Prostate Benign Prostatic Hyperplasia(BPH)- overview

1. Dept of Urology Govt Royapettah Hospital and Kilpauk Medical College Chennai 1

2. Moderators: Professors: • Prof. Dr. G. Sivasankar, M.S., M.Ch., • Prof. Dr. A. Senthilvel, M.S., M.Ch., Asst Professors: • Dr. J. Sivabalan, M.S., M.Ch., • Dr. R. Bhargavi, M.S., M.Ch., • Dr. S. Raju, M.S., M.Ch., • Dr. K. Muthurathinam, M.S., M.Ch., • Dr. D. Tamilselvan, M.S., M.Ch., • Dr. K. Senthilkumar, M.S., M.Ch. Dept of Urology, GRH and KMC, Chennai. 2

3. BPH-Pathology • Can be microscopic BPH, macroscopic BPH, or clinical BPH. • Proliferative process originates in the transition zone and the periurethral glands . • Androgens play a passive role in the proliferative process. • Growth factors such as epidermal growth factor (EGF) are involved through autocrine and paracrine stromal-epithelial interactions. 3 Dept of Urology, GRH and KMC, Chennai.

4. BPH-Pathophysiology 4 Dept of Urology, GRH and KMC, Chennai.

5. BPH-Symptoms • Obstructive LUTS – Straining, Intermittency, Hesitancy, Weak stream, Incomplete voiding sensation, overflow urinary incontinence • Irritative LUTS – Frequency, Urgency, • Nocturia • Recurrent UTI • Hematuria • Acute urinary retention 5 Dept of Urology, GRH and KMC, Chennai.

6. • Rule out other causes of voiding dysfunction or comorbidities. • Use of a voiding diary (recording times and volume) may help identify patients with polyuria or other nonprostatic disorders. BPH-Voiding diary 6 Dept of Urology, GRH and KMC, Chennai.

7. Abdominal examination - to exclude an overdistended, palpable bladder. Examination of the external genitalia - to exclude meatal stenosis or a palpable urethral mass. DRE and a focused neurologic examination should usually be performed. BPH-Examination 7 Dept of Urology, GRH and KMC, Chennai.

8. Multiple symptom scores are available. • AUA-7 Symptom Index (AUASI), • IPSS, • Madsen and Iversen, • Boyarsky and • International Continence Society Study on BPH. BPH-Symptom scores 8 Dept of Urology, GRH and KMC, Chennai.

9. IPSS- Severity of the problem • Mild symptoms (0 to 7) - assigned to watchful waiting; • Moderate (8 to 19) or severe (20 to 35) - undergo further testing or treatment, or both. IPSS-Current US and International standard Ideal instrument to grade baseline symptom severity, assess the response to therapy, and detect symptom progression in those men managed by watchful waiting. 9 Dept of Urology, GRH and KMC, Chennai.

10. IPSS Scoring system 10 Dept of Urology, GRH and KMC, Chennai.

11. • Urinalysis • Serum Creatinine • Serum PSA • Uroflowmetry • Post void residual urine • TRUS • Upper urinary tract imaging • Additional studies BPH-Investigations 11 Dept of Urology, GRH and KMC, Chennai.

12. Assists in distinguishing UTIs and bladder cancer from BPH. Urine cytology should always be requested in men if they have a smoking history. BPH-Investigations/Urinalysis 12 Dept of Urology, GRH and KMC, Chennai.

13. • Routine creatinine measurement in the standard patient is no longer recommended. • Elevated serum creatinine levels in a patient with BPH is an indication for imaging studies (usually ultrasonography) to evaluate the upper urinary tract. BPH-Investigations/Sr.Creatinine 13 Dept of Urology, GRH and KMC, Chennai.

14. Performed in patients in whom the identification of cancer would clearly alter BPH management. BPH-Investigations/Sr.PSA 14 Dept of Urology, GRH and KMC, Chennai.

