Clinical Research Directory

Multimodal Ultrasound for Differentiating Lymphedema and Lipedema

The aim of this observational study is to evaluate the diagnostic value of multimodal ultrasonography in differentiating between lymphedema and lipedema. Differentiating these two chronic conditions based solely on clinical examination can be challenging due to overlapping symptoms. This study will utilize various non-invasive ultrasound techniques-including B-mode ultrasound, strain elastography, power Doppler, and quantitative ImageJ analysis-to compare tissue characteristics among patients with lymphedema, patients with lipedema, and healthy controls. The goal is to identify reliable, non-invasive imaging biomarkers that can facilitate early and accurate diagnosis, thereby optimizing patient management.

Use of Reconstructive Microsurgery for the Treatment of Lymphedema

Lymphedema is a chronic condition characterized by the accumulation of lymphatic fluid in tissues, frequently resulting from oncological treatments, trauma, or cancer. This condition causes significant functional impairment and severely impacts patients' quality of life, requiring complex and multidisciplinary therapeutic approaches. In recent years, reconstructive microsurgery has played an increasingly important role in lymphedema treatment due to high-precision technologies. The use of ultra-high magnification operating microscopes allows the visualization of sub-millimetric vascular structures, enabling lymphatic-venous anastomoses and lymph node transfers on extremely small vessels (0.3-0.5 mm). Additionally, advanced intraoperative imaging, such as indocyanine green fluorescence, allows real-time identification of lymphatic vessels and patency assessment, improving surgical accuracy and clinical outcomes. While recent experience shows high procedural success rates, a retrospective and systematic analysis of clinical data is necessary to structuredly evaluate functional outcomes. Therefore, this retrospective study aims to analyze the clinical experience gained to define the role of advanced microsurgical technologies in optimizing the therapeutic pathway for patients with lymphedema

Remotivation Process for Improving Adherence to Lymphedema Treatment Programs in Patients With Breast Cancer-Related Lymphedema

This trial studies how well the Remotivation Process in an occupational therapy program works in improving adherence to lymphedema treatment programs in patients with breast cancer-related lymphedema. Lymphedema treatment programs are well developed and effective, but adherence to these programs are an issue. The Remotivation Process is a series of techniques that helps guide discussions between occupational therapists and their patients based on their level of motivation. This study uses the Remotivation Process by gathering patients' thoughts about their experience with lymphedema and occupational therapy services to determine their motivation and learn about the barriers they face in order to improve adherence to these programs.

Efficacy of Complete Decongestive Therapy for Limb Lymphedema: Response Profile and Predictive Modeling

Background: Complete decongestive therapy (CDT) is the standard treatment for lymphedema, but response varies by localization and laterality. Data on segmental distribution of therapeutic response and predictors of response are limited. Objective: To evaluate changes in lymphedema indicators after intensive-phase CDT, compare therapeutic response profiles across clinical subgroups, and develop a predictive model of response. Methods: Retrospective observational cohort study of 111 patients with secondary lymphedema: unilateral upper extremity, unilateral lower extremity, bilateral lower extremity. Primary outcome: percentage reduction of excess indicator (PREI) for unilateral groups and relative reduction of sum of circumferences (ΣC) for bilateral group. Secondary outcomes: topographic response profile (7 anatomical points), proportion of clinical responders (≥10%), predictive factors, and predictive model. Expected results: Identification of topographic heterogeneity of response, determination of factors of CDT resistance (especially in bilateral lymphedema), development of a validated predictive model for therapy personalization.

Hypofractionated LocoRegional Radiotherapy in Breast Cancer

The primary objective of this study is to determine if hypofractionated RT delivered over 1 week to the breast or chest wall and regional nodes (26Gy in 5 daily fractions) following BCS or mastectomy, is non-inferior to conventional fractionation to the breast or chest wall and regional nodes delivered over 3 weeks (40Gy in 15 daily fractions) in patients with node-positive breast cancer.

