A presentation on the Benign Prostatic Hyperplasia; Epidemiology; Basic Science, Aetiology, Presentation and Treatment.

1. Benign Prostatic Hyperplasia
(BPH)
Dr. M. Yigah

2. Introduction
• BPH is an extremely common abnormality.
• It is the commonest prostatic disorder
• Reduce the quality of life of the elderly
• It is histopathological diagnosis
• BPE is a clinical or imaging diagnosis.

3. Anatomy and Physiology of Prostate
• Largest male reproductive accessory organ
• 3cm long x 4cm wide x 2cm AP depth
• Enclosed in a capsule
• Puboprostatic ligament anterolaterally
• Lies anterior to the rectum
Prostatic fluid – 20% of volume of semen
• citric acid and proteolytic enzymes
• which liquefies the coagulated semen in vagina
• Converts testosterone to Dihydrotestosterone (DHT).

4. Anatomy of Prostate

5. Epidemiology
• It is the commonest prostate disease
• BPH is commoner in Ghana than in Europe or US
• commonest cause of LUTS, urinary retention & haematuria in men over 50yrs in Gh
• DRE prevalence of BPE is 62% in Gh but 36-42% in the U.S.A
• In the USA 27million men needed treatment for BPH in 2000
• Incidence of BPH increases with age (autopsy findings)
• < 40yrs - 8%
• 57 – 60yrs - 50%
• 80yrs - 88%

6. Aetiology and Pathogenesis
• Imbalance between proliferation and apoptosis
• The exact cause-and-effect of BPH remains unknown
• Androgens are central to the pathogenesis of BPH
• Testosterone is coverted to DHT by 5a –reductase (Type 1 and Type 2)
• DHT is the main mediator of prostatic growth
• Androgens are required for normal cell proliferation and differentiation
Role of growth factors like FGF, EGF are secondary

7. Pathology
• Histology
• Transitional zone and the peri-urethral glands
• Increase in the number and sizes of glands
• Glands have more complex infoldings
• Uniform columnar and basal cuboidal cells with NO ATYPIA

8. Pathology
• Gross Morphology
• Prostate is enlarged typically b/n 60 and 100 g,
• Many well circumscribed nodules
• Nodules may appear solid or cystic.
• The urethra is usually compressed to a narrow slit

9. Pathophysiology
• BPH increases the urethral resistance statically and dynamically.
• Obstructive symptoms
• Reactive Hypertrophy in an attempt to improve urine flow
• Thickening and coursing of muscle strands -- trabeculations.
• Gaps between trabeculations can form saccules that can develop into diverticula
• Decreased storage capacity and/or detrusor instability.
• Development of storage symptoms
• Age-related changes in the bladder and nervous systems worsen the storage
symptoms

10. Pathophysiology

11. Diagnosis
• Primary diagnostic challenge is to establish that the LUTS are due
to BPH and not to other pathological process like strictures,
Prostate Ca or just ageing.
• Clinical History
• Using the IPSS
• Physical examination
• Investigations

12. Clinical History
• Obstructive symptoms
• Hesitancy, Poor stream, Intermittency, Straining, Feeling of incomplete bladder emptying
• Irritative symptoms
• Frequency, Nocturia, Urgency, Urge incontinence
• Complications of BPH
• AUR – sudden painful supra-pubic distension with inability to voids
May be spontaneous or provoked (drugs, alcohol, caffeine etc)
• CUR – usually painless supra-pubic distension, difficulty voiding, overflow incontinence
• UTI – irritative symptoms with lower abdominal painfever, nausea, vomiting.
• Haematuria

13. Clinical History
• Past Medical History
• History of hematuria, diabetes,
• Nervous system disease (e.g., Parkinson disease or stroke),
• Urethral stricture disease, STDs - gonorrhoea
• Past Surgical History
• history of prior lower urinary tract surgery - urethral or bladder neck stricture.
• Previous urinary tract instrumentation
• Drug History
• Anticholinergics eg. Oxybutynin
• Sympathomimetics e.g. ephedrine (common cold)