15. • Inaccurate if the voided volume is <125 to 150 mL. • The peak flow rate (PFR; Qmax) more specifically identifies patients with BPH than does the average flow rate (Qavg). • PFR >15 mL/sec appear to have somewhat poorer treatment outcomes after prostatectomy than patients with a PFR <15 mL/ sec. • A PFR <15 mL/sec does not differentiate between obstruction and bladder decompensation. BPH-Investigations/Uroflowmetry 15 Dept of Urology, GRH and KMC, Chennai.

16. • Does not correlate well with other signs or symptoms. • Large PVR urine volumes - slightly higher failure rate with watchful waiting. • PVR urine volume is best viewed as a “safety parameter.” BPH-Investigations/PVRU 16 Dept of Urology, GRH and KMC, Chennai.

17. BPH-Investigations/TRUS • Transrectal Ultrasonography of Prostate. • Provides most accurate volume of the prostate. 17 Dept of Urology, GRH and KMC, Chennai.

18. Recommended in presence of one or more of the following: 1. Hematuria, 2. UTI, 3. Renal insufficiency (ultrasonography recommended), 4. History of urolithiasis, or 5. History of urinary tract surgery. BPH-Investigations/ Imaging of Upper Urinary tract 18 Dept of Urology, GRH and KMC, Chennai.

19. 1. Urodynamic study: Detrusor hypocontractility, if suspected. 2. Cystoscopy- Prudent before operative procedure. BPH-Investigations/Additional studies 19 Dept of Urology, GRH and KMC, Chennai.

20. BPH- TREATMENT OPTIONS WATCHFUL WAITING MEDICAL THERAPY SURGERY 20 Dept of Urology, GRH and KMC, Chennai.

21. 21 Dept of Urology, GRH and KMC, Chennai.

22. Patient driven treatment of choice. Indications: 1. Absence of absolute indication for intervention. 2. If the complications of treatment are greater than the inconvenience of the symptoms, 3. Reluctance to take a daily pill owing to side effects and/or the cost of treatment. Watchful Waiting or “Self-Help” 22 Dept of Urology, GRH and KMC, Chennai.

23. Watchful waiting-Methods 1. Decreasing total fluid intake especially before bedtime, 2. Moderating the intake of alcohol and caffeine-containing products, and 3. Maintaining timed voiding schedules. 23 Dept of Urology, GRH and KMC, Chennai.

25. Medical Therapy-Treatment Goals 1. Relieving LUTS, 2. Decreasing BOO, 3. Improving bladder emptying, 4. Ameliorating detrusor instability, 5. Reversing renal insufficiency, and 6. Preventing disease progression. 25 Dept of Urology, GRH and KMC, Chennai.

26. Medical Therapy-Agents 1. Αlpha adrenergic blockers 2. 5α-reductase inhibitors 3. Aromatase inhibitors 4. Antimuscarinic drugs 5. Phosphodiesterase inhibitors 6. Plant extracts 26 Dept of Urology, GRH and KMC, Chennai.

27. Alpha blockers Efficacy is mediated by α1 receptor Toxicity is mediated by α2 receptor Adverse effects: 1. Dizziness, 2. Asthenia, 3. Orthostatic hypertension, 4. Retrograde ejuculation. 27 Dept of Urology, GRH and KMC, Chennai.

28. Alpha blockers 1. Terazosin- Caution of hypotension needed in poorly controlled hypertension patients. 2. Doxazosin- Longer half life than terazosin (22 vs. 12 hours). 3. Tamsulosin- Most commonly employed α1 antagonist. Exhibits some degree of specificity for the α1A-adrenergic receptor .There is no need of dose titration. 4. Alfuzosin- Multiple doses is its primary limitation. Uroselective drug with no blood pressure changes. 28 Dept of Urology, GRH and KMC, Chennai.

29. Alpha blockers 5. Silodosin- Minimal effects on the cardiovascular system, retrograde ejaculation is most common. 6. Naftopidil- A relative selective α1D-adrenergic receptor antagonist. Decreases IPSS for storage symptoms. 29 Dept of Urology, GRH and KMC, Chennai.

