• Nutraceuticals in Prostate Disease: The Urologist's Role
  
• Clinical Phenotyping in Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Interstitial Cystitis
  
• Clinical Phenotyping of Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Correlation with Symptom Severity
  
• Phenotypic Approach to the Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome
• Chronic Prostatitis Clinic: Approach to Diagnosis and Treatment

Nutraceuticals in Prostate Disease: The Urologist's Role

J. Curtis Nickel, MD, FRCSC,* Daniel Shoskes, MD, MSc, FRCS(C),† Claus G. Roehrborn, MD, FACS,‡ Mark Moyad, MPH§

*Department of Urology, Queens University, Kingston, Ontario, Canada; †Department of Urology, Glick Urological Institute Cleveland Clinic Foundation, Cleveland, OH; ‡Department of Urology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; §Department of Urology, University Medical Center, Ann Arbor, MI

ABSTRACT

Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease.
 

[Rev Urol. 2008;10(3):192-206]
© 2008 MedReviews, LLC
 

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Clinical phenotyping in chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: a management strategy for urologic chronic pelvic pain syndromes

DA Shoskes¹, JC Nickel², RR Rackley¹ and MA Pontari³

¹Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH, USA; ²Department of Urology, Queens University, Kingston, Ontario, Canada and ³Department of Urology, Temple University, Philadelphia, PA, USA

ABSTRACT

     The urologic chronic pain conditions such as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis are syndromes whose evaluation and management are controversial. Part of the difficulty in diagnosis and therapy is the heterogeneity of etiologies and symptoms. We propose a six-domain phenotype, which can classify these patients clinically and can direct the selection of therapy in the most evidence based multimodal manner. The domains are urinary, psychosocial, organ specific, infection, neurologic and tenderness of skeletal muscles. This system is flexible and responsive to new biomarkers and therapies as their utility and efficacy are proven.

Prostate Cancer and Prostatic Diseases advance online publication, 22 July 2008; doi:10.1038/pcan.2008.42

Keywords: chronic prostatitis; interstitial cystitis; chronic pain

Correspondence: Dr DA Shoskes, Glickman Urological and Kidney Institute, The Cleveland Clinic, Desk A100, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
E-mail: dshoskes@gmail.com
Received 5 June 2008; accepted 26 June 2008

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Prostatic Diseases and Male Voiding Dysfunction
Clinical Phenotyping of Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Correlation With Symptom Severity

Daniel A. Shoskes, J. Curtis Nickel, Robert Dolinga, and Donna Prots
 

ABSTRACT

OBJECTIVES

To propose a clinical phenotype system (urinary, psychosocial, organ specific, infection, neurologic/systemic, and tenderness [UPOINT]) to classify patients with urologic pelvic pain to help understand the etiology and guide therapy. We wished to validate this system in men with chronic pelvic pain syndrome (CPPS). CPPS is a heterogeneous syndrome with a variable treatment response.

METHODS

A total of 90 men with CPPS were retrospectively classified in each domain of our UPOINT system
and the symptoms were measured using the Chronic Prostatitis Symptom Index.

RESULTS

The percentage of patients positive for each domain was 52%, 34%, 61%, 16%, 37%, and 53% for the urinary, psychosocial, organ specific, infection, neurologic/systemic, and tenderness domains, respectively. Of the 90 patients, 22% were positive for only 1 domain, and a significant stepwise increase was found in the total Chronic Prostatitis Symptom Index score as the number of positive domains increased. A symptom duration of >2 years was associated with an increase in positive domains (2.9 ±0.21 vs 2.3 ± 0.14, P = .01). Comparing the total Chronic Prostatitis Symptom Index score with the presence of each domain revealed significantly increased symptoms in patients positive for the urinary, psychosocial, organ specific, and neurologic/systemic domains. When this analysis was repeated for the pain subscore, the psychosocial, neurologic/systemic, and tenderness domains had significantly greater scores. Only the psychosocial and neurologic domains influenced the patients’ quality of life.

CONCLUSIONS

Applying the UPOINT system to patients with CPPS can discriminate clinical phenotypes, allowing for hypothesis testing for etiology and therapy. The number of positive domains correlated with symptom severity and a longer duration of symptoms increased the number of positive domains. Because each domain has specific targeted therapies, we propose that multimodal therapy might best be guided by the UPOINT phenotype.

