Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance

Abstract

Background: Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver.

Methods: Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard.

Results: Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity).

Conclusion: This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.

Keywords: Fluorescence imaging; Hepatic metastases; Indocyanine green; Intraoperative guidance; Surgical navigation; Tumor imaging.

Fig. 1

Representative images of intraoperative NIR fluorescence identification of liver tumors. A well-differentiated hepatocellular carcinoma shows the uptake of ICG in and around the tumor. A cholangiocarcinoma shows a rim-type fluorescence, similar to hepatic metastasis of colorectal and breast cancer and uveal melanoma. As the breast cancer and uveal melanoma liver metastases are located below the liver surface, the fluorescence does not show a rim. However, ex vivo a distinctive rim-type fluorescence signal is visible (data not shown). Of note, the fluorescence laparoscope does not possess an overlay function; the images are therefore not always aligned

Fig. 2

Sensitivity of all imaging modalities employed. Sensitivity and positive predictive value of computed tomography (CT), magnetic resonance imaging (MRI), visual inspection, laparoscopic ultrasonography (LUS), near-infrared fluorescence imaging (NIRF), and combination of LUS and NIRF. NIRF has the highest sensitivity rate among all imaging modalities. Combination of NIRF + LUS results in the detection of all hepatic tumors (100 % detection). The graph shows the sensitivity for all lesions together and divided into <10 and ≥10 mm. Sensitivity of all imaging modalities drops considerably for the detection of lesions <10 mm. However, all small lesions could still be detected by combining NIRF and LUS. Differences are not statistically significant

Fig. 3

Ex vivo fluorescence imaging of resected tumors. Rim-type fluorescence surrounding a cholangiocarcinoma (ChC, A) and a colorectal liver metastasis (CRLM, B) imaged using a FLARE^® prototype. The CRLM was not visible using fluorescence imaging during surgery, because it was located >8 mm below the liver surface. Matching microscopic images (magnification ×2 and ×40) of hematoxylin and eosin and DAPI staining sections were made of ChC (C) and CRLM (D). Fluorescence shows a sharp demarcation between normal liver tissue and fibrosis or tumor tissue. D Also shows fluorescence in a biliary duct, probably due to mechanic obstruction by the tumor. Abbreviations T tumor, F fibrosis, N normal liver tissue, B biliary duct

Fig. 4

Fluorescence imaging of benign lesions. A Intraoperative imaging of a cyst (white arrow) and a bile duct hamartoma (dashed arrow). The cyst is not visible using fluorescence imaging, but the bile duct hamartoma is. The weak fluorescence signal does not show a distinctive rim-type fluorescence and can thereby be discriminated from a malignancy. B Benign, large focal nodular hyperplasia also shows NIR fluorescence. The mechanism of ICG uptake is unknown, but potentially its biliary excretion is disturbed

Fig. 5

Intraoperative visualization of a positive resection margin of a colorectal liver metastasis. In vivo fluorescence is visible in the resection margin (white arrow), indicating a tumor-free margin of <8 mm. Ex vivo, the distinctive fluorescent rim is interrupted (dashed arrow) at the positive resection margin