30. 1. Finasteride- • Competitive inhibitor of the enzyme 5α-reductase type 2 isozyme. • Side effects- Decreased libido, ejaculatory disorder, and impotence. • Prevents recurrent gross hematuria secondary to BPH & • Effective in post prostatectomy hematuria. 2. Dutasteride- Dual inhibitor of 5αreductase types 1 and 2. 3. Zanoterone- steroidal competitive androgen receptor antagonist. Associated with severe breast pain & gynecomastia Androgen manipulation 30 Dept of Urology, GRH and KMC, Chennai.

31. 4. Flutamide- orally administered nonsteroidal antiandrogen, inhibits the binding of androgen to its receptor. 5. Cetrorelix- a gonadotropin-releasing hormone (GRH) antagonist. Primary disadvantage is its injectable form and high cost. 6. Atamestane- highly selective aromatase inhibitor. Use suspended because of negative clinical findings Androgen manipulation 31 Dept of Urology, GRH and KMC, Chennai.

32. Combination Therapy with α-Adrenergic Blockers and 5α-Reductase Inhibitors • Combination of doxazosin and finasteride exerts a clinically relevant, positive effect on rates of disease progression. Combination versus Avodart or Tamsulosin (CombAT) Trial • Combination of dutasteride and tamsulosin was more effective than either drug alone. Combination Therapy 32 Dept of Urology, GRH and KMC, Chennai.

33. Antimuscarinics • Useful for patients with coexisting OAB (Overactive bladder) symptoms. • Theoretical risk of increase in urinary retention in patients with significant obstruction due to antimuscarinic effect on detrusor. • Combination therapy with α1-adrenoceptor antagonists in carefully selected men is effective. • Men with significant obstruction and PVRU >200ml, antimuscarinics are better avoided. 33 Dept of Urology, GRH and KMC, Chennai.

34. Sildenafil, Tadalafil, Vardenafil and Udenafil are used. PDEIs improve urinary symptoms scores. Useful in men with LUTS and significant Erectile dysfunction. Possible candidate mechanisms of action include: 1. Smooth muscle relaxation in prostatic, bladder or erectile tissues, 2. Autonomic hyperactivity, 3. Calcium-independent Rho-kinase activation pathway 4. Reduced nitric oxide (NO) levels 5. Pelvic atherosclerosis theory Phosphodiesterase Inhibitors 34 Dept of Urology, GRH and KMC, Chennai.

35. Combination therapy: Concomitant use of α-adrenergic blockers and PDEIs may lead to symptomatic hypotension. Coadministration of doxazosin (4 and 8 mg daily) and tadalafil (5 mg/day or 20 mg as a single dose intermittently) leads to further lowering of blood pressure, and this combination is not recommended by the manufacturers. Phosphodiesterase Inhibitors 35 Dept of Urology, GRH and KMC, Chennai.

36. • Phytotherapeutic products are not the actual plant but are extracts derived from either the roots, the seeds, the bark, or the fruits of the various plants used. • Composition is very complex. Contains phytosterols, plant oils, fatty acids and phytoestrogens. • Serenoa Repens (Saw Palmetto Berry) extract is commonly used. • Three mechanisms of action: anti-inflammatory effects, 5α-reductase inhibition, and growth factor alteration. Phytotherapy 36 Dept of Urology, GRH and KMC, Chennai.

37. • Is a Complication associated with BPH • May be “spontaneous” or • May be “precipitated” by: • Medications Eg:anticholinergic or sympathicomimetic agents, • Urinary infection, • excessive fluid intake, and • the consequences of surgery (postoperative pain or the effects of anesthesia or analgesia or loss of mobility) may precipitate AUR. Acute Urinary Retention (AUR) 37 Dept of Urology, GRH and KMC, Chennai.