UROLOGY 73: 538 –542, 2009. © 2009 Elsevier Inc.

D. Shoskes is a paid consultant to Farr Labs and a stock holder in Triurol; J. C. Nickel has received grants/research support/scientific study from GlaxoSmithKlein, Merck, Ortho-McNeil, Stellar, Watson Pharmacueticals, Allergan, American Medical Systems, and Pfizer and is a consultant to Farr Laboratories, Merck-Frosst Canada, Ortho-McNeil, Glaxo-Smith-Kline, Triton Pharma, and Watson.
From the Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; and Queens University, Kingston, Ontario Canada
Reprint requests: Daniel Shoskes, M.D. Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195.
Submitted: July 22, 2008, accepted (with revisions): September 10, 2008

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Phenotypic Approach to the Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

J. Curtis Nickel, MD, and Daniel Shoskes, MD

There is no one unifying etiological mechanism or specific curative therapy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, there is sufficient evidence to suggest that each of the proposed mechanisms may be important in some patients, and that many of our evaluated treatments do in fact work in subgroups of patients. We hypothesize that CP/CPPS patients are not a homogenous group suffering from a single disease entity. Rather, CP/CPPS patients are actually unique individuals with differing clinical phenotypes based on various etiological mechanisms with distinctive symptom complexes and progression trajectories. We call this the “Snow Flake Hypothesis.” We propose the UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, and tenderness domains) clinical phenotyping classification; we have validated the concept in a CP/CPPS cohort and have suggested that phenotypically directed therapy will improve our clinical treatment outcomes.

Chronic Prostatitis Clinic: Approach to Diagnosis and Treatment

Dr. Daniel Shoskes

www.dshoskes.com/cpclinic.html
 

Initial Appointment

Patients should arrive with a fairly full bladder and be off of all antibiotics for at least 2 weeks (preferably 4 weeks) in order for the cultures to be accurate. If you are unable or unwilling to stop taking antibiotics, an appointment can still be made, but cultures will not be done. After registering and filling out a brief questionnaire, patients are asked to urinate into a machine to measure urine flow (Uroflow) and have an ultrasound of their bladder to assess adequate bladder emptying. A full history and physical exam is then performed along with review of any past medical records. Cultures are obtained from urine and from prostatic fluid expressed during a rectal exam. The fluid is also examined microscopically for the presence of white cells.

Approach to Prostatitis

Conceptually, there are 3 aspects of all forms of inflammatory prostatic disorders:

1. Prostatic Injury: The injury to the prostate is usually from an initial infection but could possibly be traumatic (vigorous mountain biking), mechanical (obstruction of ejaculatory ducts) or chemical (reflux of urine into prostatic ducts). The injury itself does not produce symptoms
2. Injury Response - Inflammation: In response to the injury and release of chemical messengers (chemokines and cytokines), an inflammatory infiltrate may develop. It's purpose is to remove the source of injury (eg bacteria) and assist in the healing process. This inflammatory response can produce pain and swelling. Because of the variable and interconnected innervation of the area, the pain may be felt in the area of the prostate (perineum), penis, lower back or scrotum.
3. Injury Response - Neuromuscular: In response to the injury, inflammation and pain, there can be a constellation of voiding symptoms and pain related to the pelvic muscles, nerves and bladder neck. These may include reduced stream, double voiding, frequency, nocturia, and urgency. Pelvic muscle spasm in response to infection or inflammation can propagate all the symptoms (pain, voiding, sexual). Longstanding chronic pain can change the nervous system's responses to pain and can lead to hyperalgesia (non-painful stimulus felt as painful) and allodynia (pain without a painful stimulus). Chronic pain can also lead to depression, increased stress, helplessness and hopelessness which can interfere with all aspects of quality of life.

Our approach is to determine the relative contribution of each of these factors and tailor the therapy accordingly. We use a 6 point classification that covers Urinary dysfunction, Psychosocial, Organ specific changes (bladder and prostate), Infection, Neurologic/systemic dysfunction and pelvic muscle Tenderness (UPOINT classification). Therapy is then directed at all domains that are present, combining therapies as necessary. More information is available on the UPOINT FAQ page.

