Staging of upper tract urothelial cancer with optical coherence tomography

描述(申请人提供)：上尿路上皮癌(UTUC)的诊断和治疗对泌尿科医生来说仍然是非常具有挑战性的。多年来的标准治疗一直是根治性肾输尿管切除术(RNU)。然而，对于进展率低的低风险肿瘤，RNU是一种显著的过度治疗。与RNU相比，内窥镜治疗这些低风险病例具有明显的优势，包括较低的并发症和较低的费用，如果能够做出准确的诊断，将是非常可行的。内窥镜治疗的成功依赖于对低级别和低分期肿瘤的准确识别，但UTUC的分期即使通过活检也是非常困难的。通常，由于输尿管和肾盆的操作空间有限，以及如果尝试深层活检有可能穿透输尿管薄壁，因此无法获得足够的组织标本用于病理组织学分期。因此，泌尿科医生通常只根据肿瘤的分级进行诊断，由于活检的局限性，这也是低效的，单凭这一点不足以做出某些治疗决定。因此，如果能够安全可靠地确定UTUC的分期，泌尿科医生将拥有完整的诊断信息，这将显著改善UTUC的内窥镜治疗。我们建议通过内窥镜光学相干断层扫描(OCT)来分期UTUC。OCT已经被证明能够对膀胱尿路上皮癌进行分期，这一事实支持了这种原位成像方法的可行性。膀胱尿路上皮癌在组织学上与UTUC相似，并且使用与UTUC相同的分期系统。我们已经证明，OCT可以通过体外探头获得高质量的输尿管图像。在这个项目中，我们将安装专门用于UTUC成像的OCT探头，并在包括培训在内的两个阶段的先导研究中测试UTUC分期的安全性和初步疗效 阶段和测试阶段。该项目的成功将导致：(A)设计并证明用于UTUC成像的内窥镜OCT系统是安全的，(B)测试基于OCT图像的诊断标准，以及(C)对UTUC OCT分期的准确性进行初步估计。这将证明并为更大规模的临床验证奠定基础。 公共卫生相关性：早期上尿路癌(UTUC)的内窥镜治疗可能比标准的根治性手术更便宜、更好，但目前还不能可靠地使用，因为没有可用的技术来准确地诊断UTUC。该项目将验证使用内窥镜OCT成像来安全和快速地诊断UTUC。

DESCRIPTION (provided by applicant): Diagnosis and treatment of upper-tract urothelial carcinomas (UTUC) remain very challenging for urologists. Standard management for many years has been radical nephroureterectomy (RNU). However, RNU is a significant over-treatment for low-risk tumors, which have low rate of progression. Endoscopic management of these low-risk cases bears obvious advantages over RNU, including lower co-morbidity and lower cost, and would be highly feasible if accurate diagnosis can be made. The success of endoscopic management relies on accurate identification of low-grade and low-stage tumors, but staging of UTUC is very difficult even through biopsy. Usually, adequate tissue specimens for pathohistological staging cannot be acquired because of the limited manipulation space in the ureter and renal pelvis and the potential risk of perforating thin ureteral wall if deep biopsyis attempted. Therefore, urologists typically make a diagnosis only based on the tumor grade, which is also inefficient because of the limitations of biopsy, and which, alone, is not sufficientto make certain treatment decisions. Therefore, if the stage of UTUC could be safely and reliably identified, urologists would have complete information for diagnosis, which could significantly improve endoscopic management of UTUC. We propose to stage UTUC through endoscopic optical coherence tomography (OCT). The feasibility of this in situ imaging approach is supported by the fact that OCT has already been shown to be able to stage bladder urothelial cancer, which is histologically similar to UTUC and uses the same staging system as UTUC. We have demonstrated that OCT can acquire high-quality images of the ureter through a probe ex vivo. In this project, we will implement OCT probes specifically for imaging of UTUC and test the safety and preliminary efficacy of staging of UTUC in a two-stage pilot study, including a training stage and a testing stage. Success of this project will result in: (a) an endoscopic OCT system designed and proven safe for UTUC imaging, (b) tested OCT image-based diagnostic criteria, and (c) a preliminary estimate of the accuracy of OCT staging of UTUC. This will justify and set the stage for larger scale clinical validation. PUBLIC HEALTH RELEVANCE: Endoscopic treatment of early-stage upper-tract urothelial cancer (UTUC) could be cheaper and better for the patient than radical surgery, which is the standard care, but it can't currently be reliably used because no technology is available to accurately stage UTUC. This project will validate use of endoscopic OCT imaging to stage UTUC safely and quickly.