38. • Risk factors: • Presence of LUTS, • Low PFR, and • Raised PSA • If AUR is due to increased sympathetic activity, an α-adrenergic blocker may cause spontaneous voiding after catheter removal. • In the MTOPS trial, finasteride or combination therapy of finasteride with doxazosin, but not doxazosin alone, reduced the incidence of AUR Acute Urinary Retention (AUR) 38 Dept of Urology, GRH and KMC, Chennai.

40. Indications for BPH surgery 1. Refractory urinary retention 2. Recurrent UTI 3. Recurrent gross hematuria 4. Bladder stones 5. Renal insufficiency or 6. Large bladder diverticula 40 Dept of Urology, GRH and KMC, Chennai.

41. Endoscopic Procedures • Intraprostatic stent placement • TUNA • TUMT • TVP • TURP • TIP Open prostatectomy • Retropubic prostatectomy • Transvesical prostatectomy Surgical Treatment Options 41 Dept of Urology, GRH and KMC, Chennai.

42. Intraprostatic stents • Useful in patients unfit for surgery, in either the short or the long term • Better alternative for indwelling urethral catheterization. Can be of two types: 1. Temporary stents 2. Permanent stents Endoscopic Procedures/Stenting 42 Dept of Urology, GRH and KMC, Chennai.

43. Tubular devices, made of either a nonabsorbable or a biodegradable material. 1. Spiral Stents • First-Generation Stents Eg: Urospiral (Porges) and Prosta Kath (Pharma-Plast). • Complications: hematuria with clot retention (5%), stent migration (15%), recurrent urinary tract infections (10%), and encrustation (4%). • Second-Generation Stents. To overcome the problems of the first-generation. Eg: Memokath and the Prosta Coil Endoscopic Procedures/Stenting/ Temporary Stents 43 Dept of Urology, GRH and KMC, Chennai.

44. 2.Polyurethane stents are also known as intraurethral catheters. There are three types: a. Intraurethral catheter, b. Barnes stent, and c. Trestle stent. 3.Biodegradable Stents do not need to be removed, and eventually they disappear by biodegrading . Endoscopic Procedures/Stenting/ Temporary Stents 44 Dept of Urology, GRH and KMC, Chennai.

45. Examples are Urolume &Memotherm. UroLume is a woven tubular mesh that maintains its position in the urethra by outward external pressure. Memotherm is a stent of nickeltitanium alloy that is expandable to 42 Fr with heat. Endoscopic Procedures/Stenting/ Permanent Stents 45 Dept of Urology, GRH and KMC, Chennai.

46. TUNA- Transurethral needle ablation of prostate. Increases the temperature within the prostate and induces necrosis of prostatic tissue. The aim is to increase prostatic temperature to in excess of 60° C. Uses low-level radiofrequency (RF) energy of 490kHz that is delivered by needles into the prostate and that produces localized necrotic lesions in the hyperplastic tissue Lateral lobe enlargement and a prostate of 60 g or less patients are mostly benefited. Endoscopic Procedures/TUNA 46 Dept of Urology, GRH and KMC, Chennai.

47. Adverse Effects: • Posttreatment urinary retention (13.3-41.6%) • Irritative voiding symptoms (40%) • Urinary tract infection to (3.1%). • Sexual dysfunction is rare after TUNA. • Urinary incontinence has not been reported in any series. Endoscopic Procedures/TUNA 47 Dept of Urology, GRH and KMC, Chennai.

48. TUMT- Transurethral Microwave Therapy Eg: Prostatron, Targis Mechanism of Action • Tissue exposed to a minimum of 45° C for about 60 minutes suffered hemorrhagic necrosis with uniform extirpation • Thermal damage to the adrenergic fibers • Induction of Apoptosis TUMT does not outperform TURP. Endoscopic Procedures/TUMT 48 Dept of Urology, GRH and KMC, Chennai.

