Current Status of the Management for Lymphedema in Asian Countries

[IS-2] Japanese epidemiological survey of primary lymphedema and clinical trial by gene therapy to overcome.

^〇Prof. Yukihiro Saito, Prof. Tadahiro Sasajima (Asahikawa Medical University, Asahikawa, Japan)

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Therapeutic options for management of lymphedema are limited. Furthermore, the epidemiological information about primary lymphedema is not enough at present. We performed the epidemiological survey of primary lymphedema in Japan. 1, In Japan, there are about 3600 patients of primary lymphedema, and 71% are female, 29% are male. 2, Average of patients age is 50.97, and edema appeared at 20~30 year of age in many patients. 3, The edema appeared at left side(56%) lower limb(88%). Many patients were classified into early phase(before stage 2) of ISL clinical stage. 4, Ultrasonography was performed on 51% patients, but assessment evidences were not sufficient almost all patients. 5, Main treatment for primary lymphedema was the combined physical therapy(ex. compression, manual lymph drainage), but the efficacy was not enough on the half patients.
We have previously investigated and reported the lymphangiogenic potency of HGF. Immunofluorescent analysis of lymphatic endothelial cells(LEC) was positive for the HGF receptor, c-Met. The treatment of LEC with human recombinant HGF or gene transfer of human HGF plasmid DNA resulted in a dose-dependent increase in cell growth and migration as well as increased activity of ERK and Akt significantly. Next, we tried to investigate the therapeutic efficacy of HGF gene transfer in vivo. Weekly HGF gene transfer in a rat lymphedema model intramuscularly resulted in a decrease in thickness or volume of lymphedema significantly. Serial lymphangiography by the fluorescent lymphography system revealed progressive extension of neo-lymphvascularization in HGF-treated animals. These data demonstrate that expression of HGF via plasmid transfer improves lymphedema via promotion of lymphangiogenesis. Now clinical trial involving lymphedema patients is going and we expect to observe successful therapeutic lymphangiogenesis management by HGF gene therapy.