Fluorescence-Guided Surgery for Hepatoblastoma with Indocyanine Green

Abstract

Fluorescence-guided surgery with indocyanine green (ICG) for malignant hepatic tumors has been gaining more attention with technical advancements. Since hepatoblastomas (HBs) possess similar features to hepatocellular carcinoma, fluorescence-guided surgery can be used for HBs, as aggressive surgical resection, even for distant metastases of HBs, often contributes positively to R0 (complete) resection and subsequent patient survival. Despite a few caveats, fluorescence-guided surgery allows for the more sensitive identification of lesions that may go undetected by conventional imaging or be invisible macroscopically. This leads to precise resection of distant metastatic tumors as well as primary liver tumors.

Keywords: hepatoblastoma; indocyanine green; navigation; near infrared.

Figure 1

a,b: Multiple fluorescent spots are observed under near-infrared (NIR) in the liver. Of note, some nodules show a rim-type fluorescence pattern, indicated by an arrowhead (combined fetal and embryonal subtype, post-chemotherapy).

Figure 2

a,b: The hilum of the liver in Patient 12. A giant tumor with uneven fluorescence in the left lobe along with intrahepatic metastasis (diffuse pattern) is indicated by an arrowhead. Of note, the common bile duct is also visualized, presumably due to residual fluorescence, indicated by an arrow (mixed epithelial and mesenchymal, post-chemotherapy).

Figure 3

a–g: Mixed epithelial and mesenchymal type with teratoid features, post-chemotherapy. The formalin-fixed cross section of the liver is shown (a), and the tumor is encircled with a yellow-dotted line. The tumor is heterogeneous macroscopically, and fluorescence can be observed only in the small area marked with a white-dotted line (b: white-light mode, c: NIR mode, d: mapping mode). A histological analysis showed that while the fluorescent area corresponded to well-differentiated HB (e), the non-fluorescent area consisted of poorly differentiated HB (f) and an osteoid lesion (g). Scale bar: 100 µm.

Figure 3

a–g: Mixed epithelial and mesenchymal type with teratoid features, post-chemotherapy. The formalin-fixed cross section of the liver is shown (a), and the tumor is encircled with a yellow-dotted line. The tumor is heterogeneous macroscopically, and fluorescence can be observed only in the small area marked with a white-dotted line (b: white-light mode, c: NIR mode, d: mapping mode). A histological analysis showed that while the fluorescent area corresponded to well-differentiated HB (e), the non-fluorescent area consisted of poorly differentiated HB (f) and an osteoid lesion (g). Scale bar: 100 µm.

Figure 4

a–d: Multiple metastatic HBs in the transplanted liver in vivo (a,b) and ex vivo (c,d). This patient underwent the second living donor liver transplantation [44].

Figure 5

a,b: Several pulmonary metastases are visualized in NIR mode (patient 19; transitional liver cell tumor).

Figure 6

Peritoneal metastases in the patient 8, which were successfully removed with the help of NIR mode. Normal white light mode viewing the abdominal cavity (a,c) and NIR mode (b,d).

Figure 7

Pleural metastasis visualized with the Pinpoint system. Normal white-light mode (a), NIR mode (b), and overlay mode (c) are shown. The tumor is visualized as a green color overlaid on the white-light mode view.

Figure 8

ICG is distributed to the whole body and accumulates in the liver (within a few minutes after the intravenous injection). ICG is then excreted into the biliary system and persists for up to 20–24 h. While liver tumors display non-fluorescent spots in NIR mode at a very early stage after the injection of ICG, such studies have not been performed in lungs with metastatic HBs. The selective retention of ICG can be observed in HBs in both the liver and lungs around 24 h, but excreted fluorescence remains in the bowel loops. By 72–96 h after the injection, bowel-retained ICG is excreted with feces. HB tissues retain ICG for up to two weeks. The pattern of fluorescence may vary depending on the dose of ICG, detecting device, liver function, and pathology.

Figure 9

a,b Non-specific fluorescence in the pancreas and bowel loops. The arrowhead indicates the intense fluorescence in the pancreas, but a thorough inspection denied the presence of metastases. Non-specific fluorescence in the bowl loops was also observed (indicated by an arrow).