https://scholars.lib.ntu.edu.tw/handle/123456789/144417
標題: | 肝硬化合併肋膜積水的臨床研究 Clinical Research in Hepatic Hydrothorax |
作者: | 黃培銘 Huang, Pei-Ming |
關鍵字: | 肝硬化;肝性肋膜積水;liver cirrhosis;hepatic hydrothorax | 公開日期: | 2005 | 摘要: | 肝硬化在醫學研究上一向是重要的課題,而肝硬化及其合併症在台灣更是一項重要的死因。頑固性肝性肋膜積水(refractory hepatic hydrothorax)在因肝硬化而來的併發症中,其診斷與治療仍處於急需進一步發展與研究的領域。 肝性肋膜積水的橫膈缺損是一個複雜的病態生理過程,其中牽涉多個步驟。基本上如果長期橫膈處於一個相當高壓力下,就有可能產生裂縫,而進一步有腹膜突入肋膜腔,造成突起的小泡(blebs)或者破裂而形成破洞缺損(fenestration),導致腹腔和肋膜腔積水的相流通。經由影像檢查則可直接或間接看見這些變化,這些變化包括裂縫、小泡以及破洞等。而這些變化不只因肝硬化有腹水的病人會發生,在腎衰竭作腹膜透析的病人也偶而可見。因此腹腔的壓力對橫膈缺損的形成扮演一個重要的角色。 在橫膈缺損修補的治療模式中,主要分為內科模式及外科模式,前者是利用沾粘劑(sclerotic agents)使橫膈和肺臟沾粘,來阻斷腹水的流入。後者則如器官移植或透過橫膈缺損修補術,以根治肝硬化的病情或阻斷腹腔肋膜腔積水的流通路徑為目標。本研究的方向以後者為主。 在第一部份(肝性肋膜積水之病態生理機制的探討)確立橫膈缺損的形態學類型,在此我們需要判定目前各種提出來可能的學說。因此我們借助胸腔鏡的影像學上的好處,直接觀察此類病人橫膈上的缺損。借此發現,我們希望研究出改善治療的方法。這一部份實驗結果及結論如下: 結果 : 我們將這些肝性肋膜積水產生的橫膈缺損,區分為四種形態學上的類型:第一型:沒有明顯缺損 (一位病人),第二型:在橫膈上有突起的小泡類型(4 位病人) ,第三型:在橫膈上有破裂的破洞缺損 (8 位病人),和第四型在橫膈上有若干縫隙(緩慢滲透(oozy) 類型)(一位病人)。研究中發現橫膈缺損的類型和胸部X光所表現的肋膜積水佔有的容量,並沒有直接的相互關係。 結論: 雖然肝性肋膜積水的病態生理機制曾經有許多機制被提出來。然而,把肝性肋膜積水的橫膈缺損,以胸腔鏡作研究且更進一步將結果依形態作分類的,這屬於第一次。基於這些橫膈缺損機制的研究,使得肝性肋膜積水的處理在學理上可以進一步分析、研究及控制。 第二部份(各種治療模式的比較與建立): 根據第一部份的發現,阻斷腹腔肋膜腔積水的相流通,應該可以有效降低肋膜積水的程度。不過現有各種治療方式的阻斷效果並無法達到完全無復發,也存在一定比率的成功率,有些治療方式的效果十分有限,甚至造成病人的傷害。延續第一部份研究的結果,我們搜尋分析近年來此類病患的各種治療模式的成效,更進一步基於這些橫膈缺損的形態變化,我們建立與傳統不同的治療方式。在治療過程中,這類病患最大的困難是,病患常已經存在嚴重的肝硬化,如何減少手術時帶來的傷害,並減少各器官的併發症遂成為重要的關鍵。在此情況下,我們試圖對此過程作了以下的設計(1)作病人的篩選,建立適合的手術條件標準。(2)以簡單的手術步驟,以爭取時間減少手術的傷害。(3)顧及水份的平衡,減少體液引流所造成的肝腎衰竭的產生。(4)肝硬化根本疾病的治療。這一部份治療成果及結論如下: 結果 : 從 1996年8月到2004年3月,一共有52位病人診斷有肝性肋膜積水,我們回顧了病患的病歷紀錄。4位病人是Child-Pugh class A,20 位是class B,和 28位為class C。所有病患中有28位接受肝性肋膜液的穿刺引流術而症狀緩解。其他24位病人中,有16位使用minocycline,picibanil,或betadine作化學的肋膜沾粘術;14位病人作外科的手術處理,其中7位作胸腔鏡的肋膜組織表面移植物(pleural onlay),2位作丹佛分流器(Denver shunt),2位作肋膜剝離術(pleurectomy),3位作橫膈的修補,手術處理的患者中有6位作二種術式。治療成功的比率為化學沾粘術有37.5%,外科處理有42.9%,對治療有反應的比率為50%。多變數分析(Multivariate analysis)則顯示唯有成功治療者( P=0.01,危險比率hazard ratio=0.25 ) 是存活期(從肝性肋膜積水診斷時算起)預測的獨立因子。 在手術方式的探討上,從2003年10月到2005年3月,10 位病患具有頑固性肝性肋膜積水(年紀32–83歲;6位男性和4位女性) (Child-Pugh class B~C),其中7位以胸腔鏡肋膜組織面膜,另外3位作網狀移植物覆蓋法(mesh onlay)加強,來修補橫膈缺損。在平均7.7 個月的追蹤時期當中,所有病人沒有局部再發的產生。其中兩位病患在手術後的兩個月死於食道靜脈曲張出血。此外所有病人都有更好的手術後活動能力及肺功能。 結論: 對肝性肋膜積水的病人以積極的內科(包括肋膜沾粘術, 腹腔靜脈分流術(peritoneovenous shunts), 經頸靜脈肝內門脈體靜脈分流術(transjugular intrahepatic portosystemic:TIPS ))或者外科的治療,比起保守性治療可以提高存活期,尤其能夠有至少3 個月以上時間可解決肋膜積水的治療方式,對長期存活率有較大的幫助。 在手術方式的研究方面可看出,以外科的肋膜組織面膜和網狀移植物覆蓋法來處理頑固性的肝性肋膜積水的病患,可以達到完全無復發的效果,但是其實用性還需要往更簡單的方式及減少手術併發症的方向來努力,才可發揮更好的功效。 第三部份(肝性肋膜積水橫膈缺損新的診斷模式): 如何讓頑固性肝性肋膜積水的病人,能獲得早期診斷而可以接受早期治療,是刻不容緩的問題,因此尋找一個良好的診斷方式,就相當重要。綜觀目前的診斷方法分為非侵入性(胸部X光照相術、核磁共振攝影)以及侵入性(放射性同位素照像、indocyanine染料的注射、或胸腔鏡檢查)。非侵入性檢查的診斷率不高,而侵入性的診斷方式又不是每位病患均適合執行。因此我們利用已建立的四種橫膈缺損的形態學分類,以彩色Doppler超音波做為診斷模式,找尋超音波的診斷結果是否與形態學的類型有相關。這一部份研究結果及結論如下: 結果 : 三位病人以彩色Doppler超音波發現,有經過橫膈缺損的腹腔肋膜腔的液體流動。在這些超音波有顯現橫膈缺損液體流動的病人中,手術時經由胸腔鏡發現他們橫膈有突起的小泡,讓腹腔肋膜腔積水可相流通。並且,他們胸部X光常有大量的肋膜積水。然而,在瀰漫型的橫膈缺損形態,或者水泡型的橫膈缺損但沒有明顯的胸部X光肋膜積水的患者,彩色Doppler超音波偵測橫膈缺損的運用似乎是有診斷上的限制。 結論: 彩色Doppler超音波用來偵測經由橫膈缺損的液體流動是一個快速的、簡單的、安全的和非侵入的檢查方法。這個技術使病人面臨最小劑量的輻射暴露,並且能夠準確地和動態地操作實行。假如病患臨床上的肋膜積水相當快速與顯著時,而彩色Doppler超音波檢查也見到一個明顯可見的橫膈缺損時,一個適當的治療措施就可開始。 本論文總結: 肝性肋膜積水的真正病態生理機制,大部分是橫膈缺損所造成的。彩色Doppler超音波可提供病患較簡單、安全且確切的診斷。