Prostate Benign Prostatic Hyperplasia

Prostate Benign Prostatic Hyperplasia

Daniel W. Good1, Bashar Nahas1, Simon Phipps1, Rick Popert2, Jens‐Uwe Stolzenburg3, and Stuart Alan S. McNeill1

1 Department of Urology, Western General Hospital, The University of Edinburgh and NHS Lothian, Edinburgh, UK

2 Guy’s and St. Thomas’ Hospital, NHS Foundation Trust, London, UK

3 University of Leipzig, Leipzig, Germany


Lower urinary tract symptoms (LUTS) are common in the population but are not solely due to benign prostatic enlargement (BPE), instead age‐related detrusor changes and other common medical conditions are the causative factor in many cases. Despite this, benign prostatic hyperplasia (BPH) is still a significant cause of LUTS, and this chapter attempts to explain the current evidence for the causes, investigation, complications, and management of patients with LUTS.

Keywordslower urinary tract symptoms (LUTS); benign prostatic enlargement (BPE); green light laser prostatectomy; urinary retention; benign prostatic hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is a pathological process that contributes to, but is not the sole cause of, lower urinary tract symptoms (LUTS) in ageing men [1]. Historically, LUTS have been related to bladder outflow obstruction (BOO), but the current literature attributes a significant proportion of LUTS to age‐related detrusor changes and a variety of systemic medical conditions (e.g. congestive heart failure, diabetes, etc.). In this chapter, we will discuss all issues related to the current understanding and treatment of BPH and BOO.

27.1 Nomenclature

Use of the correct terminology cannot be stressed highly enough because use of incorrect terminology may result in the inappropriate treatment of men and treatment may not be focused on the correct cause [2]. Hald rings (Figure 27.1) describe the interplay of these terms and the International Continence Society (ICS) have standardised the terminology:

  • LUTS is the accepted term, which replaces terms such as ‘prostatism’ and ‘is used to describe the subjective indicator of a disease of the lower urinary tract, however, in general cannot be used to make a definitive diagnosis’ [3] (i.e. describes storage and voiding symptoms).
  • Acute urinary retention (AUR) is ‘defined as a painful, palpable or percussable bladder, when the patient is unable to pass any urine’ [3].
  • Chronic retention of urine ‘is defined as a non‐painful bladder, which remains palpable or percussable after the patient has passed urine. Such patients may be incontinent’ [3].
  • BOO ‘is the generic term for obstruction during voiding and is characterised by increased detrusor pressure and reduced urine flow rate. It is usually diagnosed by studying the synchronous value of flow rate and detrusor pressure’ [3].
  • BPH ‘is a term used (and reserved for) the typical histological pattern which defines the disease’ [3].
  • Benign prostatic enlargement (BPE) ‘is defined as prostatic enlargement due to histologic benign prostatic hyperplasia’. The term ‘prostatic enlargement’ should be used in the absence of prostatic histology’ [3] (i.e. a clinical finding of an enlarged prostate).
  • Benign prostatic obstruction (BPO) ‘is a form of BOO and may be diagnosed when the cause of outlet obstruction is known to be BPE [3].
  • Storage symptoms (formerly referred to as irritative symptoms) ‘daytime urinary frequency, nocturia, urgency, urinary incontinence’ [4].
  • Voiding symptoms (formerly referred to as obstructive symptoms) ‘slow stream, splitting or spraying, intermittency, hesitancy, straining, terminal dribbling’ [4].
  • Postmicturition symptoms ‘sensation of incomplete emptying, post micturition dribbling’ [4].
Image described by caption.

Figure 27.1 Hald’s rings. BPH, benign prostatic hyperplasia; BOO, bladder outflow obstruction; LUTS, lower urinary tract syndrome.

27.2 Aetiology

27.2.1 Hormonal Factors Role of Androgens

The dependent relationship between the prostate and testosterone has been recognised for many years. The permissive role of dihydrotestosterone (DHT) in the pathogenesis of BPH is demonstrated by the fact that castration or hypopituitarism occurring in men prior to puberty prevents the development of BPH. Furthermore, individuals with congenital 5‐alpha reductase deficiency do not develop BPH; prostatic levels of DHT remain high in ageing men, despite the fact that peripheral levels of testosterone decrease with age [5], and androgen withdrawal leads to partial reversal of established BPH [6].

Testosterone binds directly to androgen receptors; however, the more potent form DHT is what gives a greater effect. Testosterone is converted to DHT by 5α‐reductase (5αR) II in the prostate or by 5αR I in the skin or liver. Once testosterone has diffused into the prostate and stromal epithelial cells, it binds to the androgen receptors. The majority of the testosterone binds to receptors on the cell membrane, where it is converted to DHT, which binds with greater affinity to the receptors (higher potency). The testosterone or DHT‐androgen receptor complex then binds to the nuclear membrane, inducing transcription of genes and initiating protein production. Role of Oestrogen

In ageing men, a change in the ratio of androgen to oestrogen in favour of oestrogens has been postulated to play an important role in the pathogenesis of BPH. Treatment of young dogs with androgen plus oestrogen hormones leads to early development and a greater prevalence of BPH [7]. The role of oestrogen in the development of BPH in humans is not as well understood as the role of androgens.

27.2.2 Stromal/Epithelial Interaction (Embryonic Reawakening) and Growth Factors

McNeal noted that the histological appearance of stromal tissue in BPH nodules resembles the histologic appearance of developmental mesenchyme and hypothesised that BPH is caused by reawakening of embryonic processes in a distorted form in adult life [8, 9]. Cunha [10] has demonstrated that prostatic epithelial development is dependent on androgen‐sensitive and stromal mediators. Murine urogenital sinus mesenchyme cells will induce intact male murine bladder cells to proliferate, bud, and acquire a distinctly prostatic appearance when these cells are coincubated, This inductive process is androgen dependent, and it has been found that the stromal and epithelial cells are capable of producing growth factors (i.e. peptide molecules affecting cell division and differentiation) that bind to specific membrane receptors leading to cell division and differentiation process and at other times inhibiting these processes.

It appears that growth stimulatory factors such as the fibroblastic growth factors (FGF): FGF1 (acidic FGF‐active in early life), FGF2 (basic FGF‐active in later life), FGF7, and FGF17 families (also including the keratinocyte growth factors [KGF]), vascular endothelial growth factor (VEGF), insulin‐like growth factor (IGF), and epidermal growth factors (EGF) including transforming growth factor‐α (TGF‐α), may play a role with DHT augmenting or modulating the growth factor effects. In contrast TGF‐β, which is known to inhibit epithelial cell proliferation, may normally exert restraining influences over epithelial proliferation in BPH [11]. In health, there is usually a balance between the two (Figure 27.2), and an imbalance causes BPH.

2 Schematics illustrating regulation cell growth with ellipses labeled testosterone, 5AR2, DHT, etc. (top) and growth factors affecting the prostate with boxes labeled agonist, antagonist, etc. (bottom).

Figure 27.2 (a) Regulation of cell growth and (b) growth factors affecting the prostate. EGF, epidermal growth factors; FGF, fibroblastic growth factors; IGF, insulin‐like growth factor; TGF‐β, transforming growth factor‐β.

27.2.3 Genetic Factors

Genetics have a role in the development of BPH. A retrospective case control analysis of patients who were treated surgically for BPH and control subjects at John Hopkins Hospital demonstrated that in 50% of men younger than 60 years of age undergoing prostatectomy had their BPH attributed to an inherited form of the disease, whereas only 9% of men older than 60 years of age undergoing prostatectomy had a familial risk [12].

The results are consistent with an autosomal‐dominant inheritance pattern, but the specific gene(s) involved in familial BPH or contributing to the risk of significant prostatic enlargement in sporadic cases are still to be identified [12].

27.2.4 Role of Inflammatory Pathways

Recent research suggests that inflammatory cell infiltrates, which are seen in a high percentage of men with BPH, may provide an additional source of growth factors in human BPH. The cytokines (interleukin [IL] –6 to –8) may have a role in promoting cell growth and smooth muscle contraction [13].

27.2.5 Other Causative Relationships

It seems that there is no significant relationship between the incidence of BPH and religious or socioeconomic factors [14]. However, a recent study evaluating the metabolic syndrome or obesity and LUTS showed a statistical correlation between the two. The components of diabetes (i.e. elevated fasting glucose) and hypertension were most commonly associated with BPH, and this applied to men younger than 60 years of age [15].

27.3 Pathology of BPH

The embryological and anatomical studies of McNeal contributed greatly to the current understanding of BPH. According to McNeal, the adult prostate is made up of four distinct zones (i.e. McNeal’s zonal anatomy of prostate; Figure 27.3). The peripheral zone makes up 70% of the prostate, whilst the central zone (20–25%) is the next largest zone and is cone shaped, with the base forming most of the base of the prostate and the apex located at verumontanum. The third zone is the interior fibromuscular stroma, and the periurethral transitional zone is the smallest zone but is the site where BPH develops (Figure 27.3) [8].

