Tenri Medical Bulletin
Online ISSN : 2187-2244
Print ISSN : 1344-1817
ISSN-L : 1344-1817
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Animal model of breast cancer-related arm lymphoedema
Hiroyasu Yamashiro
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2023 Volume 26 Issue 1 Pages 69-71

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Key Figure A.

Anatomy of the arm lymphatic vessels and axillary reverse mapping in a mouse model. Patent blue (dye) is injected intradermally in the palm of a nude mouse. Radial and ulnar lymph vessels and axillary lymph nodes are stained blue (⇒).

Key Figure B.

Arm lymphedema is observed following the ligation of the radial and ulnar lymphatic vessels followed by axillary lymph node dissection.

Background

Arm lymphoedema after breast cancer surgery is considered a major factor that impairs quality of life. Currently, treatment is mainly prevention by physiotherapy and there is no fundamental treatment. 1 Conventional animal models of lymphoedema are not suitable for studies of human breast cancer-related arm lymphoedema (BCRL) due to skin defects. Thus, a lymphoedema model without skin defects would contribute to research on lymphatic regeneration by cell transplantation therapy and the development of a treatment for lymphoedema.

Aim

Cell transplantation therapy may be effective as a treatment for BCRL. We aimed to develop a lymphoedema model without skin defects in which the efficacy of cell transplantation therapy could be verified.

Methods

This experiment was reviewed by the Committee on the Ethics of Animal Experiments (Faculty of Medicine, Kyoto University, Kyoto, Japan) and carried out in accordance with the Guidelines for Animal Experiments of the Faculty of Medicine, Kyoto University. We injected 0.02 ml of 5% patent blue subcutaneously into the palms of six-week-old nude mice (BALB/c, nu/nu) to identify lymph vessels (Key Figure A). 2 Subsequently, ulnar and radial lymph vessel ligation followed by axillary lymph node dissection were performed.

Results

Two mice were used in the present experiment. The diameter of the ball of the thumb was 1.837 mm on the affected side and 1.779 mm on the healthy side (t-test, P = 0.0024) on postoperative day 7 (Key Figure B); 1.891 mm and 1.827 mm (P = 0.024) on day 14; 1.823 mm and 1.774 mm (P = 0.021) on day 28; and 1. 787 mm and 1.808 mm (P = 0.567) on day 56, respectively, with a significant diameter increase on the affected side until postoperative day 28. There was no significant difference in diameter at the elbow. Histological examination showed a clear residual subcutaneous oedema even on postoperative day 56, when the diameter difference had disappeared (Figures 1a and b). No residual oedema was observed histologically on postoperative day 84.

Figure 1. Microscopic image. The affected side (a) shows marked oedema of the subcutaneous tissue (⇒) compared to the healthy side (b).

Conclusion

We have established an animal model of lymphoedema without skin defect that can be evaluated up to about 56 days postoperatively.

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