Lymphatic remapping by long-term lymphoscintigraphy follow-up in secondary lymphedema after breast cancer surgery.

The purpose of the study is to investigate long-term changes on lymphoscintigraphy and their association with clinical factors in breast cancer-related lymphedema (BCRL) patients. This single-center cohort study included BCRL patients who underwent baseline and follow-up lymphoscintigraphy. The percentage of excessive circumference (PEC) of the affected upper limb compared with the unaffected side was used as an indicator of the clinical severity of BCRL. Each 99mTc-phytate lymphoscintigraphy image was categorized according to the Taiwan lymphoscintigraphy staging system. Clinical parameters and the lymphoscintigraphy stage at baseline and follow-up were compared and analyzed. Eighty-seven patients were included. Baseline and follow-up lymphoscintigraphies were performed at median 7 (interquartile range [IQR]: 2‒14) and 78 (IQR: 49‒116) months after surgery, respectively. Both lymphoscintigraphy stage and PEC showed variable change with overall increases in their severity. Stepwise multivariable analysis revealed follow-up lymphoscintigraphy stage (P = 0.001) to be independent variables for PEC at follow-up, however, baseline lymphoscintigraphy stage was not. The clinical courses of BCRL and patients' lymphoscintigraphy patterns showed diverse changes over long-term follow-up. In addition to initial lymphoscintigraphy for diagnosis, lymphatic remapping by follow-up lymphoscintigraphy can be useful to visualize functional changes in the lymphatic system that may guide the optimal management in BCRL.

Optimal Cut-Off Value for Detecting Breast Cancer-Related Lymphedema Using Ultrasonography.

Background: We previously devised an ultrasonographic evaluation to calculate subcutaneous tissue cross-sectional area (△CSA). The reliability and accuracy of this method were demonstrated in healthy individuals and in patients with lymphedema. The purpose of this study was to estimate the optimal cut-off value of the ratio of the △CSA of the involved side (lesion side) to the contralateral side for detecting breast cancer-related lymphedema (BCRL) using ultrasonography. Methods and Results: Ultrasonographic measurements were performed 290 times in 150 patients. BCRLD was defined as a confirmed difference of >2 cm in arm circumference. BCRL confirmed by a clinician (BCRLC) was defined as the patient group that included not only BCRLD but also patients with subcutaneous thickening and abnormal findings on lymphoscintigraphy, even if the difference in arm circumference was <2 cm. The △CSAs of both upper arms and forearms were calculated by measuring the thickness of the subcutaneous tissue at four locations using ultrasonography (superior, medial, inferior, lateral) at 10 cm above the elbow and 10 cm below the elbow. With a 1.35 △CSA ratio as the cut-off value for detecting BCRLD, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were 0.88, 0.87, and 0.95, respectively. With a 1.20 △CSA ratio as the cut-off value for detecting BCRLC, the sensitivity, specificity, and AUC were 0.92, 0.89, and 0.97, respectively. Conclusions: Our findings suggest that a 1.20 △CSA ratio as determined using ultrasonography, corresponding to a tape measurement of 1.05 cm, can be considered as a diagnostic criterion for lymphedema.

Exploring Indicators of Subcutaneous Tissue Fluid Accumulation in Breast Cancer-Related Lymphedema Patients Using Fractal Analysis with Virtual Volume.

Background: Breast cancer treatment sometimes causes a chronic swelling of the arm called breast cancer-related lymphedema (BCRL). Its progression is believed to be irreversible and is accompanied by tissue fibrosis and lipidosis, so preventing lymphedema from progressing by appropriate intervention at the site of fluid accumulation at an early stage is crucial. The tissue structure can be evaluated in real time by ultrasonography, and this study aims at assessing the ability of fractal analysis using virtual volume in detecting fluid accumulation within BCRL subcutaneous tissue via ultrasound imaging. Methods and Results: We worked with 21 women who developed BCRL (International Society of Lymphology stage II) after unilateral breast cancer treatment. Their subcutaneous tissues were scanned with an ultrasound system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer. Then, a 3-Tesla MR system was used to confirm fluid accumulation in the corresponding area of the ultrasound system. Significant differences in both H + 2 and complexity were observed among the three groups (with hyperintense area, without hyperintense area, and unaffected side) (p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed a significant difference for "complexity." The evaluation of the distribution in Euclidean space showed that the variation of the distribution decreased in the order of unaffected, without hyperintense area, and with hyperintense area. Conclusion: The "complexity" of the fractal using virtual volume seems to be an effective indicator of the presence or absence of subcutaneous tissue fluid accumulation in BCRL.

Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms.

Introduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs. Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(≥7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE. Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.

Accessory Lymphatic Drainage Pathways on Indocyanine Green Lymphography in Patients with Breast Cancer-Related Lymphedema.

BACKGROUND: Current predictive models of lymphedema risk cannot predict with 100% certainty which patients will go on to develop lymphedema and which will not. Patient-specific anatomic and physiologic differences may be the missing factor. The authors hypothesize that patients with accessory lymphatic pathways may have improved lymphatic drainage, resulting in smaller limb volumes. METHODS: The authors reviewed indocyanine green (ICG) lymphography images of all patients who presented to their institution for evaluation of breast cancer-related lymphedema. Patients with unilateral upper extremity lymphedema, a full set of bilateral limb measurements, and ICG images of both limbs were included. Other variables of interest included patient demographics and length of follow-up. Patients with accessory pathways were determined independently, and conflicts were resolved with discussion. Abnormal images were also evaluated for common drainage pathways. RESULTS: Thirty patients were identified as having accessory lymphatic drainage pathways. These patients had significantly smaller limb volume differences [8.19% (SD, 11.22)] compared with patients who did not exhibit these pathways [20.74% (SD, 19.76); P < 0.001]. The most common pathway was absence or rerouting of the radial bundle to the ulnar or volar bundles ( n = 16). CONCLUSIONS: The ability to create accessory lymphatic drainage pathways may be associated with improved lymphatic drainage, resulting in smaller limb volumes. Furthermore, certain drainage pathways appear to be more common than others. Description of these pathways should be considered for inclusion in ICG lymphography image grading criteria. Further study is needed to clarify the nature of these pathways and whether these pathways affect subjective symptoms and quality of life. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging.

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by "dermal backflow" of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Association of lymphatic flow velocity with surgical outcomes in patients undergoing lymphovenous anastomosis for breast cancer-related lymphedema.

PURPOSE: Lymphovenous anastomosis (LVA) is primarily used for treating early-stage lymphedema. Here, we aimed to investigate the relationship between lymphatic flow velocity and the efficacy of LVA in breast cancer-related lymphedema patients. To this end, we assessed the transit velocity of lymphatic fluid using indocyanine green (ICG) lymphography and radioisotope lymphoscintigraphy. METHODS: We retrospectively examined patients diagnosed with breast cancer-related lymphedema who underwent LVA from January to December 2020. Patient data, including demographics, clinical stage, and postoperative surgical outcomes, were collected from electronic medical records. ICG lymphography results and dynamic lymphoscintigrams were analyzed to measure the lymphatic flow velocity and to determine the grade of the limb lymphedemas. RESULTS: Eighty patients (all female, mean age of 53.6 years) were included. The lymphatic flow velocity ranged between 0.58 and 21.5 cm/min (average, 7.61 cm/min); 37 (46.3%), 18 (22.5%), 15 (18.8%), and 10 (12.5%) arm lymphedemas were classified as lymphoscintigraphy grade 0, 1, 2, and 3, respectively. A significant association was observed between lymphatic flow velocity and lymphedema grade determined using lymphoscintigraphy and between the amount of volume reduction after LVA and preoperative lymphatic flow velocity (P < 0.05). CONCLUSIONS: Our findings suggest that lymphatic flow velocity is positively correlated with surgical outcomes in patients undergoing LVA. Therefore, surgical treatment plans for lymphedema should not be based only on the International Society of Lymphedema stage, because advanced-stage lymphedema patients with high ICG velocities can benefit from LVA alone.

ICG lymphographic findings following immediate lymphatic reconstruction in breast cancer patients.

