Clinical Research Directory

Biological Profile of Primary and Secondary Lymphedema: Inflammatory, Endothelial, Metabolic, Lymphatic, and Fibrotic Markers

This observational, cross-sectional study aims to characterize the biological profile of primary and secondary lymphedema by investigating five interconnected biological domains: Th2-related inflammation, endothelial activation, metabolic dysfunction, lymphatic biology, and tissue fibrosis. Lymphedema is traditionally considered a disorder of impaired lymphatic drainage resulting in the accumulation of interstitial fluid. However, increasing evidence suggests that its development and progression involve chronic inflammation, endothelial dysfunction, metabolic alterations, abnormal lymphatic signaling, adipose tissue accumulation, and progressive tissue fibrosis. While these mechanisms have been investigated predominantly in secondary lymphedema, the systemic biological profile of primary lymphedema remains insufficiently characterized. The study will include approximately 90 participants aged 18-45 years: 30 participants with primary lymphedema, 30 participants with secondary lymphedema, and 30 healthy control participants matched by age and sex. Each participant will attend one study visit lasting approximately 45-60 minutes. Clinical assessment will include medical history, demographic characteristics, blood pressure, body measurements, assessment of lymphedema location and clinical stage, pitting edema, Stemmer sign, skin changes, limb volume measurement by perometry, and assessment of tissue firmness. Venous blood samples will be collected to assess routine laboratory parameters and a panel of inflammatory, endothelial, metabolic, lymphatic, and fibrotic biomarkers. A standardized skin swab will also be collected for exploratory skin microbiome analysis. For the primary analysis, one representative marker will be selected in advance for each of the five biological domains: interleukin-13 (IL-13) for Th2-related inflammatory activity, soluble vascular cell adhesion molecule-1 (sVCAM-1) for endothelial activation, HOMA-IR for metabolic dysfunction, vascular endothelial growth factor C (VEGF-C) for lymphatic biology, and transforming growth factor beta 1 (TGF-β1) for tissue fibrosis. These five variables will constitute the co-primary outcomes. Secondary analyses will evaluate additional biomarkers within each biological domain and their associations with clinical severity, including lymphedema stage, limb volume, pitting edema, Stemmer sign, and skin fibrosis. The study will also investigate relationships between the different biological domains and assess differences between primary and secondary lymphedema. Exploratory analyses will characterize the skin microbiome of affected and standardized comparison sites and investigate associations between microbiome composition, clinical disease characteristics, and systemic biomarkers. In participants with primary lymphedema without a previously established genetic diagnosis, selected genetic variants associated with primary lymphedema will also be investigated. The study will provide a comprehensive assessment of biological alterations associated with lymphedema and may help clarify differences between primary and secondary disease. The findings may contribute to a better understanding of lymphedema as a complex biological and tissue disorder and provide a basis for future studies of more targeted diagnostic and therapeutic approaches.

Late Side-effects After Cervical Cancer Treatment - Prevention and Treatment

Late side-effects following gynecological cancer are predominantly symptoms from the pelvic region originating from the bowels, urinary tract, lymphatic system, genitals and musculoskeletal system. Pelvic floor dysfunctions such as urinary- and anal incontinence, pelvic organ prolapse, vaginal stenosis as well as compromised sexual function and dyspareunia appear to be highly prevalent. The incidence of gynecological cancer in Norway was 1700 in 2020 and the survival rate in Norway is among the highest in the world. Most women with cervical cancers are treated with curative intension and life expectancy at 5 years after diagnosis is \>80%. A negative impact of pelvic floor disorders on psychosocial well-being and quality of life are seen in survivors of gynecological cancer, and in cancer survivors this is found to be directly linked with patients regaining continence. Pelvic floor muscle training has few or no side effects, and is acknowledged as first line treatment for all types of urinary incontinence in women. Even though less studied, there is evidence to support pelvic floor muscle training as a safe intervention to reduce symptoms of anal incontinence and improve sexual function. A recent comparative cross-sectional study found that survivors of gynecological cancer with dyspareunia had higher stiffness and lower flexibility, coordination and endurance of the pelvic floor muscles compared to women with a history of total hysterectomy but no pelvic pain. These findings suggest a possible role for pelvic floor muscle training in the prevention and treatment of pelvic floor disorders after gynecological cancer. However, the overall quality of evidence for strengthening the pelvic floor muscles to reduce symptoms of pelvic floor dysfunctions after treatment of gynecological cancer is low. This study aims to assess the feasibility of a digital pelvic floor rehabilitation programme led by an experienced pelvic floor physiotherapist. Study subjects are women treated for cervical cancer within the past 5 years, and all included participants will receive the intervention due to the feasibility design. Participants will be assessed clinically at baseline and endpoint, partly to ensure proper pelvic floor muscle contraction. The digital intervention ensures residents in rural areas equal access to specialized pelvic floor rehabilitation.

Lymphaticovenous Anastomosis as Treatment for Lymphedema

The primary aim of this study is to investigate and test whether the use of combined indocyanine green (ICG) lymphography and ultra high frequency ultrasonography can correctly identify lymphatic vessels and venoles in close proximity to each other, for identification prior to lymphovenous anastomosis (LVA) surgery.