FEASIBILITY AND SAFETY OF TAILORED LYMPHADENECTOMY USING SENTINEL NODE NAVIGATED SURGERY WITH A HYBRID TRACER OF TECHNETIUM-99M AND INDOCYANINE GREEN IN HIGH-RISK T1 ESOPHAGEAL ADENOCARCINOMA PATIENTS

Background
Sentinel node navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy to tailor the extent of lymphadenectomy in patients with high-risk T1 esophageal adenocarcinoma (EAC). This is the first study to investigate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS.

Methods
In this prospective, multicenter pilot study, 10 patients underwent SNNS in two tertiary hospitals after radical endoscopic resection of a high-risk T1 EAC (i.e. deep submucosal invasion ≥500μm, poor differentiation, and/or lymphovascular invasion) without the clinical presence of lymph node or distant metastases (i.e. cN0M0). A hybrid tracer of technetium-99m nanocolloid and indocyanine green (^99mTc-ICG-nanocolloid) was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During thoracoscopy and laparoscopy, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection and subsequently resected (Figure 1). Endpoints were surgical morbidity, incidence of gastroesophageal functional disorders, rate of detectable SNs, and number of resected (tumor-positive) SNs per patient.

Results
Localization and dissection of SNs was feasible in all patients (10 male, median age 69), with a median of 3 SNs (range 1-7) on preoperative imaging and a median of 3 SNs (range 1-6) during surgery. The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs could not be identified due to a lack of ICG fluorescence. In four patients (40%), additional peritumoral SNs were resected after fluorescence-based detection. These SNs were not detected on preoperative imaging or intraoperatively with the laparoscopic gammaprobe as a result of the high background radioactivity of the injection site. Total procedure time was median 125 minutes (range 46-213), and patients were hospitalized for a median of 2 days (range 1-3). One patient (10%) experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional disorders. In two patients (20%), a metastasis was found in one of the resected SNs. Both patients are undergoing strict endoscopic and radiologic follow-up, which was determined in a multidisciplinary meeting based on patient’s older age (n=1) and patient's choice in combination with micrometastasis (n=1).

Conclusion
SNNS with ^99mTc-ICG-nanocolloid appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC who underwent a prior radical endoscopic resection. The exact position of this new strategy in the treatment algorithm for high-risk T1 esophageal cancer needs to be studied in future research with long-term follow-up.