而能真正阻斷橫膈缺損的相流通的治療方式,才是對此類病患的存活期有所幫忙。而一種簡單的網狀移植物覆蓋法外科橫膈缺損修補術似乎較有良好的阻斷效果。 Liver cirrhosis is an important medical research problem in Taiwan, because the prevalence rate is higher than in Western countries. The research on one of the complications of liver cirrhosis, hepatic hydrothorax, includes organ transplantation and diaphragmatic defects and surgical repair. Hepatic hydrothorax is a complex pathophysiological process. It includes multiple steps. Basically, under a long period of high-pressure stress, the diaphragm may produce some streak breaks. The peritoneum may progressively protrude into the pleural cavity and eventually produce blebs or fenestrations. They allow the ascites to communicate with the pleural cavity. These phenomenon, including oozing defects, blebs, or fenestration, may be directly or indirectly observed by means of imaging systems. These findings seem not only to occur in hepatic hydrothorax, occasionally, they have been reported in renal failure patients with continuous peritoneal dialysis. Therefore, the abdominal pressure plays an important role during the formation of diaphragmatic defects. In the model of simple blockade of the trans-diaphragmatic flow, treatment can be divided into medical or surgical management. However, the therapeutic effect of the former may be only attributed to the adhesion between the fully expanded pulmonary parenchyma and the diaphragm in blocking the trans-diaphragmatic flow. On the contrary, the latter, such as organ transplantation or the diaphragm repair model, should correct the underlying situation, including liver cirrhosis or repairing the diaphragmatic defects. In this study, we look at the role of surgical intervention. Part I Studies on the Pathophysiology of Hepatic Hydrothorax Several explanations for the development of hepatic hydrothorax have been proposed including hypoalbuminemia, hypertension of azygous vein, leakage from the thoracic duct, transdiaphragmatic lymphatic migration, and pressure gradient-directed flow through diaphragmatic defects. Thus, we should differentiate the theories. In order to solve this problem, we utilized the imaging modality of video-assisted thoracoscopy to detect the defects. According to the findings of this study, we established a further therapeutic method. The result and conclusion of the first part of the study is as follows: Results: The diaphragmatic defects stemming from the hepatic hydrothorax were classified into four morphologic types: type I: no obvious defect (one patient), type II: blebs lying on the diaphragm (four patients), type III: broken defects (fenestrations) in the diaphragm (eight patients), and type IV: multiple gaps in the diaphragm (one patient). The type of the diaphragmatic defect did not correlate with the volume occupied by the pleural effusion in the preoperative chest x-rays. Conclusion: The findings of this study allow the pathophysiology of hepatic hydrothorax to be directly visualized, and further studies concerning the treatment of hepatic hydrothorax may be based on these mechanisms. Part II Comparison and Setup of Various Modes of Intervention Based on the findings