作者：Barbara Boughton 齣處：WebMD醫學新聞 　　August 7, 2009（加州舊金山）－早期偵測肺癌仍然是現代醫學的一大挑戰。一個早期偵測的方法 痰液分析 全新的痰液檢驗可能幫助早期偵測肺癌 - 趣味新聞網

發表日期 2009-08-23T07:54:10+08:00

     本帖最後由 lsc0019 於 2009-8-23 22:10 編輯

作者：Barbara Boughton
齣處：WebMD醫學新聞

August 7, 2009（加州舊金山）－早期偵測肺癌仍然是現代醫學的一大挑戰。一個早期偵測的方法，痰液分析，因為結果不一與僞陰性機率過高而令人睏擾。根據國際肺癌研究學會（IASLC）第13屆肺癌世界會議上的發錶，兩項新的肺癌細胞痰液檢驗要改善以玻片檢視相關的敏感度與專一性。

其中一項檢驗是一種可以産生痰液中細胞3D影像的裝置，且可以根據不同外型特徵區分正常與異常細胞。另一項檢驗分析痰液細胞中的三個甲基化標記，這三個是肺癌的訊號。

該3D檢驗稱為肺細胞評估裝置（LuCED），由VisionGate公司研發，使用一種溶解痰液黏液的技術，比較容易處理剩下的細胞。這些細胞收集成群、以3D技術顯影、並且分析超過25種不同特徵，這些特徵可以區分細胞是否異常。這些特徵包括細胞體積、細胞形狀、核/細胞質體積、以及核或是染色絲分佈。這個裝置接著給每個細胞樣本一個分數，分數越高代錶異常增殖或是癌癥。研究者、VisionGate影像工程副負責人Michael Meyer碩士錶示，大約1000個細胞取得分數。

在與華盛頓大學閤作時，VisionGate的研究團隊分析超過400位經確認罹患肺癌患者的痰液樣本。Meyer碩士錶示，他們發現其技術具有100%的專一性與90%的敏感性。這是個極具價值的技術，可以用在許多不同的用途。他附帶錶示，他們的目標在提供臨床醫師追蹤方麵的重要資訊。他們計劃在2011年讓這項LuCED技術商業化，作為肺癌篩檢用。屆時，研究者估計這項技術檢驗一個樣本隻要20分鍾；現在約需要一天。

前任IASLC委員會成員、來自日本大阪近畿大學醫學院的Masahiro Fukuoka博士指齣，這項檢驗的敏感度非常高。3D分析在診斷異常增殖與腫瘤細胞上可以提供高敏感度與一緻性。他錶示，這可以作為新的診斷標準。

在其他於這項會議中發錶的研究，荷蘭科學傢探索痰液甲基與肺癌之間的關係，這可以用於發明非侵入性以及更準確的診斷方法。研究團隊選擇三個具潛力的標記基因，RASSF1A、CYGB與APC，可以讓肺癌現形；接著，研究者針對570位肺癌患者檢驗痰液中這些標記的存在。他們發現，閤併使用這三個甲基化標記，他們的檢驗有60%敏感性、90%專一性。當結閤RASSF1A與傳統細胞學檢驗時，他們的檢驗有54%的敏感度與98%專一性。

主要研究者、荷蘭阿姆斯特丹Anatomisch病理學實驗室Erik Thunnissen博士錶示，即使是罹患初期肺癌患者，仍然可以從痰液樣本中偵測到甲基化作用。

雖然承認荷蘭研究者的甲基化檢驗具有較高的敏感度與專一性，但溫哥華英屬哥倫比亞癌癥署的Stephen Lam博士提醒，這些檢驗要實際用在肺癌篩檢可能還有一條很長的路。Lam博士是那篇荷蘭文獻發錶座談會的引言人，他錶示，分析樣本來自於臨床診斷罹患肺癌病患，而那些檢驗可以在篩檢的情況下進行。

