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Background: The lymphatic system consists of the superficial and deep lymphatic system. Several diagnostic methods are used to assess the lymphatic system. Lymphoscintigraphy and indocyanine green lymphography are widely applied, both showing disadvantages, such as a poor resolution and lack of field of view. Magnetic resonance lymphography (MRL) shows satisfactory temporal and spatial resolution. The aim of this study was to assess both the superficial and deep lymphatic system in the upper extremity of healthy subjects, using an MRL protocol. Methods and Results: Ten healthy volunteers underwent an MRL examination, using a three Tesla MRI unit. Water-soluble gadolinium was used as a contrast agent. MRL images were evaluated by an experienced radiologist on image quality, enhancement of veins and lymphatic vessels, and characteristics of the latter. Overall image quality was good to excellent. In all subjects, veins and lymphatic vessels could be distinguished. Superficial and deep lymphatic vessels were seen in 9 out of 10 subjects. Lymphatic vessels with a diameter between 0.9 and 4.3 mm were measured. Both veins and lymphatic vessels showed their characteristic appearance. Enhancement of veins was seen directly after contrast agent injection, which decreased over time. Lymphatic vessel enhancement slowly increased over time. Mean total MRL examination (room) time was 110 minutes (81 minutes scan time). Conclusions: The MRL protocol accurately visualizes both deep and superficial lymphatic vessels showing their characteristic appearances with high spatial resolution, indicating the MRL can be of value in diagnosing and staging peripheral lymphedema.

Background: Lymphedema is a chronic, progressive disease consisting of tissue swelling resulting from excessive retention of lymphatic fluid. Measuring upper limb volume is crucial in patients to detect disease progression and to study the effects of treatment. The aim is to assess the validity and reliability of a newly developed system, Peracutus Aqua Meth, for measuring the upper limb volume compared with the gold standard water volumetry device. (In this study, the Bravometer was used). Methods and Results: Healthy volunteers were recruited in October 2017. Three measurements were performed per device. The obtained data were recorded per measurement, device, and researcher. Primary outcome was to determine the validity and reliability of the Peracutus Aqua Meth. Secondary outcomes were intra- and interrater reliability, measurement time, self-reported participant satisfaction, and influence of body mass index (BMI). Thirty-nine healthy volunteers were included. Mean differences in the validity in the Peracutus Aqua Meth and Bravometer were 47.26 and 78.16 mL, respectively (p = 0.04), with a Pearson's r of 0.99. Intra- and interrater reliability of the Peracutus Aqua Meth were both 0.99, in the Bravometer 0.96 and 0.97, respectively (p

Background: Assessment of lymph flow has proven challenging. Transit-time ultrasound technique (TTUT) is the first technique that provides real-time quantitative lymphatic flow values. In cardiothoracic surgery and neurosurgery, this technique has tremendous clinical value in assessing surgery quality and predicting outcomes. The objective of this study was to measure lymph flow before and after lymphaticovenous anastomosis (LVA), using TTUT.Methods and Results: Consecutive patients with peripheral lymphedema undergoing LVA were included. Preoperative workup was performed using indocyanine green (ICG) lymphangiography. Perioperatively, the Transonic(R) Microvascular Flowprobe was used to measure lymph flow before and after anastomosis. Twenty-five patients with International Society of Lymphology stage IIA (68%) and stage IIB (32%) peripheral lymphedema were included. Lymph flow velocities ranged from 0.02 to 0.80 mL/min (mean 0.25 +/- 0.19) before anastomosis and from 0.02 to 0.86 mL/min (mean 0.27 +/- 0.22) after anastomosis (p = 0.340). Mean flow values were significantly higher in the upper extremities compared with the lower extremities. Furthermore, there was a decrease in flow in patients with ICG stage IV in comparison with ICG stage III. Clinical outcomes could not be directly correlated with flow values in these individual cases.Conclusion: TTUT micro-flowprobe is a suitable instrument to measure real-time quantitative lymphatic flow in both lymphatics and LVA. It can confirm patency of lymphatic collectors and LVA peroperatively. Significantly higher lymph flow velocities were found in upper extremities in comparison with lower extremities, both before and after LVA. Further studies should be performed to evaluate lymph flow values and clinical correlation.

