SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.

INTRODUCTION: Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema. METHODS AND ANALYSIS: A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased. ETHICS AND DISSEMINATION: The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT05064176.

Evaluation of safety and performance of a new prototype self-expandable nitinol venous stent in an ovine model.

Objective: Our study was a prospective in vivo study performed on an animal model to evaluate the safety and performance of a novel venous stent designed specifically for venous applications. Methods: The novel stents were implanted in the inferior vena cava of nine sheep. The stents were deployed with different distances between the closed cell rings to test for if the segments might migrate after being deployed at maximal distance. Three different total lengths were 9, 11, and 13 cm. After 1, 3, and 6 months, vascular injury, thrombus, neointima coverage, and stent migration were evaluated through computed tomography venography and histopathology. Imaging, histology, and integration data were analyzed for each group. Results: All stents were deployed successfully, and all sheep survived until the time of harvesting. In all cases, the native blood vessel sections were intact. The segmented stent parts showed a differently pronounced tissue coverage, depending on the duration of the implantation. Conclusions: The new nitinol stent is safe and feasible to implant in the venous system with a rapid surface coverage. Alteration of stent length did not affect the development of neointimal formation and did not cause migration.

Early Disturbance of Lymphatic Transport as a Risk Factor for the Development of Breast-Cancer-Related Lymphedema.

INTRODUCTION: Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., dermal backflow) before the lymphedema is clinically visible. The main objective of this study is to investigate whether this early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of BCRL. METHODOLOGY: All patients scheduled for unilateral breast cancer surgery with axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the volume difference between both arms and hands (through circumference measurements and water displacement). Clinical BCRL was defined as a ≥5% increase in relative arm volume difference compared to the baseline value. Variables related to (1) the disturbance of lymphatic transport (through lymphofluoroscopy), (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were collected. RESULTS: We included data of 118 patients in the present study. Thirty-eight patients (39.8%) developed BCRL. Early disturbance of lymphatic transport was identified as a risk factor for the development of clinical BCRL (HR 2.808). Breast-cancer- and treatment-related variables such as axillary lymph node dissection (ALND) (HR 15.127), tumor stage (HR 1.745), mastectomy (HR 0.186), number of positive lymph nodes (HR 1.121), number of removed lymph nodes (HR 1.055), radiotherapy of the axilla (HR 2.715), adjuvant taxanes (HR 3.220) and postsurgical complications (HR 2.590) were identified as significant risk factors for the development of BCRL. In the multivariate analysis, age and ALND were withheld as independent risk factors for the development of BCRL. CONCLUSION: Lymphofluoroscopy can identify an early disturbance of lymphatic transport after breast cancer treatment. Patients with an early disturbance of lymphatic transport are considered to be a high-risk group for the development of BCRL. This study also confirms that age and ALND are predictors for the development of BCRL. Therefore, a surveillance program of these patients with lymphofluoroscopy could be useful to identify lymphedema in subclinical stages.

A prospective multicenter randomized clinical trial comparing endovenous laser ablation, using a 1470 nm diode laser in combination with a Tulip-TipTM fiber versus radiofrequency (Closure FAST™ VNUS®), in the treatment of primary varicose veins.

BACKGROUND: The treatment of chronic venous disease, has largely shifted from high ligation and stripping to endovenous thermal ablation (EVTA) techniques, because of its comparable efficacy and lack of invasiveness. This clinical trial aimed to compare the efficacy of two thermal ablation techniques, endovenous laser ablation (EVLA) 1470-nm with Tulip-TipTM fiber and radiofrequency ablation (RFA) ClosureFastTM using a non-inferiority design for occlusion rate (primary outcome). METHODS: A prospective multicenter randomized clinical trial randomized 280 patients for the treatment of great saphenous vein (GSV) reflux. Primary outcome was the GSV occlusion rate, secondary outcome factors were the possible side-effects of the treatment such as pain, ecchymosis, quality of Life (CIVIQ-20), revised Venous Clinical Severity Score (r-VCSS). One-year follow-up period. RESULTS: The total occlusion rates at one year follow-up were 96.4% and 94.5% in the EVLA and RFA groups respectively (P=0.15). Regarding secondary outcomes, such as postoperative CIVIQ-20, r-VCSS, analgesia, absenteeism, there was no significant difference between both treatment groups. CONCLUSIONS: RFA and EVLA, using a 1470 nm laser with Tulip-TipTM fiber, of the GSV results in equal occlusion rates at one year, with comparable postoperative pain and improved quality of life.

Relation Between Early Disturbance of lymphatic transport Visualized With Lymphofluoroscopy and Other Clinical Assessment Methods in Patients With Breast Cancer.

