PreCisE: A Precision laser scalpel for Cancer diagnostics and Eradication

世界人口正在迅速增长，最重要的是，同时也在老龄化。这为癌症的增加提供了动力，预计癌症人数将从2018年的1850万增加到2040年的2950万。抗击癌症的最有效战略之一是引入筛查方案，使疾病能够在可以治愈的早期阶段被发现。早期疾病也适合于微创和腔内手术，在减少发病率和更好地保存正常功能方面具有优势。人们普遍认为，微创和腔内手术的使用将继续增长，可能会与机器人辅助相结合。但是，为了实现这一雄心壮志，需要开发适当的手术工具。这包括实时诊断癌症的工具，这些工具可以与消融和切除方式相结合，以根除疾病。联合诊断和消融工具将使显微疾病能够被检测到，特别是在肿瘤边缘，浸润性生长很难与正常组织区分开来。未能根除这种微观疾病通常是治疗失败和癌症复发的原因。我们由物理学家、工程师、激光专家和临床医生组成的多学科团队已经开始通过研究一种新的基于激光的方法来解决手术硬件精度方面的不足，该方法非常适合于微创和腔内癌症手术。通过使用“超短”皮秒激光，这种激光在一系列脉冲中传递能量，长度只有几皮秒，我们已经展示了在比现有工具小2个数量级的精度上切除(消融)肿瘤的能力。重要的是，因为激光脉冲很短，所以没有时间让热量扩散到周围的组织，就像现有的手术工具一样。因此，我们已经证明了手术区域周围组织的损伤可以被限制在小于人类头发的宽度-几乎是单个细胞的规模。在临床相关的组织模型上，我们在实验室中证明了这种皮秒激光消融可以提供精确的肠道切除的一步改变，从而改变腔内结直肠癌手术。此外，我们已经证明，PS激光脉冲可以通过新型中空光纤灵活传输，从而使人们相信内窥镜的部署可以实现，并开辟了微创手术的新领域。我们现在需要利用这一基础，因此扩大了我们的临床专业知识网络，并确定了我们的技术可能真正变革的新领域。神经外科是对精确度的终极考验，即使是显微镜下健康组织的丢失也会对生活质量产生巨大影响。在头颈部手术中，尽量减少正常组织的切除，可以保留说话和吞咽的功能，对生活质量产生积极影响。同时，我们的目标是在我们在结直肠癌方面的成功成果的基础上，开发新的策略，将实时诊断成像整合到临床应用中。这项提案将把我们对激光在结直肠癌手术中的理解推向临床应用，同时探索新的应用领域(头颈和脑癌)，在这些领域，该技术也被认为具有巨大的潜在好处。

The world's population is rapidly growing and, most importantly, at the same time is ageing. This provides a driving force for the increase in cancer, which is predicted to grow from 18.5M in 2018 to 29.5M in 2040. One of the most effective strategies to combat cancer has been the introduction of screening programmes, which enable the disease to be detected at an earlier stage when it is curable. Earlier stage disease also lends itself to minimally invasive and endoluminal surgery, with advantages in terms of reduced morbidity and better preservation of normal function. There is an acceptance that the use of minimally invasive and endoluminal surgery will continue to grow, perhaps in conjunction with robotic-assistance. But, to deliver this ambition, appropriate surgical tools need to be developed. This includes tools for real-time diagnosis of cancer that can be coupled with ablative and excisional modalities to eradicate the disease. Combined diagnostic and ablative tools will enable microscopic disease to be detected, particularly at cancer margins where infiltrative growth is difficult to distinguish from normal tissue. Failure to eradicate such microscopic disease is usually the cause for treatment failure and cancer recurrence. Our multidisciplinary team of physical scientists, engineers, laser specialists, and clinicians have begun to address this shortfall in surgical hardware precision by investigating a new laser-based approach ideally suited for minimally invasive and endoluminal cancer surgery. By employing "ultrashort" picosecond lasers, that deliver energy in a series of pulses only a few picoseconds long, we have demonstrated the ability to remove (ablate) tumours on a precision 2 orders of magnitude smaller than existing tools. Importantly, because the laser pulses are so short, there is no time for heat to diffuse into surrounding tissue, as is the case for existing surgical tools. Therefore, we have shown that damage to tissue around the surgical zone can be restricted to less than the width of a human hair - almost on the scale of individual cells.On clinically relevant tissue models we have demonstrated in the laboratory that this picosecond laser ablation could provide a step change in precision resection of the bowel and hence transform endoluminal colorectal cancer surgery. Additionally, we have shown that ps laser pulses can be flexibly delivered via novel hollow core optical fibres giving confidence that endoscopic deployment can be realised and opening up new areas of minimally invasive procedures.We now need to capitalise on this foundation and have therefore expanded our network of clinical expertise and identified new areas where our technology could be truly transformative. Neurosurgery is the ultimate test of precision, even microscopic loss of healthy tissue can have a huge impact on quality of life. In head and neck surgery, minimising resection of normal tissue allows functional preservation of speech and swallowing, positively influencing quality of life outcomes. In parallel, we aim to build on our successful results in colorectal cancer by developing novel strategies for incorporating real-time diagnostic imaging aiming towards clinical application. The proposal will take our understanding of lasers in colorectal cancer surgery towards clinical application, whilst simultaneously exploring new areas of application (Head & neck and brain cancer) where the technology is also thought to have huge potential benefit.