14. Physical Examination
• Full systemic Examination
• Gen – anaemia, dehydration, oedema etc
• Abdomen – Supra-pubic tenderness – UTI, AUR
Examination of hernia orifices
Examine for any palpable structures – kidneys, bladder etc.
• Genitals – Urethral discharges, strictures, meatal stenosis, urethral mass, perineal swelling,
Phimosis, paraphimosis, meatal warts.
• DRE - To assess the size, symmetry, median lobe, surface, edges, tenderness and
overlying mucosa

15. Physical Examination
• DRE Findings
• BPH – Large, Smooth, Rubbery, Asymmetrical,
Mobile mucosa,
Median groove (present or absent).
• Prostate Ca – may feel normal
Irregular, Asymmetrical, hard with palpable,
Loss of median groove,
Fixation to surrounding mucosa
• Prostatitis - Acutely tender
Chronic forms – may feel hard and indurate

16. International Prostate Symptom Score (IPSS)
• It was developed by the AUA and adopted by the WHO
• Objective assessment of severity the LUTS and quality of life of the patients
• Used to grade baseline symptoms.
• Assess the progression of BPH
• Assess the impact of treatment on symptoms
• Not a diagnostic tool
• Severity - Mild (0 to 7), moderate (8 to 19), or severe (20 to 35)

17. IPSS

18. Investigations
1. Urinalysis (microscopic exam or dipstick)
• Helps to rule out UTI or microscopic haematuria
• Urine glucose and ketones is suggestive of DM
• Urine cytology can help detect bladder cancers
2. Urine CS
• Confirm UTI, Prostatitis etc
3. BUE and Cr
• Helps to rule out renal failure sec to the obstructive uropathy
• Renal insufficiency complicates treatment of BPH

19. Investigations
4. Serum PSA
• Prostate Ca can also produce LUTS by causing BOO
• Prostate Ca and BPH can coexist
• BPH – Serum PSA <4ng/ml (except 20% of cases)
• Serum PSA > 4ng/ml – indication for a biopsy
• 5A –RI reduces the PSA ( PSA value must be double to get true value)
• In the absence of USG PSA correlate to prostate size
NB: DRE and PSA increase the detection of Prostate Ca

20. Imaging Studies
1. Abdominal USG
• Estimate the prostate size, PVR, Detrusor Hypertrophy, Diverticula, Haematuria
• Recurrent UTI, Renal failure, Hx of urinary calculi, Hydronephrosis.
2. TRUS
• Used to estimate the correct size of the prostate
• Provides guidance for biopsy.
3. IVU or CT/MRI Urogram
• Shows renal function, bladder diverticula, calculi, fish-hooking ends of ureter, PVR
• Bladder masses
4. MCUG/RUCG - Strictures

21. Additional Test – Urodynamic studies
• Recommended in patients with moderate to severe symptoms IPPS (8 -20).
a. Uroflow measurement – Assess the Qmax or PFR
• PFR > 15m/sec - Normal
• PFR 10 – 15 – Equivocal in young men but may be normal in old patients (70 – 80)yrs
• PFR < 10 – Suggest BOO
b. Post-voids residual volume – meaured using USG or catheterization
• PVR > 200ml - indication for medical and surgical treatment
• Risk of urinary retention
c. Pressure –flow urodynamic studies
• Helps differentiate BOO from Detrusor underactivity

22. Differential Diagnosis
• Urethral strictures
• Prostate Ca
• Bladder neck obstruction
• Bladder calculus
• Neurogenic bladder
• Diabetes mellitus
• UTI
• Chronic renal failure
• Polydipsia, drugs, beverages

23. Complications of BPH
• Bladder stones
• Bladder diverticula
• Recurrent Urinary Tract Infection
• Bladder decompensation
• Urinary incontinence
• Postrenal –renal failure
• Haematuria
• Acute and Chronic Urinary Retentions

