Knowledge about the mechanisms of regeneration of the lymphatic vasculature after surgical trauma is essential for the development of strategies for the prevention and therapy of lymphedema. However, little is known about the alterations of lymphatic flow directly after surgical trauma. We investigated lymphatic function in mice using near-infrared imaging for a period of 4 weeks after surgeries that mimic sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), by removal of the popliteal lymph node (LN) alone or together with the popliteal fat pad, respectively. SLNB-like surgery did not cause changes in lymphatic drainage in the majority of cases. In contrast, lymphatic drainage impairment shown by collecting vessel rupture, dermal backflow and rerouting of lymph flow via collateral vessels were observed after ALND-like surgery. All collateral vessels drained to the inguinal LN. These results indicate that less invasive surgery prevents lymphatic decompensation. They also reveal the development and maturation of collateral lymphatic vessels after extensive surgical trauma, which reroute the flow of lymph towards a different LN. These findings might be helpful for the development of strategies to prevent and/or treat post-surgical lymphedema.
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Axillary lymph node dissection
Sentinel lymph node biopsy
Manual lymphatic drainage
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We thank Jeannette Scholl and Carlos Ochoa for excellent technical assistance and help with animal experiments. KSB received a research fellowship from the German Research Foundation (DFG: BL 1136/1-1). This study was supported by Swiss National Science Foundation grant 31003A-130627, European Research Council grant LYVICAM, Oncosuisse, Krebsliga Zurich and the Leducq Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
The experiments were performed in accordance with animal protocols approved by the Kantonales Veterinäramt Zürich.
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Lymphatic imaging of collecting LVs and collateral vessels originating from the damaged area one week after surgery. Note the slower flow in the collateral vessel draining from the injured collecting vessel, which can be seen by a slower decrease of signal intensity in the collateral compared to collecting vessel during this imaging session. Note the dilated and constricted parts of the collateral vessels (MPEG 3798 kb)
NIR imaging of collecting LVs and collateral vessels 1 week after ALND-surgery. The lymph pulses from the ankle (lower right side of the video) towards the ingLN (not shown, because it is located on the ventral side of the leg). Gentle pulsing activity is noted in parts of the collateral vessels close to the inguinal LN around the hip (MPEG 5556 kb)
In the same leg as video 2 pulsing throughout the full length of the collateral vessels and the collecting LVs is detectable three weeks after ALND surgery (MPEG 6096 kb)
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Blum, K.S., Proulx, S.T., Luciani, P. et al. Dynamics of lymphatic regeneration and flow patterns after lymph node dissection. Breast Cancer Res Treat 139, 81–86 (2013). https://doi.org/10.1007/s10549-013-2537-7