4 Illustrations depicting of McNeal’s prostate zonal anatomy with lines indicating transition zone, peripheral zone, central zone, and anterior fibromuscular stroma.

Figure 27.3 Diagram of McNeal’s prostate zonal anatomy.

McNeal’s studies demonstrated that the majority of early periurethral nodules are purely stromal, whilst the earliest transitional zone nodules represent proliferation of glandular tissue. The first phase of evolution of BPH is characterised by increased numbers of nodules, then the second phase is characterised by an increase in size of these nodules [10].

There is a significant variability in the stroma to epithelial ratio in BPH; resected tissue from small prostates demonstrates a predominance of fibromuscular stroma, while tissue from large glands removed by enucleation demonstrates primary epithelial nodules. As stated previously, BPH is primarily a stromal process associated with significant smooth muscle hyperplasia, the overall ratio of stroma to epithelium in BPH is 4:1 to 5:1 with the smooth muscle proportion of the hyperplastic stroma being approximately 40% [16]. The smooth muscle tone is regulated by the adrenergic nervous system and receptor‐binding studies demonstrate the α1a is the most abundant adrenoceptor in the human prostate.

One of the unique features of the human prostate is the presence of the prostatic capsule; it may be that the capsule provides resistance to tissue expansion caused by BPH nodules increasing in size, which in turn leads to increased urethral resistance [17].

Watanabe described the concept of presumed circle area ratio (PCAR), which is based on the theory that the change in prostatic shape, which can be observed as the prostate enlarges with BPH, is due to greater tension within the prostatic capsule with the forces within the prostate being distributed evenly including upon the prostatic urethra. As the tension within the prostatic capsule increases, the prostate assumes a more spherical shape, this being the shape with the lowest surface tension for a given volume. Watanabe assigns the prostate a PCAR that describes how near a spherical shape the prostate has become, which he has correlated with infravesical obstruction in men with BPO [18].

27.3.1 Response to Obstruction

The bladder’s response to obstruction can be characterised in two ways. Changes that lead to detrusor instability (i.e. poor compliance) give rise to symptoms of frequency, nocturia, and urgency. This can then be followed by decreased detrusor contractility, which manifests clinically by poor stream, hesitancy, intermittency, and increase in residual urine [19].

The bladder responds to outflow resistance by muscular hypertrophy, increasing the thickness of muscle fibres and infiltration of collagen between the fibres leads to diverticular formation (Figures 27.4 and 27.5). The texture of the wall of the bladder changes from a fine felt to a course net, through the gaps of which the urothelium bulges out. The interior of the bladder develops a characteristic trabeculated appearance with saccules and diverticula formation from the herniated urothelium.

Diagram depicting the radiographic appearances of the normal and the obstructed bladder before voiding (top) and post voiding with 1 normal, 2 trabeculation and 3 saccules, diverticula, and residual (bottom).

Figure 27.4 Diagram showing the radiographic appearances of the normal and the obstructed bladder.

Image described by caption.
Image described by caption.

Figure 27.5 (a) Diagram showing changes in the detrusor secondary to outflow obstruction. The urothelium is herniated between gaps in the trabeculae to form saccules and diverticula. The ureters are hooked up and obstructed. (b) Progressive failure of the detrusor.

These structural changes affect the bladder function. There is an increase in voiding pressure within the bladder, unwanted contractions occur irrespective of bladder filling, and detrusor instability, leading to storage symptoms.

Failure to relieve the outflow obstruction will eventually lead to detrusor failure. Detrusor failure leads to inability to empty the bladder completely, leading to residual urine that can give rise to complications.

27.4 Complications of BPH

Diverticula are herniations of bladder mucosa between hypertrophied bars of detrusor muscle. Once prostatic obstruction has been corrected, they can usually be ignored; however, they should be surgically removed when stones or cancer develops within them or when they are so large that they fill up whenever the detrusor is trying to expel urine and so that symptoms persist (Figure 27.6).

2 Diagrams of the progress of diverticulum. The right diagram is displaying an infection, stones, and squamous metaplasia.

Figure 27.6 Diagram of the progress of a diverticulum.

The incidence of haematuria in patients with BPE is around 2.5%, and recent evidence suggests that those patients who develop haematuria have a higher microvascular density higher compared with controls [20]. Of course, when a patient with BPE presents with haematuria, the first concern is to rule out bladder cancer and upper tract causes. In some cases, benign enlarged prostates may bleed severely and bleeding may be the principle indication for intervention using medical (5‐ARIs) or surgical (transurethral resection of prostate [TURP]) treatments.

Urinary tract infection (UTI) in residual urine is seldom cured unless obstruction is relieved; Hunter et al. reported an incidence of UTI of 5.2% in patients with BPH. The Medical Therapy of Prostate Symptoms (MTOPS) study reported an incidence of 0.1/100‐year in patients treated with placebo [20].

The incidence of bladder stones was reported to be 0.7% in a cohort of Spanish men with BOO [21]. Stones that develop in residual urine either become rounded like pebbles or assume the characteristics of a Jack‐stone.

The term ‘silent obstruction’ has been used to describe relatively asymptomatic patients who develop a variable degree of renal impairment as a result of BOO whenever the voiding pressure in the bladder exceeds about 40 cm H2O. Fortunately, the incidence of this clinical picture is low at 2.4% [21].

The yearly risk for developing acute urinary retention (AUR) is about 0.6–1.8% [22]. From the clinical and prognostic point of view, spontaneous AUR should be separated from precipitated AUR. Precipitated AUR occurs after a triggering event such as anaesthesia, sympathomimetic, or anticholinergic drugs and constipation. All other AUR episodes are classified as spontaneous; after spontaneous AUR, 15% of patients have another similar episode and a 75% will require surgery. In precipitated AUR, on the other hand, only 9% have a further episode and only 26% will require surgery [1, 23]. Armitage reported that there was higher incidence of mortality rate in the first year after AUR compared to the general male population [24]. This was linked to the fact that as men got older their comorbidities increased contributing to the higher mortality rates (Table 27.1).

Table 27.1 (a) One‐year mortality rates after acute urinary retention (b) One‐year mortality rates after acute urinary retention in patients with and without significant comorbidities.

Age (years) Spontaneous acute retention Precipitated acute retention
45–54 4.1% 9.5%
55–64 5.3% 12.5%
65–74 9.7% 17.8%
75–84 17.9 28.7
>85 32.8% 45.4%
Any age 14.7% 25.3%
45–54 1.8% without comorbidity
14.7% with comorbidities
3.4% without comorbidity
24.3% with comorbidities
55–64 2.3% without comorbidity
16.7% with comorbidities
4.5% without comorbidity
26% with comorbidities
65–74 5.3% without comorbidity
21% with comorbidities
8.1% without comorbidity
30% with comorbidities
75–84 12.5% without comorbidity
28.8% with comorbidities
18.1% without comorbidity
40.5% with comorbidities
>85 27.3% without comorbidity
44.3% with comorbidities
38% without comorbidity
54.7% with comorbidities
Any age 9.9% without comorbidity
27.2% with comorbidities
16.1% without comorbidity
38.1% with comorbidities

27.4.1 Chronic Retention of Urine

These patients present with a distended palpable bladder; renal function tests should be requested along with ultrasound of the upper urinary tract because the patient may have hydronephrosis, secondary to BOO with associated nephropathy. Obviously, these patients must be managed by inserting an indwelling urethral catheter, but one must be cautious about the possibility of postobstructive diuresis, which may lead to dehydration and electrolyte disturbances due to loss of sodium. Close monitoring of renal function and urine output are required as intensive fluid, and salt replacement may be indicated. Lying and standing blood pressure may be helpful until the patient’s urine output and overall condition stabilises. Following the relief of bilateral ureteric obstruction, tubular function usually recovers within two weeks, but full recovery of glomerular function may take up to three months. In this group of patients, catheter drainage should continue and surgery should be postponed until renal function recovery has been demonstrated because it has been proven that patients with renal failure have more complications after TURP (25 vs. 17%), and the mortality rate is increased sixfold [25].

27.5 Epidemiology and Natural History of BPH

There is a complex relationship between BPH, LUTS, BPE, and BOO. An understanding of this is important when managing a patient who presents with LUTS, to aid recognition of patients who have LUTS with or without BPE and with or without BOO. This relationship can be described using Hald rings (Figure 27.1). It shows the inter‐relationship among LUTS, BOO, and BPE. BPE may be associated with symptoms with or without BOO; it may also be associated with obstruction with or without symptoms. Symptoms may occur with obstruction with or without BPE. It is the patient with all three (BPE, BOO, and LUTS) who will benefit maximally from therapy.

Autopsy studies showed that BPH never occurs before the age of 30 and progressively increases until it reaches a prevalence of 90% for men in their 80s [26].

