) Acute bacterial prostatitis. bacteria have been suggested to result in chronic (ii) Chronic bacterial prostatitis. = non-bacterial prostatitis CPPS. The disorder has been (iii) Chronic prostatitis=chronic pelvic pain syndrome found to be associated with increased blood flow to the (CP=CPPS) prostatic capsule and diffuse flow throughout the 18 (a) Inflammatory prostatic parenchyma. (b) Noninflammatory. Inflammation of the prostate as indicated by leukocytes (iv) Asymptomatic inflammatory prostatitis. in the EPS may be present in 50% of patients with CP=CPPS on random prostate biopsies.19 Interleukins The new consensus classification recognizes pain as the (IL-1) and tumor necrosis factor (TNF-a) have been found primary component of the syndrome. The exclusion cri- in EPS from patients with CPPS.20 Nadler and associates teria include presence of active urethritis, urogenital found that IL-1b and TNF-a levels in EPS are higher in cancer, urethral stricture, or neurovesical dysfunction. men with category CPPS IIIA (inflammatory CPPS, with Patients with category III CPPS have discomfort or pain significant white cells in VB3=EPS=semen) than in those in the pelvic region for at least 3 months with variable with IIIB.20 voiding and sexual symptoms in the absence of demon- Chronic prostatitis has been reported with increased strable infection. Patients with the inflammatory subtype frequency in those with hypochondriasis, depression, of CP=CPPS have leukocytes in their EPS=post-prostate hysteria, somatization and depression.21 About 43% of the massage urine or semen. In contrast, those with the non- patients with chronic prostatitis have elevated Minnesota inflammatory subtype have no evidence of inflammation. Multiphasic Personality Inventory (MMPI) scores. Asymptomatic inflammatory prostatitis (evidence of Similar to other chronic pain syndromes, patients with inflammation in prostate biopsy=semen=EPS=voided chronic nonbacterial prostatitis experience pain as the bladder urine [VB3]; no symptoms) is diagnosed in primary complaint, have a low relationship between those with no history of genitourinary tract pain and is symptoms and findings, and have a history of multiple often diagnosed during evaluation for other genitourin- unsuccessful treatments. It is often difficult to determine ary pathology such as during prostatic biopsy to rule out

Table 2 Traditional classification of prostatitis

Acute bacterial prostatitis Acute bacterial infection of prostate; positive urine cultures; þ =7 positive blood cultures; obstructive voiding symptoms (or urinary retention); generalized symptoms of sepsis Chronic bacterial prostatitis Recurrent urinary tract infections; chronic infection of the prostate Chronic nonbacterial prostatitis Chronic discomfort or pain localized to the pelvis (genitourinary discomfort or pain); no associated bacterial infection; inflammation (WBC) noted in prostate specific specimens (EPS, VB3) Prostatodynia Chronic discomfort=pain localized to pelvis (genitourinary discomfort=pain); no infection= inflammation noted in prostate specific specimens (EPS, VB3)

EPS: expressed prostatic secretions; VB3: voided bladder urine following prostate massage. Adapted from: Drach GW et al. Classification of benign diseases associated with prostatic pain: prostatitis or prostatodynia? J Urol 1978; 120: 266.