24. Treatment of BPH

25. Treatment
1. Watchful Waiting (Self-Help)
2. Medical Therapy
3. Minimally Invasive Treatment
4. Surgical treatment
• Therapeutic response to surgery is better than medical treatment which
inturn is better than watchful waiting

26. Watchful Waiting (Self-Help)
• Often opted by patients in the absence of absolute indications for intervention.
• Do not discourage a well informed patient from pursuing this options.
• High treatment failure and concerns about disease progression.
• Offered in patients with uncomplicated BPH
• IPSS < 8 and not bothered by symptoms.
• Watchful waiting does not imply the total absence of intervention.
• Recommended when patient is already on medical therapy

27. Components of Self-Help Treatment
1. Education and Reassurance
• Discuss the causes of LUTS, including normal prostate and bladder function.
• Discuss the natural history of BPH and LUTS, including the expected future symptoms.
• Reassure that no evidence of a detectable prostate cancer has been found.
2. Fluid Management
• Advise a daily fluid intake of 1500 to 2000 mL (weather and physical activity)
• Avoid inadequate or excessive intake on the basis of a frequency volume chart.
• Advise fluid restriction when symptoms are most inconvenient (e.g. long journeys etc.)
• Advise evening fluid restriction for nocturia (no fluid for 2 hours before retiring).

28. Components of Self-Help Treatment
3. Caffeine and Alcohol
• Avoid caffeine by replacing with alternatives.
• Avoid alcohol in the evening if nocturia is bothersome.
• Replace large-volume alcoholic drinks (e.g. beer) with small-volume alcoholic drinks
(e.g. spirits)
4. Concurrent Medication
• Adjust the timing of medication especially those that worsen LUTS (e.g not before a long
journey)
• Replace antihypertensive diuretics with suitable alternatives.

29. Components of Self-Help Treatment
5. Types of Toileting and Bladder Retraining
• Advise men to double-void.
• Advise urethral milking for men with postmicturition dribble.
• Advise bladder retraining (distracting techniques, pelvic floor exercises)
6. Miscellaneous
• Avoid constipation in men with LUTS.

30. Monitoring Patients on Self-Help Treatment
• 3 monthly monitoring with
• IPSS assessments
• Review of frequency volume chart
• Peak Urinary Flow Rate (PFR)
• Serum PSA
• Post Void Residual Urine (PVR)
• Contraindicated in complications of BPH
• (AUR, CUR, Haematuria, recurrent UTI, Bladder diverticula, Uraemia etc)

31. Medical Therapy

32. Candidates for Medical Therapy
1. Patients with IPSS < 19
2. Bothersome symptoms that affect the quality of life.
3. Patients willing to make long term commitment to treatment
4. Patients with NO absolute indications for surgery
► AUR, CUR, Haematuria, Recurrent UTI etc

33. Type of Medications
1. α-adrenergic blockers
2. Androgen inhibitors
3. Antimuscarinic agents
4. Aromatase Inhibitors
5. Phosphodiesterase Inhibitors
6. Phytotherapy

34. α-Adrenergic Blockers
• Rationale for α-adrenergic blockers
►BOO caused by BPH has a static (mechanical) and dynamic (functional) component.
Dynamic obstruction is mediated by the α.A receptors of prostatic smooth muscles and
bladder neck
• Classes of α-adrenergic blockers
• Short acting Non-selective blockers – e.g. Phenoxybenzamine
• Short acting α1 selective blockers – e.g. Prazosin Alfuzosin IR
• Long acting α1 selective blockers – e.g. Doxazosin, Alfuzosin SR, Terazosin
• Subtype selective – e.g Tamsulosin 0.4 mg Daily; Silodosin 4-8mg Daily

35. α-Adrenergic Blockers
• Commonly used agents
• Tamsulosin – 0.4mg Mane
• Alfuzosin IR – 2.5mg TDS or Alfusozin SR 10mg Daily
• Prazosin – 2mg BD
• Terazosin – Start with 1mg and titrate up to maintenance (5 – 10mg) Daily
• Side Effects
• Flu-like syndrome
• Postural Hypotension
• Anejaculation
• Dizziness & Asthenia (esp. terazosin and doxazosin)
• Intra-operative Iris Syndrome

