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Title: Microvascular and lymphatic function before and after breast cancer surgery and the long-term systemic effects of cancer treatment
Author: Cintolesi, Viviana
ISNI:       0000 0004 8502 8765
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2016
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Aims. The main aim was to investigate physiological, constitutional predisposition to breast cancer-related lymphoedema (BCRL) and to identify factors associated with lymphoedema onset. The hypotheses were (i) women destined to develop BCRL (pre-BCRLs) have constitutively higher capillary filtration rate and capacity (CFR, CFC) before treatment than women who do not develop BCRL (non-BCRLs); (II) pre-BCRLs have constitutively weaker lymphatic pump function (Ppump) in the ipsilateral arm than non-BCRLs; (III) pre-BCRLs have higher venous pressure (Pv) than non-BCRLs; (IV) lymphoedema (LO) patients have higher plasma VEGF levels and decreased ang-1 and adrenomedullin (ADM) levels than non-LO and healthy controls. Methods. Hypotheses I-III were tested prospectively before and after breast cancer treatment. Hypothesis IV was a pilot study in upper/lower limb lymphoedema patients. Arm CFR and CFC were measured by venous occlusion plethysmography; PpUmp by lymphatic congestion lymphoscintigraphy; Pvwith a pressure transducer and VEGFs, ang-1 and ADM plasma levels by ELISA. Principal results, (i) CFR and CFC did not differ between arms, or between pre-BCRL and non-BCRL groups, either pre or post-surgery (p>0.23, n=7 and 6 respectively) (ii) PpumP was not affected by surgery (p=0.79, n=20) but, unexpectedly, was 74% higher in pre-BCRLs than non-BCRLs (p=0.0007, n=10 and 16). (iii) Pv was not different between pre-BCRLs and non-BCRLs. (iv) VEGF-A, VEGFR-3 and ADM levels were elevated, whilst VEGFR-1 was lower in the LO group than in healthy controls, but not different from the non-LO group. Conclusions. The major conclusion was that women with high PpUmP values pre-operatively had increased risk of developing BCRL, indicating a predisposing, constitutive difference in lymphatic physiology. CFR and CFC values did not predict the development of BCRL, nor did Pv. Cancer treatment had an effect on circulating angiogenic factors. The relationship between VEGF-A and VEGFR-1 may play a significant role in the pathophysiology of cancer-related lymphoedema.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available