To our knowledge, this study is the first evaluating the IMAGE1 S™ NIR/ICG imaging system for intraoperative real-time NIR endoscopy in OCSCC. We identified at least one SLN in each case. The SLN(s) appeared as bright fluorescent spots, on average, 4.8 ± 2.6 minutes after injection of ICG. Anatomic distribution of the SLN(s) was similar to the metastatic pattern of oral cancer, with the majority of metastases in level I and II . Regarding the tumor localization, carcinomas of the oral floor are mainly associated with metastasis in level I, II, and III, whereas carcinomas of the tongue show additional metastases in level IV. Metastases in level V are rare [22, 23]. In accordance, we detected the SLN in level I to III in patients with carcinomas of the oral floor (patient no. 1, 3, and 4). In one patient with carcinoma of the tongue (patient no. 5), one SLN in level IV was additionally detected.
The identification of SLN in the head and neck area is still controversial, although it attracted more interest in the clinical N0 neck situation of OCSCC. It provides the identification of the first drainage lymph node, which supposably is carrying the highest risk of being affected in the case of metastatic disease . After identification, a frozen section can be performed. In the case of micro-metastatic spread, a complete ND is indicated . In the absence of malignancy, the ND may be abandoned. This strategy has the potential to enable a de-escalation of surgical therapy without compromising oncological results . Several methods have been described for SLN identification. The frequently used lymphoscintigraphy with 99mtechnetium demonstrated an identification rate of 86–95% with a false-negative rate of 2–3% [4, 8, 26]. It is characterized by high tissue penetration. A drawback is the limited spatial resolution, which may affect the accuracy of the intraoperative navigation, especially if the SLN is located close to the injection site . The lack of evidence of a survival benefit of SLN mapping compared to ND in prospective controlled trials may be one reason why this technique currently is established only in a few centers.
The use of ICG for the detection of SLN successfully was introduced by Kitai et al. in 2005 in patients with breast cancer . There are several advantages of fluorescent imaging compared to radioactive tracers. The radiation-free, fluorescent dye has been in clinical use for decades and can be considered very safe, with a low rate of adverse effects [12, 13]. Furthermore, no special radiation protection is required. The costs of ICG is much lower than for a radiotracer. Besides this, the fluorescence imaging system is less expensive than a radiation detection probe . Image acquisition can be performed mono-institutional by the treating surgeon. There are a few studies that report on ICG guided SLN mapping in patients with squamous cell carcinoma of the oropharynx and oral cavity [16–19]. All authors reported good feasibility with an identification rate of 97–100%. Limitations have been described in the low tissue penetration depth of 0.5–1 cm using open imaging systems, which are positioned above the surgical field . The lymph drainage of the oral cavity and the oropharynx runs in deep fatty tissue and can be covered either by the mandible or the sternocleidomastoid muscle. A skin incision, retraction of the muscles, and subplatysmal exposure of the soft tissue are therefore currently essential .
The IMAGE1 S™ NIR/ICG is a laparoscopic imaging system. The telescope has a shorter working distance compared to an open system, and this results in an improved near-infrared image and a higher penetration depth. A dynamic examination in the surgical field could improve the SLN procedure, especially in the submandibular region. By using a holding device, the surgeon can fix the endoscope in different positions during surgery and simultaneously dissect the SLN. Besides, the endoscopic technique offers the possibility to reduce surgical access. The cervical lymph nodes are typically located in close anatomical proximity to each other. With the current system, we achieved a differentiation of single lymph nodes and the distinction between SLN and non-SLN with minimal scattering effects (Fig. 3). We were also able to identify lymph nodes at a depth of about 1.5–2 cm embedded in fatty tissue. After a rapid distribution through the draining lymph vessels, we observed the fluorescence enhancement in additional lymph nodes (SLN 2–5) with increasing observation time (Table 3). This underlines the relevance of the time-related identification of the SLN in an intraoperative setting. As a result, the intraoperative injection of ICG may prevent a false identification of higher tier nodes. If the time dependence of the ICG distribution is not considered adequately, a subgroup of lymph nodes of higher tiers may be marked and falsely identified as SLN. However, it must also be taken into account that in the case of multiple drainage patterns, several relevant SLNs can also be present.
We can confirm the secure and straightforward feasibility and real-time measurement of lymphatic drainage patterns with the IMAGE1 S™ NIR/ICG imaging system. Although ICG application and examination takes around 20 minutes, operating time may be reduced if the SLN is negative, since a complete ND would not be needed.
The scope of this evaluation refers only to an analysis of feasibility. There was no case of neck metastasis when SLN was negative, which suggests a low false-negative rate. In order to evaluate the accuracy of this method, a higher case number is necessary to determine the false-negative rate and the negative-predictive value. The purpose of continuing this study to a more significant case number is to evaluate if the removal of the SLN alone could reliably demonstrate the cervical nodal status for OCSCC. Future research should, therefore, be focused on the timely association and distribution of the fluorescent tracer and the occurrence and distribution of occult metastasis. The further development of this technology is in prospect in order to reduce the incision or to enable transcutaneous utilization.