A UK study which defined symptomatic BPH as the presence of enlarge prostate with a volume of more than 20 ml, with LUTS or reduced urinary flow rate Q max less than 15 ml s−1 estimated the prevalence of BPH as 137 in 1000 members of a population ages 40–49 years (13.8%) and 50–59 years (24%), rising to 430 in 1000 members men ages 60–69 years (43%) [27]. While histological prevalence was more dramatic: <30 years (0%), 41–50 years (23%), 51–60 years (42%), 61–70 years (71%), 71–80 years (82%), and > 80 years (>88%) [28].

Studies of total prostate volume of men in their 30s revealed that total prostate volume averaged 25 cm3, and this increased to 45 cm3 for men in their 70s. A simple guide is that 50% of men will develop histologic BPH by the age of 60 and that 50% of men with histologic BPH develop clinical BPE, whilst 50% of men with BPE develop symptoms require treatment. A 50‐year old (man) has a 25–30% lifetime chance of requiring surgical intervention for LUTS associated with BPH.

It has been shown that the concept of disease progression is also a reality. Indeed Lee et al. [29] reported the natural history of LUTS in a large cohort of symptomatic men followed for five years without treatment, which demonstrated that both storage and voiding LUTS get significantly worse with time [27].

The Olmsted County study of urinary symptoms and health status [30] showed that BPE, peak flow rate (Qmax), and LUTS were all age‐dependent and that men with significant BPE of more than 50 cm3 were 3.5 times more likely to have moderate to severe LUTS. The disease is a slowly progressive disorder with a mean increase in International Prostate Symptom Score (IPSS) of 0.18 points/year, mean decrease in Qmax by 2.1%/year (0.2 ml s−1), and a mean prostate growth of 2%/year (1–2 ml) [30].

Another study suggested that prostatic enlargement alone did not determine symptom severity, but the volume of transitional zone was the factor most strongly correlating with symptom severity [31]. This finding is consistent with Watanabe’s theory of PCAR because the relationship between PCAR and BOO is also independent of total prostate volume. The transition zone index (TZI) is the ratio of the transition zone to total prostate volume, which has been shown to correlate with the extent of BOO. It should be noted that the total prostate volume does not correlate with the extent of BOO [32]. From these observations, it is clear that significant prostatic enlargement, elongation of transitional zone, and resulting tension within the prostate or prostate capsule are determinant factors of LUTS.

Many studies have assessed the relationship between LUTS and BOO. Netto et al. [33] performed urodynamic studies on 217 patients who had moderate and severe LUTS and identified obstruction in 53% and 83%, respectively. In another urodynamic study on 222 patients who had a clinical diagnosis of BPH and a maximum flow rate less than 15 ml s−1, 80% were obstructed [34]. These studies show that urodynamic evidence of BOO is prevalent in men who have moderate to severe LUTS.

AUR should not be viewed as an irreversible result of the bladder response to longstanding obstruction because many patients presenting with AUR have more than adequate detrusor function, with evidence of a precipitating event leading to obstruction. The overall risk of AUR has been estimated to be 0.5–2.5%/year; however, the risk is cumulative and increases with age and symptom severity. The MTOPS study [20] showed that the incidence of AUR increased threefold in patients who had a prostate volume greater than 40 ml. Furthermore when PSA levels were more than 1.4 ng ml−1, there was an eightfold increase in the incidence of AUR. Jacobsen et al. [35] estimated the risk of AUR for a 60‐year old (man) who had moderate to severe symptoms was 13.7% over a 10‐year period. It also identified that an age increase from fourth to seventh decade (eightfold), IPSS >7 (threefold), flow rate < 12 ml s−1 (fourfold), and postvoid residual (PVR) >50 ml (threefold) increased the risk of AUR (Table 27.2) [36].

Table 27.2 Natural history of benign prostatic hyperplasia to cause acute urinary retention or disease progression.

Factor Reference Compared reference Risk‐fold increase
Age 70–79 years 40–49 years
Qmax (ml s−1) <12 >12
PSA >1.4 <1.4
Prostate volume (measure by TRUS) (ml) >30 <30
Severity of LUTS (IPSS measured) >7 (moderate to severe LUTS) <7 (mild LUTS)
PVR (ml) >50 <50

IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptoms; PSA, prostate‐specific antigen; PVR, postvoid residual; Qmax, peak flow rate; TRUS, transurethral ultrasound.

27.6 Investigations

The investigations for patients with LUTS start, as always, with a thorough history and clinical examination.

27.6.1 History

History should include an assessment of the type of LUTS (storage or voiding), their severity, and importantly the impact on their quality of life (QoL) and bother. It is important to assess patient general medical history to help identify causes of LUTS and if there are any associated comorbidities (e.g. congestive heart disease, diabetes, Parkinson disease, etc.). A thorough review of the patient’s medications may also help identify contributing factors. Whilst there is little to no correlation between symptoms or urodynamics and prostate size [3739], LUTS do correlate with urodynamically proven obstruction (correctly predicting nearly 90% of obstructive cases). Thus assessment of LUTS using validated self‐assessed questionnaires such as the IPSS is useful [40]. Elicitation of red flag symptoms such as haematuria, incontinence, and dysuria may necessitate urgent investigations.

27.6.2 Examination

Physical examination should focus on patient’s symptoms and comorbidities, including examination of the abdomen, external genitalia (i.e. meatal stenosis or phimosis), and digital rectal examination (DRE) of the prostate to assess for prostate cancer (PCa) and prostate size. Prostate size is estimated by feeling from side to side of the prostate the number of index finger widths, where one finger‐breadth is said to represent approximately 15 g. However, it is easier to estimate the size as small, medium, or large whilst recognising that DRE leads to an underestimation of prostate size [1]. A neurological examination should be undertaken if there is any suspicion that neurological disease that may be contributing to the symptoms (lower extremity neuromuscular function and anal tone).

27.6.3 Objective Assessment of LUTS

IPSS is a validated objective assessment of patients’ LUTS, which has good test–retest reliability and good internal consistency [41, 42]. Completion of the questionnaire yields a total score ranging from 0 to 35 (i.e. 1–7 for minimal symptoms, 8–19 for moderate symptoms, and 20–35 for severe symptoms). The IPSS correlates well with postoperative outcomes from BPH surgery where a high preoperative scores is associated with a good outcome; however, there are weak correlations with prostate volume, flow rate (FR), PVR, and age [43]. The IPSS also incorporates an assessment of the impact of LUTS on the QoL of the patient. Assessment of QoL is important because it helps in making a decision on management for their LUTS [44].

27.6.4 Urinalysis

A urinalysis should be performed to detect blood, glucose, leucocytes, and nitrites. A positive urinalysis for infection should be treated and may well account for the patients LUTS. Haematuria on urinalysis should be investigated with a flexible cystoscopy and upper tract imaging.

The previous four investigations (i.e. history, physical examination, validated questionnaire, and urinalysis) are all recommended by current international guidelines [45].

27.6.5 Frequency or Voiding Volume Chart

A 24‐ to 72‐hour diary of the patients’ fluid intake and voiding history, including approximate volumes voided, should be done. These are simple, cheap, and provide some objective information of voiding and are recommended during initial assessment of male LUTS [4]. Measurements can also elucidate the presence of polyuria and nocturnal polyuria (which may be the cause of symptoms).

27.6.6 Blood Tests

Serum creatinine levels should only be measured if renal impairment as a result of BOO is suspected (i.e. palpable bladder, high PVR and incomplete emptying of the bladder, and rarely signs and symptoms of renal failure) [4]. Routine creatinine measurement is not currently recommended as an analysis of clinical trials involving more than10 000 patients found the silent rate of renal impairment to be less than 2% [46]. With more recent trials, such as the MTOPS study, showing the risk of developing renal failure in men with LUTS to be less than 1% [47].

Prostate‐specific antigen (PSA) testing should be offered to patients after thorough advice and counselling (Table 27.3) and time to decide only if they have LUTS suggestive of BOO secondary to BPE, if their prostate feels abnormal on DRE, or they are concerned about PCa. In patients with LUTS, the PSA is predictive of the likelihood of disease progression due to BPH, with a PSA >1.4 ng ml−1 putting patients at an increased risk of disease progression [48].

Table 27.3 Prostate‐specific antigen counselling guidelines.

  • Need to highlight potential disadvantages of an abnormal result.
  • Need to balance risks and benefits of having clinically significant disease diagnosed.

You must counsel asymptomatic men about the following:

  • Cancer will be identified in <5% of men screened.
  • Benefits of screening remain controversial.
  • Sensitivity is 80%; there is no level of PSA at which prostate cancer can be excluded.
  • Specificity is 40–50%; a false‐positive is possible (UTI, age ranges, etc.).
  • If elevated, diagnostic pathway (DRE, TRUS biopsy & risks: pain, infections, bleeding – each 0.5%)
  • TRUS biopsy may miss cancer.
  • May need repeat biopsy.
  • Treatment may not be necessary.
  • Treatment may not be curative.
  • Decreased QoL as a result of treatment complications.

