Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, 1450 Biggy St. NRT6501, Mail Code 9601, Los Angeles, CA, 90033, USA.
Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs.Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling.
Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo.
Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis.
Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.
Associate Professor, Godoy Clinic, Paulista University, São Jose do Rio Preto, Brazil.
Thermotherapy has been indicated by some researchers as a treatment for lymphedema. A study comparing temperatures demonstrated that a temperature of 40°C significantly increased the transportation of lymph compared to other temperatures assessed. The aim of this study was to evaluate the possible benefits of mechanical lymph drainage accompanied with heat in the treatment of lymphedema of the lower limbs.
In a cross-over randomized study, the effect of heat on lymph drainage was evaluated in the treatment of leglymphedema. The study, performed in the Godoy Clinic in São Jose do Rio Preto, Brazil, involved seven patients (two males and five females) with leg lymphedema. The patients' ages ranged from 18 to 79 years old with a mean of 48.5 years. The subjects underwent a total of 38 assessments including 19 evaluations of mechanical lymph drainage alone and 19 combined with thermotherapy. Heat was applied using an electric blanket which was wrapped around the legs of the patients. The volume of legs was evaluated by water plethysmography before and after treatment sessions. The paired t-test was used for statistical analysis with an alpha error of p = 0.05 being considered as acceptable.
No statistically significant differences were evidenced between mechanical lymph drainage alone and lymph drainage combined with thermotherapy.
There was no obvious synergic effect in the immediate post-treatment period when heat was combined with mechanical lymph drainage in the treatment of lymphedema.
Dermatovenereology Department, Charles University 2nd Medical School and Bulovka Hospital, Prague, Czech Republic.
The basic principle of the management of lymphedema is so called complex decongestive physical therapy. This therapy is divided into two phases: (i) edema reduction phase - an initial intensive treatment phase aiming for limb volume reduction; and (ii) maintenance phase - following long-term phase to sustain a manageable limb volume. The first phase consists of a number of physical therapeutic approaches which are: manual lymph drainage, pneumatic pump drainage, low-stretch bandaging, exercises, and skin care. Long-term maintenance phase consists of self-lymph drainage, low-stretch bandaging, or compressive garments, and sometimes when indicated pneumatic pump drainage, exercises, and skin care.