of the first part, the hepatic hydrothorax may be solved after blocking the diaphragmatic defects. Despite numerous case reports describing clinical features and treatments, the optimal management of this condition remains inconclusive. Liver transplantation is the treatment of choice, but the donor is rarely available. Other treatment options include repeated thoracentesis, pleurodesis, peritoneoveous shunts, transjugular intrahepatic portosystemic shunt, and surgical repair of the diaphragmatic leak. Several management techniques are considered as temporary relief of symptoms only, and sometimes result in adverse effects, because there are no available guidelines on therapy based on good evidence. Therefore, most patients receive either aggressive intervention or supportive care. The optimal management, however, remains unclear, and few previous studies have systematically evaluated the effect of therapy on clinical outcome. The aim of this study was to evaluate the impact of medical and surgical interventions on the survival of these patients at National Taiwan University Hospital over the past years. It proves the importance of the patients’ conditions during this process and the principle of surgical treatment. To create an appropriate surgical approach, it was necessary to solve the following issues: (1) The criteria of the surgical model in this study; (2) the duration of surgical intervention lessened to prevent complications; (3) avoiding hepatorenal syndrome, keeping a balance of input and output required in this group; and (4) liver cirrhosis treated perioperatively to decrease the possibility of bias. The results and conclusion of the second part of the study is as follows: Results: Hepatic hydrothorax was diagnosed with four patients in Child-Pugh class A, 20 patients in class B, and 28 patients in class C. There were 28 patients receiving supportive care with thoracentesis for symptom relief. Among the other 24 patients, 16 were treated by chemical pleurodesis (minocycline, picibanil and beta-iodine), 14 underwent surgical interventions (Thoracoscopic pleural onlay, Denver shunt, pleurodectomy or diaphragmatic repair) and six patients received both interventions. Intervention success, defined as resolution of hydrothorax for at least 3 months, was achieved in 37.5% and 42.9% patients of the intervention group by chemical pleurodesis and surgery, respectively, with an overall success rate of 50%. Multivariate analysis showed that only intervention success (P=0.01, hazard ratio=0.25) was an independent predictor of survival benefits. In the surgical model, from October 2003 to March 2005, 10 patients (age, 32–83 years; 6 men and 4 women) with refractory hepatic hydrothorax (Child-Pugh class B~C) underwent thoracoscopic pleura (n=7) or mesh (n=3) onlay reinforcement to repair diaphragmatic defects on which this study focuses, and all patients have since been under follow-up in a prospective observation study. After a mean of 7.7 months of follow-up examinations, no local recurrence occurred in all patients. Two patients died of hemorrhage from esophageal varices two months postoperatively. All patients