It is widely accepted that an anatomically incomplete Denonvilliers' fascia exists in the region of the apex and some authors have questioned if an apical margin is a true positive margin because the “capsule” of the prostate is deficient at the apex. Another important factor is the ‘detrusor apron’, a continuation of the anterior bladder wall with the pubis, which constitutes a large portion of the anterior fibromuscular stroma . This stroma covers the entire anterior and anterolateral surface of the glandular prostate,

Kiyoshima and colleagues have extensively studied the prostate anatomy in 79 specimens to determine if a capsule does exist[11]. They found that Denonvilliers' fascia and the prostatic capsule adhered tightly at the center of the posterior aspect in 77 cases (97%). A smooth transition from the prostatic capsule to the anterior fibromuscular stroma was observed in all cases. No prostatic capsule was independently recognized at the anterior aspect in around 90% of cases because the prostatic tissue was not distinct from the anterior fibromuscular stroma. In most cases (85%), the lateral pelvic fascia connected and fused with the anterior fibromuscular stroma, and covered the outermost regions of the lateral and anterior surfaces. Also, the lateral pelvic fascia and the prostatic capsule were separated by adipose tissue in 41 cases (52%), whereas they adhered in 38 cases (48%).[11] In summary, there is a thickening of the periphery of the prostate that some may regards as a “capsule”, but it is neither complete nor consistent amongst prostates and in many cases is difficult to discern from surrounding fascial layers.

The autonomic nerves from the pelvic (inferior hypogastric) plexus supply the prostate. The plexus may be found two finger breadths lateral to the third anterior sacral foramina, lying deep to a line drawn from third sacral vertebra, the conventional level of the recto-sigmoid junction, and the palpable posterior superior surface of the pubic symphysis[12]. The prostatic “capsule” is covered by numerous nerve fibers and ganglia, which form a true periprostatic nerve network[13]. A study of twenty autopsied prostates of different age (forties, fifties, sixties and seventies) and not having cancer has given insight into the more general neuranatomy of the prostate[14]. Most densely innervated was the prostate region bordering on the neurovascular bundles (as discussed above), followed by the regions close to the seminal vesicles and posterior capsule. Innervation was found to be relatively low at the apex, dense in the inner zones and most rich in the outer regions. The peripheral zone was more densely innervated than the transitional zone, while least innervation was found in BPH tissue. A further finding was that a decrease in nerve density across all zones was demonstrated with increasing patient age.

Derived from the hypogastric plexus are the neurovascular bundles travelling adjacent to (and within Denovilliers' fascia) laterally on the prostate up to and including the apex. The role of these nerves in erectile function have been explored widely, particularly by Walsh[15-17] in the context of radical retropubic prostatectomy for cancer. The original assumption was that this neurovascular bundle is gathered at the rectolateral side of the prostate[18]. However, research at several institutions in Australia has demonstrated that the autonomic neurovascular bundles extend laterally around the prostate and converge toward the apex but are in fact not a single nerve but a plexus that has many divisions scattered throughout Denovilliers' fascia, including medially towards the midline[19, 20]. It has been stated that one fifth to one quarter of nerves can be found along the ventral circumference of the prostatic capsule[18] and that only around half of prostates will have a definitive neurovascular bundle (in addition to the more scattered nerves as discussed)[11].

Prostatic epithelial cells express the androgen receptor[31]. From the beginning of embryonic differentiation to pubertal maturation and beyond, androgens are a prerequisite for the normal development and physiological control of the prostate[32]. Androgens also help maintain the normal metabolic and secretory functions of the prostate. They are also implicated in the development of benign prostatic hyperplasia (BPH) and prostate cancer. Androgens do not act in isolation and other hormones and growth factors are being investigated[33].

Androgens also interact with prostate stromal cells which release soluble paracrine factors that are important in the growth and development of the prostate epithelium [4]. These paracrine pathways may be critical in regulation of the balance between proliferation and apoptosis of prostate epithelial cells in the adult[33].

The appropriate balance between testosterone and its 5 α reduced metabolites are key to normal prostate physiology (note the metabolic pathways for androgen metabolism are described in the Chapter 2 on Androgens by D Handelsman). The metabolism of testosterone to dihydrotestosterone (DHT) and its aromatisation to estradiol are recognised as the key events in prostatic steroid response.