A Global, Prospective, Real-World, Investigation of the Symani® Surgical System for Microsurgical Anastomosis

The objective of this clinical study is to evaluate the Symani System's safety and effectiveness for microsurgical anastomosis during free tissue transfer surgery and lymphatic surgery. The primary endpoints are: * Effectiveness: Clinical Success, defined as intraoperative anastomosis patency. * Safety: Freedom from device-related serious adverse events prior to discharge from the index hospitalization, as adjudicated by a Clinical Events Committee. Participants will receive treatment as standard of care and be asked to: * Allow the researchers to access and use their information. * If participants are undergoing a therapeutic lymphatic procedure, they will be asked to complete a questionnaire and undergo lymphedema volume assessments as part of the study. If participants are undergoing a prophylactic lymphatic procedure, they will only be asked to undergo limb volume assessments. * Participants will be asked to comply with the follow-up visits as outlined in the protocol.

Biorepository of Biomarkers for Optimization of Microvascular Treatment of Lymphedema

Researchers are collecting information, saliva, blood and tissue from subjects with lymphedema to store for future research.

Prediction Of Lymphedema In Patients With Inflammatory BreastCancer Using Preoperative Bioimpedance Measurements

To find out whether the BIA test can help identify participants with IBC who are at risk for developing lymphedema.

Lymphedema Prevention Through Immediate Lymphatic Reconstruction (LILY) Trial.

To learn if reconstruction of the lymphatic system at the time of axillary lymphadenectomy can reduce the risk of developing lymphedema.

Evaluation of Adherence to Rehabilitation: Autonomous and Guided, in the Observation and Treatment Response of Head and Neck Lymphedema in Neoplasms During Radiotherapy

Head and neck lymphedema is a common complication after treatment for head and neck cancer. It can cause swelling of the face and neck, discomfort, reduced neck and jaw mobility, swallowing difficulties, and a negative impact on quality of life. One usual treatment approach includes manual lymphatic drainage, exercises, skin care, and the use of a compression garment worn for several hours each day. However, wearing a compression garment for a long period may be difficult for patients because of discomfort, appearance, social constraints, or practical limitations, which may reduce adherence to treatment. The ARAGORN study aims to determine whether a more autonomous rehabilitation program, based on patient education, self-drainage, targeted exercises, and short-duration compression bandaging performed twice daily, leads to better treatment adherence than the usual recommended approach using prolonged compression garment wear. The main question of the study is whether patients receiving the autonomous, guided rehabilitation program are more likely to adhere to their prescribed lymphedema treatment over the radiotherapy period than patients receiving the usual recommended care. The study hypothesis is that a patient-centered, self-management approach may improve adherence by making treatment easier to integrate into daily life, while maintaining potential benefits on swelling, symptoms, function, and quality of life.

A Study Comparing Quality of Life in Patients With Lymphedema Who Undergo Surgical Treatment Versus Non-Surgical Management

This study is being done to see the long-term results for patients who choose to have surgery for lymphedema (with the vascularized lymph node transfer), compared to patients who choose not to have surgery.

The Effect of Resistance Exercise in Patients With Lower Limb Lymphedema (the LymphEx Study)

The aim of the study is to investigate the short-term (within 2 weeks) effects of resistance exercise with and without compression garments on lower limb lymphedema(LLL). Additionally, the study will explore the immediate response in LLL to resistance exercise (2 hours and 24 hours post-exercise). Participants will continously wear a circumfencential sensor at the calf (CIMON from Icompression) under a compression garment and an activity tracker (SENS Motion from SENS Innovation Aps) at the thigh for 3 periods (two with supervised exercise sessions of 2 weeks and one control period). Participants will attend supervised resistance exercise 2-3 times per week for 2 periods of 2 weeks (one with compression garment and one without). Assessments with the principal investigator will be scheduled before and after every 2 week period. Participants will keep a digital diary or diary in paper of their lymphedema related symptoms and experienced issues with the sensors or app.

