以多臨床策略切入頭頸癌治療

Abstract

身為一個頭頸外科醫師，過去二十年來致力於各種頭頸部疾病的診斷及治療，而疾病的過程不外乎：有些自己會好，有些需要藥物或放射治療，有的要手術切除更嚴重的則要手術及藥物或放射治療，一部分的病患則是怎麼治療都不會好，最終會因疾病而死亡。針對頭頸部多變的病況議題，我們從影像分析，手術重建，微創手術以及結合系統生物學，我們提出以多臨床策略切入頭頸部治療的理論。 近年來，游離皮瓣(free flap)被廣泛應用於頭頸部的重建，且被視為黃金標準，游離皮瓣最大的好處是多樣性，但是缺點是需要接血管手術時間長及術後密切皮瓣血流狀況。因此，並非每個病患都適合使用游離皮瓣重建。於是相關研究指出某些傳統的局部皮瓣(local-regional flap)在頭頸部重建仍扮演重要角色。過去5年，我們嘗試使用下頜皮瓣來取代部分游離皮瓣，透過蒐集臨床手術案例證明，下頷皮瓣確實是頭頸部重建的選項之一，優勢是可在頭頸癌的同一傷口完成、手術時間短、不需要另外一組外科醫師來協助、以及術後不需特別監測皮瓣。我們運用下頜皮瓣重建範圍從眼眶、口腔、口咽及下咽，幾乎涵蓋所有頭頸部區域，初步獲得不錯的成效。此外，我們也評估下頷皮瓣的併發症(donor-site morbidity)，經由5個指數全方位評估的結果，證實下頷皮瓣幾乎沒有併發症，是一個理想的局部皮瓣。 微創手術(minimally invasive surgery)是近代醫學發展的趨勢，在對病患施行手術時，我也一直在朝這個方向改善現有的手術方式。過去在下頜腺切除手術都是經由頸部切除，這樣的術式除了會在頸部留下疤痕外，也可能會因為傷到面神經的下頜分枝而造成患者嘴角活動功能障礙。於是我們改由經口術式，進行下頜腺切除，避免在患者頸部留下疤痕及面神經分枝的損傷。內視鏡手術本身已是微創手術，但是傳統的經鼻腦下垂體手術會有出血較多，因術中出血沾污鏡頭造成手術視野不清是無法避免的困擾。有鑑於此，我們採用二極體雷射(diode laser)來施行內視手術，雷射最大的好處是可以直接氣化組織以及進行止血，以雷射取代手術刀，解決出血狀況，有效改善手術視及縮短手術時間。 未來我們將整合臨床醫學、細胞實驗、計算系統生物及藥物設計的新概念，用來發展臨床檢驗生物標記及新穎抗癌藥物，我們的目標如下：(1)針對頭頸癌的高異質性，發展頭頸癌早期臨床診斷之癌症基因及高通用性的生物標記。(2)探討潛在癌症基因之生化調控及致病機制 (3) 分析不同危險因子、族群、腫瘤特性等因素對潛在癌症基因於分子階層之影響(4)針對潛在癌症基因及生物標記，透過新藥開發及舊藥新用等策略發展新穎抗癌藥物。

As a head and neck surgeon, I have dedicated in diagnosis and treatment for different head and neck illness. Some diseases are self-limited, some requires medicine or chemoradiation, while some need surgical treatment and/or post-operative chemoradiation. However, some patients eventually died of disease. According to the great variety of head and neck disease, a framework of multiple clinical strategies for head and neck treatment was proposed in this thesis. In recent years, free flaps are widely used in head and neck reconstruction and become the golden standard of reconstruction. However, some studies revealed that local-regional flaps played a role in head and neck defect reconstruction. Here, we propose the submental flap could replace free flap in head and neck reconstruction in some patients. From our cases control study, we verify the value of submental flap in head and neck reconstruction. For example, this flap can be done in the same incision of neck dissection, shortening the operation time, do not need the microsugical team, and easy to care post-operatively. In addition, we evaluate the donor-site morbidity by using 5 objective parameters. And we proof that the donor-site morbidity after submental flap harvest is very low. Minimally invasive surgery is a hot topic in modern medicine. To address this issue, we modified the surgical approach of submandibular gland surgery. In the past, submandibular gland was removed transcervically and left an obvious scar on the neck. We describe an intraoral approach to remove the submandibular gland in selected patents. Our technique allows the surgeon to remove the submandibular gland without external cervical incision. In addition, bleeding is a major issue in conventional transnasal pituitary gland. For bleeding problems, we take the advantage of the property of vaporizing tissue and coagulation from diode laser. Less bleeding, more clear surgical view, and shorter operation time view are achieved. In the future, we will integrate the new concepts of clinical medicine, cell-based assays, systems biology, and drug design to develop biomarkers of clinical diagnosis and novel anti-cancer drugs. Our aims are listed as follows: 1) Identifying consistent cancer genes and biomarkers for early diagnosis of HNSCC with high heterogeneity; 2) Studying the molecular pathogenesis for potential cancer genes; 3) Analyzing the molecular mechanisms of potential cancer genes depends on various factors, such as risk factors, study population, and tumor characteristics. 4) Developing novel anti-cancer therapies through multi-target drug design and new uses for old drugs.