一种新的光学器件可用于诊断基底细胞癌

检验之星

据4月25日在线发表在《美国医学协会杂志：皮肤病学》（JAMA Dermatology）上的一项小型初步研究称，一种名为多光子显微镜（MPM）的新光学技术能在临床上无创、无痛、快速诊断基底细胞癌（BCCs）。

该新技术能潜在减少从诊断到治疗的等待时间。

“该研究证实，在有限的病患群体中，这种无创体内MPM成像能提供展示一些BCC病变特征的无标记对比。”第一作者Mihaela Balu博士及其同事写到。

作为最常见的人类癌症，BCC构成了美国所有癌症病例的25%以及恶性皮肤癌的75%。目前已开发了一些光学成像技术，但漏诊风险依旧是一大问题。

MPM利用皮肤中的化学复合物，诸如角蛋白、胶原蛋白、NADH、FAD、弹性蛋白以及黑色素等。当这些复合物被激光激发时会发光，以此可以制作高清晰度的3D皮肤图像。尤其是，NADH和FAD浓度可以指示代谢活动，这在正常细胞和肿瘤细胞中是不同的。

在这项研究中，Balu博士和同事试图评价MPM在BCC肿瘤细胞巢和细胞结构成像中能做得多好。他们使用了一种最新研发的临床设备——MPTflex (JenLab GmbH)。由于MPTflex是便携式的，因此它可以对部分身体进行成像，而不是只能对肢体末端进行成像。尽管如此，对眼、鼻子以及耳朵周围区域进行成像可能依旧是一个问题。

该研究于2012年9月至2014年4月在加利福尼亚大学欧文分校贝克曼激光研究中心和内科门诊部进行。Balu博士及其同事对9例患者进行了MPM成像，并在组织活检前一共判断出10例BCCs。然后他们将MPM成像结果和组织病理学结果进行了比较。

他们发现与BCC病变相关的主要MPM特征是乳头状和网状真皮中的基底细胞巢，其中一些栅式围绕在周围细胞层。据作者称，这些是BCC病变的基本特征，与组织病理学评估结果高度吻合。

MPM同时也鉴别出BCCs的其他特征，如细长的肿瘤细胞沿着一个方向在表皮层排成一条直线，以及平行的胶原蛋白和弹性蛋白围绕肿瘤进行聚集。

作者指出，MPM的灵敏度和特异性还需更大的试验进行评估。如何解决更深层细胞巢的细胞结构依旧是个挑战，还需要进一步研究。

“我们的研究表明，体内MPM成像可以解决对应BCC病变的肿瘤巢内的细胞结构，包括表面成分，”作者总结说。“这很重要，因为在真皮表皮交界处和/或真皮处的巢基底样细胞的存在是BCC诊断的主要组织病理学标准。因此，此特征可能可以用于MPM成像诊断BCC的标准。”

在一个相关意见中，哈佛医学院的Victor Neel博士把新的MPM技术比作‘光学活检’。

他说：“与RCM（另一个光学成像技术）相比，MPM就像是看彩电，而不是黑白电视”。

然而，该技术还存在技术障碍。这包括视场有限、采集时间缓慢、穿透较浅，并且需要患者静止以避免运动伪影。此外，据Neel博士所说，较大病变的成像还涉及一个把小图像合并在一起的复杂过程。

“此外，考虑到还有简单可靠的钻取活组织检查技术，BCC标准评估时对MPM的需求可能不是特别紧急。”他继续说到。另一方面，在皮肤外科中可能会更急迫需要它。

Neel博士写到：“虽然Mohs显微外科手术是一个简洁的、经过时间考验的切除肿瘤的方法，但是它仍然过于依赖临床医生的视觉直觉，在术前‘猜’肿瘤的边缘”。

他补充说，低估术前的边缘会导至多次切除，而高估边缘会导至切除过多的正常皮肤。

他强调：“皮肤科医生应该需要其他外科专业已经发展了几十年的东西，即一个成像系统，用于评估肿瘤的存在和手术前体内肿瘤扩散的程度”。

英文原文：
New Optical Device to Diagnose Basal Cell Carcinoma

A new optical technology called multiphoton microscopy (MPM) could allow for noninvasive, painless, and rapid diagnosis of basal cell carcinomas (BCCs) in the clinic, according to a small pilot study published online April 24 in JAMA Dermatology.