Figure 5. Conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase

Testosterone, to be maximally active in the prostate, must be converted to dihydrotestosterone (DHT) by the enzyme 5α-reductase (Figure 5)[34]. DHT has a much greater affinity for the androgen receptor than does testosterone [35, 36]. DHT is about twice as potent as testosterone in studies of rats at equivalent androgen cconcentrations[37].DHT due to its greater affinity for the androgen receptor may have effects intraprostatically independent of serum fluctuations in serum testosterone levels. [35, 36].

The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences.[38] In a small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20-30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. [38] Future therapies may need to take such findings into account if they are reproduced.

DHT concentrations may remain similar to those in young men in the prostate of elderly men, despite the fact that serum testosterone levels may decline with age[34]. In the prostate, the total level of testosterone is 0.4 ng/g and the total of DHT is 4.5 ng/g[39]. The total concentration of testosterone in the blood (18.2nnmol/L[27]) is approximately 10 times higher than that of DHT. Circulating DHT, by virtue of its low serum plasma concentration and tight binding to plasma proteins, is of diminished importance as a circulating androgen affecting prostate growth[26].

A role for estrogens in the prostate pathology of the ageing male appears likely with accumulating evidence that estrogens, alone or in combination with androgens, are involved in inducing aberrant growth and/or malignant change. Animal models have supported this hypothesis in the canine model, where estrogens “sensitize” the ageing dog prostate to the effects of androgen[40]. The evidence is less clear in humans. Estrogens in the male are predominantly the products of peripheral aromatization of testicular and adrenal androgens[41]. While the testicular and adrenal production of androgens declines with ageing, levels of total plasma oestradiol do not decline. This has been ascribed to the increase in fat mass with ageing (the primary site of peripheral aromatization) and to an increased aromatase activity with ageing. However, free or bioavailable estrogens may decline due to an increase in sex hormone binding globulin, which could translate to lower intraprostatic levels of the hormone. The potentially adverse effects of oestrogens on the prostate may be due to a shift in the intra-prostatic estrogen:androgen ratio with ageing.

Estrogen, which acts through estrogen receptors (ER) α and β, has been implicated in the pathogenesis of benign and malignant human prostatic tumors[42-44]. As stated above benign prostatic hyperplasia is thought to originate in the transitional zone (TZ) and prostate cancer the peripheral zone (PZ) of the prostate. Receptor studies have found ER-α and ER-β types distributed in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ER-α expression was restricted to stromal cells of the PZ. In contrast, ER-β was expressed in the stromal and epithelial cells of PZ as well as TZ. These findings suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ER-β[43]. Investigations are ongoing and could result in a new range of therapies directed against BPH and prostate cancer. Dietary phytoestrogens (in soy and other vegetables) or selective estrogen receptor modulators are currently being investigated with regard to their role in the development of BPH and prostate cancer[41]. Such ER modifiers may oppose some of the effects of natural oestrogen by modulating ER receptors, thus reducing the local impact of androgens that need active ER receptors, effectively making them anti-androgenic compounds however this requires more investigation[45].

The only clearly defined risk factors for BPH are age and the presence of circulating androgens. BPH does not develop in men castrated before the age of forty [53]. But other factors may influence the prevalence of clinical disease. These include:

Clinical BPH appears to run in families. If one or more first degree relatives are affected, an individual is at greater risk of being afflicted by the disorder [54]. In a study by Sanda et al [55] the hazard-function ratio for surgically treated BPH amongst first degree relatives of the BPH patients as compared to controls was 4.2 (95% CI, 1.7 to 10.2). The incidence of BPH is highest and starts earliest in blacks than Caucasians and is lowest in Asians [47]. Interestingly, despite having larger prostate glands, the age-adjusted risk of BPH was the same for blacks as for whites (RR = 1.0, 95% Cl 0.8-1.2) [56]. Furthermore, in an Asian population, men presenting with BPH are likely to have higher symptom scores than blacks or Caucasians [57].

Diet has been reported as a risk factor for the development of BPH. Large amounts of vegetables and soy products in the diet may explain the lower rate of BPH in the orient when compared to westernized countries. In particular, certain vegetables and soy are said to be high in phyto-oestrogens, such as genestin, that have ant-androgenic effects by an as yet determined mechanism on the prostate in vitro [58].