49. LASERs used: Nd:YAG KTP Holmium Diode Mechanism of action: 1. Coagulation or 2. Vaporization. Endoscopic Procedures/ LASER Prostatectomy 49 Dept of Urology, GRH and KMC, Chennai.

50. • Neodymium : Yttrium-Aluminum-Garnet Laser (wavelength of 1064 nm): • Active medium consists of neodymium atoms in an yttrium- aluminum-garnet rod. • Causes thermal coagulation of the surface tissue and of areas just under the surface. • Relatively inefficient way because of the high power required. Endoscopic Procedures/ LASER Prostatectomy/Nd:YAG 50 Dept of Urology, GRH and KMC, Chennai.

51. • Potassium-Titanyl-Phosphate Laser (532-nm wavelength): • Provides an intermediate level of coagulation and vaporization. • Only half the depth of tissue penetration is reached compared with that of the Nd : YAG laser. Endoscopic Procedures/ LASER Prostatectomy/KTP LASER 51 Dept of Urology, GRH and KMC, Chennai.

52. • Photoselective vaporization of the prostate (PVP) uses a 80-W KTP laser (Greenlight PV Laser System) • KTP/532 laser energy is delivered by a side- firing glass fiber. • Sterile water irrigation is used. • Complete vaporization produces aTURP-like cavity. • Less bleeding with larger coagulation zones. • Useful in patients on anticoagulant therapy or with severe bleeding disorders. Endoscopic Procedures/ LASER Prostatectomy/PVP 52 Dept of Urology, GRH and KMC, Chennai.

53. • Holmium : Yttrium-Aluminum-Garnet Laser (2100 nmwavelength): • The energy is emitted in a series of rapid pulses • Less hemostatic properties than those of the continuous wave lasers. • The Ho : YAG laser beam is absorbed by water (unlike the Nd : YAG beam) at a wavelength of 2140 nm and causes considerable tissue vaporization. • Can also be applied to large prostates. Endoscopic Procedures/ LASER Prostatectomy/Holmium Laser 53 Dept of Urology, GRH and KMC, Chennai.

54. • TURP- Transurethral resection of the prostate Gold standard for the surgical management of BPH. Indications: 1. Moderate to severe symptoms, 2. Acute urinary retention, 3. Recurrent infection, 4. Recurrent hematuria, and 5. Azotemia. TURP 54 Dept of Urology, GRH and KMC, Chennai.

55. Antibiotic Usage: No Bacteriuria and no Catheter in situ: Single dose of Ist generation Cephalosporin + Gentamicin before surgery. Bacteriuria or Catheter in situ: Antibiotic continued till catheter removal. Traditional monopolar technology has been replaced with Bipolar resection known as Gyrus Plasma Kinetic System. TURP 55 Dept of Urology, GRH and KMC, Chennai.

56. • Gyrus bipolar system consists of a generator with 200-W capability, an RF range of 320 to 450 kHz, • Resection should be performed in a routine step by-step manner. TURP 56 Dept of Urology, GRH and KMC, Chennai.

57. Hemorrhage • Arterial bleeding is controlled by electrocoagulation. • After surgery if arterial bleeding suspected, resectoscope is reinserted to achieve hemostasis. • Venous bleeding can be controlled by filling the bladder with 100 mL of irrigating fluid and placing the catheter on traction for 7 minutes at the operating table. The balloon of the catheter is overinflated to 50 mL of fluid. TURP-Intraop Complications 57 Dept of Urology, GRH and KMC, Chennai.

58. Extravasation, or perforation of prostatic capsule Occurs in about 2% of patients. Symptoms of extravasation are restlessness, nausea, vomiting, and abdominal pain Pain is usually localized to the lower abdomen and back. Operation should be terminated as rapidly as possible but hemostasis must be secured. Over 90% of these patients can be managed simply by urethral catheter drainage and cessation of the operative procedure TURP-Intraop Complications 58 Dept of Urology, GRH and KMC, Chennai.