Background: Lymphedema affects approximate to 15% of all patients after breast cancer treatment. The aim of this review was to assess the clinical effects (improvement in arm circumference and quality of life) of lymphaticovenous anastomosis (LVA) in treating breast cancer-related lymphedema (BCRL). Methods and Results: A systematic literature search was conducted in Medline, Embase and the Cochrane Library in July 2017, to identify all studies on LVA for the treatment of BCRL. The primary outcome was limb volume or circumference reduction and the secondary outcome was the improvement of quality of life. The search yielded 686 results, of which 15 articles were included in this review. All studies reported on BCRL in terms of volume or circumference reduction. Thirteen out of the included studies reported a positive surgical effect on reduction in volume or circumference. Twelve articles mentioned qualitative measures, being symptom improvement and improvement in quality of life. The number of patients who experienced symptoms relief ranged from 50% to 100% in the studies. Conclusions: The current review showed that the effects of LVA for the treatment of BCRL are variable among studies, although overall LVA seems effective in early stage BCRL. Higher quality studies are needed to confirm the effectiveness of LVA.

Background: Secondary lymphedema is a complication following breast cancer therapy and constitutes the main form of lymphedema in the western world. The purpose of the current study was to provide a clear overview of the genetic predisposition and secondary lymphedema. Methods and Results: A systematic search was performed between February and June 2017 in MEDLINE and Embase. Search terms included Genes, Genetic Predisposition to Disease, Lymphedema, Breast Cancer Lymphedema, Secondary Lymphedema, Breast Cancer-Related Lymphedema, and Humans. Only original articles regarding the possible relationship between genetic variation and the development of secondary lymphedema in humans were included in this review. A total of 459 records were collected. After removal of duplicates, non-topic-related publications, and records not presenting original data, six full-text studies were included. Associations between genetic factors and the development of secondary lymphedema were found for variations in HGF, MET, GJC2, IL1A, IL4, IL6, IL10, IL13, VEGF-C, NFKB2, LCP-2, NRP-2, SYK, VCAM1, FOXC2, VEGFR2, VEGFR3, and RORC. Conclusions: In patients with secondary lymphedema following breast cancer therapy, genetic variations were found in 18 genes. These compelling, although preliminary, findings may suggest a possible role for genetic predisposition in the development of lymphedema following breast cancer therapy. This notion may add to the classical, more mechanistic explanation of secondary lymphedema.

Purpose: Lymphedema of the arm is one of the most common and underestimated side effects of breast cancer treatment. It is known to negatively affect the quality of life (QoL) in breast cancer survivors. However, there are multiple questionnaires used to measure QoL in lymphedema patients. The current study aimed to determine the most complete and accurate questionnaire. Methods: A systematic literature search in Cochrane Library database CENTRAL, MEDLINE, and EMBASE was conducted in August 2016 by two independent researchers. The strategy used for the search was: ((Lymphedema[Mesh]) AND (Quality of life[Mesh])). All QoL questionnaires for patients with breast cancer-related lymphedema (BCRL) were included. An overview of the assessed QoL domains and arm symptom-specific questions was made, to assess the most complete and accurate questionnaire. Results: A total of 142 studies were identified, of which 49 met the inclusion criteria and 15 different questionnaires were extracted. The Lymphedema Quality of Life Inventory (LyQLI), assesses all QoL domains, except for the possibility of wearing the clothes of choice, and assess all specific arm symptoms. The Lymphedema Functioning, Disability, and Health (Lymph-ICF) Questionnaire assesses all QoL domains, except for sexual functioning, and does assess all specific arm symptoms. Conclusion: According to the results obtained, the LyQLI and Lymph-ICF questionnaires were the two most complete and accurate questionnaires to assess QoL in patients with BCRL, because these questionnaires assess the largest number of QoL domains and specific arm symptoms.