The study of migrant populations with their heterogeneous exposures to the environment, increases the probabilities of identifying potential risk factors for BPH. Therefore, the association of alcohol, diet, and other lifestyle factors with obstructive uropathy was investigated in a cohort of 6581 Japanese-American men, examined and interviewed from 1971 to 1975 in Hawaii. After 17 years of follow-up, 846 incident cases of surgically treated obstructive uropathy were diagnosed with BPH. Total alcohol intake was inversely associated with obstructive uropathy (P < 0.0001). The relative risk was 0.64 (95% confidence interval: 0.52-0.78) for men drinking at least 25 grams of alcohol per month compared with nondrinkers. Among the 4 sources of alcohol, a significant inverse association was present for beer, wine, and sake, but not for spirits. No association was found with education, number of marriages, or cigarette smoking. Increased beef intake was weakly related to an increased risk (p = 0.047), while no association was found with the consumption of 32 other food items in the study [59].

It has not been possible to delineate any other risk factors for BPH such as coronary artery disease, liver cirrhosis or diabetes mellitus. There is also no causal relationship between prostatic malignancy and benign hyperplasia [47].

BPH is a histological diagnosis but its clinical manifestations occur after growth has occurred to such a degree and in such a strategic location within the gland, namely the transitional zone, that it impairs bladder emptying and results in LUTS. One can therefore consider the natural history of BPH as involving three phases:

(i) The pathological or first phase of BPH is asymptomatic and involves a progression from microscopic to macroscopic BPH. Microscopic BPH will develop in almost all men if they live long enough but in only about half will progress to macroscopic BPH. This would suggest that additional factors are necessary to cause microscopic to progress to macroscopic BPH [60]. The pathological phase involves development of hyperplastic changes in the transitional zone of the prostate [61].

(ii) The clinical or second phase of BPH involves the progression from pathological to ‘clinical BPH’ which is synonymous with the development of LUTS. Only about one half of patients with macroscopic BPH progress to develop clinical BPH [60]. BPH consists of mechanical and dynamic components and it is these components that are responsible for the progression from pathological to clinical BPH [62]. In clinical BPH, the ratio of stroma to epithelium is 5: 1 whereas in the case of asymptomatic hyperplasia the ratio is 2.7:1. A significant contribution is therefore made by stroma to the infravesical obstruction of BPH [63]. While there is wide variability in prostate growth rates on an individual level, prostate volume appears to increase steadily at about 1.6% per year in randomly selected community men [64].

(iii). There is probably a third phase, during which clinical BPH progresses. This progression may be defined as a deterioration of clinical variables such as lower urinary tract symptoms (LUTS), health-related quality of life and peak flow rate, increased prostate size, or unfavourable outcomes such as acute urinary retention and BPH-related surgery [65]. However, there is evidence from longitudinal studies[49, 66], and to a lesser extent from the placebo arms of large controlled studies[67, 68], that clinical BPH is a progressive disease. Symptom worsening is by far the most frequently occurring progression event. Identifying those patients at risk of BPH progression is crucial to optimize their management [65].

Several theories have been proposed to explain the etiology of the pathological phase of BPH. The major theories include the hypotheses that pathological BPH is due to[69-71]: 1) Dihydrotestosterone (DHT) hypothesis- a shift in prostatic androgen metabolism that occurs with aging, which leads to an abnormal accumulation of dihydrotestosterone, thus producing the enlarged prostate. This is supported by the fauilure of BPH development in men castrated before puberty.

2) Embryonic reawakening theory- assumes a reawakening of the embryonic induction potential of prostatic stroma. In summary, a change in the prostatic stromal-epithelial interaction that occurs with aging occurs, which leads to an inductive effect on prostatic growth.

3) Stem cell theory featuring an increase in the total prostatic stem cell number and/or clonal expansion of the stem cells into amplifying and transit cells that occurs with aging.

4) Inflammatory theory- Prostatic inflammation may contribute to prostate growth due to the induction of cell growth due to the presence of inflammatory markers and agents stimulating growth.

Lower urinary tract symptoms (LUTS) suggestive of BPH are highly prevalent and the majority of LUTS in men is produced by BPH, but may be contributed to by a variety of conditions (Fig. 5). LUTS are traditionally divided into voiding or obstructive and storage or irritative symptoms (Table 2). Voiding symptoms are more common, however it is storage symptoms that are most bothersome and have a greater impact on a patient's life[72, 73]. The prevalence of clinical BPH rises with age and approximately 25% of men age 40 or over will suffer from LUTS [74].

Figure 6. Conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase

In the past, LUTS suggestive of bladder outflow obstruction (BOO) secondary to BPH were referred to as ‘prostatism’, once other causes such as a urinary tract infection or prostate cancer were excluded. The pathology behind the symptoms was thought to be obstruction due to prostatic gland enlargement alone. However, today it is recognised that voiding/obstructive symptoms result from direct urinary flow obstruction whilst storage/irritative symptoms appear to be due to secondary bladder dysfunction [76].