had better postoperative pulmonary function. Conclusion: For patients with hepatic hydrothorax, aggressive medical or surgical intervention may confer a survival benefit over supportive management, especially when resolution of hydrothorax can be maintained for at least three months. The use of pleura and mesh onlay reinforcement of the diaphragm is an encouraging treatment modality for refractory hepatic hydrothorax. Part III New Diagnostic Method to Detect Diaphragmatic Defects in Hepatic Hydrothorax Early diagnosis and treatment is an important issue to attenuate the poor condition of refractory hepatic hydrothorax. Several diagnostic methods have been reported for diagnosis of hepatic hydrothorax, including biochemical analysis of ascitic and pleural fluid, conventional radi¬ography, radioisotope imaging, indocyanine green dye, magnetic resonance imaging studies, and thoracoscopy. Among these methods, ultrasonography may be considered as the easiest method and has the benefit of real-time diagnosis of anatomical integrity and flow studies across the diaphragm in patients with hepatic hydrothorax with and without massive ascites. The present study was performed in order to directly demonstrate the presence or absence of peritoneo-pleural communication by color Doppler ultrasonography and was verified by video-assisted thoracoscopic surgery. Furthermore, we evaluated the effect of color Doppler ultrasonography in the morphology of diaphragmatic defects and compare with the above studies. The result and conclusion of the third part of the study was as follows: Results: Three patients were found to have transdiaphragmatic flow from the peritoneal to the pleural cavity in color Doppler ultrasonography. Among these ultrasonography positive findings, bleb defects were noted thoracoscopically on the diaphragm, and they had massive pleural effusion in the radiologic study. However, in the diffuse oozing diaphragmatic defect or in the bleb defect without obvious radiologic study, color Doppler ultrasonography seems to be limited. Conclusions: Color Doppler ultrasonography is a simple, safe and rather non invasive method to confirm passage of ascitic fluid across the diaphragm. Color Doppler ultrasonography may play just as an important role in identifying hepatic hydrothorax as the etiology of pleural effusion in patients with chronic liver disease. Summary: The mechanism of hepatic hydrothorax has been proposed such that pleural effusion in cirrhotic patients, and the transdiaphragmatic flow of ascitic fluid through a diaphragmatic defect, is considered the most probable factor. Furthermore, color Doppler ultrasonography is a simple, safe and definitive method to confirm passage of ascitic fluid across the diaphragm. Either aggressive medical or surgical intervention, only intervention success is an independent predictor of survival benefits. Compared with other methods, the reinforcement of diaphragm defects is an encouraging treatment for refractory hepatic hydrothorax. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/55461 | 其他識別: | zh-TW |
顯示於: | 臨床醫學研究所 |
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