PREVENT: PeRomEter Visualization to ENd Treatment-related Lymphedema

This research study is to learn about breast cancer patients' opinions about screening for lymphedema (a side effect of breast cancer treatment in which the arm can become heavy, painful, and/or swollen) and their satisfaction with the lymphedema screening program.

A Post-market, Real-world Experience: Expanding Access to Care by Incorporating the Symani® Surgical System and Enabling Surgeons

The objective of this study is to evaluate the Symani System's safety and effectiveness for microsurgical anastomosis during free tissue transfer surgery and lymphovenous anastomosis surgery. The primary endpoints are: * Effectiveness- Rate of intraoperative anastomosis patency at first attempt. * Safety- Freedom from device-related adverse events. Participants will receive treatment as standard of care and be asked to: * Allow the researchers to access and use their information. * If participants are undergoing a lymphedema procedure, they will be asked to undergo a questionnaire as part of the study. * Participants will be asked to comply with the follow-up visits and complete all study procedures/questionnaires as outlined in the protocol.

Systemic Therapy of Open-label Prophylactic Pravastatin or Pentoxifylline/Tocopherol Prevention of Lymphedema Advancing to Eventual Fibrosis: an Interventional Registry-embedded Bayesian Randomized Trial for Radiation Sequelae (STOP4-LATE-FIBROSE)

To learn if pentoxifylline and vitamin E or pravastatin can reduce radiation-induced lymphedema/fibrosis.

Effectiveness of a Tele-Rehabilitation-Based Exercise and Self-Lymphatic Drainage Program Supported by Self-Management for Breast Cancer-Related Lymphedema

A total of 64 women, aged between 20 and 65 years, diagnosed with stage I or II breast cancer-related lymphedema and not meeting the exclusion criteria, who registered at the outpatient clinics of the Department of Physical Medicine and Rehabilitation, Istanbul University Istanbul Medical Faculty, will be included in our thesis study, which is planned to be prospective, randomized, and single-blind. Participants will be informed verbally and in writing about the study's purpose, duration, and method of implementation, and written informed consent will be obtained. They will be asked to sign an "Informed Consent Form." Participant assessment and follow-up forms will be completed before and after treatment. Participants who meet the inclusion criteria will be numbered according to their order of admission and then randomly assigned to either the intervention group or the control group by a computer program. All participants will receive a face-to-face education session about breast cancer-related lymphedema, including exercise, self-lymphatic drainage, skin care, compression garment use, and self-management, together with an educational brochure. Participants in both groups will be asked to continue wearing their prescribed compression garments throughout the study. In addition to this education, the intervention group (G1) will join live Zoom sessions with the study physician three times a week for 8 weeks to perform the exercise and self-lymphatic drainage program under real-time supervision. Each session will include approximately 30 minutes of therapeutic exercises followed by 15 minutes of self-lymphatic drainage. The control group (G2) will receive the same exercise and self-lymphatic drainage program in brochure format, including written instructions and illustrations. Participants will be asked to perform the exercise and self-lymphatic drainage program at home three times a week for 8 weeks without live online supervision.

Gut Microbiota in Patients With Limb Lymphedema and Recurrent Lymphangitis

Lymphedema is a chronic and progressive disease of the lymphatic vessels which affects about 300 million people worldwide. Patients may experience recurrent soft tissue infection of the limb affected by lymphedema, in terms of erysipelas, lymphangitis or cellulitis. No previous study has ever investigated the possible role of the gut microbiota in the genesis of acute infectious/inflammatory episodes in these patients. Our hypothesis is that lymphedema patients with recurrent soft tissue infections are characterized by pro-inflammatory changes in the microbiota.

