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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 109-112

Indocyanine green fluorescence imaging-guided resection of colorectal liver metastasis


Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

Date of Submission07-Jul-2020
Date of Decision26-Oct-2020
Date of Acceptance28-Oct-2020
Date of Web Publication01-Sep-2021

Correspondence Address:
Dr. I-Shu Chen
Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City 813414
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCRP.JCRP_30_20

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  Abstract 


Most people with colorectal cancer eventually develop liver metastasis. Small liver metastasis can be hard to identify and sometimes missed during liver resection. We present our experience and suggest intraoperative navigation using indocyanine green near-infrared fluorescence imaging to ensure complete surgical eradication of liver metastases from colorectal cancer.

Keywords: Indocyanine green, liver metastasis, near-infrared fluorescence, surgical resection


How to cite this article:
Kang CH, Chen IS. Indocyanine green fluorescence imaging-guided resection of colorectal liver metastasis. J Cancer Res Pract 2021;8:109-12

How to cite this URL:
Kang CH, Chen IS. Indocyanine green fluorescence imaging-guided resection of colorectal liver metastasis. J Cancer Res Pract [serial online] 2021 [cited 2021 Dec 5];8:109-12. Available from: https://www.ejcrp.org/text.asp?2021/8/3/109/324924




  Introduction Top


Colorectal cancer is the most common cancer in Taiwan, and is the third leading cause of cancer-related deaths.[1] About half of these patients will develop liver metastasis during the course of the disease, causing two-thirds of deaths. Liver resection is the treatment of choice for patients with liver metastasis of colorectal cancer, and it provides the greatest chance of long-term survival.[2] Tumor recurrence after radical resection of liver tumors is not uncommon, due to undiagnosed occult tumors and positive margins. Indocyanine green near-infrared fluorescence imaging can be used to prevent missed tumor.

Indocyanine green (ICG) has been widely used in clinical settings to estimate cardiac output and liver function since its approval by the US Food and Drug Administration in 1954.[3] Over the past two to three decades, ICG fluorescence imaging has gained widespread acceptance for use in the intraoperative visualization of blood flow and lymph nodes.[4] Ishizawa et al. reported in 2009 that an intravenous injection of ICG caused “bull's eyes” of fluorescence to be formed around primary or metastatic tumors in the liver.[5] This is because ICG binds to plasma proteins, and protein-bound ICG emits light with a peak wavelength of around 830 nm when illuminated with near-infrared light. Following intravenous injection, ICG is rapidly taken up by hepatocytes, thus quickly disappearing from the bloodstream (half-life: 3–4 min).[6] Primary or metastatic liver tumors fluoresce because they retain the preoperatively injected ICG as a result of biliary excretion disorders in the cancerous tissues. ICG positivity in a tumor is not a biological marker of malignancy, and most malignant tumors just tend to retain more ICG for a longer period compared to that of benign lesions or abnormal liver tissue. Benign tumors can also be ICG positive if bile excretion dynamics are abnormal within or surrounding the tumor.[7] The dose of ICG most frequently used to identify liver tumors is 0.5 mg/kg body weight administered, 1–14 days prior to surgery.


  Case Report Top


A 56-year-old male presented to our hospital with obstructive defecation and bloody stool intermittently for 6 months. He had no known history of other systemic diseases, previous abdominal trauma, or surgery. Colonoscopy demonstrated an annular tumor over the rectosigmoid junction, 15 cm from the anal verge. Abdominal computed tomography (CT) showed eccentric wall thickening at the rectosigmoid junction with lumen narrowing and some regional lymph nodes, and a 0.5-cm liver cyst at S4a. He underwent three-dimensional (3D) laparoscopic low anterior resection and a pathologic examination confirmed well-differentiated adenocarcinoma without lymph node metastasis, and the tumor stage was pT3N0M0, Stage IIA. Therefore, he did not receive adjuvant chemotherapy. However, an elevated level of serum carcinoembryonic antigen (from 1.2 ng/mL to 7.3 ng/mL) was noted 7 months later, and abdominal sonography and abdominal CT revealed a rim-like enhanced hypodense mass measuring 2.4 cm over the left lobe of the liver. Liver metastasis was suspected, so he was referred to our liver surgeon. Liver CT was performed 1 month later to completely survey the liver tumor, and a bigger 3.2-cm solitary liver metastasis was noted [Figure 1]. Because of tumor size progression, we re-arranged preoperative liver sonography to investigate whether there was a new occult liver tumor. As expected, another hypoechoic nodule was found at S6 of the liver, about 1.4 cm in size, and small liver metastasis was favored [Figure 2].
Figure 1: Liver computed tomography scan indicating a rim-enhanced hypodense liver metastasis

