1 Benign Prostatic Hyperplasiaİbrahim Umur Kepsutlu | Orhun Ufuk Tipi | Zeynepgül İnkaya

2 Προστάτης (prostátēs) :protector, guardian

3 Functions Participates in the control of urine output from the bladder and in the transmission of seminal fluid during ejaculation. Contributes to the seminal plasma a spectrum of small molecules and enzymes like fibrinolysin, coagulase which facilitate fertility. Safeguards sperm viability by reducing the acidity of the urethra. It facilitates and enhances sperm motility by contributing albumin to seminal plasma. Prostatic acid phosphatase is involved in the nutrition of spermatozoa. Secretes a high level of zinc to human seminal plasma which acts as an antibacterial agent.

4 Constituents 30% of semen.

5 Embriology

7 Location posterior to the pubic symphysis superior to theperineal membrane inferior to the bladder anterior to the rectum

8 Dimensions 20 gr, 3 cm in length, 4 cm in width, 2 cm in depth.

9 Histology Glandular Tissue & Fibromuscular Stroma

10 Zones

11 Definition Genelde prostatın transitional zonunda, sekretuar ve stromal hücrelerin çoğalması ile karakterize Progressive Non malign Prostat büyümesine bağlı mesane çıkımında gelişen obstrüksiyon ve buna sekonder alt üriner sistem disfonksiyon belirtileri

12

15 Etiology Increased number of epithelial and stromal cells in periurethral area of prostate (Hyperplasia)

16 Production/DestructionEpithelial or stromal proliferation Androgens Impaired programmed cell death

17 Transiently proliferative cellsStem Cells Stem cells of prostate Transiently proliferative cells Block Programmed cell death

18 Estradiol/Bioavailable testosteroneAndrogens With increasing age: Testosterone Dihydrotestosterone Androgen receptors Estradiol/Bioavailable testosterone

19 But… The prostatic androgen is: Dihydrotestosterone(90% Testicles, 10% Adrenals) 5α redüktaz Testosterone DHT

20 5α redüktaz Type 1 >>>Skin and liverType 2 >>> Prostate *Can be inhibited by Finasteride and Dutasteride *The portion that is in stromal cells is the key to androgenic amplification.

21 ? Estrogens May play a role in induction of Androgen Receptors (AR)May increase the amount of Ars ER-α >>> Stromal ER-β >>> Epithelial Intraprostatic estrogen isincreased in BPH ?

22

23 Growth Factors Keratinocyte growth factor (KGF)Epidermal growth factor (EGF) Insulin-like growth factor I-II (IGF 1-2) Fibroblast growth factor (FBF) Transforming growth factor (TGF)

24 Genetics and Familial FactorsFamilial BPH Surgery in age<60 Prostate volume = 82.7 mL 3 or more relatives in family history Sporadic BPH Surgery in age>60 Prostate volume = 55.5 mL

25 Pathophisiology Anatomical obstruction Primary obstruction(Pressure increase in proximal of obstruction) Secondary obstruction (Retention – Infection – Hydronephrosis)

26

27 Prostate hyperplasia Increased urethral resistance Compensatory changes in bladder Elevated detrusor Decreased storage pressure function + Age related changes Urinary frequency, Urgency, Nocturia

28 Periurethral transition zone

29 Bladder’s response Beginning phase Compensatory phaseNormal pressure Morphological changes in smooth muscle and collogen Trabeculation, Diverticulation, Cellule Decompensatory phase Muscle tissue is replaced by connective tissue Increase in bladder weight Increase in pressure Detrusor instability

31 Diverticula

32 Decreased detrusor contractilityObstruction Bladder changes Detoriation of urinary stream, hesitancy, intermittency, increased residual urine Symptoms of frequency and urgency Decreased detrusor contractility Detrusor instability + Decreased compliance

33 In later stages… Bilateral ureter ectasia UretohydronephrosisChronic kidney failure

34 Epidemiology Not seen before age of 30. 40 years 8% 50 years 40%

35 Diagnosis History Symptom Score Physical Examination (DRE)Voiding Diary Urinalysis, Culture PSA Uroflowmetry PVR Creatinine

36 Symptoms Obstructive Irritative Slow stream Pollakiuria IncontinanceTerminal dribbling Splitting/ Spraying Hesitancy Irritative Pollakiuria Nocturia Dysuria Urgency

37 Semptomlar spesifik değil!Prostat büyüklüğü ile semptom şiddeti kesin bağlantılı değil!

38 Symptom Scoring Madsen-Iversen Symptom Score for Benign Prostatic Hyperplasia Boyarsky Symptom Score for Benign Prostatic Hyperplasia AUA International Prostate Symptom Score (IPSS) Disease-Specific Quality-of-Life ( QOL)