Testing for Increased Lipoproteins (a) [LP(a)] in Lymphedema Patients: Li-LY

Lymphedema is a chronic disease that causes lymph to accumulate in the interstitial tissue. The lymphatic network is involved in the metabolism of lipids and lipoproteins, and this accumulation leads to lipid deposits in the tissues involved. The level of lipoprotein(a) \[LP(a)\] has been shown to be a cardiovascular risk factor, which is partly genetically determined and influenced by certain factors (chronic renal failure, statin treatment, sporting activity or a diet low in saturated fatty acids...). Plasma levels of LP(a) lipoproteins (a) are linearly associated with an increased risk of myocardial infarction and carotid and femoral vascular stenosis. We currently manage patients with primary or secondary lymphedema, whatever the etiology, in the vascular medicine and explorations unit at Nice University Hospital. Those taking part in intensive inpatient decongestive therapy benefit from a blood test, in particular for lipids \[total cholesterol, triglycerides, HDL and LDL cholesterol, apolipoproteins A and B and Lp(a)\]. Our team observed an elevated Lp(a) level \>30 mg/dL in 10 of the 17 patients in whom we carried out this test (whether or not dyslipidemia existed, and whether or not it was known or treated). This is a very high prevalence compared with the general population, in whom an increased level is found in 25% of patients. In view of the impact of Lp(a) on cardiovascular risk and the involvement of the lymphatic system in lipoprotein metabolism, it seems essential to verify our preliminary results on a larger population. In this multicenter cross-sectional trial, we propose to perform Lp(a) lipoprotein assays in lymphedema patients to determine whether there is an increase in this marker in this pathological context. We will also study the concordance of this level with cardiovascular risk assessment scores such as SCORE2/SCORE2-OP and the coronary calcium score. We will look for factors influencing plasma LP(a) levels, both general factors suspected of playing a role and factors specific to lymphedema.

AVAST Anomalies Vasculaires Associées au Syndrome de Turner (Vascular Abnormalities Associated With Turner Syndrome)

Turner syndrome is a genetic condition, rare, due to the total or partial absence of one X chromosome, affecting 1/2500 newborn female. It combines almost constantly short stature and ovarian failure with infertility. Other anomalies are inconstant: morphological characteristics of varying intensity, associated malformations, and increased risk of acquired diseases ... The prognosis of patients reaching the Turner Syndrome is linked to cardiovascular complications (congenital heart disease, dilatation of the ascending aorta with risk of dissection or rupture of aneurysm), causing early mortality with reduction of life expectancy of at least 10 years. For these reasons, screening for heart disease and dilatation of the ascending aorta is established and is intended to prevent the complications associated with medical treatment and / or surgery to increase life expectancy and reduce the co-morbidities. On the vascular level, the recommendations other than those relating to the monitoring of the diameter of the ascending aorta include research of renal artery stenosis by doppler ultrasound if the patient is hypertensive and looking for lymphedema. However, other arterial lesions were described in the literature, outside of the aneurysm of the ascending aorta. These peripheral arterial lesions can also be life and / or functional prognosis of the patient. Ascending aorta dilation seems not to be exclusive in Turner syndrome. In addition, specific vascular lesions outside the affected artery are described: hepatic cirrhosis by vascular depletion, lymphedema and varicose veins. The prevalence of venous or lymphatic disease is unknown. A single-center review of 9 cases of patients followed at the University Hospital of Strasbourg showed the presence of vascular lesions discovered incidentally during assessments performed for reasons other than cardiovascular screening: cystic lymphangioma, internal carotid aneurysm, agenesis of the inferior vena cava, early varicose veins, embryonic cerebral artery, etc ... None of these patients showed any dilatation of the ascending aorta or heart disease. Peripheral vascular abnormalities in this patient group are exclusive. In this study, we seek to demonstrate that arterial disease in Turner syndrome involve the entire arterial territory and is not confined to the ascending aorta. Screening for arterial lesions should be performed on the entire arterial vascular tree and regularly in the course of time, especially as the presence of cardiovascular risk factors increases with the age of these patients. The venous and lymphatic vascular damage in the literature and in our series of cases in University Hospital of Strasbourg description should also lead to the detection of these lesions. These vascular complications can be alone responsible for the reduction in life expectancy or responsible for serious morbidity. Improved screening of associated vascular lesions is necessary to enable the best prevention of cardiovascular complications. It is also to establish the prevalence of vascular anomalies, whether arterial, venous or lymphatic, to better understand the disease and its management. By collecting systematically karyotype leading to diagnosis, it may be possible to make a link between the genetic defect and heart or vascular disease.

