間質性膀胱炎之膀胱內藥物治療及症狀影響因子評估

Abstract

研究目的: 臨床上間質性膀胱炎的治療一直沒有共識。多數的治療方式缺乏療效及持久性。病患的症狀嚴重度被視為診斷及治療的重要指標。本研究針對臺灣間質性膀胱炎對傳統藥物治療無效的病患，以膀胱內玻尿酸灌注及肉毒桿菌毒素注射來治療，評估二者治療效果。此外我們分析病患的人口學及臨床特徵，和其症狀嚴重度的關係，試圖尋找間質性膀胱炎症狀嚴重度的預測因子。 材料與方法: 本研究為一前瞻性病例追蹤研究。研究對象為間質性膀胱炎對於傳統藥物治療無效的病患，依治療方式分為二組。第一組以膀胱內灌注玻尿酸治療，第二組以膀胱內注射肉毒桿菌毒素加上灌注玻尿酸治療。總共治療時間為6個月。每位病患在治療前，治療開始後一個月，及治療結束時接受主觀及客觀的症狀嚴重度評估，包括間質性膀胱炎症狀及問題指標，疼痛指數，排尿日誌紀錄等。在治療開始後一個月及治療結束時，自我評估整體反應分數。我們分析這些症狀嚴重度指標在各組內和兩組間的變化，評估玻尿酸灌注和肉毒桿菌毒素注射的治療效果。此外我們以重複測量的回歸模式，分析病患的人口學及臨床特徵，和其症狀嚴重度的相關性。 結果: 總共80位病患進入本研究，75位女性及5位男性。其中56位病患接受膀胱內灌注玻尿酸治療，24位病患接受及膀胱內注射肉毒桿菌毒素加上灌注玻尿酸治療。在單一玻尿酸灌注治療組內，間質性膀胱炎症狀及問題指標，疼痛指數，日間及夜間排尿次數，在治療開始後一個月及六個月有顯著的降低，最大排尿量有顯著的增加。在肉毒桿菌毒素注射加上玻尿酸灌注治療組內，間質性膀胱炎症狀指標和日間排尿次數，在治療開始後一個月及六個月有顯著的降低，而間質性膀胱炎問題指標和疼痛指數，在治療開始後六個月有顯著的降低。比較二組的治療結果，大部分的症狀嚴重度指標在各治療時間點無明顯差異。我們以單變項及多變項分析病患人口學及臨床特徵和症狀嚴重度的相關性。發現麻醉下膀胱最大容積，疾病症狀時間，體重，及有無工作等四個因子和間質性膀胱炎的症狀嚴重度有顯著相關。 結論: 在六個月的治療追蹤期間，本研究顯示膀胱內灌注玻尿酸對於間質性膀胱炎對傳統藥物治療無效的病患，為一有效的治療，但膀胱內肉毒桿菌毒素注射則無明顯的治療加成效果。在多變項分析下，我們發現麻醉下膀胱最大容積，疾病症狀時間，體重，及有無工作等四個因子和間質性膀胱炎症狀嚴重度有明顯相關, 為其可能的預測因子。

Objectives: There is little consensus on the best form of treatment for interstitial cystitis/painful bladder syndrome (IC/PBS). To determine the therapeutic effectiveness of intravesical hyaluronic acid (HA) instillation and botulinum toxin A (BTX-A) injection, we design a prospective case series study using these two agents in treatment of patients with refractory IC/PBS. The associations between demographic and clinical factors and symptoms severity in these patients were evaluated to identify the predictors of symptom severity of IC/PBS. Materials and Methods: Patients diagnosed as IC/PBS failed to conventional treatments were enrolled in this study. The participants were allocated into two therapeutic groups: intravesical HA instillations weekly for 4 weeks and then monthly for 5 months, or intravesical BTX-A injections once plus HA instillations as the former. An O‘Leary-Sant IC Symptom and Problem Index (ICSI, ICPI), VAS pain scale, 3-days voiding diary were recorded a t baseline, month 1, and month 6. A self-assessment global response assessment (GRA) was recorded at month 1 and month 6. Univariate and multivariate analysis were performed to assess the associations between social-demographic and clinical factors and symptom severity of IC/PBS. Results: A total of 80 patients (75 women and 5 men) were enrolled. Fifty six received intravesical HA instillations treatment alone and 24 patients received intravesical BTX-A injections plus HA instillations. In HA treatment group, statistically significant decreases in ICSI, ICPI, pain score, daytime frequency and nocturia episodes were observed at month 1 and month 6 compared to baseline. Statistically significant increase in functional bladder capacity was noted at month 1 and month 6. Twenty six (46.4%) patients at month 1 and 24 (42.9%) patients at month 6 had a successful result. In BTX-A plus HA treatment group, statistically significant decreases in ICSI and daytime frequency were observed at month 1 and month 6 compared to baseline. Significant decreases in ICPI and pain score were found at month 6. Eleven (45.8%) patients at month 1 and 12 (50.0%) patients at month 6 had a successful result. Changes in most outcome parameters at different time point showed no significant difference between 2 treatment groups. After univariate and multivariate analyses, certain characteristics that associated with symptom severity of IC/PBS were maximum bladder capacity under anesthesia (MBC), duration of symptoms, body mass index, and employment status. Conclusions: Intravesical HA instillations showed therapeutic effectiveness and tolerance in treatment of patients with refractory IC/PBS. The BTX-A injections plus HA instillations had no additive benefit than HA instillation alone. MBC and symptoms duration were the possible predictive factors of symptom severity in patients with refractory IC/PBS. In addition, BMI and employed status were found to be associated with symptom severity in these patients.