*3.3.2 Fluorescence-guided detection of lymph node metastases in colorectal cancer and the sentinel lymph node technique*

Indocyanine green fluorescence imaging can also be used as a potential tool for enhancing the accuracy of the staging of patients with primary colorectal cancer through the detection of sentinel lymph nodes. The search in electronic databases was performed and eligible data were taken from 248 patients in a review published by Emile et al. [17], which looked at the overall sensitivity and specificity of (ICG) (NIR) fluorescence in sentinel lymph node detection in colorectal cancer. The median values for the sensitivity, specificity, and accuracy rates were 73.7, 100, and 75.7, respectively. Other several studies, even though none was a prospective one, considered the ICG method feasible in colorectal cancer and also for lower rectal tumors, especially in order to detect the lymphatic drainage across the lateral lymph nodes, as studied by the teams of Nagata et al. [18], Kawahara et al. [19], Cahill et al. [20], and Liberale et al. [21]. Another method used in correctly and precisely identifying the lymph node involvement is one-step nucleic acid (OSNA), as it can offer a quick method of characterization of the lymph nodes. On the other hand, near-infrared (NIR) laparoscopy, together with indocyanine green (ICG), can identify relevant nodal tissue *in situ* during surgery. The association between the OSNA, laparoscopy, and NIR-ICG was studied in an RCT by Yeung et al. [22],

#### **Figure 6.**

*X-ray angiography of the inferior mesenteric artery (IMA) with contrast media. Its supplies arterial blood to organs of hindgut-distal 1/3 of the transverse, splenic flexure, descending colon, sigmoid, rectum.*

#### *The Use of Indocyanine Green in Colorectal Surgery DOI: http://dx.doi.org/10.5772/intechopen.100301*

a research during which ICG was administered around the tumor, while endoscopy was conducted at a moment previous to the operation. NIR-identified fluorescent lymph nodes were first labeled and then sent for whole-node OSNA review. Both traditional histology and OSNA were used to examine and analyze "fresh" lymph nodes dissected from the typical resection specimen. Furthermore, the fluorescent lymph node status was compared to that of non-ICG nodes in order to determine their predictive value. OSNA is concordant with normal histology, but only a minority of nodes detectable by complete pathological examination was identified for OSNA on fresh dissection, according to the study's findings. To provide an intraoperative evaluation of nodal tissue in patients with colorectal cancer, OSNA can be performed at the same time as NIR and ICG lymphatic mapping. Patients with colorectal cancer can benefit from this treatment.

A study performed by Vuijk et al. [23] looking at the lymph node involvement in gastrointestinal tumors assessed the sentinel lymph node technique with Nanocoll, and ICG- and CEA-targeted fluorescent imaging, and settled to the following conclusions: sentinel lymph node interventions in gastric cancer resections using indocyanine green (ICG) linked to Nanocoll outperformed normal ICG, but could not offer details on possible lymph node metastasis. Besides that aspect, the carcinoembryonic antigen (CEA)-targeted fluorescent imaging technique by using SGM-101 was successful in both pancreatic and colorectal cancers. A large phase III multicenter trial with the corresponding results would be able to complete the missing data.

Simultaneously, in which concerns lymph node invasion, the concept of ultrastaging appeared recently in the specific literature. Furthermore, studies were compiled, such as the one by Hirche et al. [24], in which regards ultrastaging of colon cancer by sentinel node biopsy using fluorescence navigation with ICG Overall, the ICG fluorescence technique found a mean of 1.7 sentinel lymph node (SLN) in 25 out of 26 patients (with a detection rate of 96%). Metastatic involvement of the SLN was detected in 9 out of 11 nodal positive patients by conventional histopathology. The sensitivity of the method was 82% in the case of colon carcinoma. The drawn conclusion of the abovementioned study was that the ICG fluorescence technique is a new but feasible method for SLNB of colon carcinoma and permits ultrastaging with improved accuracy, but with limited validity (so far) due to the small number of cases (**Figures 7** and **8**).

### *3.3.3 ICG in metastatic colorectal cancer*

ICG is metabolized by the liver and accumulates in areas of slower bile metabolism, a situation that can be encountered in primary liver cancers and colorectal secondary determinations (metastases), as found by the teams of Peloso et al. [25] and van der Vorst [26]. A tumor cluster of cells as small as 200 tumor cells can be identified by ICG, allowing surgeons to find foci of a minimum of 1 mm,

#### **Figure 7.**

*Colorectal cancer concept. Development of cancer from the colon or rectum to the whole large intestine. Stages of spreading tumor to the lymph nodes and vector flat illustration of other internal organs.*

#### **Figure 8.**

*Metastatic colon carcinoma, in lymph node. Tumor component is on the left and lymphoid component is on the right, magnification 200×.*

as it was shown by Ishizawa et al. [27]. The practical aspect of finding liver masses is that they have to be superficial, and the fluorescence methods can look at the maximum depth of infiltration of up to 10 mm. A combination of the application of intraoperative ultrasound and fluorescence techniques was shown to increase the identification rate of colorectal metastatic lesions, as it was researched by Kaibori et al. [28]. In patients suffering from liver fibrosis, nevertheless, areas that have a slow bile metabolism might give false-positive fluorescence. ICG fluorescence can be employed to qualitatively and quantitatively depict changes at a molecular and cellular level in the living organism, and to objectively display liver tumor information, to define hepatic tumor boundaries, and to detect residual tumors, achieving an intraoperative real time coloration and the successful navigation of the liver parenchyma in the targeted zone, as mentioned by Shizawa et al. [29]. A recent meta-analysis included studies on 587 patients showing that ICG fluorescence in the field of liver surgery does decrease operative time, blood loss, hospital stay, and postoperative complications if we are to mention a study done by Qi et al. [30]. As mentioned in subchapter 3.2.2 (ICG in liver surgery), the ICG fluorescence technique is for sure viewed as an intraoperative method that allows the detection of additional superficial hepatic metastases of colorectal cancer, a fact underlined by Liberale and team [31] in an article in which PubMed and Medline literature databases were searched for articles on the use of ICG in the setting of clinical studies on CRC (**Figures 9** and **10**).

## *3.3.4 Evidence of ICG usefulness in robotically assisted colorectal surgery*

As previously shown in the previous subsections of the chapter, ICG fluorescence imaging is increasingly being used, tested, and documented in different areas of abdominal surgery. The constant improvement in the method and in the technological possibilities enables easy use and facilitates operative decision-making, also in robotically assisted colorectal surgery, as it is communicated in a study published by Vilz et al. [32]. Additional information offered there was that the first individual studies underlined an important reduction in the incidence of anastomotic leakage after colorectal anastomosis through the use of ICG fluorescence angiography (FA, 9.1% vs. 16.3%; p = 0.04). First feasibility research studies also emphasized lymph node detection or navigation, as well as the possibility to visualize the ureter (**Figure 11**).

*The Use of Indocyanine Green in Colorectal Surgery DOI: http://dx.doi.org/10.5772/intechopen.100301*

**Figure 9.** *Immunofluorescence of multiple human tumor metastatic cells growing in tissue culture for research purposes.*

**Figure 10.** *Human liver cancer cell growth. 3D illustration.*