Investigation of the Effectiveness of Progressive Resistance Exercise Training in the Management of Lymphedema.

This study aims to investigate the effect of progressive resistance exercise training on the clinical findings and functional outcomes of lymphedema in individuals who develop upper extremity lymphedema after breast cancer treatment (surgery, chemotherapy and/or radiotherapy).

LYMPHA Procedure for the Prevention of Lymphedema After Axillary Lymphadenectomy

Lymphedema is a chronic, progressive, and debilitating condition that occurs with disruption or obstruction of the lymphatic system, which commonly occurs a result of breast cancer therapy. The purpose of this study is to determine if the use of a low risk lymphatic reconstruction procedure at the time of axillary lymph node dissection will reduce the risk of developing lymphedema. Additionally, to determine if this procedure improves objective outcomes of lymphedema and patient quality of life

Relationship Between Balance and Body Awareness in Lymphedema Patients

Lymphedema (LE) is a chronic condition caused by the accumulation of protein-rich fluid in the subcutaneous tissue as a result of insufficiency of the lymphatic system . Primary LE occurs due to an anomaly in the development of the lymphatic system, while secondary LE occurs as a result of subsequent damage to the lymph vessels or lymph nodes. The incidence of LE in the literature varies. It is thought that there are approximately 140-250 million patients with LE worldwide. While the incidence of LE is 1.4 in every 1000 people, primary LE accounts for one-fourth of this. Chronic inflammation, cellulitis, pain, fatigue, deformity, difficulty in movement, and difficulty in functional use of the affected extremity may occur due to untreated LE (5-6). Loss of joint mobility and developing asymmetry affect the individual's balance (7-9). To our knowledge, there are a limited number of studies evaluating lymphedema and balance (10-11). This study will evaluate individuals with unilateral edema in the lower extremity. We think that balance will be affected due to the increase in volume in the extremity, feeling the extremity heavy and feeling fullness. Body awareness is defined in physical therapy texts as a type of treatment aimed at awareness of how the body is used in terms of function, behavior and interaction with self-other (12-13). Body awareness includes attention directed to the body both in motion and motionless. It refers to awareness of both sensory inputs and motor control related to the integration of breath and movements, coordination and balance (14). Studies on body image in LE patients are also insufficient. As far as we can see, there is no study in the literature examining the relationship between balance and body awareness in lower extremity lymphedema patients with different lymphedema levels (mild, moderate, severe) according to objective assessment criteria in Turkish patients. In this study, our hypothesis is that balance and body awareness are more affected in patients with severe lymphedema compared to patients with mild and moderate lymphedema associated with secondary unilateral lower extremity lymphedema. Therefore, we aimed to compare female individuals with secondary unilateral lymphedema with healthy volunteer female individuals. Our study will include 28 female individuals with unilateral secondary lower extremity lymphedema who applied to Kayseri City Hospital, Physical Therapy and Rehabilitation Hospital between March 2023 and June 2023 and who meet the study criteria, and 28 healthy female individuals in the same age group. The sample group consisted of patients who had undergone lymphoscintigraphy in the past and were diagnosed with lymphedema as a result of scintigraphy and applied to Kayseri City Hospital, Physical Therapy and Rehabilitation Hospital for LE treatment. The "G\*Power 3.1" package program was used in the computer environment to evaluate the power and sample size of our study. As a result of the analysis, when the power is targeted as minimum 85% and the error amount is 0.05, the minimum sample size required to find a significant difference between the means has been determined as 28 individuals for each group (15). Individuals will be evaluated once. 1\. Maclellan RA, Couto RA, Sullivan JE, Grant FD, Slavin SA, Greene AK. Management of Primary and Secondary Lymphedema: Analysis of 225 Referrals to a Center. Ann Plast Surg. 2014; Aug;75(2):197-00. 2. Földi M, Földi E. Földi's textbook of lymphoLÖgy for physicians and lymphedema therapists (2nd ed.)Elsevier, Munich. 2006. 3. NLN Medical Advisory Committee. The diagnosis and treatment of lymphedema 2011. 4\. Rockson SG, Rivera KK. Estimating the population burden of lymphedema. Ann N Y Acad Sci. 2008;1131:147-54. 5. Andersen L, Hojris I, Erlandsen M, Andersen J. Treatment of breast-cancer-related lymphedema with or without manual lymphatic drainage--a randomized study. Acta Oncol. 2000;39(3):399-05. 6.Johansson K, Ingvar C, Albertsson M, Ekdahl C. Arm Lymphoedema, Shoulder Mobility and Muscle Strength after Breast Cancer Treatment ? A Prospective 2-year Study. Adv Physiother. 2001;3(2):55-66. 7\. Özkal Ö, Topuz S, Konan A, Kısmet K. Alt Ekstremite Yanık Yaralanması Olan Bireylerde Ağrı, Kinezyofobi, Denge Ve Fonksiyonellik Arasındaki İlişkinin İncelenmesi. Ankara Eğt. Arş. Hast. Derg. 2017;50(3):122-8. 8\. Truszczyńska A, Dobrzyńska M, Trzaskoma Z, Drzał-Grabiec J, Tarnowski A. Assessment of postural stability in patients with lumbar spine chronic disc disease. Acta of bioengineering and biomechanics. 2016;18(4):71-77. 9. Hassan B, Mockett S, Doherty M. Static postural sway, proprioception, and maximal voluntary quadriceps contraction in patients with knee osteoarthritis 68 and normal control subjects. Annals of the rheumatic diseases. 2011;60(6): 612-618. 10. Orhan C, et al. Meme Kanseri Tedavisiyle İlişkili Lenfödemi Olan Hastalarda Lenfödem Şiddetinin Yaşam Kalitesi, Üst Ekstremite Fonksiyon

