排尿功能障礙 膀胱過動症及前列腺 ( 攝護腺 ) 相關疾病 長庚大學 泌尿外科 林口長庚紀念醫院黃世聰 膀胱尿道前列腺之解剖 女性 膀胱頸 輸尿管 逼尿肌 膀胱 前列腺 尿道 骨盆肌肉肌膜層 尿道括約肌 男性 儲存尿液 膀胱功能 排放尿液 下泌尿道症狀 Lower ower Urinary Tract Symptoms 儲存方面 頻尿 LUTS 其他症狀 下腹部疼痛不適 小便量少 排尿疼痛 尿失禁, 多尿 尿道括約肌緊閉 尿道括約肌放鬆 尿急性, 應力性, 滿溢性, 夜尿. 解小便完滴尿夜間尿床... 排尿方面 小便無力小便延遲小便需用力 其他原因引起的失禁 尿排不乾淨 尿滯留... 佔總人口 %-20% 排尿功能障礙 - Incontinence - 尿失禁 Retention 尿滯留 尿急性尿失禁 定義 : 當病人有強烈尿意感時合併不自主的尿液外漏現象 男多於女 常見的原因膀胱 尿道發炎尿路結石前列腺肥大情緒緊張 焦慮 1
應力性尿失禁 定義 : 當病人腹部壓力增加, 如用力咳嗽 打噴嚏或運動時合併不自主的尿液外漏現象 女多於男 常見的原因多產婦肥胖停經後前列腺或尿道手術後 頻尿 尿急性尿失禁 膀胱過動症 尿急 儲存尿液期間膀胱逼尿肌放鬆 尿道括約肌緊閉 膀胱過動症 Overactive Bladder 小便禁不住常常跑廁所強烈地想要排尿的感覺想小便時還沒到廁所就尿出來聽到水聲或碰到冷的東西就想小便 整體而言, 6 個人中一個人有膀胱過動症的症狀 在亞洲國家的研究發現, 膀胱過動症的盛行率約 0%, 但其中只有不到 20% 的病患尋求治療 年紀越大膀胱過動症的罹病率越高 男性和女性罹患膀胱過動症的比率相似 膀胱過動症的盛行率 罹病率 (%) 40 3 30 2 20 1 10 0 男性女性 人數 =,204 18 24 2 34 3 44 4 4 64 6 74 7+ 年紀 ( 歲 ) 資料來源 : 美國 膀胱過動症及尿失禁的盛行率 : 台灣 19.0% 18.6% 18.% 40.0% 3.0% 30.0% 膀胱過動症與年齡的關係 : 台灣 18.0% 17.% 17.0% 18.0% 17.1% 膀胱過動症 應力性尿失禁 混合性尿失禁 2.0% 20.0% 1.0% 10.0% OAB SUI MUI 16.%.0% 16.0% 膀胱過動症應力性尿失禁混合性尿失禁 Chen GD. NeuroUrol Urodyna 2003, 22:109-117 0.0% 20-30 >30-40 >40-0 >0-6 >6 平均 18.6% Chen GD. NeuroUrol Urodyna 2003, 22:109-117 2
膀胱過動症的症狀分布情形 : 台灣 30.0% 2.0% 20.0% 21.1% 2.% 1.0% 12.6% 10.0% 9.1%.0% 0.0% 頻尿尿急夜尿尿急性尿失禁 Chen GD. NeuroUrol Urodyna 2003, 22:109-117. Nature History of IDO To assess the clinical outcome among a cohort of women with urodynamically proven IDO over a period of 10 years 132 women were identified following examination of 197 consecutive records from 1992-1997 with 76 (67%) returning questionnaires. Median follow up was 8 years (6 9), and the duration of symptoms was 13 years (9 18). Morris AR. BJOG 2007; 11:239-246. Morris AR. BJOG 2007; 11:239-246. Nature History of IDO -- Conclusions Disease symptoms fluctuated in severity and QoL were worse in non-responders to therapy Urge incontinence at presentation was associated with treatment failure (P = 0.001) as was nocturia (P = 0.04), Urodynamic variables were not associated with outcome Only 6.% women not responding to therapy would improve with time. Morris AR. BJOG 2007; 11:239-246. Morris AR. BJOG 2007; 11:239-246. 3
Gothenburg Longitudinal Study Prospective longitudinal study was initiated to assess LUTS in a random sample of women (age 20) from an urban Swedish population in 1991 The same women who responded in 1991 and who were still alive and available in the Swedish National Population Register 16 yr later were reassessed using a similar self-administered postal questionnaire Wennberg AL. Euro Urol 2009 in press Gothenburg Longitudinal Study A total of 2911 women were surveyed in 1991 1408 women were available in 2007 for reassessment OAB definition according to 2002 ICS guideline 77% overall response rate to postal questionnaire (1081 out of 1408 women) Wennberg AL. Euro Urol 2009 in press Wennberg AL. Euro Urol 2009 in press Wennberg AL. Euro Urol 2009 in press Wennberg AL. Euro Urol 2009 in press 4