The new technology could potentially reduce wait time from diagnosis to treatment.

"This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions," write first author MihaelaBalu, PhD, and colleagues from the University California, Irvine, and Saarland University, in Saarbrucken, Germany.

As the most common human cancer, BCC comprises 25% of all cancer cases and 75% of malignant skin cancers in the United States. Several kinds of optical imaging techniques have already been developed, but the risk for misdiagnosis remains a problem.

MPM takes advantage of chemical compounds in the skin, such as keratin, collagen, NADH, FAD, elastin, and melanin. When excited by a laser, these compounds emit light that can be used to create high-definition, 3-D images of the skin. In particular, NADH and FAD concentrations provide an indication of metabolic activity, which differs in normal cells compared with tumor cells.

In the study, DrBalu and colleagues sought to evaluate how well MPM can visualize BCC tumor nests and their cellular structures. They used a recently developed clinical device called MPTflex (JenLab GmbH). Because it is portable, MPTflex allows for imaging parts of the body rather than only the extremities. Imaging areas near the eyes, nose, and ears, though, may still pose a problem.

The study took place between September 2012 and April 2014 at the University of California, Irvine, Beckman Laser Institute and Medical Clinic, in California. DrBalu and colleagues performed MPM imaging on nine patients and looked at a total of 10 BCCs before biopsy. Then they compared MPM images to histopathologic findings.

They found that the main MPM feature associated with BCC lesions was nests of basaloid cells in the papillary and reticular dermis, with some showing palisading at the peripheral cell layer. These features are characteristic of BCC lesions and "correlated well" with histopathologic evaluation, according to the authors.

MPM also identified other features found in BCCs, including elongated tumor cells in the epidermis aligned in one direction and parallel collagen and elastin bundles surrounding the tumors.

The sensitivity and specificity of MPM still needs evaluation in a larger trial, the authors point out. Resolving the cellular structure of deeper nests also remains "challenging" and requires further study.

"Our study shows that in vivo MPM imaging can resolve the cellular structure inside the tumor nests corresponding to BCC lesions that include superficial components," the authors concluded. "This is important because the presence of nests of basaloid cells at the dermoepidermal junction and/or in the dermis is the main histopathologic criterion for BCC diagnosis. Therefore, this feature can be potentially used as a criterion for BCC diagnosis with MPM imaging."

In a linked opinion, Victor Neel, MD, PhD, of Harvard Medical School, likened the new MPM technology to an "optical biopsy."

"Compared with RCM [another optical imaging technology], MPM is like watching television in color instead of black and white," he enthused.

Technical obstacles exist, however. These include limited field of view, slow acquisition time, shallow penetration, and the need for patients to remain still to avoid motion artifacts. Additionally, imaging larger lesions would involve a tricky process of stitching together smaller images, according to Dr Neel.

Furthermore, the need for MPM in standard evaluation of BCC may not be "particularly urgent," he continued, given the simple and reliable technique of punch biopsy. On the other hand, there may be an "urgent need" for it in dermatologic surgery.

"Although Mohs micrographic surgery is an elegant, time-tested procedure to remove tumors, it still relies too heavily on the clinician's visual intuition to 'guess' at the initial presurgical margins of the tumor," Dr Neel writes.

Underestimating the presurgical margin can result in multiple excisions, whereas overestimating the margin results in unnecessary removal of too much normal skin, he added.

"Dermatologic surgeons should demand what every other surgical specialty has developed decades ago, namely, an imaging system to assess the presence of tumor and extent of in vivo tumor spread prior to surgery," he emphasized.

DrKonig is cofounder of JenLab GmbH (Jena, Germany). Dr Neel reports no relevant financial relationships.


信源地址：http://www.medscape.com/viewarticle/843702

来源：艾兰博曼医学网