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 174 prostate cancer in men with elevated serum prostate cytes in the post-massage specimen compared to the specific antigen (PSA) level or infertility evaluation pre-massage sample indicate NIH category II prostatitis, (increased leukocyte count in seminal fluid). whereas leukocytosis alone indicates NIH category IIIA. Category IIIB is suggested by an absence of bacteria or leukocytes in the post-massage specimen. While using this test, urethritis can be ruled out by a repeat VB1 Diagnostic evaluation collection. The positive predictive value and false-nega- tive rate of PPMT are similar to the Meares-Stamey test.5 Acute bacterial prostatitis Shoskes and associates from the NIH Chronic Prostatitis This is a serious condition usually affecting men between Collaborative Network recently reported that by culturing 20 and 45 y of age and is associated with sudden onset of EPS or semen for 5 days rather than the conventional 2 fever, chills and malaise. Patients often present with days, an additional 7.5% of CPPS patients would be found frequency, dysuria, poor stream, feeling of incomplete positive for bacteria localizing to the prostate gland.27 emptying and discomfort in the pelvis and abdomen. Sometimes there is also back pain. Physical examination reveals a sick patient with Chronic non-bacterial prostatitis=chronic pelvic tenderness in the area of the bladder. Rectal examination pain syndrome is very painful. A hot, enlarged, tender prostate is felt. Patients may sometimes have an abscess requiring Symptoms of chronic non-bacterial prostatitis are differ- drainage to control fever and infection. ent from those of chronic bacterial prostatitis and include The diagnosis is made on the basis of history, clinical pain in lower back, tip of the penis, suprapubic area, examination and laboratory studies. Urinalysis may perineal discomfort, frequency, dysuria, weak stream, reveal bacteriuria and pyuria. Urine cultures are manda- incomplete emptying and painful ejaculation. tory to define the cause and guide therapy. Cultures are Krieger and associates demonstrated that first urine always positive in patients with acute bacterial prostatitis. and MSU have low sensitivity in CPPS, whereas the combination of EPS and post-massage urine are most A CT scan is advised if the patient shows poor response to 28 therapy or examination reveals a soft, tender prostate useful for diagnosis. They also have shown that the with a potential abscess. leukocyte count in post-massage urine is more reliable compared with the analysis of EPS, which is sometimes difficult to recover. Such methods, although useful in Chronic bacterial prostatitis some patients, have not been always reproducible. By using 16S rRNA gene-based polymerase chain This is a common cause of recurrent UTI in men. Patients reaction (PCR), Hochreiter and associates recently found with chronic prostatitis can be asymptomatic between that bacteria are absent in histologically normal prostates episodes of recurrent UTI. Symptoms develop in presence and noted good correlation of inflammation with bacter- of acute UTI due to E. coli, Klebsiella, Pseudomonas spp., ial gene detection.29 They suggest that bacteria may have Enterococci, Staphylococcus aureus or coagulase negative a role in inflammatory prostatitis. Staphylococcus. The National Institutes of Health Chronic Prostatitis Over 90% of symptomatic patients have chronic Symptom Index (NIH-CPSI) provides a valid outcome prostatitis=chronic pelvic pain syndrome. Patients have measure for men with chronic prostatitis.1 The index is discomfort or pain in the pelvic region for at least 3 easily self-administered and is commonly used in clinical months, variable voiding and sexual symptoms in the practice. absence of documented UTI.

Identification of CPPS patients most likely to Lower urinary tract localization studies respond to antibiotics The lower urinary tract localization technique, Meares- 23 Using a 16S recombinant RNA reverse transcriptase- Stamey four-glass test consists of collection of initial polymerase chain reaction (RT-PCR) for the detection of voided urine (VB1), mid stream or second voided urine bacterial genomic fragments, Shoskes and Shahed have = (MSU VB2) representing urethral and bladder specimens, shown that bacterial signals could predict the response to respectively. Expressed prostatic secretions (EPS) are col- antibiotic therapy in men with NIH category III CPPS.13 lected during prostatic massage. Voided bladder sample These authors reported that patients with negative cul- (VB3) is then collected after prostatic massage. All the tures and signals do not respond to antimicrobials and specimens are cultured along with microscopic examina- recommend that such patients should be managed by tion of the sediment in VB1,VB2 and VB3 and EPS is anti-inflammatory or neuromuscular therapies. This tech- subjected to a wet mount microscopy. The test, however, nique, however, has no practical significance as the test is is largely abandoned by urologists in North America currently unavailable to the average clinician. since it is expensive, cumbersone, does not predict response to therapy and may lead to false-positive and 24,25 false-negative results. Nickel suggested a more simple Asymptomatic inflammatory prostatitis (AIP) and less expensive screening technique (Pre- and post- massage test, PPMT).26 In this, urine specimens are col- Men with AIP are asymptomatic and are detected by lected before and after a vigorous prostatic massage. either prostatic biopsies performed for an elevated PSA or Increased number of uropathogenic bacteria and leuko- during an infertility work-up.31