This concept has been further refined in that obstructive symptoms are thought to result not only from mechanical obstruction due to glandular enlargement, but also dynamic obstruction secondary to contraction of the smooth muscle of the prostate, urethra and bladder neck. This dynamic obstruction is a result of sympathetic nervous system mediated stimulation of α-1adrenoceptors. Storage symptoms appear to be caused by detrusor instability related to detrusor muscle changes in response to obstruction, such as bladder wall hypertrophy and collagen deposition in the bladder[77, 78]. The role of adrenoceptor subtypes in the bladder in this process is currently being investigated. Adrenoceptors may be further sub-divided into α _1Aand α _1Dsubtypes, with α _1Apredominant in the prostate and α 1D in the bladder. Thus blockade of α _1Amay be necessary for reduction of obstruction whereas the blockade of α _1Dmay be required to relieve storage symptoms [79] (see below).

New research has also suggested that the aetiology of LUTS related to BPH is even more complex than outlined above with extra-prostatic mechanisms such as bladder wall ischaemia and changes in the central nervous system being implicated [80]. Normal lower urinary tract function is complex, and theoretically any disruption of the pathway for micturition (Figure 7 below) may lead to LUTS [81].

It is also worth noting the relationship between LUTS and sexual dysfunction, with sexual dysfunction being highly prevalent in men with LUTS [82]. By sexual dysfunction, we refer to decreased libido, erectile dysfunction, decreased ejaculation and other ejaculation disorders. Kassabian [83] expands on the relationship and agrees with Leilefeld et al [84] in suggesting that the relationship is coincidental and both are common in the ageing male.

Figure 7. Normal micturition pathways (reproduced with permission from Physiology and pathophysiology of lower urinary tract symptoms, Drugs of Today, Vol 37, p. 7, Michel MC [81]).

As prostate volume increase with age, the likelihood of acute urinary retention (AUR) and symptom severity both increase while urinary flow rates fall. In one study of more than 2000 men, those with a maximum urinary flow rate (Qmax) <12 ml/s had a 4 times greater risk for AUR than did men with a Qmax >12ml/s [85]. AUR is usually painful and necessitates the insertion of a per urethral indwelling or suprapubic urinary catheter.

If the urinary retention is not dealt with in a timely fashion, the detrusor muscle becomes distended and damaged, contributing to poor detrusor function and an inability to adequately empty the bladder. The retention of urine becomes painless over time, and the sequelae of retained urine such as recurrent UTI, calculi and renal impairment may develop.

Furthermore, a situation of overflow incontinence may develop whereby the bladder automatically empties once the volume reached exceeds its new, larger capacity. The passage of urine is typically uncontrolled, and this may often be the first presentation for someone with advanced BPH. The bladder remains full despite the emptying, which is only partial.

In situations of chronic retention, there is no guarantee that by relieving the bladder outflow obstruction, the detrusor will return to normal functioning. These patients often need to use intermittent self catheterisation or have permanent drainage to keep their bladder empty and to reduce damage to the upper urinary tract, even after definitive treatment for BPH.

Perhaps the best host defence against infection in the lower urinary tract is the normal flow of urine and bladder emptying that accompanies normal urinary tract functioning. In BPH, bladder outflow obstruction results in disruption of this mechanism with retention and pooling of urine in the bladder, giving organisms the opportunity to multiply rather than be flushed out. Despite this logical assumption, there is little evidence in the literature to support this theory. Nevertheless, men with significant clinical BPH are probably at risk of UTI, and men with UTI should be assessed for signs of BPH.

In developed countries, the most prevalent cause of bladder calculi is bladder outlet obstruction owing to BPH [86].Of those who undergo prostate surgery for BPH, approximately 2% of all patients are found to have bladder stones [87]. Stones occur in this situation due to urinary stasis combined with high urinary solute concentrations, which leads to crystal precipitation [88]. Chronic infection with urease-producing organisms may predispose to the development of stones and rarely stones pass from the upper tract to act as a nidus in the bladder [88] . Bladder calculi associated with BPH remain an absolute indication for transurethral resection of the prostate (TURP)[89, 90] because of the risk or recurrence of stone formation. However, the necessity of surgery is being challenged by the expanding use of medical management in treating BPH [90].

