Info

+ + +

PVR> 150 mL

+

+

+ + + + +

IPSS, International Prostate Symptom Score; PVR, post-void residue; Qmax, maximum urinary flow rate. Adapted with kind permission from Trachtenberg, J. BJU Int. 2005, 95, 6-11.

prostate or bladder cancer, hypocontractive bladder, overactive bladder, abacterial prostatitis, or a UTI. Prostate surgery can also be a cause of refractory incontinence. There are also a number of nonurological causes including neurological diseases such as Parkinson's disease and back surgery. Some of the prostate-related causes of LUTS are discussed in this section.

6.24.10.1 Prostate Surgery and Incontinence

Prostate surgery can contribute to transient, short- or long-term incontinence. Radical retropubic prostatectomy is a surgical procedure used in prostate cancer, which involves the removal of adenomatous tissue via an incision in the surgical capsule of the prostate. However, this technique can result in refractory incontinence. One study of 146 prostate cancer patients showed that stress urinary incontinence was evident in the majority of patients (95%) after surgery, with the main cause of incontinence being intrinsic sphincter deficiency.65 Another study in 120 prostate cancer patients showed that radical prostatectomy had a significant impact on nocturia and voiding frequency in a small proportion of patients.66

6.24.10.2 Prostatitis

Prostatitis is an extremely common condition, which is classified into several subgroups. Acute bacterial prostatitis is the result of an acute pathogenic infection and can lead to chronic bacterial prostatitis. Chronic nonbacterial prostatitis, or chronic pelvic pain syndrome (CPPS), is a multifactorial condition that may be linked to other conditions such as bladder neck obstruction, urethral stricture, detrusor sphincter, dyssynergia, or dysfunctional voiding. Nonculturable organisms and sexually transmitted infections (e.g., Chlamydia trachomonas) are also possible causes.

CPPS is the most common form affecting up to 14% of men, and approximately 50% will have this condition at some time in their life. CPPS is typically characterized by chronic discomfort or pain, which can occur in the lower back, tip of the penis, suprapubic area, and perineal area. Urinary symptoms include urinary frequency, dysuria, weak stream, incomplete emptying, and painful ejaculation; inflammation can also be present.67

Although the underlying causes of CPPS are not fully understood, there is evidence to suggest that immunologic, neurologic, endocrine, and psychologic factors all contribute as shown in Figure 17. It is thought that an initiation event such as an infection or trauma leads to inflammation, often characterized by abnormal levels of proinflammatory markers (cytokines), which have been shown to correlate with symptoms and play a role in nociception.68 This inflammatory reaction is also linked to a number of other contributory factors; for example, increased levels of the inflammatory markers TNF-a and interferon-g (IFN-g) can alter the surface of epithelial cells resulting in increased inflammatory infiltration and decreased steroid hormone production. There is also evidence to suggest that inflammation increases the activation of nerve growth factor, an important neurotrophin involved in the regulation of nociceptive nerves and C-fibers, and this may lead to 'sensitization' to pain. A role for testosterone has also been

Endocrine

Altered androgen receptors

Local inflammation inhibits testosterone synthesis

Lower testoster local inflammi autoimmune re

Local inflammation inhibits testosterone synthesis

Lower testoster local inflammi autoimmune re

Testosterone inhibits effects of NGF

Immune response Imbalance of cytokines

Nervous system

Neurogenic inflammation with NGF Low local levels of p-endorphin

I anti-inflammatory: IL10

Autoimmune process

Reduced stress l IL6, IL10 leve

Reduced stress l IL6, IL10 leve

Stress-induced mast cell degranulation

Psychological factors Stress

Anxiety/depression

Figure 17 The role of immunologic, endocrine, neurologic, and psychologic factors in the development of chronic pelvic pain syndrome (CPPS) INF, interferon; IGF, insulin-like growth factor; IL, interleukins; NGF, nerve growth factor; TNF, tumor necrosis factor. (Reproduced with kind permission from Pontari, M. A.; Ruggieri, M. R. J. Urol. 2004, 172, 839-845.)

implicated. The inflammatory process can also inhibit the production of endogenous opioids such as b-endorphins, further enhancing the pain evident in CPPS.69

Given the multiple etiologies, prostatitis can be extremely difficult to diagnose and treat. Acute bacterial prostatitis is usually diagnosed via dipstick testing of midstream urine, together with bacterial cultures. If bacteria are present, then it is typically treated by hydration and intravenous antibiotics such as cephalosporins followed by oral antibiotics such as quinolones or co-trimoxazole. For those patients with recurrent (chronic) bacterial prostatitis, symptoms should be present for at least 3 months, and the management approach is both curative and suppressive, i.e., a long-term course of antibiotics with follow-up to check for relapse.70 When leukocytes are present in prostatic secretions and ejaculate then inflammatory CPPS is suspected; other diagnostic measures include symptomatic questionnaires such as the Chronic Prostatitis Symptom Index, transrectal ultrasound, and the presence of obstruction assessed via urodynamics or endoscopic investigations.

However, due to the absence of approved pharmacotherapy in this area, the management of CPPS is often a 'trial-and-error' approach. At present, the three most commonly used medications are antibiotics, anti-inflammatories, and a1-adrenoceptor antagonists (a-blockers). A recent review of randomized placebo-controlled trials using antibiotics, a1-adrenoceptor antagonists, and anti-inflammatories has shown that the greatest response rates in CPPS have been observed with alfuzosin 5 mg (65% versus 24% for placebo after 6 months), rofecoxib 50 mg (63% after 6 weeks), and quercetin 500 mg (67% versus 20% for placebo after 4 weeks).71

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