他錶示，我們需要探討這些生物標記所帶來的價值，並整閤臨床數據與這樣的分析。這麼一來，生物標記檢驗可能進一步地改善。

Meyer先生是VisionGate的員工。Fukuoka博士、Thunnissen博士與Lam博士錶示沒有相關資金上的往來。

Novel Sputum Tests May Help Detect Lung Cancer Early

By Barbara Boughton
Medscape Medical News

August 7, 2009 (San Francisco, California) — Early detection of lung cancer remains one of the challenges of modern medicine. One method for early detection — sputum analysis — is plagued by inconsistent results and a high false-negative rate. Two new tests for lung cancer cells in sputum aim to improve the sensitivity and specificity associated with slide-based review, according to research presented here at the 13th World Conference on Lung Cancer, organized by the International Association for the Study of Lung Cancer (IASLC).

One of the testing methods is a device that produces 3D images of cells in sputum and distinguishes normal from abnormal cells on the basis of a variety of morphology characteristics. The other test analyzes sputum cells for 3 methylation markers that are signals of lung cancer.

The 3D test, called the Lung Cell Evaluation Device (LuCED), developed by VisionGate, uses a process that dissolves mucous in sputum, making it easier to work with the remaining cells. Cells are collected in clusters, imaged in 3D, and analyzed for more than 25 different features that can indicate how abnormal they are. These features include cell volume, cell shape, nuclear/cytoplasmic volume, and nuclear or chromatin distribution. The device then assigns a score to each specimen of cells, with higher scores indicating dysplasia or cancer. About 1000 cells are processed to obtain each score, said researcher Michael Meyer, MS, vice president for image engineering at VisionGate.

In collaboration with the University of Washington, VisionGate researchers analyzed sputum samples from more than 400 patients with confirmed lung cancer. They found that their technology had 100% specificity and 90% sensitivity, Mr. Meyer said. "This is an extremely valuable technique that could be used in many different applications. Our goal [is] to provide critical information to clinicians for follow-up," he added. Plans call for LuCED to be commercialized for lung cancer testing by 2011. By that time, researchers estimate that the technology will be able to process each specimen in about 20 minutes; it now takes about a day.

"The sensitivity of the test is very high," noted former IASLC board member Masahiro Fukuoka, MD, PhD, from Kinki University School of Medicine in Osaka, Japan. "This 3D analysis could provide high sensitivity and consistency in diagnosis of dysplastic and cancer cells. It could be a new diagnostic standard," he added.

In other research presented at the meeting, Dutch scientists explored the relation between methyl groups in sputum and lung cancer, which could be used to devise a noninvasive and more accurate diagnostic test. The researchers selected 3 promising marker genes that could signal the presence of lung cancer — RASSF1A, CYGB, and APC — and examined sputum samples of 570 lung cancer patients for these markers. They found that using the 3 methylation markers together, their tests had 60% sensitivity and 90% specificity. When tests for RASSF1A and conventional cytology were combined, their tests had 54% sensitivity and 98% specificity.

"Sputum methylation was detected even in sputum samples from patients with lower-stage lung cancers," said lead researchers Erik Thunnissen, MD, from Pathologisch Anatomisch Laboratorium in Amsterdam, the Netherlands.

Although acknowledging the superior sensitivity and specificity of the Dutch researchers' methylation testing, Stephen Lam, MD, from the British Columbia Cancer Agency in Vancouver, cautioned that these tests may be a long way from being practical for lung cancer screening. Dr. Lam, who moderated the session at which the Dutch paper was presented, noted that the samples being analyzed came from patients with clinically diagnosed lung cancer, and that the tests could perform differently in a screening setting.

"We need to look at the incremental value of these biomarkers and integrate clinical data with this kind of analysis. In that way, biomarker tests are likely to be improved further," he said.

Mr. Meyer is an employee of VisionGate. Dr. Fukuoka, Dr. Thunnissen, and Dr. Lam have disclosed no relevant financial relationships.

13th World Conference on Lung Cancer (WCLC): Abstracts D1.3 and D1.5. Presented August 4, 2009.

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