Applications Of ICG Fluorescence Imaging In The Surgical Treatment Of Hepatic Malignant Tumor

Objective:The primary liver cancer is one of the most common malignancies in China, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The complete tumor resection remains the mainstay of treatment. However, the recurrence rate is relatively high due to some neglected minimal tumor foci in the remnant liver. Indocyanine green (ICG) has been used to locate and visualize the tumor lesion through its autofluorescence. This study aims to evaluate the clinical application of ICG near infrared fluorescence imaging in the surgical treatment of HCC.Method:(1) From October 2014 to January 2015, consecutive 24 HCC patients elected for liver resection were selected from the Chinese PLA General Hospital. ICG (0.5 mg/kg) was injected intravenously a couple of days prior to surgery (mean 47.5h,20h-5d). During the operation, the tumor lesions were visualized using a handheld fluorescent detector probe. After complete removal of the tumor lesions, the remnant liver was re-detected, especially the surgical margin. All suspected foci were removed and sent for frozen section immediately. The pathological results, the number and size of the suspected foci, and their depth to liver surface were recorded. Fluorescence imaging of the isolated tumor specimens were performed. The maximum diameter and fluorescence imaging characteristics of the tumor were also recorded. The tumor histology and differentiation degree were analyzed by routine pathological examination. Patients were regularly followed up after operation.(2) 48 patients with primary liver cancer were enrolled. Abdominal ultrasound and enhanced computed tomography (CT) scan were performed prior to surgery. Upon laparotomy, surgeons located the tumor and searched for new lesions with intraoperative ultrasound (IOUS), and recorded the detection results. The diagnositic sensitivity and specificity of tumor foci were compared between preoperative abdominal ultrasound, enhanced CT, and IOUS. Cases with procedural strategies changed by the new findings of IOUS were recorded.(3) 42 patients with pathology-proven HCC elected for hepatectomy were enrolled. ICG (0.5 mg/kg) was injected intravenously a couple of days prior to surgery. The 42 parients were randomly divided into Group A (22 patients) and B (20 patients). Patients in Group A underwent operations guided by real-time ICG fluorescence imaging, with in vivo surgical margin sent for frozen section. Patients in Group B underwent operations guided by IOUS, with in vivo surgical margin scanned by ICG fluorescence imaging and sent for frozen section afterward. After tumor resection, the remnant liver was thoroughly scanned by ICG fluorescence imaging and IOUS, and the newly detected suspicious foci were removed with all morphological and histological features recorded. The tumor specimens of the two groups were cut and examined by ICG fluorescence imaging ex vivo, and the tumor size, its fluorescence imaging pattern, depth to liver surface, and pathological finding were recorded and statistically analyzed. Patients were regularly followed up after operation. Result:(1)19 (79.2%) of the 24 primary tumor lesions were detected by ICG fluorescence imaging on the liver surface, with a mean depth of 0.36cm (0-0.65cm). Five (20.8%) lesions were not detected. The mean depth was 1.52cm (0.9-2.6cm).13 new suspicious lesions were detected in the remnant liver with a mean depth of 0.30cm (0-0.6cm) and a mean diameter of 0.65cm (0.2cm-1.2cm). Pathological results showed that there were 3 (23.1%) of cancer,2 (15.4%) of dysplasia,4 (30.8%) of cirrhotic nodule,2 (15.4%) of inflammatory change, and 2 (15.4%) of fatty change. Highly-differentiated HCCs (22.2%) and a few moderate-differentiated HCCs showed typical tumor hallmark. Furthermore, most moderate-differentiated HCC (77.8%) and all poorly-differentiated HCCs showed the ring-like fluorescent image of the tumor adjacent tissue.3 cases were diagnosed with recurrence during the follow-up of 1 year and all of them were performed by operation in addition with comprehensive treatment.(2) Among 69 tumor lesions detected in the 48 patients (32 HCC,11 ICC,5 metastatic tumor),56 lesions were confirmed to be malignant tumor by pathology examination, with a mean diameter of 3.62cm (0.5-7.5cm; 9 lesions of≤1cm,18 of 1-2cm and 29 of>2cm). The results showed that the sensitivity and specificity of tumor lesion detection with IOUS were higher than those with preoperative abdominal ultrasound (P<0.05). No statistical significance was found comparing IOUS and preoperative CT scan. For the tumor of≤1cm in diameter, the detection rate of IOUS was significantly higher than those of preoperative CT scan and ultrasound (P<0.05). Procedural strategies of 13 patients were changed by IOUS findings.(3) After tumor resection guided by real-time ICG fluorescence imaging, there were no positive finding on the surgical margins of all 22 cases in Group A. But in the 20 cases of Group B undergoing IOUS-guided surgery, there were 3 cases (15%) with residual tumor foci detected on their surgical margins by ICG fluorescence imaging and confirmed by pathology. Combined use of ICG fluorescence imaging and IOUS to scan the remnant liver in vivo detected new tumor foci or dysplasia in 10 cases 8 by ICG fluorescence imaging (80%, of 0-0.7cm in depth) and 3 by IOUS (30%, of 0.7-2.7cm in depth). Furthermore, most moderate-differentiated HCC and all poorly-differentiated HCCs and ICC showed the ring-like fluorescent image of the tumor adjacent tissue.4 cases were diagnosed with recurrence, in which 3 were solitary and 1 was multiple. During the follow-up of 1 year, all of them were performed by operation in addition with comprehensive treatment.Conclusions:ICG fluorescence imaging technique can visualize the primary liver tumor nodules in real-time during the whole process of tumor resection, and can also scan the surgical margin to detect the residual tumor foci. It can scan the remnant liver in vivo to detect new lesions. Combined with IOUS, ICG fluorescence imaging can better detect the deeper-located lesions, improving the detection rate of the residual lesions. The ICG fluorescence imaging technique can advance the current practice of RO resection of primary liver tumor and improve the overall surgical outcomes.