INTRODUCTION: Lymphedema of the upper extremity is one of the most feared complications following breast cancer treatment. Lymphofluoroscopy is a sensitive instrument for detection of lymphedema and visualization of superficial lymphatic transport, thus suitable for early detection. Early detection of lymphedema is important as it can prevent lymphedema to progress into more severe stages and minimalize impact on quality of life and medical costs. OBJECTIVE: To determine agreement between the presence of early disturbance of the lymphatic transport and outcome of clinical measurement tools evaluating the development of lymphedema. METHODS: A prospective study was conducted in 128 breast cancer patients scheduled for breast cancer surgery. Patients were evaluated before surgery and 1, 3-, 6-, 9-, and 12-months' post-surgery. Cohen's Kappa was used to determine agreement between presence of early disturbance in lymphatic transport and presence of pitting/increased skinfold thickness/increased Percentage Water Content ratio (PWC)/increased arm-hand volume (circumference measures and water displacement). RESULTS: For pitting status (Kappa 0.23), for skinfold thickness (Kappa 0.29) and the PWC ratio (Kappa 0.21) a minimal agreement was found. The circumference measurement had a minimal agreement for 5% volume difference (Kappa 0.22) and no agreement for 3% volume difference (Kappa 0.19). Sensitivity was weak for all clinical assessments. The specificity was excellent for pitting status, skinfold thickness, PWC ratio, and for 5% volume difference. For 3% a high specificity was found. CONCLUSION: The clinical tools assessed in this study were not able to predict an early disturbance of the lymphatic transport seen on lymphofluoroscopy.

Impact of a compression garment, on top of the usual care, in patients with breast cancer with early disturbance of the lymphatic transport: protocol of a randomised controlled trial.

INTRODUCTION: Breast cancer-related lymphoedema (BCRL) is a common phenomenon. When lymphoedema is diagnosed late, options for treatment are diminished. Therefore, early diagnosis and treatment are very important to alter the potential deleterious evolution. Lymphofluoroscopy visualises the superficial lymphatic architecture in detail, giving the opportunity to detect a disturbance in the lymphatic transport (ie, dermal backflow) before the lymphoedema is clinically visible.The main objective is to investigate if there is an additional effect of a compression garment on top of the usual care (ie, information and exercises) in patients with early disturbance of the lymphatic transport after breast cancer treatment. Development of clinical lymphoedema and/or deterioration of the dermal backflow visualised by lymphofluoroscopy is investigated. METHODOLOGY: All patients scheduled for breast cancer surgery with unilateral axillary lymph node dissection or sentinel node biopsy in the Multidisciplinary Breast Clinic of the University Hospitals Leuven are being considered. Patients are assessed before surgery and at 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. At each visit, a clinical assessment is performed determining the volume difference between both arms and hands (through circumference measurements and water displacement), the water content, the extracellular fluid, the pitting status and the skinfold thickness. Quality of life questionnaires are filled in. At each visit, a lymphofluoroscopy is performed as well. When a disturbance of the lymphatic transport is seen on lymphofluoroscopy, without the presence of clinical lymphoedema, the patient is randomised in either a control group receiving usual care or a preventive treatment group receiving usual care and a compression garment (whether or not combined with a glove). ETHICS AND DISSEMINATION: The trial is conducted in compliance with the principles of the Declaration of Helsinki (2008), the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements. This protocol has been approved by the Ethical Committee of the University Hospitals Leuven. Results will be disseminated by peer-reviewed scientific journals and presentation at international congresses. TRIAL REGISTRATION NUMBER: NCT03210311 CONCLUSION: The investigators hypothesise that development of clinical BCRL can be prevented and/or the dermal backflow can be stabilised or improved, if a preventive treatment with compression garment is started in the early phase of disturbance.

The influence of gender on patency rates after iliac artery stenting.

OBJECTIVE: The purpose of this study was to investigate the influence of gender on the long-term outcome after iliac artery stenting and to assess gender-specific differences of the influence of risk factors on treatment success and patency rates. METHODS: Between January 2000 and December 2006, 404 percutaneous transluminal angioplasties with primary stent deployment for symptomatic iliac artery occlusive disease were performed at our center. These included 128 interventions in women and 276 interventions in men. RESULTS: Whereas average age was significantly higher (65.9 ± 12.9 years; P = .007) and arterial hypertension more frequent (60.9% vs 49.3%; P = .032) in women, hyperuricemia (7.0% vs 14.1%; P = .047) and a positive smoking status (61.7% vs 74.3%; P = .014) were more frequently observed in men. Fontaine stage was more advanced (stages III and IV) in women than in men (P = .028; P < .001). Technical success was 97.7% in women and 99.3% in men. Overall complication rate was higher in women compared with men (P = .002), mostly caused by access site hematomas (4.7% vs 0.4%) and pseudoaneurysms (8.6% vs 2.5%). Patients were followed up for 45.0 ± 33.3 months. Restenosis developed in 16.8% of cases in women and in 14.6% of cases in men and was treated in 73.7% by an endovascular approach. Primary patency rates at 1, 3, 5, and 7 years were 90.3%, 77.2%, 60.2%, and 46.4% in women and 89.9%, 71.5%, 63.6%, and 59.7% in men, respectively (P = .524; log-rank, .406). Secondary patency rates were 97.2%, 91%, 81.5%, and 70.3% in women and 97.1%, 89.1%, 82.6%, and 78% in men, respectively (P = .959; log-rank, .003). Multivariate analysis identified lower age as the only independent risk factor for recurrent disease in both groups. Age-defined subgroup analysis showed a restenosis/reocclusion rate of 23.9% in men and 22.1% in women older than 63.5 years (P = .861) but 32.1% in men and 49.1% in women younger than that (P = .034). CONCLUSIONS: Our data suggest that although women are older and present with a more advanced stage of peripheral arterial occlusive disease, endovascular therapy is equally effective irrespective of gender. Surprisingly, the subgroup of young female patients had a specifically poor outcome.