The incidence of haematuria with BPH is uncertain however, in a retrospective review of almost 4000 patients undergoing TURP, Mebust et al [89] noted that haematuria was an indication for surgery in 12% of patients. It is hypothesised that BPH, with its increased acinar and stromal cell proliferation, stimulates increased vascularity via angiogenesis. These new and prolific vessels may be easily disrupted leading to recurrent bleeding [91].This is supported by Foley et al [92] who found the microvessel density to be higher in those patients with BPH having haematuria after histological studies. It is also hypothesised that 5-α reductase inhibitors may reduce angiogenesis and theoretically, reduce prostate bleeding. Thus finasteride, has been suggested as an option in treating the problem of haematuria[93-95].

The definition of detrusor instability is the development of a detrusor contraction which exceeds 15cm H ₂O at a bladder volume of less than 300ml [96]. Detrusor instability is not a specific term related to BPH, but implies LUTS secondary to a detrusor problem. These symptoms are normally storage related and consist of urgency, frequency, urge incontinence and nocturia. In BPH, the normal dynamics of the bladder are altered due to detrusor muscle stretching as a result of retention of urine and contraction against an obstructed outlet. Although not completely understood, some of the detrusor instability may be related to changes at the adrenoceptors level, rather than just from obstruction and its consequences alone. In normal bladder physiology, β-adrenoceptors are believed to be involved in the relaxation of the bladder during storage of urine [80]. In some patients, however, the administration of noradrenaline leads to contraction of the detrusor muscle which may be blocked by α-1 adrenoceptor antagonist [97]. This implies the presence of α-adrenoceptors in the detrusor muscle in at least some patients. Furthermore, α-adrenoceptor antagonists have been shown to relieve storage and voiding symptoms in men without obstruction and storage symptoms in women[80, 98-101]. α adrenoceptor subtypes in the human bladder are predominantly of the α _1Dand α _1Atype. In animal models, the α _1Dreceptors become more abundant with obstruction[102], and it may be speculated that this is the case in humans and that these receptors, once up-regulated, play a role in storage symptoms [80].

Renal insufficiency results from obstructive uropathy secondary to the bladder outlet obstruction of BPH. In an analysis of patients receiving treatment for BPH, 13.6% (range 0.3-30%) had renal insufficiency [87]. Certainly, an abnormal creatinine is an indication to further investigate the upper urinary tract with imaging. Obviously, other concurrent causes of renal insufficiency need to be excluded. Those patients with renal insufficiency undergoing surgery are at increased risk (25%) of postoperative complications such as acute renal failure and urosepsis compared to patients without (17%) insufficiency [89].

As BPH is a true hyperplasia, more cells produce a greater amount of PSA[103]. It has been suggested that many PSA elevations detected and investigated in clinical practice may in fact be due to BPH leading Stamey to controversially argue that PSA is a better marker of BPH than of prostate cancer[103, 104]. One approach to distinguish the two conditions when PSA is elevated is to perform a free-to-total PSA ratio: more free PSA than complexed PSA suggests BPH rather than prostate cancer. A ratio of around 20% or greater for free PSA is considered more likely to represent BPH than cancer[105]. PSA is discussed further in the investigations section below.

In terms of complications of BPH, quality of life (QOL) issues have gained more attention since the landmark paper of Girman et al over a decade ago[106]. They highlighted in their study of several thousand men that moderate to severe urinary symptoms have a significant impact on men's lives in terms of degree of bother, worry, interference with daily living, and psychological well-being. The impact of BPH on QOL has been highlighted in many recent studies[107, 108] and such studies continue to be important in raising awareness of BPH in the community and the ability of men to seek treatment for BPH. Comprehensive surveys of men, such as the Men in Australia Telephone Survey (MATeS), provide contemporaneous data that men are interested in their health and the QOL impact of problems such as LUTS secondary to BPH[109, 110].

The American Urologic Association (AUA) Symptom Index was developed as a standardised instrument to assess the degree of bladder outlet obstruction in men [98]. It is widely used and consists of seven questions that assess emptying, frequency, intermittency, urgency, weak stream and straining with each graded with a score of 0-5. Total score ranges 0-35. The index categorises patients as:

The International Prostate Symptom Score (I-PSS) is a modification of the AUA Symptom Index adding a single question assessing the quality of life or bother score based on the patient’s perception of the problem (Figure 8)[114]. Both the AUA and I-PSS questionnaires, although not specific for BPH, prostate volume, urinary flow rate, post-void residual volume or bladder outlet obstruction, have been validated and are sensitive enough to be to be used in the evaluation of symptoms and selection of treatment[115-117]. Many would argue that the bother score is the primary determinant of whether or not a patient proceeds to further treatment.