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 175 sulfamethoxazole (TMP-SMX) alone or in combination Treatment (Figure 1) depending on the organism(s), whereas fluoroquinolones Acute bacterial prostatitis is almost always curable (ciprofloxacin=levofloxacin) or TMP-SMX5 may be used with appropriate antimicrobials and antibiotics such for outpatient therapy.32 The antibiotics should be con- as fluoroquinolones and cephalosporins, respectively. tinued for 4 weeks.5 Patients with chronic bacterial prostatitis, however, may Patients may benefit from alpha-blockers to relax the have residual bacteria in the prostate following therapy. prostate and anti-inflammatory agents. Per-urethral cathe- terization is not advised as it may prolong the infection or result in epididymitis. Suprapubic cystostomy may occa- NIH category I (acute bacterial prostatitis) sionally be required for painful urinary retention. Patients also need bed rest, analgesics and stool softeners. Oral fluoroquinolones are appropriate for patients who A poor response to antibiotic therapy may be due to the are able to tolerate fluids and can be managed on an development of a prostatic abscess which, if documented outpatient basis. However, many patients with acute by ultrasound or CT scan, can be drained by transurethral bacterial prostatitis need hospital admission due to the or transperineal approach. acute and severe pain, which requires intravenous (i.v.) fluids and i.v. antibiotics. Those on i.v. antibiotics are later switched to oral therapy as soon as possible based on the outcomes of cultures and susceptibility data. NIH category II (chronic bacterial prostatitis) The i.v. antibiotics commonly used include quinolones (ciprofloxacin or levofloxacin),5 gentamycin, cephalo- Treatment of chronic bacterial prostatitis is of two types: sporins, vancomycin, penicillin and trimethoprim- curative and suppressive.

Figure 1 Management algorithm for prostatitis syndromes.

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 176

Figure 1 Continued.

Curative therapy. This includes a 12-week course of TMP- continued.5 This includes TMP-SMX, nitrofurantoin, tetra- SMX (30% cure rate) or fluoroquinolones (levofloxacin= cycline or cephalothin continued for 6 – 10 weeks. norfloxacin=ciprofloxacin) (75% cure rate).5 If the patient continues to have symptoms after anti- biotic therapy, repetitive prostatic massage is advised Suppressive therapy. If the patient becomes asymptomatic along with further course of antibiotics. Prophylactic but cultures remain positive after 4 – 6 weeks of antibiotics, low-dose antibiotics are indicated for those whose a low-dose suppressive dose of antibiotic may need to be infection recurs.

