A fluorescence guided steerable laser tool for precision resection of early stage cancers

在英国，每年有4万人被诊断出患有结直肠癌，男性的终生风险为1:16，女性为1:18。国家肠癌筛查项目被证明是有效的，接受筛查的个体生存率提高了16%。重要的是，在早期疾病的检测方面已经发生了转变，结肠镜检查发现息肉的病例占40%，癌症的病例占10%。因此，通过内窥镜手段切除这些早期癌前/癌性肿瘤的需求越来越大。然而，从传统手术到内窥镜技术的转变带来了挑战。现有的手术方法是使用相对繁琐的电切割设备对组织进行加热，由于操作受限和外科医生缺乏精细的控制，这是具有挑战性的。在某些情况下，由于结肠病变占据了“前面向”内窥镜切除方法无法切除的部位，因此无法切除结肠病变。这导致不理想的手术有时会导致严重的并发症，如肠穿孔。红外线激光对外科手术很有吸引力，因为人体组织中的水会强烈吸收这种辐射。此外，“超快”即皮秒脉冲激光器以如此短的脉冲传递能量，热效应最小，组织可以被烧蚀，产生的陨石坑仅限于脉冲入射的区域。因此，通过精确灵活地将能量输送到特定的肿瘤区域，它们可以被干净地移除，最大限度地减少对周围组织的损害和肠道穿孔的风险。另一个优点是激光消融可以改善止血，减少出血并发症。不幸的是，内窥镜手术中激光的使用受到了严重的限制，因为缺乏一种合适的灵活的传输系统，能够处理所需的高强度。通过EPSRC的资助，我们开发了一种新的光纤系列，非常适合激光手术。特别是这些纤维提供了以前无法达到的波长和脉冲能量。它们的直径很小（人类头发的大小），具有高度的灵活性，为需要在体内发挥激光作用的微创外科治疗开辟了新的途径。研究表明，这种纤维能够提供红外线和超快激光，具有足够的功率，可用于烧蚀硬和软生物组织，并且在机械和化学上都很坚固。它们可以弯曲到非常小的直径（几毫米），并且明显优于目前最先进的手术激光输送技术。此外，新的成像技术正在兴起，利用分子特异性地附着并标记癌组织。这些被标记的肿瘤，在正确照射下，会发出荧光或“发光”，从健康组织中脱颖而出。这对于在标准照明下不可见的小的、早期的、扁平的肿瘤特别有用，使它们易于可视化，有助于精确的手术干预。它还将促进肿瘤的完全根除，帮助避免肿瘤复发的问题。由于其精度（远远超过热内窥镜工具），激光能量可以利用这一功能并准确地靶向肿瘤。通过我们的医疗保健合作伙伴关系，我们将实现这些纤维的全部潜力，并创造一种由荧光标记引导的新型可操纵的手术工具。我们的合作伙伴包括赫瑞瓦特大学的高功率激光应用和生物光子学专家以及利兹大学的临床专家。雷尼绍公司在医疗应用方面有很强的商业活动，可以利用这项技术，爱丁堡分子成像有限公司开发了这种新型荧光标记。我们将共同利用这项技术开发一种可用于其他危及生命的疾病的挽救生命的结肠直肠外科手术。

In the UK 40,000 people are diagnosed every year with colorectal cancer which carries a life-time risk of 1:16 for men and 1:18 for women. The National Bowel Cancer Screening Programme is proving effective, with a 16% survival benefit for screened individuals. Importantly, there has been a shift in the detection to earlier disease with screening colonoscopy picking up polyps in 40% of cases and cancers in 10% of cases. There is therefore a growing demand to remove these early precancerous/cancerous tumours by endoscopic means. However, the shift away from conventional surgery to endoscopic techniques presents challenges. Existing procedures using relatively cumbersome electrical cutting devices to apply heat to the tissue are challenging to perform due to restricted access and a lack of fine control for the surgeon. In some cases it is not possible to remove colonic lesions due to them occupying sites inaccessible to "forward facing" endoscopic excision methods. This results in a non-ideal procedure sometimes resulting in serious complications such as bowel perforation. Infrared lasers are attractive for surgery because the water in human tissue strongly absorbs this radiation. Additionally, "ultrafast" i.e. picosecond pulsed lasers deliver energy in such short pulses that thermal effects are minimal and tissue can be ablated with the resulting crater restricted only to the area on which the pulse was incident. Therefore, by precisely and flexibly delivering the energy to specific tumorous areas they can be cleanly removed minimising both damage to surrounding tissue and the risk of bowel perforation. Another advantage may come from improved haemostasis with laser ablation, reducing bleeding complications. Unfortunately, the use of lasers for endoscopic surgery has been severely limited due to the lack of a suitable flexible delivery system capable of handling the high intensities required. Through EPSRC funding we developed a new family of optical fibres that are ideally suited for laser surgery. In particular these fibres deliver wavelengths and pulse energies previously unattainable. They have a small diameter (scale of a human hair) and are highly flexible and open up new routes for minimally invasive surgical therapies where the action of the laser is required within the body. The fibres were shown to deliver infrared and ultrafast lasers with adequate power for the ablation of hard and soft biological tissue and are mechanically and chemically robust. They can be bent to very small diameters (a few mm) and significantly outperform the current state-of-art technologies for laser delivery in surgery. Additionally, new imaging techniques are emerging using molecules that specifically attach to, and mark, cancerous tissue. These marked tumours, when correctly illuminated, will fluoresce or "light-up" and stand out from healthy tissue. This is particularly useful for small, early stage, flat tumours that are not visible under standard illumination allowing them to be readily visualised aiding a precise surgical intervention. It will also facilitate complete eradication of the tumours, helping to avoid problems with tumour recurrence. Due to its precision (far exceeding that of thermal endoscopic tools) laser energy can exploit this function and accurately target tumours. Through our Healthcare Partnership we will realise the full potential of these fibres and create a novel steerable surgical tool guided by the fluorescent marker. Our partnership consists of experts in high power laser applications and biophotonics at Heriot-Watt University and clinical expertise at the University of Leeds. Renishaw Plc have strong commercial activity in medical applications and can exploit the technology and Edinburgh Molecular Imaging Ltd developed the novel fluorescence marker. Together we will exploit this technology to develop a life-saving colorectal surgical procedure transferable to other life-threatening conditions.