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Figure 2: Liver sonography showing another small liver metastasis

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According to our standard protocol for liver surgery, he received a preoperative ICG 15-min retention test (ICG-r15 test) for liver function estimation with an ICG dose of 0.5 mg/kg body weight and showed 1.14%. He underwent laparoscopic hepatectomy 5 days after the ICG-r15 test. During surgery, we used ICG fluorescence imaging (Olympus, VISERA ELITTE II system (Olympus Medical System Corp., Tokyo, Japan)) and intraoperative ultrasound to identify liver tumors. In addition to the two tumors found during the preoperative examinations, two other superficial tumors sized 0.7 cm and 0.8 cm were seen only on intraoperative ICG fluorescence imaging. All the tumors were removed smoothly without complications. A total of four liver tumors were pathologically diagnosed as metastases from colorectal cancer [Figure 3]. During the surgical resection, ICG fluorescence imaging was also used to distinguish between tumor borders and normal liver parenchyma in real time [Figure 4]. Finally, the resected margins were all free of tumor microscopically (R0 resection).
Figure 3: Indocyanine green fluorescence imaging. (a) Tumor 1 at S2 with rim-type fluorescence. (b) Tumor 2 at S6 with rim-type fluorescence. (c) Tumor 3 at S4. (d) Tumor 4 at the posterior side of S5

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Figure 4: Distinguishing the demarcation between tumor border and liver parenchyma in real time

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One month after hepatectomy, further chemotherapy was suggested. However, because the patient lived in a different city, he decided to receive chemotherapy at a nearby hospital, and therefore he did not return to our hospital.


  Discussion Top


Preoperative conventional imaging techniques using ultrasound, contrast-enhanced CT, and/or magnetic resonance imaging are currently used to diagnose cancer and as an aid to guide its resection.[8] However, liver metastases of colorectal cancer might be multi-foci, and small intrahepatic tumors are difficult to diagnose. The goal of surgery should be to resect all metastases with negative histological margins while preserving sufficient functional hepatic parenchyma.[9]

During conventional surgery, visual appearance, palpation, and intraoperative ultrasound findings are the only available means for discriminating between tumor and normal tissues, and consequently for determining whether or not an adequate tumor-free margin has been obtained.[10] During laparoscopic surgery, palpation lacks of tactile feedback. Peloso et al. published in 2012 that intraoperative ultrasound offers the undeniable advantage of real-time visualization, but it also has several shortcomings: (i) it cannot detect lesions of ≤3 mm in size; (ii) its accuracy is highly dependent on the skill and experience of the operator; (iii) the images it provides are two dimensional rather than 3D; (iv) there is a superficial blind area, about 1 cm under the liver surface; and (v) the ultrasound probe cannot achieve a good interface on a nodular surface of a cirrhotic liver.[11]

ICG is retained in tumorous tissues even after excretion from the background hepatic parenchyma, leading to clear identification of liver tumors by intraoperative ICG fluorescence imaging. In contrast to intraoperative ultrasound, ICG fluorescence imaging can identify superficial hepatic lesions with excellent sensitivity of 96%–100%.[12] It can also detect small or occult tumors, that would be missed by conventional imaging techniques.[3] Nevertheless, the tissue penetration of the fluorescence emitted by ICG ranges from only 5 to 10 mm.[13] All of the lesions missed by intraoperative ultrasound are superficially located, whereas the lesions missed by ICG fluorescence imaging are deep. This suggests a potential role in using both intraoperative ultrasound and ICG fluorescence imaging in a complementary fashion to increase sensitivity and the chance of complete resection.[14] Purich et al. demonstrated that when intraoperative ICG fluorescence imaging is used in conjunction with intraoperative ultrasound, ICG could detect additional superficial malignant lesions in 11.6% of patients.[12]

Intraoperative histopathological analysis of frozen tumor margins is expensive, is time consuming, and may be inadequate in the presence of large lesions.[15] Defective biliary clearance in the transition area between tumor and normal liver tissue and in liver tumors has been shown to result in ICG retention, which can be visualized using an ICG fluorescence imaging system.[14]

Therefore, intraoperative real-time ICG fluorescence imaging can help to ensure a surgical margin.