DRE, digital rectal examination; PSA, prostate‐specific antigen; QoL, quality of life; TRUS, transurethral ultrasound; UTI, urinary tract infection.

27.6.7 Other Investigations

FR and PVR assessment is usually performed in the outpatient department or nurse‐led clinic. A FR and PVR is recommended by National Institute for Health and Care Excellence (NICE) for all patients having been referred for specialist advice [4]. A FR should have a total volume voided of at least 150 ml and inspection of the shape of the curve produced should be carried out because the flow patterns for urethral stricture and BPO have different characteristics. After this, a PVR should be performed. For a FR to be reliable, it should be measured on a voided volume of at least 150 ml of urine, and there should be two separate FRs. Normal age‐specific FRs (Qmax): <40 years: >21 ml s−1; 40–60 years: >18 ml s−1; and >60 years: >13 ml s−1. The urinary flow test is unable to distinguish between a poorly contractile bladder and BOO. To illustrate this, peak flow rates >15 ml s−1 have been shown to have urodynamic proven BOO in 30% of patients, while those with flows 10–15 ml s−1 have BOO in 60%; however, a FR < 10 ml s−1 up to 90% have urodynamic proven BOO [49] (Figure 27.7). This is especially important to establish prior to a surgical intervention as patients whose symptoms are caused by BOO, the likelihood a TURP alleviates their symptoms is >90%, whereas those without BOO will be nearly 60% [50].

2 Graphs depicting flow rates in normal (top) and in benign (bottom) enlargement of the prostate.

Figure 27.7 Flow rate (a) normal (b) in benign enlargement of the prostate.

PVR is calculated with abdominal ultrasound after the patient has voided by multiplying the length, width, and height of the measured bladder ×0.7 (i.e. the ellipsoid area calculation). It is, however, not reproducible, and there is a large inter‐rater variability. Pretreatment PVR is very weakly associated with treatment outcome. There is inconsistency amongst guidelines with regard to the level at which intervention should be undertaken (200 ml for European Association of Urology, 300 ml for the British Association of Urological Surgeons (BAUS) and 350 ml for American Urological Association (AUA). In all patients with persistently elevated PVR > 200 ml. bladder dysfunction is likely, and therefore, upper tract imaging (renal ultrasound) should be undertaken to exclude upper tract deterioration (e.g. hydronephrosis).

Cystoscopy or imaging of upper urinary tract (renal ultrasound or computed tomography [CT]) is recommended only if there is a history of recurrent infection, sterile pyuria, haematuria, profound symptoms, calculi, pain, or chronic retention.

Urodynamics can categorise the degree of obstruction and can differentiate between patients with a poorly contractile bladder and those with BOO. The purpose of offering urodynamics is to detect those patients without clear BOO who have the lowest benefit from surgery. The Abrams–Griffiths number can also help to determine if the patient has BOO [51].

The routine use of urodynamics for all patients before surgery is unrealistic and expensive; however, it is of value in certain subsets of patients [52]. Therefore, indications for urodynamic test are: (i) patients who are going surgery and have an equivocal FR <150 ml or Qmax >15 ml s−1 (ii) <50 years old or > 80 years old, (iii) Patients with a PVR > 200–300 ml, (iv) those with a suspicion of neurologic bladder dysfunction (e.g. Parkinson disease, history of spinal injury, multiple sclerosis, etc.) (v) Previous radical pelvic surgery or unsuccessful previous BPH treatment (i.e. medical or surgical).

27.7 Management

The three main treatment aims in patients with BPE and LUTS are [45, 53]:

  1. Relief of symptoms.
  2. Improvement in QoL.
  3. Preventing disease progression.

The treatments offered to patients depend on the balance between the severity of patients’ symptoms and degree of bother and their preferences with regard to outcome and complications.

There has been a large shift in treatment patterns for patients with LUTS in the last one to two decades from one of surgical intervention to medical management [54]. There has been a decrease in the number of TURP being performed as a result of increased use of medical treatment, with up to a 60% reduction in TURP rates in certain parts of the world. [54].

Treatment modalities available:

  1. Watchful waiting and conservative treatment
  2. Medical management:
  3. Monotherapy

    1. Combination therapy

  4. Surgical management

27.7.1 Watchful Waiting

Watchful waiting (WW) [5557] is a management option where the patient is monitored by their doctor without active intervention for LUTS. The key to this management option is that patients and doctors use conservative interventions until symptoms progress or complications of BPE arise. It has been established that despite BPH being a progressive disorder, many patients (i.e. more than two‐thirds) do not need surgery. Roughly speaking, more than one‐third of patients symptoms tend to improve, more than one‐third stay the same, and a less than one‐third worsen [58].

Conservative interventions [59] include:

  • Explaining about postmicturition dribble and how to perform urethral milking.
  • Discussing containment products to manage storage LUTS (urinary incontinence).
  • Storage LUTS, suggestive of overactive bladder (OAB), can benefit from supervised bladder training, advice on fluid intake, lifestyle advice, and if needed, containment products.
  • Discussing external collecting devices (e.g. sheath appliances and pubic pressure urinals) for managing storage LUTS (particularly urinary incontinence) in men before considering indwelling catheterisation.
  • Discussing intermittent bladder catheterisation before indwelling urethral or suprapubic catheterisation to men with voiding LUTS that cannot be corrected by less invasive measures.
  • Discussing long‐term indwelling urethral catheterisation for whom medical management or surgery is not appropriate or unwanted or who are unable to manage intermittent self‐catheterisation.

Lifestyle modifications include:

  • Reduction of fluid intake in the evening
  • Avoidance of irritant substances (e.g. caffeine, alcohol, smoking, etc.)
  • Timed or organised toilet scheduling and bladder training
  • Altering patient medications or time of delivery (e.g. diuretics, decongestants, antihistamines, and antidepressants)
  • Treatment of constipation.

Education about the disease, natural history of it, potential complications and reassurance are also important. Watchful waiting is recommended for patients with mild symptoms (IPSS <7) or moderate to severe symptoms but not reduction is QoL [52].

27.7.2 Medical Management

  1. a) Herbals

In Europe, herbal medications have been used to treat LUTS for many years [60], with most interest in Saw Palmetto (Serenoa repens). Indeed, an early meta‐analysis demonstrated improvements in peak FR and nocturia in comparison to placebo [61]. However, an updated meta‐analysis with long‐term outcome data recently demonstrated that there was no difference in symptom score reduction or peak flow rate improvement between S. repens and placebo [62]; hence, its use has not been recommended [45].

  1. b) Alpha‐blockers (α‐blocker)

The mode of action of α‐blockers is to block the α‐receptors located in the prostatic smooth muscle and bladder neck that mediate contraction and thereby reduced flow and the development of LUTS. Blocking these receptors mediates relaxation of the tissues, thereby easing the flow of urine through the lower urinary tract [63]. Some of the α‐blockers have also been shown to cause apoptosis of the prostatic epithelium, which may also contribute to their effect [64].

There are two main types of α‐receptors (α1 and α2 receptors). The α1 receptors are located mainly in the urinary tract in particular the α1α subtype; however, the α2 receptors are also located elsewhere in the body including blood vessels which accounts for some of the unwanted side‐effects of α‐blockers, especially the less selective ones such as phenoxybenzamine [65, 66]. The different types depend on their uroselectivity; uroselevtive α1a‐blockers include Tamsulosin and alfuzosin and nonselective α1‐blockers are doxazosin and terazosin [67].

There are many α1‐blockers now available, and each have similar efficacy for treatment of LUTS but have differing side‐effect profiles. The main side effects of α‐blockers are mild, occur in about 15% of patients, and include (more common with non‐neuroselective blockers): orthostatic hypotension, headache, dizziness, asthenia, drowsiness, and ejaculatory problems (i.e. retrograde ejaculation, more common with the uroselective blockers) [47]. Tamsulosin has a lower rate of orthostatic hypotension but a higher likelihood of ejaculatory problems (i.e. retrograde ejaculation) than the other α‐blockers. Intraoperative floppy iris syndrome during cataract surgery is an important side effect to bear in mind when commencing patients on α‐blockers especially tamsulosin which can be seen in up to 86% of patients and about 15% with alfuzosin [68, 69]. There is progressive miosis (i.e. pupil constriction) regardless of dilatory use, billowing of the flaccid iris, and iris prolapse into the incision site that can lead to posterior capsular rupture with vitreous loss and intraocular pressure rise. Though its effects can be prevented with use of atropine, it is best to avoid α‐blocker use in all patients contemplating cataract surgery. However, in experienced hands, intraoperative floppy iris syndrome can be anticipated and compensatory techniques employed (such as topical atropine preoperatively, iris retractors, pupil expansion ring, or use of viscoadaptive ophthalmic viscosurgical device with reduced fluidic parameters) to prevent complications leaving excellent visual outcomes [67].

