Department of Surgery, University of California San Diego, CA; Department of Surgery, VA San Diego Healthcare System, San Diego, CA; Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.
Department of Surgery, University of California San Diego, CA; Department of Surgery, VA San Diego Healthcare System, San Diego, CA.
Surgery. 2022 Oct;172(4):1156-1163. doi: 10.1016/j.surg.2022.05.029. Epub 2022 Aug 1.
Indocyanine green has been used for fluorescence-guided surgery of liver metastasis and labeling of liver segments. However, indocyanine green is nonspecific, and indocyanine green labeling does not always clearly outline tumor margins. In addition, it is difficult to distinguish between a tumor and its adjacent liver segment colored with indocyanine green alone. In the present study, we performed fluorescence-guided surgery in an orthotopic colon-cancer liver metastasis mouse model by labeling the metastatic liver tumor with an anti-carcinoembryonic antigen fluorescent antibody and with indocyanine green restricted to the adjacent liver segment.
A liver metastasis model was established with human LS174T colon cancer tumor fragments. To label the tumor, mice received SGM-101, an anti-carcinoembryonic antigen antibody conjugated to a near-infrared fluorophore (700 nm), currently in clinical trials, 3 days before surgery. Indocyanine green (800 nm) was injected after ligation of the tumor-bearing Glissonean pedicle with fluorescence labeling restricted to the liver segment adjacent to the tumor. Bright-light surgery and fluorescence-guided surgery were performed to resect the liver metastasis. To assess recurrence, mice underwent necropsy 3 weeks after surgery and the tumor was weighed.
Fluorescence-guided anatomic left lateral lobectomy and fluorescence-guided partial liver resection were both performed with color-coded double labeled imaging. Tumor weight 3 weeks after surgery was significantly lower with fluorescence-guided surgery compared to bright-light surgery (38 ± 57 mg vs 836 ± 668 mg, P = .011) for partial liver resection.
The present study provides a proof-of-concept that color-coded and double labeling of the tumor and adjacent liver segment has the potential to improve liver metastasectomy.
吲哚菁绿已被用于肝转移荧光引导手术和肝段标记。然而,吲哚菁绿是非特异性的,并且吲哚菁绿标记并不总是能清晰地勾勒出肿瘤边界。此外,仅用吲哚菁绿很难区分肿瘤与其相邻的肝段。在本研究中,我们通过用抗癌胚抗原荧光抗体标记转移性肝肿瘤并用吲哚菁绿限制在相邻肝段,在原位结直肠癌肝转移小鼠模型中进行荧光引导手术。
用人 LS174T 结肠癌细胞肿瘤片段建立肝转移模型。为了标记肿瘤,小鼠在手术前 3 天接受 SGM-101,这是一种正在临床试验中的近红外荧光团(700nm)缀合的抗癌胚抗原抗体。在结扎肿瘤携带的 Glissonean 蒂后,注射吲哚菁绿(800nm),将荧光标记限制在肿瘤相邻的肝段。进行亮灯手术和荧光引导手术切除肝转移。为了评估复发,手术后 3 周对小鼠进行尸检,并称重肿瘤。
用双色标记成像进行荧光引导解剖性左外侧叶切除术和荧光引导部分肝切除术。与亮灯手术相比,荧光引导手术切除部分肝后 3 周肿瘤重量明显降低(38 ± 57mg 与 836 ± 668mg,P=.011)。
本研究提供了一个概念验证,即肿瘤和相邻肝段的彩色编码和双标记有可能改善肝转移切除术。