A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema.

Abstract Objective Indocyanine green fluorescent lymphography may be useful in patients undergoing lymphatic surgery for secondary lymphedema. This clinical trial aimed to confirm whether indocyanine green fluorescent lymphography is useful for evaluating lymphedema, identifying lymphatic vessels suitable for anastomosis, and confirming patency of a lymphaticovenular anastomosis in patients with secondary lymphedema. Methods This phase III, multicenter, single-arm, open-label clinical trial (HAMAMATSU-ICG study) investigated the accuracy of lymphedema diagnosis via indocyanine green fluorescent lymphography compared with lymphoscintigraphy, the identification rate of lymphatic vessels at the incision site, and the efficacy for confirming patency of a lymphaticovenular anastomosis. The external diameter of the identified lymphatic vessels and the distance from the skin surface to the lymphatic vessels based on preoperative indocyanine green fluorescent lymphography were measured intraoperatively under surgical microscopy. Results When the clinical decision for surgical indication at each research site was made, the standard diagnosis of lymphedema was considered to be correct. In 26 upper extremities, a central judgment committee blinded to the clinical presentation confirmed the imaging diagnosis as accurate in 100.0% of cases, whether assessments were made via lymphoscintigraphy or indocyanine green lymphography. In contrast, in 88 lower extremities, the accuracy rates of diagnosis based on those made by the central judgment committee were 70.5% and 88.2% for lymphoscintigraphy and indocyanine green lymphography, respectively. The external diameter of the identified lymphatic vessels was significantly greater in the lower extremities than in the upper extremities (0.54 ± 0.21 mm vs. 0.42 ± 0.14 mm, p Conclusions Indocyanine green fluorescent lymphography may be useful for improving the management of patients with secondary lymphedema from the outpatient setting to the operating room.