研發快速診斷急性膽囊炎的方法

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题名:	研發快速診斷急性膽囊炎的方法 Development of a rapid diagnostic method for acute cholecystitis
作者:	蘇培元
贡献者:	臨床醫學研究所碩士班
关键词:	細胞因子;膽汁;急性膽囊炎 cytokines;bile;acute cholecystitis
日期:	2011-07-26
上传时间:	2011-10-17 16:54:51 (UTC+8)
出版者:	中國醫藥大學
摘要:	研究背景 & 研究目的急性膽囊炎主要的臨床表現為右上腹痛和發燒。主要造成急性膽囊炎的原因為膽內結石或膽內的淤泥堆積阻塞住膽囊的頸部或膽囊管，造成膽囊內的膽汁的分泌受阻，因而造成急性膽囊炎。在有膽內結石或膽內淤泥的患者中，每年約有百分之一到百分之四的人會造成急性膽囊炎或相關的嚴重併發症，包括膽結石性胰臟炎。如果被延遲診斷，可能會造成膽囊併發症，例如壞死、化膿或穿孔。東京準則(Tokyo Guideline)是目前在診斷急性膽囊炎和評估嚴重度的準則中，最被廣泛使用的。目前來講，診斷急性膽囊炎包括臨床表現、實驗室數據和影像學表現，但是其診斷準確性仍不是很高。細胞因子(cytokine)是一種參與多種免疫反應的傳介質，其中包括IL-1, IL-8, IL-10, 和TNF均參與促進發炎的機制。在此，我們假設膽汁中這些前驅發炎的細胞因子可能會比血液中的細胞因子含有更能準確診斷出急性膽囊炎的指標，因其能直接反應出膽囊的發炎狀態。因此我們得已依據膽汁中的細胞因子含量發展出一種能準確診斷出急性膽囊炎的方法。研究方法我們收集八位急性膽囊炎的患者(包含五位男性和三位女性；平均年齡66歲；年齡分布從47歲到83歲) 已及八位健康成人的膽汁。八位病患中有五位患者接受約四至六天的膽汁引流，每天的膽汁均被收集。在研究組中有五位患者是依據東京準則被診斷出有急性膽囊炎，且有開刀後病理組織上急性膽囊炎的確診，定義為第一組(group 1)，另外有一組獨立的三位病患被歸到研究組第二組(group 2)，此組患者也是依據東京準則被診斷出有急性膽囊炎但是無病理組織報告確診。研究期間為西元2010年一月至2011年三月。細胞因子測量(包含(IL-8, IL-1β, IL-6, IL-10, TNF和 IL-12p70))是利用Cytometric bead array的免疫檢測方式來定量。研究結果在研究第一組中(group 1)，所有病患均有發燒、白血球過多、右上腹痛和影像學的診斷。在急性膽囊炎的患者中，平均細胞因子IL-8和IL-1β的濃度偏高，而在健康成人的膽汁中IL-8和IL-1β的濃度均很低。另外的四個細胞因子則在急性膽囊炎和健康成人表現上均為低值。這個結果在另一獨立的研究第二組中(group 2) 也有類似表現。細胞因子(IL-8和IL-1β)在急性膽囊炎中的含量明顯比健康成人的含量高(p < 0.05)，且在經過引流治療後的四至六天後仍持續偏高。至於在不同嚴重度的急性膽囊炎中，細胞因子(IL-8和IL-1β)則無明顯統計上的差異。研究結論我們建議膽汁中高的細胞因子(IL-8和IL-1β)含量在診斷急性膽囊炎時具有重要意義，因其能直接反應出局部的發炎反應。此外，細胞因子(IL-8和IL-1β)高含量的表現會持續偏高到引流治療後的第六天。雖然此研究有些實驗上的限制，例如病例數不多和檢測細胞因子的技術不普及，但其結果可幫助臨床醫師在診斷早期急性膽囊炎的準確性，尤其是在意識不清的患者身上。 based on cytokine levels in bile. Methods: Bile samples were collected from eight acute cholecystitis patients (5 males and 3 females; median age, 66 years; range, 47–83 years) and eight healthy adults. Daily biles were collected for 4-6 days from drainage in five of the eight patients. Five patients who were diagnosed with acute cholecystitis according to the Tokyo Guideline were included in the study group (group 1). This diagnosis was confirmed by pathological examination of the cholecystectomy samples. Another independent three patients who were clinically diagnosed with acute cholecystitis according to the Tokyo guideline but without pathological verification were included in the study group as group 2. The period of bile collection was between January 2010 and March 2011. Cytometric bead array immunoassays were performed to measure proinflammatory cytokine (IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70) levels in these samples. Results: In study group (group 1), all patients had fever, leukocytosis, abdominal pain and imaging confirmed. The IL-8 and IL-1β levels in the acute cholecystitis patients (group 1) were high level. Both these cytokines were present in low levels in the healthy adults. The other four cytokines were present in similar low levels in the patients and healthy adults. This result can also be found in another independent study group (group 2). IL-8 and IL-1β had significant higher level in acute cholecystitis than healthy adults (p < 0.05) and constantly retained in high level for 4 to 6 days after treatment with drainage. No significant difference was observed between the each severity grade of acute cholecystitis. Conclusions: We suggest that high IL-8 and IL-1β levels in bile are important for detection of acute cholecystitis because they may be directly related to local inflammation. In addition, the levels of these two cytokines remained high on the 6th day after treatment with gallbladder drainage. Although there were some limitations in the study, including small case numbers and unpopular measure method for cytokine detection, these results can help clinicians diagnose acute cholecystitis more accurately in the early disease phase, especially in unconscious patients.
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