  Conclusion Top


ICG is available, affordable, safe, and excreted exclusively by the liver. In our hospital, patients planned for liver surgery routinely receive an ICG-r15 test as a part of preoperative liver function estimation with an intravenous injection of ICG (0.5 mg/kg body weight) within 2 weeks prior to surgery. Subsequently, we use intraoperative ultrasound combined with ICG fluorescence imaging to detect small and occult tumors. In summary, ICG fluorescence imaging can demarcate liver tumors and also allow for real-time assessments of the resection margin.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wang YW, Chen HH, Wu MS, Chiu HM; Taiwanese Nationwide Colorectal Cancer Screening Program. Current status and future challenge of population-based organized colorectal cancer screening: Lesson from the first decade of Taiwanese program. J Formos Med Assoc 2018;117:358-64.  Back to cited text no. 1
    
2.
Alvarez FA, Sanchez Claria R, Oggero S, de Santibañes E. Parenchymal-sparing liver surgery in patients with colorectal carcinoma liver metastases. World J Gastrointest Surg 2016;8:407-23.  Back to cited text no. 2
    
3.
Nakaseko Y, Ishizawa T, Saiura A. Fluorescence-guided surgery for liver tumors. J Surg Oncol 2018;118:324-31.  Back to cited text no. 3
    
4.
Terasawa M, Ishizawa T, Mise Y, Inoue Y, Ito H, Takahashi Y, et al. Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc 2017;31:5111-8.  Back to cited text no. 4
    
5.
Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, et al. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer 2009;115:2491-504.  Back to cited text no. 5
    
6.
Landsman ML, Kwant G, Mook GA, Zijlstra WG. Light-absorbing properties, stability, and spectral stabilization of indocyanine green. J Appl Physiol 1976;40:575-83.  Back to cited text no. 6
    
7.
Lim HJ, Chiow AK, Lee LS, Tan SS, Goh BK, Koh YX, et al. Novel method of intraoperative liver tumour localisation with indocyanine green and near-infrared imaging. Singapore Med J 2019.  Back to cited text no. 7
    
8.
Nowicki TK, Markiet K, Szurowska E. Diagnostic imaging of hepatocellular carcinoma-A pictorial essay. Curr Med Imaging Rev 2017;13:140-53.  Back to cited text no. 8
    
9.
Poultsides GA, Schulick RD, Pawlik TM. Hepatic resection for colorectal metastases: The impact of surgical margin status on outcome. HPB (Oxford) 2010;12:43-9.  Back to cited text no. 9
    
10.
Takahashi H, Zaidi N, Berber E. An initial report on the intraoperative use of indocyanine green fluorescence imaging in the surgical management of liver tumors. J Surg Oncol 2016;114:625-9.  Back to cited text no. 10
    
11.
Peloso A, Franchi E, Canepa MC, Barbieri L, Briani L, Ferrario J, et al. Combined use of intraoperative ultrasound and indocyanine green fluorescence imaging to detect liver metastases from colorectal cancer. HPB (Oxford) 2013;15:928-34.  Back to cited text no. 11
    
12.
Purich K, Dang JT, Poonja A, Sun WY, Bigam D, Birch D, et al. Intraoperative fluorescence imaging with indocyanine green in hepatic resection for malignancy: A systematic review and meta-analysis of diagnostic test accuracy studies. Surg Endosc 2020;34:2891-903.  Back to cited text no. 12
    
13.
Kawaguchi Y, Velayutham V, Fuks D, Christidis C, Kokudo N, Gayet B. Usefulness of indocyanine green-fluorescence imaging for visualization of the bile duct during laparoscopic liver resection. J Am Coll Surg 2015;221:e113-7.  Back to cited text no. 13
    
14.
Boogerd LS, Handgraaf HJ, Lam HD, Huurman VA, Farina-Sarasqueta A, Frangioni JV, et al. Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance. Surg Endosc 2017;31:952-61.  Back to cited text no. 14
    
15.
Lieto E, Galizia G, Cardella F, Mabilia A, Basile N, Castellano P, et al. Indocyanine green fluorescence imaging-guided surgery in primary and metastatic liver tumors. Surg Innov 2018;25:62-8.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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