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 177 The long-term results of antimicrobial therapy with Phytotherapies such as quercetin (a bioflavonoid),38 regard to recurrence and symptom eradication, however, pentosan polysulfate,5 systemic medications (gabapentin, are unknown5 although eradication of the pathogen in EPS tricyclic antidepressants, and striated muscle relaxants), has been reported in 92% of patients 3 months after therapy and stress reduction therapy have also been tried. Quer- and in 70 – 80% of those evaluated at 12 – 24 months.33 cetin has been reported to result in symptom relief in 67% Results with TMP-SMX have remained poor (cure rates of patients in a preliminary double-blind placebo trial.38 between 15 and 60%)34 compared to quinolones.35 Larger well-designed, randomized, placebo-controlled studies are, however, warranted. Finasteride has been reported to provide symptom Indications for surgery relief when used in patients with benign prostatic hyper- Surgical therapy is only the last resort and is used for plasia (BPH) and CPPS with improvement in the NIH- 39 bladder neck obstruction, urethral strictures, and pro- CPSI and BPH symptom scores, whereas pentosan static calculi in conjunction with persistent bacterial polysulfate has been found to be effective in those with presence in the prostate. Radical transurethral resection suprapubic pain and irritative voiding symptoms. Shahed of the prostate (TURP) or total prostatectomy is indicated and Shoskes have demonstrated induction of anti-oxidant only in those whose the prostatic fluid persistently grows enzyme gene expression in CPPS and suggested that 40 the same bacterium, and only after the confirmation of the CPPS may be targeted with anti-oxidant therapy. prostatic origin of the bacterium by prostatic biopsy.5 Radical TURP may result in incontinence and erectile Heat therapies dysfunction and may not always relieve symptoms. Transurethral microwave hyperthermia41 and transure- thral microwave thermotherapy (TUMT)42 have been NIH category IIIA (inflammatory chronic pelvic pain used in the treatment of chronic nonbacterial prostatitis. syndrome) and IIIB (non-inflammatory chronic These techniques increase temperature of the prostate pelvic pain syndrome) resulting in symptom relief. TUMT has been reported to improve symptom scores by 74.9% with minimal mor- In view of uncertainty about etiology, treatment of bidity.43 In a randomized, double-blind, sham-controlled chronic nonbacterial prostatitis remains speculative. study using validated prostatitis symptom severity index Most treatment is aimed at relieving symptoms and not and symptom frequency questionnaires, Nickel and at curing the disease. In addition, it is not clear whether associates have demonstrated beneficial effect of TUMT therapy for IIIA and IIIB prostatitis syndromes should compared to the sham group.42 Fifty per cent of patients differ because the role of inflammation in these syn- in the sham group had a favorable response to a subse- dromes is incompletely understood. quent TUMT. Patients in the TUMT group continued to Use of antibiotics in NIH category III is based on the have symptomatic improvement over 21 months. uncertain etiology and the possibility that a potential A few European studies have shown that transurethral pathogen or a cryptic nonculturable organism may be needle ablation (TUNA) improves the symptoms and causative. A 6-week course has been suggested, which well being in patients with chronic nonbacterial prostati- may be continued for a further 6 weeks if the symptoms < 5 tis with small ( 20 ml) prostates over a follow up period improve. The same type of antibiotics that are used in of 12 months.44,45 Those with severe symptoms (NIH category II are combined with agents for chlamydia and score, 30 – 43) have been reported to have greater and ureaplasma such as tetracyclines. Combination of analgesics, earlier (at 3 months) improvement than those with mild alpha-blockers (tamsulosin) antibiotics (TMP-SMX, to moderate symptom scores (score, < 30) with 12% less fluoroquinolones or tetracycline), and muscle relaxants requirement for analgesics, alpha-blockers and antibiotics such as diazepam coupled with prostatic massage and compared with the non-TUNA group. supportive therapy (perineal support, pelvic floor phy- Heat therapies in prostatitis are currently only experi- siotherapy, biofeedback and relaxation therapy) has been mental with potential for minimal benefit. They may be reported to yield higher cure rate and relief of pain and offered as a last resort in patients willing to accept the voiding symptoms compared to antibiotics alone and is 36 potential morbidity and likelihood of failure of symptom the treatment option favored by most urologists. relief.5 Alpha-1a blockers have been found to result in durable symptom relief and improved recurrence rates in both bacterial and non bacterial chronic prostatitis.37 Some NIH category IV (asymptomatic inflammatory patients with severe discomfort may require TURP. prostatitis, AIP) Nickel advocated concurrent ‘triple-therapy’ for cate- gory IIIB prostatitis including high-dose alpha-blockade, No specific treatment is warranted in these patients a short-term narcotic analgesic and a muscle relaxant such except in those with elevation of PSA or infertility. as diazepam.5 The patient is advised to stay off work for the first 2 weeks, following which the narcotic analgesic is replaced by a nonsteroidal anti-inflammatory agent such as ibuprofen or acetaminophen with codeine and diaze- Role of prostatic massage in prostatitis pam is tapered. The alpha-blocker is continued for 3 months or longer. Biofeedback, relaxation exercises, Prostatic massage has recently been re-popularized,46 psychotherapy and lifestyle changes are advised if triple partly due to the failure of medical therapy to improve therapy fails. symptoms and partly due to the belief that chronic

