Clinical translation of video assisted micrographic surgery for staged cancer removal

 描述(由申请人提供)：癌症切除治愈的关键限制因素是通过冷冻切片组织学莫氏手术确定阴性手术切缘的成本和时间。我们建议视频辅助显微外科手术(VAMS)作为一种新的范式来指导显微手术以改善皮肤癌切除的结果和患者体验。虽然线扫描共聚焦显微镜可以有效地指导手术切除，但我们建议开发和实施三模式线扫描版本来提供实时的边缘状态。我们将首先在非介入研究中评估该系统，然后在大容量皮肤癌手术实践中进行介入临床试验。我们建议最终改变根治性的癌症手术。治愈的可能性在于获得无肿瘤平面的能力，即“手术切缘清晰”。确认清晰边缘的金标准是通过评估苏木精和伊红染色的切片来实现的。在广泛的癌症需要多次切除的情况下，困难就会出现。这会增加手术时间、费用和潜在的围手术期并发症。我们建议改进和翻译一种新的共焦三模式装置的使用，该装置允许在不到3分钟的时间内直接显示切除标本的整个周边和深层边缘。在初始切除标本显示切缘阳性的情况下，这有可能将总手术时间减少85%至95%。我们将首先研究非黑色素瘤皮肤癌，并评估莫氏显微外科手术中用于边缘控制的三模式设备的敏感性和特异性。这项改造将把莫氏手术转变为视频辅助显微外科手术(VAMS)。我们还将确定对于需要一次以上切除的复杂癌症，使用VAMS和MoHS在手术时间和降低成本方面的差异。共聚焦设备已被用于评估非黑色素瘤皮肤癌。然而，我们建议在美国进行第一次介入性临床试验，以评估该方法的使用。由于快速生成高质量共焦图像所需的时间，美国尚未做到这一点。

 DESCRIPTION (provided by applicant): The key limiting factor in cancer excision for cure is the costly and time consuming ascertainment of negative surgical margins by Mohs surgery with frozen section histology. We propose video assisted micrographic surgery (VAMS) as a new paradigm to guide microscopic surgery to improve outcomes and patient experience in skin cancer excision. Although line scanning confocal microscopy may usefully guide surgical excisions, we propose to develop and implement a tri-modal line scanning version to deliver real-time margin status. We will evaluate the system first in non-interventional studies, and then interventional clinical trials in a high volume skin cancer surgery practice. We propose to ultimately transform curative cancer surgery. Potential for cure resides in the ability to achieve tumor free plane i.e. "clear surgical margins". Gold standard for confirmation of clear margins is achieved by evaluating sections stained with hematoxylin and eosin. Difficulties arise in cases of extensive cancers requiring multiple excisions. This leads to increased operative time, cost and potential perioperative morbidity. We propose to refine and translate the use of a novel confocal trimodal device that allows direct visualization of the entire peripheral and deep margin of the excised specimen in under 3 minutes. This has the potential to decrease total operative time by at 85% to 95% in cases where initial excision specimen shows margin positivity. We will begin by working with nonmelanoma skin cancer and evaluating sensitivity, specificity of the trimodal device for margin control in Mohs micrographic surgery. The modification will transform Mohs surgery into Video Assisted Micrographic Surgery (VAMS). We will also define differences in operative time and decreased cost resulting from use VAMS vs. Mohs for complex cancers requiring more than one excision. Confocal devices have been used to evaluate nonmelanoma skin cancer. However we propose the first interventional clinical trial in the United States to evaluate use of this methodology. This has not yet been done in the United States because of the time required to generate high quality confocal images quickly.