39 IPSS

40 Question eight refers to the patient’s perceived quality of lifeQuestion eight refers to the patient’s perceived quality of life. The first seven questions of the I- PSS are identical to the questions appearing on the American Urological Association (AUA) Symptom Index which currently categorizes symptoms as follows: Mild (symptom score less than of equal to 7) Moderate (symptom score range 8-19) Severe (symptom score range 20-35)

41 Voiding diary

43 Urinalysis A urinalysis and urine culture check for a urinary tract infection that might be the cause of the symptoms. Urinalysis—examination of a urine sample under a microscope—is performed in all patients who have lower urinary tract symptoms. Urinalysis is often the only laboratory test needed when symptoms are mild (International Prostate Symptom Score of 1 to 7) and the medical history and physical examination suggest no other abnormalities. Urine culture (an attempt to grow and identify bacteria in a laboratory dish) is performed when a urinary tract infection is suspected.

44 PSA Prostat spesifik antijen (PSA) prostat epitel hücrelerinden salgılanan glikoprotein yapıda bir proteazdır. Helps check for prostate cancer, which can cause the same symptoms as BPH. PSA values alone are not helpful in determining whether symptoms are due to BPH or prostate cancer because both conditions can cause elevated levels. However, knowing a man's PSA level may help predict how rapidly his prostate will increase in size over time and whether problems such as urinary retention are likely to occur. 0 to 4 ng/mL is considered normal. (Recently been challenged and lower thresholds have been recommended (<2.5 ng/mL))

45 Uroflowmetry In this noninvasive test, a man urinates into an electronic device that measures the speed of his urine flow. A slow flow rate suggests an obstruction of the urethra. If the flow rate is high, urethral obstruction is unlikely, and therapy for BPH will not be effective in most instances. A normal urine flow rate is 15 mL per second or higher. Maksimum akım hızı < 10 ml/sn obstrüksiyon varlığını gösterir.

46 PVR The post-void residual (PVR) urine test measures the amount of urine left in the bladder after urination. The test is used to help evaluate: Incontinence, urination problems and  enlarged prostate (benign prostatic hyperplasia, or BPH). The amount of leftover (residual) urine can be measured by draining the bladder with a thin flexible tube (catheter) or by using ultrasound. The catheter method has a slight risk of causing infection or injury to the tube leading from the bladder (urethra). But the catheter method is safe when done carefully. And it may be less expensive than ultrasound. 100 cc den fazla olan rezidüel idrar, boşaltım bozukluğunu işaret eder.

47 Pressure-Flow Urodynamic StudiesThese studies measure bladder pressure during urination by placing a recording device into the bladder and often into the rectum. The difference in pressure between the bladder and the rectum indicates the pressure generated when the bladder muscle contracts. A high pressure accompanied by a low urine flow rate indicates urethral obstruction. A low pressure with a low urine flow rate signals an abnormality in the bladder itself, such as one related to a neurological disorder.

48 Additional Methods CystoscopyUltrasonography (abdominal, renal, transrectal) CT MRI IVU/IVP

50 Earlier studies concentrated on the ultrasonographic appearances of prostate abnormalities such as benign prostatic hyperplasia (BPH), carcinoma of the prostate (CAP), prostatitis, prostatic abscess, and prostatic calculi. Since the introduction of the PSA screening test and early detection of prostate cancer, the role of TRUS has changed; it is mainly used to visualize the prostate and to aid in guided needle biopsy.

51 Differential DiagnosisCystitis Prostatitis Prostatodynia Prostatic abscess Overactive bladder (OAB) Carcinoma of the bladder Foreign bodies in the bladder (stones or retained stents) Urethral stricture due to trauma or a sexually transmitted disease Prostate cancer Neurogenic bladder Pelvic floor dysfunction

52 Prognosis Prostat hacmi > 30 ml Psa > 2.5 ng/ml Pvr > 150 mlMah < 10 ml/sn

53 Treatment Conservative Medical Surgical

54 Conservative Watchful waiting is the recommended strategy for patients with benign prostatic hyperplasia (BPH) who have mild symptoms (International Prostate Symptom Score/American Urological Association Symptom Index [IPSS/AUA-SI] score ≤7) and for those with moderate-to-severe symptoms (IPSS/AUA-SI score ≥8) who are not bothered by their symptoms and are not experiencing complications of BPH. In those patients, medical therapy is not likely to improve their symptoms and/or quality of life (QOL).