All α1‐blockers have a rapid onset of action (48 hours) and a similar efficacy producing an increase in peak flow rate of 2–3 ml s−1 and a 4–6 point improvement in IPSS score. Though they do not alter the natural history and long‐term disease progression (i.e. progression to AUR or need for surgery), they can significantly reduce symptoms by at least 30–40% [47, 70].

Alpha‐blockers are recommended medical therapy for patients with moderate (8–19 on IPSS) to severe (20–35 on IPSS) LUTS. Patients should be initially be reviewed after 4–6 weeks of therapy and then every 6–12 months [4].

  1. c) 5‐alpha reductase inhibitors (5‐ARIs):

There are two drugs available in this class, finasteride, which is a type II 5α‐reductase inhibitor, and dutasteride, which is a type I & II 5α‐reductase inhibitor [71]. These 5‐ARIs block the action of the 5‐AR enzyme and therefore the conversion of testosterone to DHT, the more potent ligand.

Finasteride causes a reduction in DHT by 75%; however, dutasteride causes a reduction of DHT by 95% [22]. This causes atrophy of the prostatic glandular epithelial cells and leads to a 20–30% reduction in prostatic volume; however, 5‐ARIs have a slow onset of action varying from 2 to 12 weeks, with peak effect after 6–9 months [72]. Unlike α1‐blockers, 5‐ARIs prevent BPH disease progression, and in addition, they lead to a 2–3 point improvement in IPSS symptom scores and increase peak flow rate by 1.5–2.5 ml s−1 [22, 47, 73].

5‐ARIs reduce the incidence of AUR and the need for surgical intervention by around 50% compared to placebo (i.e. relative‐risk reduction 57%) [22, 47, 73]. However as the incidence of AUR is low, translating, the absolute risk reduction to only 4%, or numbers needed to treat to prevent one AUR episode is 25 [22]. Similarly, there was a 55% relative‐risk reduction for need for surgical intervention as compared to the placebo groups. Nonetheless, 5‐ARIs are recommended for use in patients with LUTS and if patients are at high risk of disease progression (i.e. high risk criteria – >70 years of age, prostate >30 g, Qmax <12 ml s−1, or PSA >1.4 ng ml−1) [4]. The bigger the prostate size, the greater the improvement of symptoms. Some advocate the use of 5‐ARIs in patients at high risk of disease progression but who do not have bothersome symptoms to prevent disease progression [74]. Furthermore, 5‐ARIs can lower the microvessel density and VEGF, leading to a reduction in haematuria complications secondary to BPH, in addition to theoretically reducing bleeding during and after TURP [75].

5‐ARIs tend to reduce PSA by about 50%, and evidence suggests that it reduces the incidence of PCa by nearly 25% for finasteride and a relative‐risk reduction of 40% for dutasteride, albeit both with an observed increase in the risk of high‐grade tumours [76]. Theories for these observations include 5‐ARIs reduce the size of the prostate and increase the sensitivity of PSA for the detection of PCa, and as a consequence increasing the detection of higher grades of cancer, (i.e. 5‐ARIs have a lesser reduction of PSA level in high‐grade PCa, leading to more biopsy and increased high‐grade detection). Alternatively, others have advocated that 5‐ARIs themselves change tissue architecture by inducing histological changes leading to higher‐grade cancers. Nonetheless, ongoing trials aim to answer these questions.

Adverse events are usually well tolerated and include erectile dysfunction, altered libido, ejaculatory disorders (low‐volume ejaculate), and rarely, gynecomastia and breast tenderness.

  1. d) Combination Therapy (α‐blocker and 5‐ARIs)

The MTOPS trial, which randomised 3047 men to placebo, doxazosin, finasteride, or combination of doxazosin and finasteride with four to five years follow‐up showed a clear advantage for combination therapy in reducing the risk of disease progression (i.e. relative‐risk reduction 66%), risk of AUR (relative‐risk reduction 81%), and the need for surgery (relative‐risk reduction 67%) [47].

Similarly, the CombaAT trial, randomised 4844 men to either dutasteride, tamsulosin, or combination of the two with a four‐year follow‐up [77]. Combination therapy was significantly better in reducing the risk of disease progression (i.e. relative‐risk reduction 44%), risk of AUR (relative‐risk reduction 68%), and the need for surgery (relative‐risk reduction 71%). Combination therapy also provides greater symptom improvement benefit than either monotherapy regimens alone. Hence, combination therapy may be recommended in patients with bothersome moderate to severe LUTS who are at high risk of disease progression [4].

Combination therapy has similar adverse event profiles to other treatment modalities [44].

  1. e) Anticholinergics

Patients with symptoms suggesting OAB can benefit from combination therapy of a α1‐blocker and an anticholinergic if storage symptoms have not improved with monotherapy alone [4, 78]).

  1. f) Phosphodiesterase‐5 inhibitors:

There has been some benefit in LUTS improvement with the use of phosphodiesterase‐5 (PDE‐5) inhibitors [79]. However, these are still considered experimental with ongoing trials aimed at establishing an evidence‐based practice and a linkage between LUTS and erectile dysfunction. Acute Urinary Retention and Its Management

AUR is the most common urological emergency and is a significant burden on urology services around the world [80]. It affects between 2.2 and 6.8 per 1000 men more commonly in older men with 10% of men older than 80 years of age having an episode of AUR [36]. The impact on QoL is similar to a bout of renal colic [81], and the cost of hospital admission ranges between $2500 and $7500 if a TURP is performed [82]. AUR is also associated with an increased risk of mortality within a year of occurring. In men 74–84 years of age, mortality within the year is between 12.5 and 28.8% depending on comorbidities (Table 27.1) [24].

The management of AUR starts with catheterisation to relieve the patient’s discomfort. The most common route in the UK is urethral catheterisation with 98% of urologists reporting this method [83]. Suprapubic catheterisation (SPC; Figure 27.8) is an alternative method. Advantages of SPC include avoiding damage to the urethra, bladder neck, reduced catheter bypassing, and a lower rate of UTI. However, it has a reported 2.8% risk of bowel injury and 1.8% risk of mortality, consequently in patients with previous abdominal surgery or if the bladder is not palpable blind SPC insertion is not recommended [84, 85].

3 illustrations depicting infiltration if local anaesthesia to find the bladder, with a disposable suprapubic cannula passed down the track.

Figure 27.8 Infiltrating local anaesthesia to find the bladder. A disposable suprapubic cannula is passed down the track.

The next step in the management is to take a thorough history and examination to try to ascertain if the cause of AUR is likely to be secondary to BPE. A DRE allows the urologist to assess for BPE or PCa. Urinalysis should be performed to exclude a UTI or haematuria, whilst blood tests to assess renal function (i.e. urea, creatinine, and estimated glomerular filtration rate) should be performed. If these tests indicate a cause other than BPE to be the likely cause of the AUR then urodynamics (e.g. functional bladder disorders), cystoscopy (e.g. urethral stricture), or CT or MRI of the nervous system (e.g. neurological disorder) should be performed [86].

Then it should be determined whether hospital admission is required or if an ambulatory care programme is suitable for the patient. Indications for hospital admission include: urosepsis, gross haematuria, residual volume > 1 l, postcatheterisation diuresis, unusual symptomatology, and those unable to cope with a urethral catheter or ambulatory care programme [82, 87]. Worldwide hospitalisation rates for AUR vary wildly with only 1.7% in Algeria to 100% in France [88].

The timing of the trial without catheter (TWOC) should be at 48–72 hours because it has been shown that after 72 hours of catheterisation the complication rate associated with catheterisation significantly increases, most notably haematuria, urosepsis, and urine bypassing around the catheter [89]. Despite this, internationally and in most instances logistically and practically TWOCs take place after five days of catheterisation [90].

The role of medications in AUR is an important consideration. In 1976, it was first identified by Caine and colleagues that alpha‐blockers improve the success rate of TWOC [91]. Since then, five randomised controlled trials and a Cochrane review have been performed. Four randomized controlled trials (RCTs) compared alfuzosin to placebo with one comparing tamsulosin to placebo. Four of the trials favoured the use of alpha‐blockers over placebo for success rates of TWOC, corroborated by the Cochrane review, [92].

The largest and landmark RCT was the ALFAUR study where 360 patients were randomised to either placebo or 10 mg of alfuzosin daily [93]. A TWOC was performed at three days, and after a successful TWOC, all patients were randomised to receive a further six months of alfuzosin or placebo. This study showed that at six months, the alfuzosin group had a higher TWOC success rate (i.e. 61.9 vs 47.9%) and a lower rate of surgery requirement (i.e. 17.1 vs 24.1%) compared to placebo. However, a study following patients for a further six years after an episode of AUR managed in this way found that the majority (76%) of those receiving alfuzosin eventually required surgery or had another episode of AUR [23].