Figure 8. International Prostate Symptom Score (I-PSS) Sheet[118, 119]

Prostatitis is a common condition that must be excluded from other causes of LUTS and is a common cause of visits to primary care physicians and urologists. It may present as an acute bacterial infection or may be chronic, occasionally progressing to a debilitating illness. In practice, the clinical diagnosis of prostatitis depends on the history and physical examination, but there is no characteristic physical finding or diagnostic laboratory test. Patients with prostatitis experience considerable morbidity and may remain symptomatic for many years. Unfortunately, there is limited understanding of the pathophysiology and optimal treatment for most patients.

Prostatitis has been sub-classified and an abbreviated version is in table 6.

Clinical features suggestive of acute prostatitis (Type 1, in Table 6 above) include dysuria and urinary frequency as well as perineal pain (Table 7). Systemic symptoms such as fever, rigors, myalgia and sweats are often a feature. On examination, the patient is normally febrile, and may be overtly septic depending on the infection severity. A digital rectal exam finds an extremely tender prostate which is often intolerable to the patient. An abscess is occasionally palpated.

Investigations should include a mid-stream urine sample for microscopy, culture for bacteria, and antibiotic sensitivity. The most common organisms are typical uropathogenic bacteria such as Escherichia coli. Blood cultures for bacteria and antibiotic sensitivity should also be considered. Prostatic massage is usually contraindicated in patients with acute prostatitis due to pain and the risk of precipitating sepsis. A treatment regime is highlighted in Table 8. If there is failure to respond to therapy, evaluation for a prostatic abscess using a tran-srectal ultrasound scan or computed tomography scan may be required. If necessary, perineal or transurethral drainage of an abscess may be undertaken. At least 4 weeks of antibiotic therapy is recommended in all patients to try to prevent chronic bacterial prostatitis. Following resolution of acute prostatitis, the urinary tract should be investigated for any structural problems[123, 124].

As the presentation may be localised to the genital region or non-specific (see Table 7) a careful history and examination along with specialised diagnostic tests are needed to identify this condition. Investigations may involve prostatic massage to express organisms and/or white blood cells for analysis. Urine sample collection is often done in phases to aid in the localisation process: first void urethral urine; mid-stream bladder urine; post-prostatic massage sample. Urine microscopy and quantitative culture is then undertaken. Semen analysis for excessive white blood cell numbers may also be indicative of chronic prostatitis. A serum prostate specific antigen measurement may be undertaken and is often raised, especially in acute prostatitis or in an active phase of chronic prostatitis. Trans-rectal ultrasound is considered but not recommended to differentiate the different forms of chronic prostatitis. Urinary tract localisation procedures (culture of first void urethral urine; mid-stream bladder urine; post-prostatic massage samples of urine correlating to urethra, bladder and prostate) although theoretically correct, are often not used in clinical practice[123, 124].

The various classifications of chronic prostatitis are listed in Table 6. Patients with chronic bacterial prostatitis (type II prostatitis) experience recurrent episodes of bacterial urinary tract infection caused by the same organism, usually E. coli, another Gram-negative organism, or enterococcus. Between symptomatic episodes of bacteriuria, lower urinary tract cultures can be used to document an infected prostate gland as the focus of these recurrent infections. Acute and chronic bacterial prostatitis represent the best understood, but least common, prostatitis syndromes[123, 124].

Unfortunately, more than 90% of symptomatic patients have chronic prostatitis/chronic pelvic pain syndrome (type III). This term recognizes the limited understanding of the causes of this syndrome for most patients and the possibility that organs other than the prostate gland may contribute to this syndrome. Urological pain (normally in the perineum or associated with voiding or intercourse) is now recognised as a primary component of this syndrome. Active urethritis, urogenital cancer, urinary tract disease, functionally significant urethral stricture, or neurological disease affecting the bladder must be excluded. Patients with the inflammatory subtype (type IIIA) of chronic prostatitis/chronic pelvic pain syndrome have leukocytes in their expressed prostatic secretions post prostate massage urine or in semen.

In contrast, patients with the non-inflammatory subtype of chronic prostatitis (type III B) have no evidence of inflammation. In essence, they have no evidence of active infection nor of inflammation on available investigative techniques taken at a particular point in time. Repeat investigations are therefore done to be sure adequate sampling has been undertaken. This condition may be difficult to treat and requires intensive counselling, information and reassurance to the patient to be successfully managed[124].

