肋膜疾病治療策略: 醫學工程的創新

Abstract

肋膜疾病，是臨床的一個重要挑戰。肋膜疾病，從良性的氣胸到惡性的肋膜轉移以及惡性肋膜積水都屬之。原發型自發性氣胸通常發生於瘦、高、無過往肺臟疾病之年輕男性。在絕大多數原發型自發性氣胸的病患，引起氣胸的原因是在上肺葉的肺尖部，出現一個或數個氣泡。對於反覆發作之原發型自發性氣胸之病患，以胸腔鏡手術切除漏氣的氣泡加上肋膜沾粘術是標準的手術方式。近年來文獻上，開始有學者利用vicryl mesh覆蓋在切除氣泡之縫合釘上。此法可以蓋住切除之肺臟組織，促進肋膜沾粘，進一步減少術後氣胸復發機率。臺大醫院以及長庚醫院進行多中心大規模臨床試驗NRPB計畫已證實確實有效，且術後追蹤情況良好，無重大併發症發生。初步結果可證實此構思是正確的，但試驗迄今對於使用vicryl mesh仍有疑慮。首先，以台灣現今醫療技術與醫材開發之實力，要發展並改良出更好的產品並非難事；其次，vicryl mesh並非原發型自發性氣胸之相對應適應症產品(off-label use)；更者，手術操作過程中發現vicryl mesh並不完全服貼於手術之部位，因此如能發展更適合原發型自發性氣胸之相對應適應症劑型產品，對於病患之術後是更有助益。在我們的研究中，我們證明我們自製的PCL membrane在紐西蘭大白兔上面成功完成沾黏術。此外，惡性肋膜轉移也是常見的癌症併發症。目前為止，並沒有一個好的治療方法可以處理這樣的難題，而這種病人的平均存活時間，只有六到九個月。因此，一種由光動力手術為主的治療方式逐漸被重視。光動力手術的優勢在於這種治療方式可以清除掉肉眼看不見的癌細胞，進而延長病人的存活時間。我們研究了過去十年在台大醫院之臨床經驗，我們發現到針對肺癌或胸腺瘤併肋膜轉移的患者(M1a)，光動力手術能夠提高三年以及五年存活率到68.9%以及57.4%。此外，和同時期沒有接受光動力、只接受傳統治療的肺癌族群做比較，平均存活時間從17.6個月，提高到39.0個月(P=.047)。成功證明了光動力手術確實對肋膜轉移的患者，有可行性，更有臨床上顯著的存活優勢。

Pleural diseases, including benign or malignant conditions, are clinical challenges. Benign one, like primary spontaneous pneumothorax, usually occurs in young, lean young men. In most cases, the cause of pneumothorax is rupture of blebs at apex of the lung. A novel method using coverage of the endoscopic suture line by a large absorbable vicryl mesh during thoracoscopic surgery was proved to be safe and feasible. Theoretically, the mesh can strengthen the suture line and induce local fibrosis surrounding the suture line, and reduce the rate of recurrent pneumothorax and prolonged air leakage. We investigate the Poly-ε-caprolactone (PCL) membrane pleurodesis by using New Zealand White rabbits, which was sacrificed for examination one month later. Gross evaluation of pleurodesis score revealed that dense PCL membrane produced moderate pleural adhesion, while porous PCL membrane exhibited significantly higher pleurodesis scores. (P<0.05) Control group with thoracoscopic examination alone produced almost no pleurodesis (P<0.05). The porous PCL membrane produces more intensive adhesion than dense one. Western blot showed fibronectin expression was more evident in the porous PCL than dense one (P<0.05). Therefore, fibronectin plays an important role in the process of pleurodesis. On the other hand, the malignant one, such as pleural spreading from cancer, is even more difficult to treat. Monotherapy with surgery fails to have a better survival benefit than palliative chemotherapy, the currently accepted treatment. We retrospectively reviewed the clinical characteristics and treatment outcomes of patients with lung cancer or thymoma with pleural seeding who underwent pleural photodynamic therapy (PDT) and surgery between 2005 and 2013. Eighteen patients enrolled in this study. The mean patient age was 52.9 ± 12.2 years. Lung cancer was the inciting cancer of pleural dissemination in 10 patients (55.6%), and thymoma in 8 (44.4%). There was no procedure-related mortality. Using Kaplan-Meier survival analysis, the 3-year survival rate and the 5-year survival rate were 68.9% and 57.4%, respectively. We compared the PDT lung cancer patients with those receiving chemotherapy or target therapy (n=51) and found that the PDT group had better survival than non-PDT patients (mean survival time: 39.0 versus 17.6 months; P=.047). With proper patient selection, radical surgical resection combined with intrapleural photodynamic therapy for pleural spread in patients with non-small cell lung cancer or thymoma is feasible and may provide a survival benefit.