RESUMEN
Background: Vascular endothelial growth factors (VEGF) and inflammatory cytokines are indicated to be implicated in lymphedema development. We aimed to describe changes in microvascular filtration and VEGFs in a patient cohort vulnerable to breast cancer-related lymphedema development correlated with data on lymphatic morphology and function. Methods: Consecutive node-positive breast cancer patients operated in the axilla and evaluated approximately 12 months after adjuvant locoregional radiotherapy were studied. Capillary filtration rate (CFR) and isovolumetric pressure of the arms were measured by strain gauge plethysmography, and 13 blood proteins were quantified by Luminex and Elisa technology in 28 patients and 18 healthy controls. Results: The CFR was reduced in both arms from baseline to 1-year follow-up (ipsilateral: P = 0.016 and contralateral: P = 0.001). When stratifying lymphatic complications (morphologic abnormalities and/or breast cancer-related lymphedema), CFR reached a lower steady-state in the arms with normal morphology (I:P = 0.013 and C:P = 0.013) whereas the ipsilateral arm with lymphatic complications remained unchanged (P = 0.457). In patients with lymphatic abnormal vessels, the levels of VEGF-D were 86% higher than in patients with normal lymphatic vessels (P = 0.042), whereas levels of VEGFR-3 were 64% higher (P = 0.016). Conclusions: Through one year of follow-up, CFR did not decrease in the lymphatic complicated treated arms as observed in noncomplicated treated arms. The patients had increased levels of VEGF-D and VEGFR-3. This correlation suggests that VEGF plays a role in the appearance of subcutaneous abnormal lymphatic vessels in the treated arms, which also maintain a fluid filtration/drainage mismatch up to one year after breast cancer treatment.
RESUMEN
In patients with breast cancer-related lymphedema, distinct lymphatic patterns and changed lymphatic contractile function have been described, but it is unknown how these characteristics change over time and to what extent they appear before clinical edema is detectable. Recently, we described the lymphatic morphology and function in a cohort of breast cancer patients shortly after radiation therapy (RT). In the current study, we investigate lymphatic function and morphology in the same cohort after 1 year of follow-up. Methods: The study population consisted of 28 breast cancer patients investigated 12 months after adjuvant locoregional RT. Lymphatic contraction frequency (CF), propulsion velocity, and the morphology of lymphatic vessels in the upper extremities were described in vivo using near-infrared fluorescence imaging. Lymphatic stress test was performed using hyperthermia. Results: At 1 year after RT, (n = 28) 46% of the patients presented with lymphatic morphological abnormalities with a degree of dermal backflow and 21% had developed clinical breast cancer-related lymphedema. In the ipsilateral arm, CF was 23% lower than in the contralateral arm (P = 0.04). Since primary examination, CF in the ipsilateral arm decreased by 40% (P = 0.03), whereas no change was observed in the contralateral arm. During hyperthermia, the ipsilateral arms with lymphatic complications were not able to increase CF as the remaining subgroups. Conclusions: Lymphatic function in the ipsilateral arm deteriorated over time after adjuvant breast cancer therapy. Furthermore, the presence of abnormal torturous lymphatic vessels in asymptomatic arms appeared to be associated with weak lymphatic reserve pumping capacity.
RESUMEN
BACKGROUND: Lymphedema is a highly feared complication of breast cancer treatment, but the underlying complex mechanisms are still unknown. Thus, we investigated the lymphatic morphology and contractility in the lymphatic vessels of arms of high-risk breast cancer patients treated for node-positive early breast cancer. METHODS: In this prospective cohort study 32 women treated for unilateral node-positive breast cancer were enrolled and studied 36 ± 23 days after loco-regional radiotherapy. Near-infrared fluorescence imaging was used to assess morphology and function of the superficial lymphatic vessels. Strain-gauge plethysmography was performed to evaluate the capillary filtration of fluid.Both arms were investigated, with the non-treated arm acting as control. The patients were questioned about the presence of lymphedema yearly and finally 574 ± 118 days after ended radiotherapy. RESULTS: Morphologically, 25% of the treated arms expressed lymphatic vessel abnormalities compared to the control arms (p = 0.0048). No difference in functional parameters (maximal pumping pressure, p = 0.20; contraction frequency, p = 0.63; contraction velocity, p = 0.55) was found between the treated and control arms. Patients who later developed lymphedema had a difference in velocity compared to those who did not develop lymphedema (p = 0.02). The capillary filtration rate was similar between the two arms (p = 0.18). CONCLUSIONS: Peripheral lymphatic vessels were morphologically changed in the ipsilateral arm in 25% of the patients and patients who later developed lymphedema showed an early increase in velocity. Other functional parameters and capillary filtration were unchanged in this early phase. These discrete changes might be early indicators of later development of lymphedema.