Finally, asymptomatic inflammatory prostatitis (type IV) is diagnosed in patients who have no history of genitourinary tract pain complaints. It is often an incidental finding on prostatic biopsy done for other reasons (eg a raised PSA). Treatment is usually not required.

All patients should have investigations as outlined above. A summary of treatment options is included (Table 9).Those patients with chronic prostatitis secondary to bacterial infection (type II) require a prolonged course of antibiotics (often up to 3 months) and should then be re-cultured to ensure eradication of the organism. Some urologists argue that these patients should also have investigation of their urinary tract by way of cystoscopy and at minimum, an ultrasound to ensure no anatomical abnormality that may be responsible.

Patients with asymptomatic prostatitis (IV) require no treatment but those with the inflammatory (IIIA) and non-inflammatory (IIIB) are more difficult.

Patients with type IIIA disease have excessive leucocytosis in their specimens but no bacteria. However, because their symptoms may be due to a pathogen that is difficult to isolate, a further course of antibiotics (6-12 weeks) with coverage of chlamydia and ureaplasma[122] is indicated. If this antibiotic course is not therapeutic, then concentration should be focus on anti-inflammatory medications (which may be used in conjunction with the course of antibiotics). If anti-inflammatory treatment fails, then patients should be treated as below, for type IIB.

Current treatment for Type IIIB patients requires multiple therapies. Triple therapy with high dose α-blocker (3 month minimum), analgesia and muscle relaxant (benzodiazepines).Initially, a narcotic analgesic should be changed to a non-steroidal anti-inflammatory (NSAID) if a response occurs after 2 weeks. The NSAID should be continued for at least 6 weeks, but stopped if there is no response at 2 weeks. If the triple treatment fails, other avenues must be explored, including biofeedback, relaxation exercises psychotherapy and lifestyle changes (soft cushions, cease bike-riding). The focus is on improving quality of life and minimising symptoms, not curing the disease[122].

As outlined by Tubarro et al[111], the aim of investigations for LUTS should be threefold: (1) to evaluate the possible relationship between prostatic enlargement, lower urinary tract symptoms and signs of bladder outlet obstruction; (2) to quantify the severity of benign prostatic enlargement-related symptoms and signs and (3) to rule out the presence of a prostate cancer.

Urinalysis is used to screen for urinary tract infection as a cause of LUTS in order to identify those with microscopic or macroscopic haematuria. A formal urine culture may be undertaken if the analysis was suspicious for infection.

Although there is a high degree of intra-individual variation in the PVRU it may still provide valuable information with regard to bladder emptying. It may not distinguish adequately between bladder outlet obstruction or poor detrusor function and the United States guidelines on BPH suggest it is an optional investigation because of this variability [87] . Greater than 300ml is considered a potential risk factor for upper urinary tract dilatation and renal impairment[125]. The PVRU does have the advantage of being used as a monitoring investigation in those opting for non-surgical therapy for BPH. It is readily and quickly performed in the office or hospital setting using portable ultrasound equipment.

Most guidelines on investigation of BPH recommend this investigation and an elevated serum creatinine would be an indication to evaluate the upper urinary tract[113].

Urinary tract ultrasound or computerised tomography are appropriate modalities. Most would consider upper tract imaging as mandatory if haematuria was present and recommend it if there was a history of urolithiasis, urinary tract infection or renal insufficiency. Intravenous pyelography still has a role in certain cases, as other modalities do not outline the anatomy of the collecting system with such definition[111].

Urodymanics is a general term for a collection of investigations useful in quantifying the activity of the lower urinary tract during micturition[126]. Complete pressure-flow urodynamics are complex and usually involves fluoroscopy, video recording, bladder and rectal pressure measurement, as well as an assessment of urine flow. The simplest urodymamics are pressure-flow studies, requiring only voiding into a measuring device to obtain flow rates, and may easily be done in the office setting.

With regard to the investigation and diagnosis of conditions underlying LUTS, when considering inexpensive, safe and completely reversible treatments, one may opt to avoid urodynamics studies initially. However, when considering irreversible, expensive or potentially morbid therapy, such studies are considered mandatory. Many patients will not have urodynamics studies based on the first premise above[126]. However, in reality, many surgeons and physicians will have simple pressure-flow studies easily available and will perform these as part of an initial consultation. More complex studies require time and are costly, and so should be reserved for particular situations as discussed below.

Uroflowmetry is considered by some as the single most useful urodynamic technique for the assessment of obstructive uropathy. The purpose of the uroflow examination is to record one or more micturitions that are representative of the patient’s usual voiding pattern. Therefore, more than one micturition is often required and it is necessary to confirm with the patient if the flow was better, worse or about the same as their normal pattern, otherwise intra-individual variability may lead to false assumptions[127]. The study may be performed in the office or as part of other urodynamic studies in the laboratory or operating suite.