59. Intraoperative Priapism Managed by injecting an α-adrenergic agent (Ephedrine or Phenylephrine) directly into the corpora cavernosa. Post Op complications Failing to void (6.5%), Bleeding requiring transfusion (3.9%), and Clot retention (3.3%). TURP- Complications 59 Dept of Urology, GRH and KMC, Chennai.

60. • TUR syndrome occur in 2% of the patients. • TUR syndrome is secondary to dilutional hyponatremia. • Amount of fluid absorbed were dependent on the height of the fluid by the patient. This could not be achieved when the fluid level was below 60 cm H2O. • Usualy serum sodium concentration reaches below 125 mEq/dL. • Risk is increased if the gland is larger than 45 g • resection time is longer than 90 minutes. • Clinical Features: mental confusion, nausea, vomiting, hypertension, bradycardia, and visual disturbance. TUR Syndrome 60 Dept of Urology, GRH and KMC, Chennai.

61. • Effective in treating patients with LUTS caused by BOO. • Useful in younger patients, especially if the prostate is smaller than 30 g. • Efficacy is comparable in such patients with TURP. • Simple technique and low morbidity. • With a Collings knife, an incision is made at the 5- and 7-o’clock positions or on one side of the midline only. It starts just distal to the ureteral orifice and ends just proximal to the verumontanum. TUIP-Transurethral Incision of Prostate 61 Dept of Urology, GRH and KMC, Chennai.

62. Advantages: 1. Lower re-treatment rate and 2. More complete removal of the prostatic adenoma 3. No risk of TUR syndrome Disadvantages: 1. Need for a lower midline incision 2. Longer hospitalization and convalescence period. 3. Increased potential for perioperative hemorrhage. Open Prostatectomy 62 Dept of Urology, GRH and KMC, Chennai.

63. 1. All indications for endoscopic procedures apply for open procedure also. 2. Prostate weighing more than 75 gms 3. Associated large bladder diverticula requiring diverticulectomy 4. Ankylosing conditions of the hip 5. Large bladder calculi not amenable to endoscopic removal 6. Recurrent and complex urethral conditions, Eg.Stricture, hypospadias repair 7. Associated inguinal hernia Open Prostatectomy- Indications 63 Dept of Urology, GRH and KMC, Chennai.

64. 1. Small fibrous gland 2. Presence of prostate cancer and 3. Previous prostatectomy or pelvic surgery Open Prostatectomy- Contraindications 64 Dept of Urology, GRH and KMC, Chennai.

65. 1. Urinary incontinence 2. Erectile dysfunction 3. Retrograde ejaculation 4. Urinary tract infection 5. Bladder neck contracture 6. Urethral stricture 7. Need for a blood transfusion 8. Deep vein thrombosis and pulmonary embolus Open Prostatectomy-Potential Risks 65 Dept of Urology, GRH and KMC, Chennai.

66. Retropubic Prostatectomy-Millin’s 66 Dept of Urology, GRH and KMC, Chennai.

69. 1. Excellent anatomic exposure of the prostate 2. Direct visualization of the prostatic adenoma during enucleation to ensure complete removal 3. Precise transection of the urethra distally to preserve urinary continence 4. Clear and immediate visualization of the prostatic fossa after enucleation to control bleeding 5. Minimal to no surgical trauma to the urinary bladder Retropubic Prostatectomy- Advantages 69 Dept of Urology, GRH and KMC, Chennai.

70. Transvesical Prostatectomy- Freyer’s 70 Dept of Urology, GRH and KMC, Chennai.

73. Advantages 1. A suited for large median lobe protruding into the bladder 2. Clinically significant bladder diverticulum 3. Large bladder calculi 4. Preferable for obese men Disadvantages 1. Less direct visualization of the apical prostatic adenoma. 2. Apical enucleation is less precise 3. May affect postoperative urinary continence 4. Hemostasis is more difficult Transvesical Prostatectomy 73 Dept of Urology, GRH and KMC, Chennai.

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