Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema.

Background And Aims: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood.

Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.

Background: Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function.

Lymphatic dysfunction, not aplasia, underlies Milroy disease.

Objective: Milroy disease is an inherited autosomal dominant lymphoedema caused by mutations in the gene for vascular endothelial growth factor receptor-3 (VEGFR-3, also known as FLT4). The phenotype has to date been ascribed to lymphatic aplasia. We further investigated the structural and functional defects underlying the phenotype in humans.

Recent advances in breast cancer-related lymphedema of the arm: lymphatic pump failure and predisposing factors.

Axillary surgery for breast cancer may be followed, months to years later, by chronic arm lymphedema. A simple 'stopcock' mechanism (reduced lymph drainage from the entire limb through surviving lymphatics) does not explain many clinical aspects, including the delayed onset and selective sparing of some regions, e.g.

Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb.

Background: Mutations in the FOXC2 gene cause lymphedema distichiasis, an inherited primary lymphedema in which a significant number of patients have varicose veins. Because lymphedema distichiasis is believed to be caused by lymphatic valve failure (reflux), and FOXC2 is highly expressed on venous valves in mouse embryos, we tested the hypothesis that FOXC2 mutations may be linked to venous valve failure and reflux.

Methods And Results: The venous system of the leg was investigated with Duplex ultrasound.

A quantitative lymphoscintigraphic evaluation of lymphatic function in the swollen hands of women with lymphoedema following breast cancer treatment.

In BCRL (breast cancer-related lymphoedema), arm swelling is unevenly distributed and some regions are partly or entirely spared. In particular, the hand may or not be swollen, but when involved functional impairment can be substantial. We have found previously that, when the ipsilateral hand is spared of swelling (in a limb with swelling proximal to the hand), the local lymph drainage rate constant (k) is at least as high as in the contralateral hand, contrary to the traditional 'stopcock' concept of reduced lymph drainage from the whole limb.

Lymphoedema-distichiasis and FOXC2: unreported mutations, de novo mutation estimate, families without coding mutations.

Lymphoedema-distichiasis (LD) is a syndromic form of primary lymphoedema, where mutations in the gene for the developmental transcription factor FOXC2 have been shown to be causative. The disorder has been considered very rare, but our group has now ascertained 34 families and 11 sporadic cases in the UK. Two families with LD have no mutation in the coding region of FOXC2, although both are consistent with linkage to the FOXC2 locus.

Regional distribution of epifascial swelling and epifascial lymph drainage rate constants in breast cancer-related lymphedema.

Background: The view that breast cancer-related lymphedema (BCRL) is a simple, direct mechanical result of axillary lymphatic obstruction ('stopcock' mechanism) appears incomplete, because parts of the swollen limb (e.g., hand) can remain nonswollen.

Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm that sometimes follows breast cancer treatment. Clinically, both skin and subcutis are swollen. Edema is considered to be predominantly subcutaneous and of an even distribution.

Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis.

Lymphatic vessels are essential for the removal of interstitial fluid and prevention of tissue edema. Lymphatic capillaries lack associated mural cells, and collecting lymphatic vessels have valves, which prevent lymph backflow. In lymphedema-distichiasis (LD), lymphatic vessel function fails because of mutations affecting the forkhead transcription factor FOXC2.

Expansion of microvascular bed and increased solute flux in human Basal cell carcinoma in vivo, measured by fluorescein video angiography.

Human basal cell carcinoma (BCC) offers a unique opportunity to assess directly the microvascular abnormalities in a human cancer in vivo. Our objectives were to assess angiogenesis, perfusion, and changes in small solute exchange kinetics. The microcirculation of BCC and a normal (control) skin site was studied in 15 patients by laser Doppler fluximetry and videoangiography after rapid i.