Figure 9 indicates the most common urinary flow parameters measured. Of these, the peak flow rate is the most closely correlated with the extent of outflow obstruction (Table 10). Total voiding time is prolonged in obstruction and has a reduced Qmax. Poor detrusor contractility is impossible to distinguish from bladder outflow obstruction on uroflowmetry so other urodynamics investigations such as a cystometry are indicated.

Figure 9. Uroflowmetry in a normal individual- diagram above and actual reading below.

Figure 10. Abnormal patterns of uroflowmetry: A) This is likely to represent the flowmetry pattern of a patient with bladder outlet obstruction. The maximum flow reached is around 10ml/sec and the flow rate is prolonged. A diagnosis cannot be made from this reading alone but is certainly characteristic of someone with obstructed voiding and having normal detrusor muscle function. B) This pattern of intermittent flow usually represents abdominal straining in an attempt to overcome outflow obstruction. The peak flow rate may be normal or high, especially if outlet resistance is reduced.

Various measurements may be used to define detrusor pressures (e.g. Abram-Griffiths nomogram) and urethral sphincter pressures as an aid to diagnosis in specific circumstances. This is relevant in patients with LUTS who have had a stroke (or other neurologic disease) where bladder function may have sensory deficits or unstable detrusor contractions, that may need alternate management. Nevertheless, detrusor instability is not considered a negative factor with respect to the outcome of BPH surgery[111], provided it is adequately managed. Some have even suggested that the detection of detrusor instability in patients with LUTS is only of minor diagnostic importance[128].

There is no evidence that pressure-flow studies should be mandatory prior to surgical (or medical) intervention. However, prior to transurethral resection of the prostate (TURP) it has been recommended that the following patients undergo pressure-flow studies:

The performance of this investigation depends on patient history and proposed surgical intervention. It is necessary where there is a history of microscopic or macroscopic haematuria to exclude bladder tumours or stones. A history of urethral strictures, bladder tumours or prior lower urinary tract surgery should also prompt this investigation. Surgeons may also use urethroscystoscopy when planning different surgical treatments or invasive therapies.

Compared to TRUS, methods of determining prostate size such as DRE, urethrocystoscopy and retrograde urethrography are poor[130]. It is often conducted in unison with biopsies of the prostate for suspected carcinoma, but is also a useful tool for assessing the size of an enlarged prostate so that the best mode of management may be undertaken, such as open versus endoscopic surgery. Two planes of measurement are needed to mainatain accuracy and reproducibility with a common formula used being: W x W x H x pi/6.[131]

The amount of prostate actually protruding into the bladder (i.e median lobe) on ultrasound may also be important in predicting response to medical treatment after an episode of retention (more protrusion, increased risk of failing trial of void).[132]

Currently PSA is not recommended as part of the diagnostic workup for BPH and it is currently used in the context of case finding, staging, treatment response and monitoring of prostate cancer in patients.[133-135] It may have a role in population based-screening for prostate cancer in the future once larger studies mature.[135] An interesting observation by Stamey and colleagues from 1317 consecutive men undergoing radical prostatectomy at Stanford University during the past 20 years has been the reduction in size of prostate cancers identified by PSA testing 1983. Thus, with downward stage migration, a PSA taken in today’s environment now likely represents benign prostate enlargement rather than prostate.[104]

Following on from this, recommendations have been made concerning the role of PSA in the patient with BPH [136]. This statement acknowledged that PSA levels are used as part of the decision-making process in men presenting with LUTS in the context of excluding prostate cancer and thus testing for it would be part of any consultation in any case. As outlined previously, distinguishing the two conditions when PSA is elevated may be aided by a free-to-total PSA ratio. A ratio of around 20% or greater for free PSA is considered more likely to represent BPH than cancer[105].

Furthermore, the consensus panel contended that PSA may be used as a surrogate for prostate volume and potentially a biomarker for disease progression (as it increases along with patient symptoms and deciding who may benefit from medical treatment. For example, it was emphasised that men with a PSA of ≥1.5ng/ml should be considered to be at increased risk of BPH progression. To support such assumptions in a practical sense in men with BPH, those with a higher PSA have been found to benefit greatest from 5 α-reductase treatment (along with those men having larger prostates) [137]. More data on such uses of PSA in men with BPH is likely to emerge in the future.