These results along with the results of MTOPS and CombAT indicate that alpha‐blockers either pre‐ or post‐AUR in patients with BPE merely delay the need for surgery with no real effect on altering disease progression, and therefore,we feel that physicians should always strongly consider the use of 5‐ARIs (to prevent disease progression in high‐risk patients or those who have had an AUR episode) or alternatively early surgery (TURP) [20]. A management algorithm used locally in our unit is shown in Figure 27.9.

Acute urinary retention management algorithm illustrating arrows connecting boxes labeled patient in painful urinary retention, catheterize and drain bladder, admit to hospital, ambulatory care program, etc.

Figure 27.9 Acute urinary retention management algorithm. BOO, bladder outflow obstruction; BPE, benign prostatic enlargement; DRE, digital rectal examination; HPCR, high‐pressure chronic retention; SPC, suprapubic catheterisation; TWOC, trial without catheter; UTI, urinary tract infection. Chronic Urinary Retention

Is divided largely into two separate groups, high‐pressure chronic retention (HPCR), where there is high detrusor pressure at the end of micturition, and low‐pressure chronic retention (LPCR) [94, 95]. The constant raised pressure in HPCR leads to back pressure in the kidneys and resultant hydronephrosis and ultimately renal impairment. In LPCR, patients have large‐volume bladders, which are compliant and tend to have low detrusor pressures, low FRs, and high residual volumes. In both condition LUTS are uncommon or mild and can be affected by nocturnal enuresis (e.g. drop in urethral resistance during sleep) [96].

Presentation of men with chronic urinary retention is varied and can be asymptomatic or low‐volume micturition, increased frequency or hesitancy, nocturnal enuresis, a palpable but painless bladder, or signs of chronic renal impairment [95, 97].

Initial assessment of these men should involve a urinalysis for signs of infection, a renal panel blood test (i.e. urea and electrolytes). In patients with HPCR, renal ultrasound can be performed to demonstrate hydronephrosis. PSA should be avoided because this will be elevated from chronic urinary retention.

Management is somewhat complex and is mainly dictated by the presence of renal impairment (Figure 27.10).

Image described by caption.

Figure 27.10 Flow chart of chronic retention management. HPCR, high‐pressure chronic retention; ISC, intermittent self‐catheterisation; LPCR, low‐pressure chronic retention; LTC, long‐term catheterisation; LUTS, lower urinary tract symptoms; SPC, suprapubic catheterisation; TURP, transurethral resection of prostate; UTIs, urinary tract infections. Polyuria and Nocturnal Polyuria

Polyuria or nocturnal polyuria s a syndrome where >33% of the total urine output occurs during the night [98]. It is essential to get patients to complete a three‐day voiding diary which incorporates the volumes of voided urine; this enables the calculation of ratio of daytime to night‐time urine volume voided.

The causes of nocturnal polyuria include congestive heart failure, obstructive sleep apnoea, nephrotic syndrome, autonomic neuropathy, chronic kidney disease, venous insufficiency, neurologic diseases like Parkinson and Alzheimer diseases, and idiopathic [98].

Oedema‐forming states lead to nocturnal polyuria due to the mobilisation of the oedema during recumbency which the kidneys process and produce urine at night. Obstructive sleep apnoea is associated with atrial natriuretic peptide (ANP) release. Neurologic conditions cause a change in the diurnal secretion of ANP and anti‐diuretic hormone (ADH) leading to increased retention of urine and increased production of urine at night. In chronic kidney disease, the kidneys are maximally concentrating the urine and this leads to an increased urine production at night. However, in many cases, there is no definitive cause that can be found.

The mainstay of evaluation is with a three‐day voiding diary with volumes voided to be included. This is followed by a thorough history and examination focused to the causes listed previously. If bladder dysfunction is suspected, then this can be treated or further investigation started with urodynamics. Targeted investigations for other causes can be performed also.

The evidence base for the treatment of nocturnal polyuria is limited with only a few RCTs. Conservative measures such as fluid restriction six hours before bedtime has limited affect. Loop diuretics taken 6–10 hours before bedtime have also been shown to have some limited impact.

The medication with the greatest evidence for its use is Desmopressin (a synthetic analogue of vasopressin), which works by mimicking the actions of ADH (reduces urine production). There have been 2 placebo controlled RCTs assessing the effect of Desmopressin on nocturnal polyuria. The largest by Wang et al. [99] was more than 12 months and showed a reduction in the number of times men needed to void at night of 2 less than placebo, with NNT = 2. There were significant improvements in sleep duration and QoL. While Rezakhaniha et al. [100] have shown a reduction in the number of times voiding at night and increased duration of sleep with desmopressin 100 mcg per night compared with placebo.

Important potential side effects include hyponatraemia (14%), headache, nausea, dizziness, and peripheral oedema. This medication is currently not licenced for the treatment of nocturnal polyuria.

27.8 Surgical Management

Surgical management is recommended for patients with BPH or BPE related complications: [45]

  1. LUTS refractory to medical therapy
  2. Recurrent UTIs
  3. BPH or BPE – related visible haematuria refractory to treatment (5‐ARIs)
  4. Renal insufficiency secondary to BOO
  5. Bladder stone(s)
  6. Recurrent urinary retention
  7. Urinary retention who have failed at least one trial without catheter

Patients who refuse medical therapy or have unacceptable side effects from medications are also candidates for surgery.

The gold standard of surgical management is TURP, except for patients with very small prostates where transurethral incision of the prostate (TUIP) or very large prostates where open (i.e. Millin) prostatectomy remains the gold standard [45]. New techniques such holmium laser enucleation of the prostate (HOLEP) are becoming a more accepted alternatives for both TURP and Millin prostatectomy. Numerous minimally invasive techniques are also being evaluated.

  1. Standard Treatments:

    1. i) TUIP

The bladder neck is divided through a resectoscope, either under general or local anaesthesia, best suited for prostates <30 ml. The incision is made with a diathermy electrode or laser which is said to cause neither pain nor bleeding (Figure 27.11).

2 Diagrams depicting bladder neck incision, with a 6 o’clock incision going right through the bladder neck gaping widely.

Figure 27.11 Bladder neck incision. A 6 o’clock incision avoids damage to the penile neurovascular bundles. The incision goes right through the bladder neck which is seen to gape widely.

Just where to cut through the bladder neck is a matter of surgical preference and training. Some surgeons performing only one incision and others two. Wherever the bladder neck is incised, the patient must be warned of retrograde ejaculation.

  1. ii) TURP

Since being pioneered in 1909 and since its use flourished after the invention of the resectoscope in the 1940s, TURP has been the mainstay procedure for urologists [101]. TURP is still considered the benchmark and standard for all treatments for BPH and BOO with prostates >30–< 100 ml. The purpose of the operation is to remove enough of the obstructing tissue from the cranial inner zone of the prostate to allow the bladder to empty freely. TURP has been shown to improve symptoms in more than 90% of patients and improve the mean IPSS score by 62% after 12 months postoperatively and improve peak flow rate by 120% (9.7 ml s−1) [102]. The requirement for repeat surgical intervention (redo TURP or other procedures) within 10 years is approximately 10–15% (i.e. 2%/year) [103].

27.8.1 Technique

Immediately before prostatectomy, the urethra and bladder are examined to rule out strictures, cancers, diverticula, and stones. There are several different styles of transurethral resection, however, the most commonly used is the technique described first described by Blandy.

27.8.2 Objectives

Transurethral resection removes all the adenoma proximal to the verumontanum and leaves behind a shell of connective tissue and compressed adenoma. Great care is taken to preserve the verumontanum because the intramural sphincter lies so close to it. The neurovascular bundles to the penis are also very close to the membranous urethra and diathermy must be used sparingly in their vicinity. The tissue distal of the verumontanum is left behind (Figure 27.12).

2 Diagrams of the objective of transurethral resection of prostate depicting transurethral prostatectomy (top) and enucleative protastectomy (bottom).

Figure 27.12 The objective of transurethral resection of prostate (TURP) (a) is the same as that of open prostatectomy (b) namely to remove all the tissue from the transitional zone.

27.8.3 Steps of the Operation

Begin by identification of the verumontanum and sphincter. Then the circular fibres of the bladder neck are revealed by resecting the overlying middle lobe tissue (Figure 27.13). Bleeding from the 5 and 7 o’clock arteries of the prostate is controlled by diathermy. The lateral lobe on one side is freed from the bladder neck and capsule by cutting a trench near the midline starting at 1 or 11 o’clock to allow the bulk of the lateral lobe to fall backwards (Figure 27.14). Bleeding from the anterior prostatic arteries is sealed with coagulation. The remainder of the lateral lobe adenoma is then removed with a series of downwardly directed cuts, exposing the capsule (i.e. the thin layer of remaining adenoma which is right up against periprostatic fat and veins). After one lobe has been resected, the same procedure is applied to the other side (Figure 27.15). It only remains to clean away any little tags of tissue that have been overlooked and to obtain perfect haemostasis. Throughout the resection the surgeon must continually refer back to the landmarks of the verumontanum, sphincter and bladder neck.