Progression of OAB Symptoms A Prospective Longitudinal Study in Men Aged 4 Years N=19, 84.4% N=317, 13.7% N=4, 1.94% 1992 20% No OAB 3% OAB dry 0% 42% OAB wet 1% Wennberg AL. Euro Urol 2009 in press 60% 74% % 38% 12% 7% 2003 Milsom I. & Irwin DE study group. Goteborg University, Sweden Gothenburg Longitudinal Study Conclusion A marked overall increase in the prevalence of UI, urgency, OAB, and nocturia from 1991 to 2007. The cumulative incidences of UI, urgency, and OAB were 21%, 20%, & 20%, respectively Both incidence and remission of most symptoms were considerable. Wennberg AL. Euro Urol 2009 in press Factors Affecting Bladder Function & Lower Urinary Tract Local factors: mucosa, GAG? Hormone changes Bladder outlet obstruction Aging Ischemia High nocturnal diuresis Concomitant diseases Neurologic diseases Andersson KE. Urology 2003; 62:3-10. Is OAB a Progressive Disease?-- Conclusions OAB are not static but dynamic, and many factors may contribute to incidence, progression, or remission. The distinction between permanent and fluctuating cases may have important clinical and scientific implications. Urge incontinence (OAB wet) and age are factors for disease severity progression Diagnosis of Overactive Bladder
Patient History Voiding Diary Record Focus on medical, neurologic, and genitourinary symptoms Review voiding patterns and symptoms voiding diary Review medications Evaluate functional and mental status Fantl JA et al. Agency for Healthcare Policy and Research; 1996; AHCPR Publication No. 96-0686. Physical Examination Perform general, abdominal (including bladder palpations), and neurologic examinations Perform pelvic and rectal examinations in women and rectal examination in men Observe for urine loss with stress (eg, cough, Valsalva, etc.) Fantl JA et al. Agency for Healthcare Policy and Research; 1996; AHCPR Publication No. 96-0686. Highly Recommended Diagnostic Tests 病史 (History) 整體評估 (General assessment) 症狀及其嚴重程度 (Qualification of symptoms) 生活品質的影響 (Effects on quality of life) 身體檢查 (Physical examination) 尿液常規檢查 (Urinalysis) 餘尿的預估 (Estimate of post-voiding residual urine, PVR) Abrams P, et al. Lancet 2000;3:213-8 Differential Diagnosis The Symptoms of OAB Overlap With Those Attributed to BOO Benign prostatic hyperplasia (BPH) Prolapse Atrophic vaginitis Pelvic floor dysfunction Interstitial cystitis Diabetes GU malignancy Urinary tract infection Bladder Spasm Overactive Bladder Frequency, Urgency, and/or Urge Incontinence Bladder Dysfunction Irritative Bladder Outlet Obstruction (BOO) Obstructive Hesitancy, Weak Stream, Straining, Dribbling 6