55 Medical Alpha-1–receptor blockers Alpha-adrenergic receptor blockersPhosphodiesterase-5 enzyme inhibitors 5-alpha reductase inhibitors

56 Alfa-1 Blockers A significant component of LUTS secondary to BPH is believed to be related to the smooth-muscle tension in the prostate stroma, urethra, and bladder neck. The smooth-muscle tension is mediated by the alpha-1-adrenergic receptors; therefore, alpha- adrenergic receptor–blocking agents should theoretically decrease resistance along the bladder neck, prostate, and urethra by relaxing the smooth muscle and allowing passage of urine. Doksazosin, terazosin, alfuzosin, tamsulosin, and silodosin.

57 Hafif ya da orta semptomatik veya ameliyat istemeyen hastalar tarafından kullanılır.Baş dönmesi, senkop, postural hipotansiyon, halsizlik ,baş ağrısı ,nazal konjesyon, akomodasyon bozukluğu gibi yan etkiler görülebilir. Etkisi Prostat boyutundan bağımsızdır. AÜSS’nı dindirme açısından finasteridden ve plasebodan daha etkindir. Prostat büyümesini engellemez, BPH’nın doğal seyrini değiştirmez. Günümüzde orta ve şiddetli AÜSS’u bulunan BPH’lı hastalar için en yaygın kullanılan ilk medikal tedavi seçeneğidir

58 5-alpha Reductase InhibitorsFinasterid Dutasterid

59 Both finasteride and dutasteride actively reduce intraprostatic DHT levels by more than 80%, improve symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH. Adverse effects are primarily sexual in nature (decreased libido, erectile dysfunction, ejaculation disorder). Both finasteride and dutasteride may reduce serum prostate-specific antigen (PSA) values by as much as 50%. The decrease in PSA is typically maximally achieved when the maximal decrease in prostatic volume is noted (6 months). 

60 Etkileri 1-3 ayda başlar ancak maksimum yarar ortalama 6 aylık süre sonunda gözlenmektedir.BPH’nın doğal seyrini değiştirir. -AÜR riskini azaltır -BPH ile ilgili cerrahi geçirme riskini azaltır Yan etkileri çoğunlukla cinsel işlevle ilgilidir. 5-Redüktaz inhibitörleri ile tedavi prostat kanseri saptanmasını engellemez. Serum PSA değerinin ikiyle çarpılması ile doğru değere ulaşılır PSA > ng/mL, büyük prostatlı (>40 gr), orta veya şiddetli AÜSS’u bulunan olgular daha fazla yarar görür

61 Surgical The oldest surgical method to treat BPH is an open prostatectomy, in which an incision is made through the skin to reach the prostate. Doctors use this method less often now, but it is still preferred if the prostate is very large. Surgery that does not require an incision through the skin is usually used. The surgical instruments are passed up the urinary opening in the penis to the location of the prostate. This is described as a transurethral surgery of the prostate. Transurethral resection of the prostate (TURP) is the surgery for benign prostatic hyperplasia that has been studied the most. It is the surgery that is used the most to treat symptoms of BPH. All other surgeries are compared to TURP. In TURP, part of the prostate is removed.

62

63 Some of the other surgeries that have been studied and compared to TURP include:Transurethral incision of the prostate (TUIP), in which incisions are made in the prostate that cause it to press less on the urethra. Laser therapies(green light), in which a laser is used to make incisions in or remove a portion of the prostate. Transurethral microwave therapy (TUMT), in which microwave energy is used to destroy a portion of the prostate through heating. Transurethral needle ablation (TUNA), in which a heated needle is used to destroy a portion of the prostate.

64 Indications In general, no treatment is needed for men who have only a few symptoms and are not bothered by them. Treatment— usually surgery—is required in the following situations: kidney damage due to inadequate bladder emptying a complete inability to urinate after treatment of acute urinary retention incontinence due to overfilling or increased bladder sensitivity bladder stones infected residual urine recurrent blood in the urine despite treatment with medication symptoms that have not responded to medication and are troublesome enough to diminish quality of life

65 References Berry, SJ, Coffey, DS, Walsh, PC, et al. The development of human benign prostatic hyperplasia with age. J Urol 1984;132:474. Roehrborn, C. G. Contemporary Diagnosis And Management Of Benign Prostatic Hyperplasia. Newtown, Pa: Associates in Medical Marketing Co., Inc, 2009 Dönmez, İ, Mungan, N.A., Prevalance of BPH: national realities. Üroonkoloji Bülteni, Aralık 2011 Balbay M.D : Prostat. Güneş Kitapevi, Ankara s 1-4 Kumar, V.L. & Majumder, P.K. International Urology and Nephrology (1995) 27: 231. doi: /BF Campbell – Walsh UROLOGY, Wein, Kavoussi, Novick, Partin, Peters