Reversing External-beam Radiotherapy-associated Fibrosis Syndrome: an Interventional Bayesian Adaptive Randomized-controlled Orphan Drug Platform Trial for Orodental Sequelae (Reverse-fibrose)

To find out if adding medication can help treat or prevent lymphedema and/or fibrosis related to radiation therapy, in survivors of head and neck cancer. Researchers will compare these drugs to find the most effective therapy for preventing or limiting these side effects.

Boosted Compression for Lower Limb Chronic Edema

Patients: Patients targeted in this proposal comprise individuals afflicted by chronic edema/lymphedema of the lower limbs. Intervention: The intervention entails the incorporation of boosted compression alongside standard care during the intensive treatment phase. Boosted compression involves thrice-daily re-application of a multicomponent short stretch compression bandage, aimed at enhancing the efficacy of compression therapy within edema treatment. Comparison: Comparison will be made between the experimental intervention (boosted compression) and the prevailing standard edema treatment, which adheres to the complex decongestive therapy as stipulated by healthcare services, utilizing a single daily application of compression bandage. Standard care is administered under the supervision of trained physical therapists, specialized in edema treatment. Outcome: Primary outcomes encompass the determination of: 1. the requisite number of treatment days to attain a non-pitting edema state during the intensive phase of edema treatment; and 2. the non-inferiority of boosted compression in maintaining reduced edema volume during the maintenance phase assessed at 1y of follow-up. Secondary outcomes encompass assessments of: Quality of Life, acceptance, and adherence to boosted compression, alongside evaluations of time and cost-effectiveness associated with its implementation.