Is Urodynamic Testing Necessary? It is appropriate to treat lower urinary tract symptoms based upon history and physical exam alone Reserve urodynamics for persistence despite appropriate therapy potential hazards of therapy incontinence outflow obstruction neurogenic bladder Wein A. In: Campbell s Urology. Philadelphia, Pa: WB Saunders; 2002; 8th ed: 90-906. Treatment Options for Overactive Bladder Behavioral therapy Surgical/modulatory therapies Pharmacotherapy Behavioral Therapy Modify symptoms through systematic changes in patient behavior or the environment Behavioral modification therapies dietary modification bladder training pelvic floor muscle exercises adjunct therapies scheduled/assisted voiding Burgio KL. JAMA 2002, 288:2293-2299. Treatment Options Behavioral therapy Surgical/modulatory therapies Pharmacotherapy Burgio KL, Ann Intern Med 2008; 149:161-169 7
Surgical/Modulatory Therapies Surgical/Modulatory Therapies InterStim Denervation central peripheral and perivesical Acupuncture Electroacupunture Electrical stimulation/neuromodulation Overdistention Augmentation cystoplasty Treatment Options Behavioral therapy Surgical/modulatory therapies Pharmacotherapy Pharmacologic Therapy Muscarinic Receptor Distribution Antimuscarinic agents are the mainstay for treating OAB OAB symptoms are relieved by inhibition of involuntary bladder contractions increased bladder capacity Treatment can be limited by side effects such as dry mouth, GI effects (eg, constipation) & CNS effects Dizziness Somnolence Cognitive impairment, especially memory CNS Iris/ciliary body Lacrimal gland Salivary glands Heart Stomach and esophagus Colon Tachycardia Bladder (retention) Constipation Blurred vision Dry eyes Dry mouth Dyspepsia Abrams P, Wein AJ. The Overactive Bladder A Widespread and Treatable Condition. 1998. 8
Drugs Used in the Treatment of OAB Anti-muscarinic antagonists oxybutynin tolterodine propiverine propantheline hyoscyamine trospium Hormone vaginal estrogen oint Alpha receptor antagonists doxazosin tamsulosin alfuzosin prazosin terazosin Others imipramine desmopressin Ouslander JG NEJM 2004, 30:786-799. Wein AJ. J Urol 2006, 17:S0-S10. Anti-muscarinic Receptor Antagonists for OAB Antimuscarinic and α-adrenergic Combination Therapy in Men with BOO Propantheline Oxybutynin Hyoscyamine Propiverine Tolterodine Trospium Solifenacin Darifenacin Ouslander JG NEJM 2004, 30:786-799. Randomized, controlled trial 0 men 2 80 years of age (average 69 years) mild/moderate BOO on Pressure Flow Study concomitant IDO Study design complete QoL9 UROLIFE questionnaire prior to study onset one week tamsulosin 0.4 mg qd, then randomized to receive concomitant tolterodine 2 mg bid or continue tamsulosin monotherapy repeat QoL9 and PFS at 12 weeks Athanasopoulos A et al. J Urology 2003;169:223-226. Antimuscarinic and α-adrenergic Combination Therapy in Men with BOO: Effects on Urodynamic Parameters Maximum detrusor pressure (cm H 2 O) Maximum flow rate (ml/second) Pressure at maximum instability (cm H 2 O) Volume at first unstable contraction (ml) Tamsulosin (n = 2) Mean Change from Baseline.2 +1.16 2.16 P value 0.0827 