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Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the affected area. It can be an inherited condition (primary lymphedema) or occurs after cancer surgery and lymph node removal (secondary lymphedema). It causes a significant morbidity and is a common disabling disease affecting more than 200 million people worldwide, however there is no curative treatment for primary or secondary lymphedema.
Primary lymphedema is an inherited condition whereas secondary lymphedema develops after cancer treatments. Despite common phenotype, a molecular and histological comparison of these two pathologies has never been performed. Primary lymphedema is associated with heterozygous inactivating mutations of the gene encoding vascular endothelial growth factor C and D receptor (VEGFR-3). Primary lymphedema is rare, affecting 1 in 100,000 individuals. Secondary lymphedema is the most common cause of the disease and affects more than 200 million people worldwide.
Secondary lymphedema occurs months, sometimes years after cancer surgery suggesting that lymphedema is not only a side effect of the surgery, but involves modifications of the lymphatic architecture as well as its microenvironment, in particular adipose tissue that accumulates in the limb.
There is no cure for lymphedema because of the lack of identified therapeutic strategies able to restore collecting lymphatic draining function in the arm or in the leg. The goal will be to establish if these pathologies which possess a common denomination exhibit a similar gene expression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| primary lymphoedema | Experimental | patients with primary lymphoedema |
|
| secondary lymphoedema | Experimental | patients with secondary lymphoedema |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Micro-biopsies | Procedure | Two micro-biopsies of limb tissue will be carried out, one on the lymphedema and one in the upper limb not affected. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of RNA transcripts between lymphoedema limb and healthy limb | The gene expression profile of primary and secondary lymphedema will be determined by high-throughput RNA sequencing (RNAseq) or next-generation sequencing (NGS). It is a molecular methodology that allows the rapid sequencing of thousands to millions of RNA molecules simultaneously, determining the unique and specific order of nucleic acid bases. It is a random sequencing of the whole transcriptome which is used to identify and quantify the RNA resulting from the transcription of the genome at a given time. | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| LYVE-1 expression in primary and secondary lymphedema by immuno-histology | LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) will be determined from immunodetection and staining performed on paraffin sections of lymphedema tissue in comparison with healthy tissue | Day 1 |
| Podoplanin expression in primary and secondary lymphedema by immuno-histology |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julie MALLOIZEL-DELAUNAY, MD | Contact | +33 (0)5 61 32 30 33 | malloizel-delaunay.j@chu-toulouse.fr | |
| Charline DAGUZAN | Contact | +33 (0)5 61 77 84 99 | daguzan.c@chu-toulouse.fr |
| Name | Affiliation | Role |
|---|---|---|
| Julie Malloizel-Delaunay, MD | University Hospital, Toulouse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toulouse Hospital | Recruiting | Toulouse | France |
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| ID | Term |
|---|---|
| D008209 | Lymphedema |
| ID | Term |
|---|---|
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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cross-sectional sample of patients with primary or secondary lymphoedema.
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Podoplanin expression will be determined from immunodetection and staining performed on paraffin sections of lymphedema tissue in comparison with healthy tissue |
| Day 1 |
| Chromatography analysis of Lipids in adipose tissues from primary and secondary lymphoedema | To describe lipid profile in adipose tissues from primary and secondary lymphoedema, in comparison to the healthy limb by chromatography analysis expressed in pg lipid/mg protein. | Day 1 |