The handheld HEMS can significantly aid in the detection and visual confirmation of pharyngeal tumors located behind the oral cavity or nasal cavity by ICG-enhanced imaging with vivid color. Of note is that it can be freely operated intraoperatively by surgeons. Because of the high sensitivity of ICG fluorescence imaging, ICG fluorescence imaging under HEMS can assist surgeons in the identification and resection of tumors which have invaded the parapharyngeal space behind the internal carotid artery, internal jugular vein, and lower cranial nerves.

We have demonstrated a successful method of distinguishing cancer from healthy tissue and the optimum surgical time with HEMS in animal models [14]. Application of endoscopic and robotic surgery for the parapharyngeal space lesions enables surgeons to perform minimally invasive surgery with superior results [15]. However, we need to be able to detect parapharyngeal tumors in deeper and invisible areas when palpation is not possible. This is required in order to resect tumors safely and can be aided through effective tumor detection carried out with ICG fluorescent imaging.

ICG fluorescence imaging is effective for the detection and resection of the parapharyngeal space tumors which enables greater preservation of functions.

According to the sentinel theory, metastatic lymph nodes are directly connected with primary tumors via lymphatic canals. Lymphatic chemotherapy is defined as chemotherapy using lymphatic canals between metastatic lymph nodes and primary tumors. This therapy is viewed as an ultimate cancer treatment which is both highly effective and noninvasive.

In the following, we consider a newly developed lymphatic chemotherapy procedure targeting the SLN using intra-arterial (I-A) chemotherapy for oral cancer in order to improve prognosis and to preserve organs while avoiding surgical complications [11, 16–18]. Our concept of lymphatic chemotherapy is shown in Fig. 5.2. Namely, the schema of lymphatic chemotherapy demonstrates an anticancer drug administered to the primary cancer which moves selectively to SLNs via lymphatic canals. As a result, the anticancer drug is accumulated in the SLNs and results in a higher anticancer drug concentration in the SLNs than non-SLNs. Because cis-diamminedichloroplatinum (CDDP) is the most promising drug for the treatment of head and neck cancers, we have adopted intra-arterial chemotherapy administered to the primary cancer so as to increase the CDDP concentration. To examine the potential advantages, we compared the CDDP concentration of SLNs with that of non-SLNs. The mean CDDP concentrations in the SLNs and non-SLNs were 1.2 μg/g and 0.35 μg/g, respectively. Our ICG fluorescence procedure revealed that all metastatic lymph nodes, including SLNs, were without false-negative SLNs. However, of 7 metastatic lymph nodes, one was not identified by means of the conventional radiocolloid method [11]. Detection of SLNs was clearly demonstrated by ICG fluorescence imaging (Fig. 5.3). The mean number of SLNs was 5.6 (3–8). ICG fluorescence imaging showed a greater number of SLNs than seen when injecting radiocolloid intratumor (mean 3.4). SLNs detected by ICG fluorescence imaging included all of the SLNs detected by the conventional radioactive method.

In the case of oral cancer with neck metastasis, modified radical neck dissection is often conducted to prevent cancer recurrence. However, this procedure can be the cause of severe postoperative complications. Instead of neck dissection and the associated surgical complications, minimally invasive lymphatic chemotherapy targeting neck metastasis based on the sentinel concept may contribute to the development of a revolutionary cancer treatment. This could potentially provide a superior method for the treatment of head and neck cancer which has been a key objective for researchers over many years. In our research, we consider I-A chemotherapy administered to primary oral cancers as not only organ preservation therapy but also a newly developed lymphatic chemotherapy targeting neck metastasis in order to improve prognosis.

In our examination we evaluate the effect of lymphatic chemotherapy targeting neck metastases in patients with oral cancer (T3N2bM0) by measuring CDDP concentrations in metastatic lymph nodes and pathological effects [19].