4 Diagrams depicting the verumontanum, with the middle lobe resected until the bladder neck is visible.

Figure 27.13 (a) The verumontanum; (b–d) the middle lobe is resected until the bladder neck is visible.

Image described by caption.

Figure 27.14 (a) A trench is made between the bladder neck and adenoma at 1 o’clock, allowing the lateral lobe to drop back. (b) The lateral lobe is then resected (c–d) same to the other side.

3 Diagrams depicting little bits of adenoma resected, especially around the apices and the verumontanum.

Figure 27.15 Any little bits of adenoma that have been left are resected especially around the apices and the verumontanum (a–c).

27.8.4 Postoperative Management

A three‐way irrigating catheter is used by most surgeons, and saline is used as the irrigating fluid. The irrigation is stopped when the effluent is reasonably clear and the catheter can usually be removed after 48 hours. Others prefer to use a two‐way catheter, and rely on intravenous fluids and a diuretic to keep the bladder irrigated. Patients may go home once successfully passing urine after catheter removal but are advised not to take vigorous exercise for another 10–14 days because of the risk of secondary haemorrhage.

27.8.5 Complications [103, 104107] Early Complications

Primary haemorrhage on the operating table requiring blood transfusion (10%) is a major complication, but can largely be reduced by a preliminary coagulation of the rim of the prostate at the 2, 10, 5, and 7 o’clock positions where the prostatic arteries are found.

One must bear in mind UTI or sepsis (4–20%) are possible in the postoperative period and that they should be treated promptly to lessen morbidity, although this has decreased in recent years due to the use of prophylactic antibiotics.

Urinary retention occurs (3–9%) postoperatively. This might be due to either an element of poor bladder contractility, failure to resect enough tissue to alleviate the obstruction, or a clot is blocking the exit passage. Catheterisation will be required, and a further TWOC attempted for the first two. If this fails, urodynamics can help diagnose the cause. A bladder washout can clear out clots.

Perforation is also a possible complication. The capsule is thinner than the loop of the resectoscope, so perforations are inevitable. Small perforations do not carry significant risk; however, larger ones may lead to excessive bleeding or fluid extravasation leading to TURP syndrome.

If distilled water is used as an irrigant, there is a risk of haemolysis leading to tubular obstruction by haemoglobin and acute renal failure. Nonelectrolyte solutions that do not haemolyse the blood should always be used (e.g. glycine, glucose, or one of the proprietary sorbitol–mannitol mixtures).

TURP syndrome (<1%) is caused by absorption of the irrigant fluid during TURP or rarely transurethral resection of bladder tumour (TURBT) or percutaneous nephrolithotomy (PCNL). Glycine (1.5%), the most commonly used irrigant, is hypotonic (200 mosmol l−1) compared to plasma; therefore, its absorption will lead to fluid overload, dilutional hyponatraemia, and glycine toxicity.

  1. The fluid overload leads early on to hypertension, shortness of breath, pulmonary oedema, and possibly cardiac failure. If left untreated or fluid overload, continues bradycardia and hypotension ensue. The fluid overload also causes the cardiac atria to release atrial natriuretic peptide, which causes an osmotic diuresis and results in loss of salts.
  2. Dilutional hyponatremia, resulting from the excess fluid, shifts water from plasma into the brain. In severe cases leading to cerebral oedema and herniation, which can lead to death if untreated. Symptoms usually start when sodium levels are <130 with restlessness, confusion, or delirium. If sodium drop to <115, seizures ensue and the patient can become unresponsive and comatose.
  3. Glycine is metabolised mainly in the liver (90%) and kidneys (10%) into glycolic acid, ammonia, and water (leading to worsening of the fluid overload and hyponatremia). It is an inhibitory amino acid neurotransmitter, and in the retina, it slows down neurotransmissions to the cerebral cortex, which can manifest as seeing halos or flashing lights or transient blindness. In the face, can cause prickling or numbing sensations. Rarely if left untreated or large amounts absorbed, the inhibition can cause bradycardia and hypotension.

Risk increases if the prostate is >45 ml (1.5%), or the resection time is >60 minutes (2%). Even if solutions are used that cannot cause haemolysis, if a sufficiently large volume enters the vascular space, there will be dilution of the plasma electrolytes, especially sodium, and disturbance of muscle and nerve function.

This syndrome is rare because intravasated fluid is usually rapidly excreted by diuresis, but in very frail old men, this diuresis may be prevented by an inappropriate secretion of the ADH.

Precautions to avoid extravasation of irrigating fluid include (i) keeping the level of the fluid below 20 cm above the operating table; (ii) stopping the resection if large veins are opened or large perforation done; (iii) limiting resection time; and (iv) avoiding TURP in >100‐ml prostates.

Recognition is key, if the patient is under a general anaesthetic, hypertension or even hypotension and cardiac arrhythmias with decreased O2 saturation should elude to TURP syndrome; otherwise visual and fascial symptoms, sudden confusion, or irritability if a spinal is used. No treatment is usually needed if the patient is well and is having a good diuresis. Alternatively, a loop diuretic, which induces a diuresis that results in loss of more water than sodium, can be used, such as 40 mg of furosemide. In severe cases of hyponatremia (e.g. uncontrollable epileptic fits), 50 ml of hypertonic solution (29.2% saline) may be given intravenously – preferably through a central venous line in the intensive care unit, with an aim of correcting 1 mmol l−1 h−1 as to avoid rapid correction that lead to central pontine myelinolysis or demyelination which can results in paralysis.

Late complications include urethral strictures (2–9%), urinary incontinence (0.5%) (Figure 27.16), retrograde ejaculation (50–90%), and bladder neck stenosis (5%).

4 Diagrams depicting appearance of normal, open, during, and after supramembranous intramural sphincter has been cut at 7 o’clock.

Figure 27.16 Appearance after supramembranous intramural sphincter has been cut at 7 o’clock.

The risk of impotence after prostatectomy is <10%, and it increases with the age of the patient. Because the neurovascular bundles to the penis are so close to the verumontanum, coagulation in this region may damage them.

Mortality rate is usually low between 0.2 and 0.4%; however, even this figure is decreasing with advancements in equipment and anaesthetic techniques.

Before the national prostatectomy audit was performed in 2004, emergency TURP was being performed at initial AUR presentation. However, this audit identified that surgery immediately following AUR was associated with greater morbidity and mortality than with elective TURP [108]. There were greater intra‐ and postoperative complications, including bleeding requiring transfusion and 30‐day mortality in the patients who underwent emergency TURP. As such careful consideration should be undertaken prior to performing a TURP at initial AUR presentation.

  1. iii) Open prostatectomy

Transvesical open prostatectomy, which carried a low risk of mortality at the time of only 5%, was first popularised by the Irish Urologist Sir Peter Freyer in 1912 [102]. The open retropubic prostatectomy was popularised by Terence Millin in the 1940s, and it provided better exposure, better control of bleeding, and allowed for a lower rate of urinary incontinence than the previous procedures [103]. The mortality rate was less than 1% and was mainly due to haemorrhage, myocardial infarction, or respiratory complications. Other complications include low rates of bladder neck contracture (2%), impotence in 15–20%, and retrograde ejaculation in up to 80% [104]. In the developed world, open prostatectomy is performed in less than 1% of patients; however, in the developing world is up to 55–60% [41]. The recent increase in power of lasers the resultant increase in efficacy for use with large prostates has led to a further reduction in the number of open prostatectomy being performed.

  1. a) Transvesical prostatectomy

This is the classic procedure. Through a cystostomy, the index finger is forced into the internal meatus until it splits to open a plane of cleavage between the adenoma and the so‐called ‘surgical capsule’ (Figure 27.17). The finger enucleates the adenoma. Once the adenoma is removed, there may be a torrent of bleeding from the arteries at the neck of the bladder which are difficult to see or suture. Large stitches are placed at the neck of the bladder (Figure 27.18). The difficulty of securing precise haemostasis is the reason why this operation was replaced by that of Millin.

  1. b) Retropubic prostatectomy (Millin operation)
Image described by caption and surrounding text.

Figure 27.17 (a) Freyer transvesical prostatectomy. The salient lobes of the prostate are circumcised with the diathermy, and (b) a finger forced into the internal meatus to split the anterior commissure, and then enucleate the adenoma.

Diagram depicting large stitches in the neck of the bladder to help control bleeding after adenoma has been cut.

Figure 27.18 After the adenoma has been enucleated sutures at each quadrant help to control bleeding.

Make a Pfannenstiel incision. Wipe away the fat around the preprostatic veins and divide them between suture ligatures. The layer of areolar tissue and fat is now carefully wiped laterally with a Lahey pledget in the hope of preserving the neurovascular bundles of the penis (Figure 27.19).