36. Androgen Suppressant
• Rational for androgen suppressants
• The conversion of testosterone to DIT by the 5α reductase type 2 promotes the
proliferation of the neoplastic cells hence depriving the BPH of androgens causes the
involution of the prostate.
• Reducing the size of the prostate reduces the mechanical obstruction.
• Men with larger prostate achieve the greatest benefits
• Limitations
• Takes about 6mo for Maximal reduction of prostate volume after initiation.
• Does not remarkably improve LUTS.
• Very undesirable side effects

37. Classification of Androgen Suppressants
1. Gonadotropin-Releasing Hormone Analogues
• Nafarelin acetate, Leuprolide, Cetrorelix
2. Progestational Agents
• 17α-Hydroxycortisone, Megestrol,
3. Antiandrogens
• Flutamide, Oxandrolone, Bicalutamide, Zanoterone
4. 5α-Reductase Inhibitors
• Finasteride, Dutasteride

38. Androgen Suppressants - 5α Reductase Inhibitors.
• Finasteride (Proscar®) - 5mg Daily
• Dutasteride - 500 mcg daily
• Dutasteride greater suppression of serum DHT.
• Finasteride also helps prevent recurrent gross haematuria sec to BPH
• They can reduce prostate volume by 20%
• Little improvement in LUTS (IPSS reduces by 1 and PFR increases by 1)
• They reduces the Serum PSA by 50%
• Baseline PSA should be checked before starting the medication.
• Multiply PSA value by 2 for patient on the drug to assess risk for Carcinoma.
• Side Effects – breast disorders, loss of libido, erectile dysfunction

39. Combination Therapy
• E.g. Tamsulosin with dutasteride (400mcg:500mcg)
• Lepor and coworkers (1996)
• For all outcome (with the exception of prostate vol) there was no significant
difference between those on combination therapy (Finasteride and Terazosin) and
those on only Terazosin
• MTOP Trials
• Pt who received combination therapy were significantly less likely to experience LUTS
and BPH progression than those receiving either monotherapy

40. Other Androgen Suppressants
• Zanoterone
• Steroidal competitive adrenoceptor antagonist.
• Has minimal therapeutic effect on the prostate volume, IPSS and PFR.
• Side effects – Gynaecomastia and Breast pain
• Flutamide
• Nonsteroidal antiandrogen that inhibits the binding of androgen to its receptor.
• Did not produce any significant difference compared to patients on the placebo
• Arotamse Inhibitor (Oestrogen inhibitor)
• No effects on PFR or Prostate volume

41. New Medical Treatment
1. ß3 Agonist (Mirabegron)
• The first of a new class of drugs agonists enhance ß3 bladder relaxation during bladder
filling by blocking the adrenoreceptors in the detrusor muscle.
• Mirabegron can increase bladder capacity without blocking contractility
• Helps to improve continence and micturating frequency
2. Phosphodiesterase Inhibitor
• Sildenafil, Tadalafil
• Side effect of improving erection is welcomed since erectile dysfunction is common is
patients with LUTS

42. Phytotherapy
• Hypoxis rooperi (South African Star Grass)
• Urtica SPP (Stingling nettle)
• Serenoa repens B (American dwarf palm)
• Cucurbitapepo (pumpkin seed) Pygeum africanum (African Plum

43. Minimally Invasive
Treatments

44. Minimally Invasive Treatment Modalities
• Transurethral Resection of the prostate (TURP)
• Transurethral Microwave Therapy (TUMT)
• Transurethral vaporization of prostate (TUVP)
• Transurethral Needle Ablation of Prostate (TUNA)
• Transurethral Incision of the Prostate
• High Intensity Focused Ultrasound (HIFU)
• Laser Therapy (TULIP)
• Intra-urethral stent
• Transurethral balloon dilatations