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans 178 bacterial infection exists in the blocked prostatic ducts or 11 Blacklock NJ. The anatomy of the prostate: relationship with microabscesses. Antibiotic coverage is recommended prostatic infection. Infection 1991; 19(Suppl 1): 111. along with prostatic massage as the latter can disseminate 12 Nickel JC et al. Pathogenesis of chronic bacterial prostatitis in an 5 animal model. Br J Urol 1990; 66: 47. the intraprostatic cryptic bacteria. 13 Alexander RB, Brady F, Ponniah S. Autoimmune prostatitis: In a recent study, 46% of evaluable patients had more evidence of T-cell reactivity with normal prostatic proteins in than 60% improvement in the symptom severity, whereas men with a history of prostatitis. J Urol 1997; 157: S934. 27% had improvement in the frequency of symptoms.47 14 Persson BE, Ronquist G. Evidence for a mechanistic association Thirty-three per cent of patients experienced a marked between nonbacterial prostatitis and levels of urate and creati- subjective improvement. The combination of prostatic nine in expressed prostatic secretion. J Urol 1996; 155: 958. 15 Meares EJ. Prostatitis. Med Clin North Am 1991; 75: 405. massage and antibiotics for refractory prostatitis albeit 48 16 Nickel JC, Costerton JW. Bacterial localization in antibiotic- promising, needs further confirmation. refractory chronic bacterial prostatitis. Prostate 1993; 23: 107. 17 Nickel JC et al. bacterial biofilms: influence on the pathogenesis, diagnosis and treatment of urinary tract infections. J Antimicrob Chemother 1994; 33: 41. Conclusions 18 Cho IR et al. Prostate blood flow characteristics in the chronic prostatitis=chronic pelvic pain syndrome. J Urol 2000; 163: Prostatitis is diagnosed by symptoms or microscopy= 1130 – 1133. culture of segmented urine samples and expressed pro- 19 True LD et al. Prostate histopathology and the chronic prostati- static secretions. The condition is poorly understood and tis=chronic pelvic pain syndrome: a prospective biopsy study. difficult to treat. From a diagnostic and therapeutic J Urol 1999; 162: 2014. 20 Nadler RB et al. IL-1 beta and TNF-alpha in prostatic secretions standpoint, bacterial prostatitis should be distinguished are indicators in the evaluation of men with chronic prostatitis. from chronic pelvic pain syndrome. Further research is J Urol 2000; 164: 214 – 218. warranted to better understand the etiology and patho- 21 Berghuis JP et al. Psychological and physical factors involved in genesis of prostatitis syndrome and thereby improve the chronic idiopathic prostatitis. JUrol1998; 159: 1422. diagnosis and therapy of this common condition. Agents 22 Krieger JN, Nyberg L Jr, Nickel JC. NIH Consensus Definition that modulate the inflammatory response and the inter- and Classification of Prostatitis. JAMA 1999; 282: 236 – 237. 23 Meares EM, Stamey TA. Bacteriologic localization patterns in cellular and neurobiological signaling may, in future, play bacterial prostatitis and urethritis. Invest Urol 1968; 5: 492. an important role in the treatment of chronic pelvic pain 24 Moon TD. Questionnaire survey of urologists and primary care syndrome. Future randomized studies should focus on physicians’ diagnostic and treatment practices for prostatitis. determination of the true efficacy of various treatment Urology 1997; 50: 543. modalities. Studies aimed at more effective delivery of 25 Nickel JC et al. Diagnosis and treatment of prostatitis in Canada. antimicrobial=immunological agents may improve the Urology 1998; 52: 797. outcome of therapy. 26 Nickel JC. The pre and post massage test (PPMT): A simple screen for prostatitis. Tech Urol 1997; 3: 38. 27 Shoskes DA et al. Bacterial cultures of urine, prostatic fluid and semen of men with chronic pelvic pain syndrome: role References of culture for 2 vs 5 days [Abstract 102]. J Urol 2000; 163 (Suppl): 24. 1 Litwin MS et al. The National Institute of Health Chronic Pros- 28 Krieger JN, Jacobs J, Ross SO. Detecting urethral and prostatic tatitis Symptom Index: development and validation of a new inflammation in patients with chronic prostatitis. Urology 2000; outcome measure. Chronic Prostatitis Collaborative Research 55: 186 – 192. Network. J Urol 1999; 162: 369 – 375. 29 Hochreiter WW, Duncan JL, Schaeffer AJ. Evaluation of the 2 Nickel JC, Nyberg LM, Hennenfent M. Research guidelines for bacterial flora of the prostate using 16S rRNA gene based chronic prostatitis: consensus report from the first National polymerase chain reaction. JUrol2000; 163: 127 – 130. Institutes of Health International Prostatitis Collaborative Net- 30 Shoskes DA, Shahed A. Presence of bacterial signal in expressed work. Urology 1999; 54: 229 – 233. prostatic secretions predicts response to antibiotic therapy in men 3 McNaughton-Collins M et al. Quality of life is impaired in men with chronic pelvic pain syndrome [Abstract 99]. JUrol2000; 163 with chronic prostatitis: results from the NIH Cohort Study (Suppl): 23. [Abstract 98]. J Urol 2000; 163(Suppl): 23. 31 Dimitrakov J et al. Recent developments in diagnosis and therapy 4 Weidner W et al. Chronic prostatitis: a thorough search for of the prostatitis syndromes. Curr Opinion Urol 2001; 11:87– 91. etiologically involved microorganisms in 1461 patients. Infection 32 Bjerklund Johansen TE et al. The role of antibiotics in the treat- 1991; 19(Suppl 3): 119 – 125. ment of chronic prostatitis: a consensus statement. Eur Urol 1998; 5 Nickel JC. Prostatitis: evolving management strategies. Urol Clin 34: 457 – 466. North Am 1999; 26: 737 – 751. 33 Weidner W et al. Outcome of antibiotic therapy with cipro- 6 National Institutes of Health Summary Statement. Presented at floxacin in chronic bacterial prostatitis. Drugs 1999; 58(Suppl 2): the National Institutes of Health=National Institute of Diabetes 103 – 106. and Digestive and Kidney Disease Workshop on Chronic Pros- 34 McGuire EJ, Lytton B. Treatment with trimethoprim-sulfametha- tatitis. National Institute of health, Bethesda, December, 1995. zole. Urology 1976; 7: 499. 7 Nickel JC, Bruce AW, Reid G. Pathogenesis, diagnosis and treat- 35 Schaeffer AJ, Darras FS. The efficacy of norfloxacin in the ment of the prostatitis syndromes. In: Krane, RJ, Siroky MB (eds). treatment of chronic bacterial prostatitis refractory to Clinical Urology. Lippincott: Philadelphia, 1994, p 925. trimethoprim-sulfamethoxazole and=or carbenicillin. J Urol 1990; 8 Elert A et al. Isolated candial prostatitis. JUrol2000; 163: 244. 144: 690. 9 Kaplan SA et al. Pseudodyssynergia (contraction of the external 36 Barbalias GA, Nikiforidis G, Liatsikos EN. Alpha-blockers for the sphincter during voiding) misdiagnosed as chronic nonbacterial treatment of chronic prostatitis in combination with antibiotics. prostatitis and the role of biofeedback as a therapeutic option. J Urol 1998; 159: 883 – 887. JUrol1997; 157: 2234. 37 Barbalias GA. Clinical and therapeutical guidelines for chronic 10 Special Report on Prostatitis: Initiatives and Future Research. prostatitis. Letter to the Editor. Eur Urol 2000; 37:116– 117. Highlights of the Second International Prostatitis Collaborative 38 Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men Network Meeting, 3 – 5 November 1999, Bethesda, MD. Rev Urol with category III chronic prostatitis: a preliminary prospective, 2000; 2: 158 – 166. double-blind, placebo-controlled trial. Urology 1999; 54: 960 – 963.