0.0001 0.0690 Tamsulosin + Tolterodine (n = 2) Mean Change from Baseline 8.24 +1.32 11.16 P value 0.0082 0.0020 <0.0001 +30.40 0.0190 +100.40 <0.0001 Athanasopoulos A et al. J Urology 2003;169:223-226. Antimuscarinic and α-adrenergic Combination Therapy in Men with BOO: Effects on QoL Improved QoL Mean Score (QoL 9 UROLIFE) 640 620 600 80 60 40 20 00 480 460 42.2 P = NS 48.2 Baseline 12 Weeks P = 0.0003 2 628.4 Tamsulosin Tamsulosin + Tolterodine (n = 2) (n = 2) Athanasopoulos A et al. J Urology 2003;169:223-226 9
Antimuscarinic and α-adrenergic Combination Therapy in Men with BOO: Adverse Events Discontinuations tamsulosin/tolterodine 3 dry mouth [tolterodine] 2 hypotension [tamsulosin] 2 tamsulosin (hypotension) No effects on PVR No acute urinary retention Athanasopoulos A et al. J Urology 2003;169:223-226 Antimuscarinic and α-adrenergic Combination Therapy: Study Conclusions Combination therapy produced a significant reduction in maximum detrusor pressure and increase in maximum flow rate following 12 weeks of treatment Combination therapy produced a significant increase in patient QoL The addition of tolterodine did not produce acute urinary retention at 12 weeks Athanasopoulos A et al. J Urology 2003;169:223-226 Overall Conclusions -- OAB Overall Conclusions -- OAB The recent ICS definition of overactive bladder emphasizes the symptomatic nature of the disease and provides a foundation for diagnosis and initial treatment by nonspecialists Overactive bladder is a significant, highly prevalent, global medical condition The prevalence of overactive bladder increases with age OAB affects all aspects of quality of life It is appropriate to treat lower urinary tract symptoms based on history and physical exam alone Treatment options include behavioral therapy, pharmacotherapy, and surgery Antimuscarinic agents are the mainstay of pharmacotherapy for OAB Additional antimuscarinic agents to alpha-blockers may be helpful for patients with BPH and OAB How to Approach Patients with LUTS in a Simple Ways? Patient Goal Approach identify the main problem urgency/frequency/incontinence/nocturia life style modification or change diet or water restriction behavior therapy voiding diary, timed or scheduled voiding pharmacology therapy alpha blockers, antimuscarinics surgical/modulatory therapy 什麼是攝護腺? 攝護腺也叫前列腺 男人特有的腺體是一種大小與形狀和胡桃類似的腺體, 位於膀胱頸的正下方, 包圍在尿道和膀胱交接處 10
膀胱 逼尿肌肉層膀胱黏膜膀胱頸 前列腺 男性 括約肌 尿道 男性下泌尿道構造 良性攝護腺肥大 (BPH) 對象 : 好發 0 歲以上男性 原因 : 多為老化現象 症狀 : 膀胱無力, 如 : 頻尿 夜尿 小便細且慢 小便困難 小便中斷 影響 : 影響性功能及生活品質, 嚴重者可能導致反覆性尿路細菌感染 血尿, 甚至於造成腎臟衰竭 良性攝護腺肥大 (BPH) 良性 " 則表示這些細胞並非癌細胞 BPH 並不是癌症, 而且也不會導致癌症, 是一種自然且正常的老化現象, 常發生於 0 歲以上的男性 沒有人確知導致 BPH 的原因, 但看來似乎與體內荷爾蒙平衡因老化而發生改變有關 在 60 歲以後, 一半以上的男性會罹患 BPH 到了 80 歲,10 位男性中大約就有 8 位患有此症 尿流的控制 導引精液射出方向及力量 攝護腺的分泌液是精液的重要成分, 與生育有某種程度關係 有男性荷爾蒙的作用 攝護腺的生理功能 攝護腺肥大 (BPH) 造成膀胱出口阻塞 (BOO) 及排尿困難 Bladder Component Myogenic? Neurogenic? Aging? Static Component glandular and stromal Dynamic component smooth muscle tone 如何診斷攝護腺肥大 (BPH)? 1. 病史及直腸指檢 (DRE) 2. 血液篩檢 ( 攝護腺特異性抗原,PSA) 3. 經直腸前列腺超音波 (TRUS) 4. 尿路動態功能檢查 (UDS). 經靜脈尿路攝影術 (IVU or IVP) 6. 排尿膀胱攝影圖 (voiding cystourethrography,vcug) 11
