Abstract
Oral squamous cell carcinoma (OSCC) frequently metastasizes to cervical lymph nodes, which is the most known prognostic factor. Screening methods to identify sentinel lymph nodes (SLNs) are therefore of great interest for the management of potential neck metastasis. The purpose of this study was to evaluate the clinical benefit of double SLN mapping with indocyanine green (ICG) and 99m-technetium–tin colloid ( 99m Tc–tin colloid) for sentinel node navigation surgery (SNNS). Between 2007 and 2010, 16 patients diagnosed with OSCC were investigated by SLN biopsy using the double mapping method. 99m Tc–tin colloid was injected into the peri-tumoural region on the preoperative day, and ICG was administered intraoperatively in the same position to assist in detecting nodes during surgery. Based on the gamma-ray signal and near-infrared (NIR) fluorescence of ICG, SLNs were identified and thereafter assessed pathologically and genetically for cancer involvement. Radio-guided detection was successful for all patients. ICG mapping identified a relatively larger number of nodes, suggesting that several non-SLNs were potentially involved. The double mapping method assisted surgeons to explore SLNs. Since the ICG fluorescence was shielded by the subcutaneous fatty tissue and the muscle layer including platysma and sternocleidomastoid, it was necessary to retract the tissue away from nodes.
In oral squamous cell carcinoma (OSCC), the nodal status of cervical lymph nodes is the most important prognostic factor. In the literature, approximately 20–30% of patients have been reported to harbour lymphatic metastasis. To obtain adequate staging and a better prognosis, elective neck dissection (END) has frequently been performed for clinically N0 patients. This brings with it the disadvantage of unnecessary neck dissection, which significantly lowers health utility, for those who are pathologically diagnosed N0 after the surgery. Hence, sentinel node navigation surgery (SNNS), which enables accurate diagnosis, has received considerable attention.
Detection methods for sentinel nodes include blue dyes, indocyanine green (ICG), and radio-guided systems. Blue dyes such as patent blue and indigo carmine have commonly been used to identify nodes during surgery. These enable immediate detection in a simple procedure; however, sentinel lymph nodes (SLNs) in the head and neck area are generally less stained as compared to those at other tumour sites. In addition, blue staining surrounding the primary tumour frequently blurs the visibility of the surgical margins, which may lead to inadequate resection.
With the radio-guided approach, conventional SLN mapping is performed by injecting a radio-colloid, such as 99m-technetium–tin colloid ( 99m Tc–tin colloid) or 99m Tc–sulpur colloid, into the peri-tumoural site followed by sequential lymphoscintigraphy, which enables the preoperative identification of SLNs and surgical planning. Further, single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), which is used for various malignancies, provides a clear overview with three-dimensional (3D) anatomical location. Intraoperative sentinel node navigation relies on the acoustic signal generated by a hand-held gamma-ray probe. Although the radioactive signal penetrates through skin and subdermal tissue, identifying lymph nodes located in close proximity to the primary tumours is frequently impeded by the background signal – the so-called ‘shine-through’ effect.
The SLN biopsy technique using ICG fluorescence imaging has been reported recently for various tumour types, including breast, colon, and gastric cancers. For head and neck cancers, the clinical use of ICG has been increasing and various protocols have been reported. Since ICG is not visible with the naked eye, it does not interfere with the visible identification of the tumour margins, unlike the blue dyes. ICG migrates through the lymph node basins; however, its rapid infiltration frequently contributes to a limited diagnostic window, which may result in improper excision of false-negative SLNs. Also, it is known that near-infrared (NIR) fluorescence is shielded by the subcutaneous fatty tissue and the thick muscle layer of platysma and sternocleidomastoid. To resolve these limitations of optical dyes, hybrid tracers such as ICG–human serum albumin (HSA) and ICG– 99m Tc nanocolloid have been introduced. The aim of the current study was to assess the utility of the hybrid tracing method detecting ICG and 99m Tc during SNNS for OSCC.
Patients and methods
Patients and tumour characteristics
A total of 16 patients were enrolled in this study. All patients underwent primary surgical treatment for T1 and T2 squamous cell carcinoma of the oral cavity. Cervical lymph node metastasis was clinically and radiologically absent at the time of the initial visit.
There were 10 men and six women; their median age was 65.5 years (range 49–82 years). The location of the primary tumour was the tongue ( n = 7), oral floor ( n = 3), lower gingiva ( n = 3), upper gingiva ( n = 2), and buccal mucosa ( n = 1) ( Table 1 ).
| Patient | Age, years | Sex | Primary site | Total No. of defined SLNs by lymphoscintigraphy | SLN location | Intraoperative findings | No. of excised SLNs | Metastasis (No. of positive nodes) | |
|---|---|---|---|---|---|---|---|---|---|
| RI | ICG | ||||||||
| 1 | 60 | M | Tongue | 1 | R level II | 1 | 1 | 1 | − |
| 2 | 71 | F | Oral floor | 3 | L level I, III | 4 | 4 | 4 | − |
| 3 | 50 | M | Oral floor | 2 | R level I | 3 | 3 | 3 | − |
| 4 | 78 | M | Tongue | 1 | L level I | 1 | 1 | 1 | − |
| 5 | 64 | F | Upper gingiva | 1 | R level II | 1 | 2 | 2 | − |
| 6 | 70 | F | Upper gingiva | 1 | L level I | 1 | 1 | 1 | + (1) |
| 7 | 58 | M | Tongue | 3 | L 2× level I, III | 3 | 4 | 4 | − |
| 8 | 63 | F | Buccal mucosa | 2 | R level I, II | 2 | 3 | 3 | − |
| 9 | 82 | M | Lower gingiva | 1 | L level I | 1 | 3 | 3 | − |
| 10 | 75 | M | Tongue | 1 | R level II | 2 | 2 | 2 | − |
| 11 | 49 | M | Oral floor | 1 | R level I | 1 | 1 | 1 | + (1) |
| 12 | 52 | F | Tongue | 2 | R level I, III | 2 | 2 | 2 | − |
| 13 | 72 | M | Tongue | 1 | L level I | 1 | 2 | 2 | − |
| 14 | 69 | F | Tongue | 2 | R 2× level I | 2 | 2 | 2 | − |
| 15 | 54 | M | Lower gingiva | 2 | L level I, II | 2 | 2 | 2 | − |
| 16 | 81 | M | Lower gingiva | 1 | L level I | 1 | 2 | 2 | − |
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