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Autologous lymph node transplantation as therapy for breast cancer related lymphedema

The lymphatic circulation is disrupted frequently when lymph nodes are removed as part of cancer diagnosis and therapy. Unfortunately, the development of post-surgical lymphedema in these patients is not uncommon. While the stimulation of lymphangiogenesis with molecular therapeutic agents has received considerable attention, there is reason to believe that the re-establishment of “normal” fluid dynamics after tissue injury involves more than the simple regeneration of the lymphatics.

The loss of lymph nodes may have a much more negative impact on tissue-fluid balance than has been considered in the past. Available evidence suggests that the absorption of protein-free water into the capillaries of the nodes has an important role in the regulation of pressure and volume in downstream anatomical elements of the lymphatic system. The autologous transplantation of lymph nodes into the surgical resection site could facilitate the restoration of normal lymph transport in the affected limb.

We believe that it is the absence of the lymph nodes after excision for cancer that shifts the balance toward a predisposition for lymphedema, not necessarily an inability to regenerate new lymphatic vessels.

We hypothesize that the autologous transplantation of a lymph node into the excision site will improve tissue drainage compared to treatment with selected lymphangiogenic molecular agents alone or no treatment at all.

Our primary objective is to test whether lymph node transplantation improves lymph transport in a sheep node excision model. We are also investigating whether VEGF-C/Ang-2 administration via a novel implantable gel will enhance lymph transport parameters with or without autologous node transplantion.

Current therapeutic measures are applied to patients with entrenched edema and the outcome is often unsatisfactory. In the case of breast cancer-related post-surgical lymphedema, the timeline of the disorder can be linked to the removal of lymph nodes. Therefore, it is likely that a higher success rate may be achieved with treatment started early (lymph node transplantation) since the chronic sequelae of events leading to lymphedema might be prevented.