45. Transurethral Resection of the Prostate (TURP)
• An electric wire loop is used together with an endoscope to remove the
prostate between the bladder neck and the verumontanum to the depth of
the the surgical capsule.
• The gold standard for BPH treatment
• Monopolar (M-TURP) vs Bipolar (B-TURP)
• M-TURP requires non-ionic irrigant –e.g. water, glycine, sorbitol
• B-Polar reguires iso-osmolar irrigants e.g normal saline

46. Transurethral Resection of the Prostate (TURP)

47. Complications of TURP
• Haemorrhage
• Perforation of prostatic capsule
• TUR Syndrome due to (dilutional hyponatraemia)
• Bladder neck contracture
• Urethral stricture
• Urinary incontinence due to damage to internal and/or external sphincters.
• Need for retreatment – due to intra-op errors and complications like strictures.
• Urinary storage symptoms
• Ejaculatory problems

48. Transurethral Microwave Therapy (TUMT)
• Locally thermoablate prostate tissue while maintaining a normal temperature
in the normal surrounding non-targeted tissue.
• A special catheter generates the electromagnetic waves
• Treatment < 44oC – Hyperthermia
• Treatment > 44.5oC – Thermoplasty
• Treatment > 65oC - Thermoablative
• Downside- collateral damage to nontarget tissues

49. Transurethral vaporization of prostate (TUVP)
• Similar technology used for the TURP
• Resectoscope is replaced with an electrode that vaporizes the prostate
• Electrode has a large surface area
• Simultaneous controlled vaporization and coagulation

50. Transurethral Needle Ablation of Prostate (TUNA)

51. Transurethral Incision of the Prostate (TUIP)
• Disruption of the capsule helps to alleviate the symptoms.
• Cold knife, hot knife, resectoscope or even laser
• Ideal for younger patients with a small prostate <30g with fertility wishes .
•

52. Laser Therapy
• LASER - Light Amplification by Stimulated Emission of Radiation.
• Laser energies – Neodymium-Yttrium-Aluminium garnet (Nd-Yag or Yag Laser)
• Holmium-Yag-Laser
• Diode Laser
• Laser balloon
• The laser therapy can be used for
• Coagulation necrosis prostatectomy
• Transurethral laser incision (TULIP)
• Endoscopic laser ablation of prostate (ELAP)
• Transurethral vaporization of the prostate (TUVP)
• Vaporization and resection

53. Prostatic Stent
• A stent is placed in the prostatic urethra to
relieve obstructions
• Indications:
• Used for patient with Acute and Chronic Urinary
Retention who are unfit for surgery
• Complications
• Recurrent UTI, Stent migration, Encrustation.

54. Prostate Urethral Lift (Urolift)

55. Contraindications to Minimally Invasive
Treatments
• BPH with complications
• Retention of urine (Acute or Chronic).
• Recurrent UTI
• Diverticula
• Hydroureter and Hydronephrosis
• Calculi in bladder or diverticula
• Gross haematuria
• Progressive renal failure
• These are absolute indications for surgery (TURP or Open Prostatectomy)

56. Open Prostatectomy

57. Approach to Open Prostatectomy
• It is suitable for patients with a very large gland or complicated BPH
• BOO symptoms improved very well
• PFR increases to more than 20ml/sec
• Less likely to have another surgery.
• Two main approach to Open Prostatectomy
• Retro-pubic (Millin’s) Prostatectomy
• Transvesical Prostatectomy

58. Retropubic Prostatectomy

59. Retropubic Prostatectomy

60. Transvesical Prostatectomy

62. Complications
• Haemorrhage
• Clot retention
• Urinary Tract Infection
• Epididymo-orchitis
• Persistent vesico-cutaneous fistula
• Wound infection
• Incontinence of urine
• Impotence, Retrograde ejaculation, Infertility
• Urethral strictures, Bladder neck stenosis
• Damage to ureters
• DVT and/or PE

63. References
• Robbins Pathology 9th Edition
• Atlas of Human Anatomy 6th Edition
• Wheaters Functional Histology
• Clinically Oriented Anatomy 7th Edition
• Campbell-Walsh Urology
• BAJA Principles and Practice of Surgery