Therapies

Based on the classification of the prostatic disorder using the above scheme, some or all of the following treatment options are available. A study examining the short and long term results of patients treated at our clinic is here.

Supportive Measures:

All chronic prostatitis patients may derive some benefit from general supportive measures such as hot (sitz) baths, avoiding food triggers (caffeine, spicy foods, alcohol) and using a cushion for prolonged sitting. If these don't help the symptoms however, then they need not be continued.

Antibiotics:

Antibiotics alone, especially if chosen on the basis of cultures of prostatic fluid and degree of prostatic penetration can be effective, although protracted courses are often required. Up to 60% of men with a first occurrence of chronic prostatitis will respond completely to antibiotics alone. Since most of our patients have typically failed multiple previous courses of antibiotics, we seldom use them as the only therapy. We do look for yeast/fungi in our cultures and treat with antifungal medications if the cultures are positive. We have not found anti-fungal therapy to be helpful if these cultures are negative. Most men with chronic prostatitis will have positive cultures for low counts of typical skin bacteria. It is unlikely that treatment of these bacteria will improve symptoms. If treatment eliminates the bacteria but symptoms are not improved, prolonged courses of antibiotics are not helpful and may be harmful. Most antibiotics typically used for prostatitis have anti-inflammatory properties as well, so having symptoms improve temporarily while taking antibiotics is not proof that an infection is present.

Bioflavonoids:

Quercetin is a natural antioxidant bioflavonoid which has been shown to improve inflammation and symptoms in men with nonbacterial prostatitis/chronic pelvic pain syndrome. We have been using quercetin either alone or in combination with bee pollen, which has shown beneficial effects in European studies.

Alpha Blockers:

Use of alpha blocking agents can improve the urinary stream and often reduce the other voiding symptoms in patients with chronic prostatitis. We usually start with tamsulosin (Flomax) or alfusozin (Uroxatral) in patients with voiding symptoms and those who do not empty their bladders well.

Neuromuscular Therapy:

If infection and inflammation have been ruled out, symptoms may be caused by a primary neuromuscular problem such as pelvic muscle spasm. Therapies include pelvic floor physical therapy, biofeedback, acupuncture, muscle relaxants, and anti-spasmodics. Referral to a pain specialist may be necessary. If chronic pain has led to stress, depression or an inability to cope, psychologic or psychiatric referral can be helpful (and it's use in conjuction with other therapies does NOT mean that the condition is "all in your head"!).
Interstitial Cystitis Therapies:

The symptoms of interstitial cystitis and chronic prostatitis can significantly overlap. In our experience, men with interstitial cystitis typically have more urinary pain and frequency than those with prostatitis and their pain is worse with a full bladder and better or even gone after urination. Therapies we have used with success in men with interstitial cystitis include quercetin, Atarax, Elavil, Lyrica and Neurontin. In extreme cases, neuromodulation can be used.

Transurethral Resection (TUR):

Transurethral resection of the prostate is rarely indicated in chronic prostatitis and can make the patient worse if done in the face of ongoing infection and inflammation. Resection of prostatic calcifications, especially those along the "surgical capsule" of the prostate is risky and seldom effective. There are however unusual specific circumstances where TUR may play a role.

1) In the patient with recurrent bacterial prostatitis and concurrent significant benign enlargement of the prostate (BPH). Recurrent infections may be due to incomplete emptying of the bladder due to BPH. If medical therapy of the BPH is not effective, then TUR of the prostate after ensuring that ALL INFECTION IS CLEARED is a reasonable approach.
2) Central prostatic stones associated with recurrent infection or obstruction of the ejaculatory ducts that drain the seminal vesicles. In contrast to the peripheral speckled calcifications seen most often in patients with chronic prostatitis, rarely some patients will have larger stones that are nearer to the urethra and may cause blockage, which is seen by transrectal ultrasound. A very limited TUR of the prostate and/or ejaculatory ducts can clear these stones, removing the source of infection or obstruction.
3) Ejaculatory duct obstruction. Occasionally transrectal ultrasound will demonstrate obstruction of the seminal vesicles, either by scar tissue, prostatic cysts or stones. An incision of the duct or cyst can provide relief in these rare cases.