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.

The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial.

The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL.

Does Manual Lymphatic Drainage Add Value in Reducing Suprafascial Fluid Accumulation and Skin Elasticity in Patients With Breast Cancer-Related Lymphedema?

OBJECTIVE: The purpose of this study was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD) versus that of traditional and placebo MLD, when added to decongestive lymphatic therapy (DLT) for the treatment of breast cancer-related lymphedema (BCRL) (EFforT-BCRL trial), on the suprafascial accumulation of lymphatic fluid and skin elasticity. METHODS: In this multicenter, 3-arm, double-blind, randomized controlled trial (EFforT-BCRL trial), 194 participants (mean age = 61 [SD = 10] years) with unilateral BCRL were recruited. All participants received standardized DLT (education, skin care, compression therapy, exercises) and were randomized to fluoroscopy-guided, traditional, or placebo MLD. Participants received 60 min/d of treatment during the 3-week intensive phase and 18 sessions of 30 minutes during the 6-month maintenance phase. During this phase, participants were instructed to wear a compression garment, to perform exercises, and to perform a self-MLD procedure once daily. This study comprises secondary analyses of the EFforT-BCRL trial. Outcomes were the amount of fluid accumulation in the suprafascial tissues (local tissue water, extracellular fluid, and thickness of the skin and subcutaneous tissue) and skin elasticity at the level of the arm and trunk. Measurements were performed at baseline; after intensive treatment; after 1, 3, and 6 months of maintenance treatment; and after 6 months of follow-up. RESULTS: At the level of the arm, there was a significant improvement over time in the 3 groups for most of the outcomes. At the level of the trunk, no remarkable improvement was noted within the individual groups. No significant interaction effects (between-group differences) were present. Only skin elasticity at the level of the arm, evaluated through palpation, showed a significant interaction effect. CONCLUSION: All 3 groups showed similar improvements in response to DLT regardless of the type of MLD that was added. The effect of the addition of MLD to other components of DLT for reducing local tissue water and extracellular fluid or skin thickness and for improving skin elasticity and fibrosis in participants with chronic BCRL was limited. IMPACT: Although MLD has been applied all over the world for many years, evidence regarding its added value in reducing arm volume in patients with BCRL is lacking. These results show that adding MLD to other components of DLT has limited value in reducing local tissue water and extracellular fluid or skin thickness and in improving skin elasticity and fibrosis in patients with chronic BCRL. To date, there is no clinical indication to continue including time-consuming MLD in physical therapist sessions for patients with chronic BCRL.

The ICC Compression Questionnaire: A Comprehensive Tool to Evaluate Compression Materials or Devices Applied in Subjects with Lymphedema or Chronic Venous Disease.

Background: Compression therapy is an important part of the treatment of patients with lymphedema or chronic venous disease. However, there is no validated questionnaire evaluating the effect of compression and its acceptance by the patient. Therefore, the aims of this study were to construct a questionnaire evaluating the effect of compression and its acceptance by the patient, that is, the Dutch ICC Compression Questionnaire (ICC-CQ), to investigate its reliability and validity, and to translate it into English. Methods and Results: Eleven experts in applying compression and 51 Dutch patients with experience of using compression were involved in the construction process. One part of the ICC-CQ has to be completed by the patient and evaluates seven domains. The other part has to be completed by the health care provider and comprises three domains. Reliability and validity of the final version was investigated in a new group of 79 Dutch-speaking patients with lymphedema or chronic venous disease, wearing compression garments (N = 52) or bandages (N = 27). Except for one domain, the Intraclass Correlation Coefficients for test-rest/interrater reliability ranged from 0.55 to 0.93. Cronbach's alpha for internal consistency ranged from 0.71 to 0.97. Eighty-nine percent of the patients fully understood the questionnaire indicating good face validity, and 87% found it complete indicating good content validity. Construct validity was considered good since 10 out of 11 hypotheses were accepted. Conclusion: The ICC-CQ is the first reliable and valid questionnaire evaluating different kinds of compression and the experience by patients with lymphedema or chronic venous disease.

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.

Sensory signs and symptoms in women with self-reported breast cancer-related lymphedema: a case-control study close up.

PURPOSE: It is not clear to what extent signs and symptoms other than arm swelling, including pain, altered sensory function, and body perception disturbances, differ between women with measurable and non-measurable breast cancer-related lymphedema (BCRL). A case-control study was performed to compare these signs and symptoms between (1) women with self-reported BCRL with objectively measurable swelling; (2) women with self-reported BCRL without objective confirmation; and (3) a control group with no self-reported BCRL. METHODS: The three groups were compared for (1) the severity of self-reported signs and symptoms of BCRL, (2) problems in functioning related to BCRL, (3) pain-related outcomes, (4) sensory functions, and (5) body perception. RESULTS: All self-reported outcomes related to signs and symptoms of BCRL and problems in functioning were significantly different between the control group and the other two groups with and without measurable self-reported BCRL (p < 0.001-0.003). Except for "skin texture" (p = 0.01), "hand swelling" (p=0.301) and 'difficulty writing' (p=0.676), no differences were found between groups. For pain-related outcomes, sensory function, and body perception, significant differences were only found for the mechanical detection threshold (p < 0.01) and self-reported disturbances in body perception (p < 0.001) between the self-reported BCRL groups and control group. CONCLUSIONS: Diverse signs and symptoms related to BCRL, sensory function, and perception were different among women with self-reported BCRL compared to controls. No differences between women with and without measurable self-reported BCRL were found. IMPLICATIONS FOR CANCER SURVIVORS: The presence of self-reported BCRL, with or without measurable swelling, is a first indication for the need of further diagnostic evaluation.

The Interrater Reliability of the Scoring of the Lymphatic Architecture and Transport Through Near-InfraRed Fluorescence Lymphatic Imaging in Patients with Breast Cancer-Related Lymphedema.

Background: Of the 1.38 million women who are diagnosed every year with breast cancer worldwide, 21% will develop arm lymphedema. Near-infrared fluorescence lymphatic imaging (NIRFLI) is an effective method for real-time evaluation of the lymphatic system. Reliability studies of the scoring of this NIRFLI are lacking. The aim of this study is to investigate if evaluation of the superficial lymphatic architecture and transport in patients with breast cancer-related lymphedema through NIRFLI can be performed in a reliable way. Methods and Results: The outcome parameters used to assess agreement were the presence of lymphatic transport from the injection sites, of dermal backflow patterns, of efferent lymphatic vessels, and of lymph nodes. The NIRFLI evaluations were scored before and after a break separately by two assessors. Twenty patients with lymphedema of the arm and/or hand were included. After the injection, there was weak to very strong agreement regarding the presence of transport from the injection sites (K = 0.459-1.000). The interpretation of the type of dermal backflow pattern varied from weak (WK = 0.452) to very strong agreement (WK = 1.000) between the two assessors. Agreement in the visualization of efferent lymphatic vessels was weak before and after the break (K = 0.490 and K = 0.571) and agreement regarding the presence of lymph nodes was very strong (K = 1.000). Conclusion: Overall, there was moderate to strong agreement between the assessors when evaluating the lymphatic architecture and transport through NIRFLI. The study has been registered at clinicaltrials.gov (NCT02609724).