請就過去 1 個月內的排尿狀態, 圈選下列問題 : Q1 排尿後仍有殘尿感 無 0 次中有 1 次 1 少於一半 2 約一半 3 多於一半 4 幾乎每次 Q2 如廁後 2 小時內, 要再去廁所 0 1 2 3 4 Q3 有排尿中斷現象 0 1 2 3 4 Q4 無法控制的尿意感 0 1 2 3 4 Q 有尿流速變弱的現象 0 1 2 3 4 Q6 開始排尿或排尿中需用力 0 1 2 3 4 Q7 睡覺時需如廁的次數 0 1 2 3 4 ( 以上 ) 攝護腺特異抗原 (Prostate Specific Antigen, PSA) 與攝護腺癌或攝護腺發炎 增生肥大有關 每年增加速度 : 0.7 ng/ml 數值越來越高需考慮攝護腺癌之可能性 不是偏高異常就是癌 參考值 :<4.0 ng/ml 臨床意義 : 應用於前列腺疾病的初步篩檢 病情監控與治療追蹤 攝護腺特異抗原 (Prostate Specific Antigen, PSA) 與攝護腺癌或攝護腺發炎 增生肥大有關 每年增加速度 : 0.7 ng/ml 數值越來越高需考慮攝護腺癌之可能性 不是偏高異常就是癌 參考值 :<4.0 ng/ml 臨床意義 : 應用於前列腺疾病的初步篩檢 病情監控與治療追蹤 RICHARD E. ZIGEUNER,UROLOGY 62 (3):42, 2003 12
攝護腺肥大的治療原則 良好生活習慣的建立養成正確的排尿習慣適度的補充水分避免刺激性食物或冷飲或飲酒 適度的運動 觀察與定期追蹤 藥物治療 自助導尿的施行 手術治療膀胱鏡前列腺刮除術雷射前列腺手術 攝護腺肥大的藥物 甲型腎上腺素抑制劑 這種藥可讓膀胱出口緊繃的平滑肌肉鬆弛, 改善排尿困難的症狀 但這種藥物並不能縮小肥大的攝護腺 使用此種藥物少數人可能會有頭暈目眩及下肢水腫的副作用 患有低血壓症狀的人, 在服用此藥物時, 要特別小心注意血壓的變化及減緩姿勢變化的速度 排尿功能障礙之藥物治療 前列腺肥大 甲型腎上腺素阻斷劑 選擇性 較不影響血壓 tamsulosin (0.2mg/tab) 非選擇性 doxazosin XL (4mg/tab) terazosin (2mg/tab) alfuzosin (10mg/tab) 排尿功能障礙之藥物治療 前列腺肥大 男性賀爾蒙抑制劑 Finasteride (Proscar) 波斯卡 α 還原酶 (α reductase) type 2 抑制劑, 阻斷 (dihydro-testosterone, DHT) 產生減輕前列腺增生肥大 Dutasteride (Avodart) 適尿通 α 還原酶 (α reductase) type1 及 2 抑制劑, 阻斷 DHT 生成, 抑制前列腺增生肥大 攝護腺肥大的藥物 男性賀爾蒙抑制劑這種藥物的原理是抑制男性賀爾蒙生成, 讓攝護腺縮小, 但可能會產生性功能障礙的副作用 (-10%) 這種副作用在攝護腺縮小 停藥後, 就會恢復正常了 但攝護腺又會因停藥而再度發生肥大 若考慮使用這種藥物時, 最好與主治醫師及配偶商量後再決定 需要長期服用停止服藥後, 攝護腺又會變大, 因此需要長期服藥 但 80 歲以後, 攝護腺肥大的速度就會變慢, 所以服藥的時間長短, 可取決於年齡和病症 攝護腺肥大的手術治療 適應症 嚴重的阻塞症狀造成反覆性的尿滯留 併發反覆性的尿路細菌感染 經藥物治療無效且嚴重影響生活品質 產生其他併發症如血尿 膀胱結石 影響腎臟功能 懷疑有惡性腫瘤 13
攝護腺微創手術治療 : 高溫治療與支架放置 經尿道攝護腺刮除手術 (TUR-P) 常用的一種治療攝護腺肥大非常有效的手術治療方法, 只要直接把內視鏡放入尿道, 利用電刀切除造成阻塞的攝護腺, 並將其取出 經驗豐富的醫師認為其手術效果十分良好, 但手術中也可能發生併發症 術後第一年, 滿意度高達 80%-90% 術後第五年, 需再手術者 % 手術死亡率是 0.2% 術後之後遺症 18% 出血 血塊阻塞 感染 水中毒 肺水腫 腎衰竭甚至休克 尿失禁 膀胱頸及尿道狹窄 陽萎 精液逆流 Laser Materials/Properties Infrared light: primarily absorbed by water Visible and UV light are absorbed by hemoglobin and melanin As wavelength becomes shorter scatter begins to dominate the penetration of light 攝護腺炎 可分急性或慢性發炎 ; 細菌 非細菌性 對象 :30 歲 -0 歲男性 性生活頻繁原因 : 細菌感染或不明原因的發炎 症狀 : 發冷發熱 小便困難, 排尿疼痛 頻尿 骨盆不適 影響 : 慢性發炎的不適感影響性功能及生活品質 14
攝護腺癌 對象 : 好發 60 歲以上男性 原因 : 原因不明 可能與攝取過多高油脂食物 體質或環境有關 症狀 : 早期多無症狀 隨著腫瘤長大可能發生膀胱無力, 如 : 頻尿 夜尿 小便細且慢 小便困難 小便中斷 等症狀 影響 : 視癌細胞惡性程度及侵犯範圍可以接受觀察 手術 放射線治療 賀爾蒙或化學治療 Taiwan Age-standardized rates 死亡率與發生率 (Per 10 ) 台灣攝護腺癌病患平均存活率 N = 1,868 平均存活率 : 84 months (7 yrs) 不正常的排尿習慣 錯誤一 : 因為醫師說憋尿不好, 所以一有尿意感就趕快上廁所以免發炎感染? 錯誤二 : 因為頻尿 尿多, 所以要避免喝水? 錯誤三 : 因為工作忙, 沒有時間上廁所 憋尿? 1
養成正常的排尿習慣 適當的補充水份 100 至 2000 西西 養成定時上廁所習慣 2. 至 3 小時, 以不超過 4 小時為原則 避免刺激性飲料咖啡 紅茶 酒 辣椒 胡椒 維持良好生活習慣 定期適度的運動 如何保養攝護腺? 長期久坐 騎摩托車 腳踏車等, 都會直接刺激攝護腺充血 腫脹不適 喝酒 吃刺激性食物也會間接影響攝護腺功能, 都要盡量避免 服用某些感冒或抗過敏藥物後會加劇攝護腺肥大的症狀, 造成排尿困難甚至尿滯留, 必須小心避免 食物應把握清淡營養為原則, 建議的補充品包括南瓜子和茄紅素 維生素 E 和鋅片 16