Prostate Cancer and Prostatic Diseases Management of prostatitis HS Gurunadha Rao Tunuguntla and CP Evans

39 Leskinen M, Lukkarinen O, Marttila T. Effects of finasteride in 43 Mene MP et al. Transurethral microwave hyperthermia in the 179 patients with inflammatory chronic pelvic pain syndrome: a treatment of chronic non-bacterial prostatitis. J Urol 1998; 159: double-blind, placebo-controlled, pilot study. Urology 1999; 53: 1422 – 1423. 502 – 505. 44 Giamakopoulos X et al. Chronic nonbacterial prostatitis and 40 Shahed A, Shoskes DA. Oxidative stress in prostatic fluid of men TUNA: 5 years clinical experience. Presented at the XVth Congress with chronic pelvic pain syndrome: correlation with bacterial of the European Association of Urology,12– 15 April 2000, Brussels. growth and treatment response [Abstract 103]. J Urol 2000; 163 45 Chang PH, Tsai EM, Chiang CP. Pilot study of transurethral (Suppl): 24. needle ablation (TUNA) in treatment of nonbacterial prostatitis. 41 Kuz’min MD, Ivanov IuB, Bukharin OV. Treatment of chronic J Endourol 1997; 11: 367 – 370. prostatitis complicated by asthenozoospermia using transure- 46 Nickel JC et al. Prostatitis unplugged? Prostatic massage revisi- thral radio-wave hyperthermia. Urologiia 1999; 4:36– 39. ted. Tech Urol 1999; 5:1– 7. 42 Nickel JC, Sorensen R. Transurethral microwave thermother- 47 Nickel JC et al. Repetitive prostatic massage therapy for chronic apy for nonbacterial prostatitis: a randomized double-blind refractory prostatitis: the Philippine experience. Tech Urol 1999; 5: sham controlled study using new prostatitis specific assess- 146 – 151. ment questionnaires. J Urol 1996; 155: 1950 – 1954; discussion 48 Dimitrakov J et al. Recent developments in diagnosis and therapy 1954 – 1955. of the prostatitis syndromes. Curr Opinion Urol 2001; 11:87– 91.

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