Impact of Endoscopic Indocyanine Green Fluorescence Imaging on Superselective Intra-arterial Chemotherapy for Recurrent Cancer of the Skull Base

Discussion

Chemoradiotherapy for head and neck cancer plays an important role in organ preservation, however, there are many cases, such as paranasal cancer, for which conventional systemic chemotherapies are ineffective. Cisplatin is the most promising drug for therapy of head and neck cancer. When high doses of cisplatin are administered, various adverse effects can be observed, such as gastrointestinal toxicity, renal toxicity and hematological toxicity. For chemoresistant cancer, including paranasal sinus cancer, superselective I-A chemotherapy is considered to increase the concentration of the anticancer drug in cancer tissue, exerting powerful effects on chemoresistant tumors (1-5). This procedure is reportedly capable of achieving a positive prognosis as well as good organ preservation.

To achieve an effective therapeutic result for recurrent skull-base cancer with I-A chemotherapy, precise evaluation of the tumor-feeding artery and drug distribution is required (6). However, DSA cannot always clearly detect the border between the normal mucosa and surface-invasive tumor. CTA clearly displays the border between normal structure and deeply invasive cancer mass by using 3-dimensional sections. Therefore, CTA in addition to DSA provides more precise identification of the blood supply to the tumor (1, 6, 7). However, it is at times not possible to confirm the tumor-feeding artery in patients with paranasal sinus cancer who have dental metal or reconstruction plates, or surface invasion (17). Furthermore, repeated CTA increases X-ray exposure, which is a significant problem not only for patients but also for medical staff.

Recently, the ICG fluorescence technique was developed and has been used in various fields (3, 11-14). The excitation and emission profiles for ICG lie in the NIR wavelengths, which allow penetration and imaging of vessels below a few millimeters of tissue (11). It provides visualization of the blood supply to reconstructed organs, and sentinel lymph nodes in cancer surgery, including head and neck cancer (3, 12, 14, 18). ICG fluorescence has been used for navigation surgery and intraoperative detection of cancer (11, 19, 20).

We have previously reported that the ICG fluorescence technique can be a very useful method for treating oral or paranasal cancer with I-A chemotherapy in patients with dental metal (15, 17). However, previously employed ICG fluorescence cameras such as PDE are too large to insert within the pharynx or nasal cavity in order to observe tumor-feeding arteries of tumors there. As a result, we were unable to obtain precise information concerning blood supply to tumors located behind the oral or nasal cavity. As recent endoscopic ICG fluorescence imaging has enabled the visualization of the blood supply to intra-abdominal organs (20), we applied endoscopic ICG fluorescence technique for the visualization of the blood supply to skull-base cancer at I-A chemotherapy. In order to observe the blood supply to the skull base, we inserted the ICG fluorescence endoscope in the nasal cavity for all patients. However, the 5.8 mm diameter of the ICG endoscope is a little larger than the flexible endoscope typically employed. Consequently, some patients complained of experiencing slight pain on the insertion of the ICG endoscope.

The nearer the ICG fluorescence endoscope was inserted to the recurrent tumor, the higher excitation of ICG and the deeper penetration of the tissue was obtained up to10 mm. We were able to confirm whether the whole tumor had been successfully covered and filled with the anticancer drug in all cases. As a result, we were able to conduct superselective I-A chemotherapy effectively and safely for recurrent skull-base cancer with critical nerves or organs associated with dysphagia, or visual disturbance. A finer and more sensitive endoscope for ICG fluorescence imaging is required for the detection of blood supply to cancer of the skull base.

We found that the endoscopic ICG fluorescence technique was a very useful method even in patients with recurrent skull-base cancer who had undergone reconstruction using reconstruction plate. For tumors with multiple feeding arteries, ICG fluorescence in superselectively infused arteries was evaluated clearly and lucidly. As ICG fluorescent imaging continues to produce fluorescence for more than 10 min, it is necessary to be aware of the former fluorescent areas prior to ICG infusion to the additional feeding arteries to the skull-base cancer.

However, tumors invading at a depth greater than 10 mm require another imaging method, such as simultaneous CTA. Once the stained field of each feeding artery has been detected by CTA in the case of tumors invading the base of the skull or face, the endoscopic ICG fluorescence technique can then be used to compensate for deficiencies in CT angiography by identifying the feeding artery precisely and safely. As it is difficult to insert the 5.8 mm diameter of the ICG endoscope within the nasal cavity without pain, we inserted 0.1% epinephrine and 4% lidocaine gauze into the nasal cavity prior to the treatment.

It should be noted that a fine and sensitive endoscope for ICG fluorescence imaging is required for the detection of skull-base cancer. This technique is feasible and also achieves new promising options for skull-base or paranasal sinus cancer. Further investigations may lead to development of a new minimally invasive multimodal therapy targeting advanced skull-base cancer in the future.