2 Diagrams depicting the fascia incised on either side of the dorsal veins which are then sutured and divided (top) and the penile neurovascular bundle is displaced laterally and backwards (bottom).

Figure 27.19 The fascia is incised on either side of the dorsal veins which are then sutured and divided (a) and the penile neurovascular bundle is displaced laterally and backwards (b).

Make a transverse incision with a diathermy needle at the junction of the bladder and prostate using the coagulating current to control bleeding (Figure 27.20). As the prostate is thin anteriorly, the incision needs only to be 2 or 3 mm deep before the inner zone adenoma is exposed (Figure 27.21). The plane of cleavage between capsule and adenoma is opened with scissors on each side.

Illustration depicting the capsule of the prostate incised with the diathermy to expose the adenoma. Lines indicate diathermy needle, retractor bladder, adenoma, peritoneum, etc.

Figure 27.20 The capsule of the prostate is incised with the diathermy to expose the adenoma.

Illustration depicting a plane between capsule and adenoma developed with scissors. Lines indicate long curved scissors, fat and veins, symphysis pubis, fat, bladder, and side blades of Millin’s retractor.

Figure 27.21 The plane between capsule and adenoma is developed with scissors.

A finger is firmly thrust into the lumen of the prostatic urethra, breaking through the thin anterior commissure. The nipple of the verumontanum can be felt. Pressure down on either side of the verumontanum breaks into the plane between adenoma and capsule (Figure 27.22) and leaves a strip of intact urothelium along the midline.

2 Schematics with labels capsule and lateral lobe (top) and split, capsule, and veru (bottom).

Figure 27.22 First on one side, then the other, the plane between adenoma and capsule is developed with the finger. Then a second plane is developed between the groove at the side of the verumontanum so as to liberate the lateral lobe completely.

First one lateral lobe and then the other are enucleated with the finger and brought out into the wound (Figure 27.23). Opening a bladder neck spreader reveals the middle lobe, attached to one or other lateral lobe (Figure 27.24). This is dissected from the bladder neck with the diathermy needle leaving only the strip of mucosa leading down to the verumontanum which is cut across well proximal to the sphincter.

Illustration depicting 2 lateral lobes delivered out of the prostatic shell. Lines indicate left lateral lobe, enucleated adenoma from right lobe, middle lobe, bladder, vulsellum, veru, incised capsule, etc.

Figure 27.23 Both lateral lobes are now delivered out of the prostatic shell.

Illustration depicting the middle lobe dissected from the bladder neck. Lines indicate bladder neck muscle fibres, mucosa of bladder, diathermy needle, bladder neck spreader, and trigone and bladder neck.

Figure 27.24 The middle lobe is dissected from the bladder neck.

The retropubic approach permits perfect haemostasis. First a 2–0 absorbable suture is passed through the bladder, bladder neck, and capsule at each end of the transverse incision to control bleeding from the main prostatic arteries (Figures 27.25 and 27.26). Smaller vessels along the cut edge of the bladder are underrun with fine sutures.

Illustration depicting Badenoch’s sutures placed at each corner to secure the main arteries of the prostate.

Figure 27.25 Badenoch’s sutures are placed at each corner to secure the main arteries of the prostate.

Illustration depicting haemostasis completed by sutures at the bladder neck.

Figure 27.26 Haemostasis is completed by sutures at the bladder neck.

Occasionally an artery continues to spurt from inside the prostatic capsule which is difficult to see. The capsule may be everted by a suture which picks up the lining (Figure 27.27). Traction on the suture reveals the source of the bleeding which is controlled by suture ligature or diathermy.

Illustration depicting the capsule everted by a suture which picks up the lining.

Figure 27.27 Bleeding from inside the prostatic capsule can be located by everting the capsule with a suture.

A three‐way irrigating catheter is put in the bladder; the wound is closed and a suitable drain is made. The drain is removed at 48 hours and the catheter on the fourth or fifth day when, if generally well, the patient may go home.

  1. iv) Holmium laser procedures

The holmium aluminium garnet laser has a wavelength of 2140 nm which allows rapid absorption by water allowing rapid vaporisation of the tissue to a depth of 0.4 mm and a result coagulation depth of 3–4 mm [109]. There are three different techniques that can be utilised by holmium laser. Ablation (HoLAP) which uses the laser to vaporise and create a cavity over the surface of the prostate, resection (HoLRP) which involves removal of pieces of tissue using the cutting action of the laser fibre, and enucleation (HoLEP) which is similar to open prostatectomy in that the laser is used to develop the plane between the adenoma and capsule and the lobes are dissected out before they are morcellated to allow removal.

HoLEP has now superseded the other two techniques and has long‐term evidence to support its use. Its clinical efficacy is at least equivalent to TURP with reduced risk of bleeding and blood transfusion requirement and reduced length of hospitalisation and catheterisation time. However, it requires a longer operative time and has similar complication rates [110]. It has more durable evidence to support its use than photo‐vaporisation of the prostate (PVP) although this evidence is also starting to mature [109]. Furthermore, evidence suggest that it can contend with open (i.e. Millin) prostatectomy for >100‐ml prostates with less blood loss and shorter hospital stays and catheterisation times, but longer operative time, with no difference in symptom improvements (90% improvements) and complication rates.

The advent of laser prostatectomy has made day‐case surgery for BPH now a realistic possibility with more than 90% of cases performed as day cases in some institutes.

  1. c) Minimally invasive therapies

Over the last 20 years there has been an explosion in the number of other possible treatment options, with many focused on treating increasingly elderly and comorbid patients. The introduction of bipolar TURP improved the safety profile of the procedure by reducing the risk of TURP syndrome [111]. Many of these are not routinely used in clinical practice in the UK, however, are being used elsewhere and therefore it is important to appreciate them.

  1. i) Transurethral microwave thermotherapy (TUMT)

Delivers heat to the prostate through a transurethral catheter by computer‐regulated microwaves (915/1296 MHz). It delivers heat >45 °C which destroys prostatic tissue and has a cooling system to protect the urethra during the procedure.

It is the most popular minimally invasive method worldwide because it avoids the need for anaesthesia (i.e. outpatient procedure) and has a short learning curve. Morbidity mainly involves the need for prolonged catheterization and there is a 2–10% failure rate. It is not recommended by NICE but is recommended by the EAU guidelines where no suitable alternative exists [4, 112].

  1. ii) Transurethral needle ablation of the prostate (TUNA)

Delivers low level radiofrequency (460 kHz) to the prostate via needles resulting in temperatures over 100 °C, which destroys prostatic tissue. It is simple and safe and can be performed without anaesthesia. Symptom scores improve by 8–10 points and peak flow rate by 3–4 ml s−1, although there has only been one RCT, and there is little long‐term data [113, 114]. It is not recommended by NICE but is recommended by the EAU guidelines where no suitable alternative exists [4, 112].

  1. iii) Transurethral electro‐vaporization (TUVP)

Delivers uninterrupted high‐intensity electrical energy to the prostate using modified transurethral equipment including a rollerball electrode with a larger surface area. It requires continuous bladder irrigation to prevent overheating of urine. Several RCTs have shown similar rates of symptom score improvement and peak FRs to TURP although higher rates of storage symptoms and dysuria. The disadvantage is that the efficacy of the electrode decreases as the tissue desiccates which makes it difficult for larger prostates [102, 115].

  1. iv) Laser prostatectomy:

Four types of laser energies have been used for the treatment of BPE (Nd:YAG, Holmium:YAG, KTP:YAG, and diode).

Greenlight laser prostatectomy (KTP:YAG laser) was an improvement from the earlier Nd:YAG laser by doubling the frequency using a potassium‐titanyl‐phosphate‐KTP crystal this produced a different laser [116]. The resultant KTP:YAG laser (greenlight) beam has a different wavelength to the Nd:YAG laser, and it sits within the visible green region of the electromagnetic spectrum (unlike the Nd:YAG which is in the infrared portion) [117].

The KTP laser is selectively absorbed by haemoglobin in tissue but fully transmitted through aqueous irrigation fluids and therefore is PVP. Absorption of KTP laser leads to instant removal of prostate tissue by photothermal vaporisation of heated intracellular water [118]. The optical penetration of the KTP laser is only 1–2 mm which allows a focused and efficient vaporisation [119]. More advanced KTP systems (e.g. HPS and XPS) have been developed which allow wider beams of increased intensity and enabled larger prostates to be tackled [120].

Efficacy for the greenlight laser prostatectomy has shown similar improvements in IPSS and FR as with TURP with shorter length of stay, reduced blood loss, and better intraoperative safety; however, it is also a slight higher reoperation rate in the long term for it [121].

Aug 6, 2020 | Posted by in UROLOGY | Comments Off on Prostate Benign Prostatic Hyperplasia

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