BACKGROUND: Immediate lymphatic reconstruction (ILR), performed at the time of axillary lymph node dissection (ALND), has demonstrated promising reductions in breast cancer-associated lymphedema. However, questions remain over the effects of adjuvant therapies on the continued patency of the lymphaticovenous anastomosis. Our study aimed to assess lymphographic outcomes, including ICG pattern and LVB patency, in patients at high risk for breast cancer-associated lymphedema following axillary ILR. METHODS: Baseline ICG lymphography studies performed during ILR of 15 patients were compared to repeat ICG studies obtained during second-stage breast reconstructive procedures to assess for changes in lymphatic flow patterns through the at-risk arm and transit into the axilla. RESULTS: All 15 patients in this study demonstrated linear lymphatic flow in baseline lymphography. Repeat lymphographic studies showed linear lymphatic transit in 12/15 patients. Of these 12 patients, 10 received chemotherapy, and all 12 received post-mastectomy radiation (PMRT). Dermal backflow patterns were recorded in 3/15 patients. All 3 patients received chemotherapy and 2/3 underwent PMRT. Additionally, repeat ICG studies of 7/12 lymphedema-free patients demonstrated clear visualization of linear ICG flow from the lymphatics of the arm into the axilla. CONCLUSION: We have demonstrated that ICG lymphography can be implemented as a postoperative tool to assess lymphatic function in patients who have undergone ILR in the axilla. Repeat ICG studies in the majority of patients demonstrated linear ICG flow similar to baseline studies. Additionally, ICG flow patterns through the axilla in repeat lymphography provided visual evidence supporting sustained LVB patency, despite axillary irradiation.

Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL. METHODS: MRI at 3.0 T of upper extremity and torso anatomy, fat and muscle tissue composition, and T2 relaxometry were applied in left and right axillae of healthy control (n = 24) and symptomatic BCRL (n = 22) participants to test the primary hypothesis that fat-to-muscle volume fraction is elevated in symptomatic BCRL relative to healthy participants, and the secondary hypothesis that fat-to-muscle volume fraction is correlated with MR relaxometry of affected tissues and BCRL stage (significance criterion: two-sided p < 0.05). RESULTS: Fat-to-muscle volume fraction in healthy participants was symmetric in the right and left sides (p = 0.51); in BCRL participants matched for age, sex, and BMI, fat-to-muscle volume fraction was elevated on the affected side (fraction = 0.732 ± 0.184) versus right and left side in controls (fraction = 0.545 ± 0.221, p < 0.001). Fat-to-muscle volume fraction directly correlated with muscle T2 (p = 0.046) and increased with increasing level of BCRL stage (p = 0.041). CONCLUSION: Adiposity quantified by MRI is elevated in the affected upper extremity of women with BCRL and may provide a surrogate marker of condition onset or severity. CLINICAL TRIAL: NCT02611557.

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).

Assessment of Arm Volume Using a Tape Measure Versus a 3D Optical Scanner in Survivors with Breast Cancer-Related Lymphedema.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema.

Precise staging of breast cancer-related lymphedema (BCRL) is important to guide treatment-decision making. Recent studies have suggested staging of BCRL using indocyanine green lymphangiography (ICG-L) based on the extent of lymphatic injury and dermal backflow patterns. Currently, the benefits of ICG-L compared to conventional clinical staging are unknown. For this study, we included 200 patients with unilateral BCRL. All BCRL patients were staged using ICG-L and clinical exam. The amounts of excess arm volume, fat mass and lean mass were compared between stages using Dual Energy X-Ray Absorptiometry. Multivariate regression models were used to adjust for confounders. For each increase in the patient's ICG-L stage, the excess arm volume, fat mass and lean mass was increased by 8, 12 and 6.5 percentage points respectively (P < 0.001). For each increase in the patient's clinical ISL stage, the volume was increased by 3.5 percentage points (P < 0.05), however no statistically significant difference in the lean and fat mass content of the arm was observed for ascending stages. However, the residual plots showed a high degree of variance for both ICG-L and clinical staging. This study found that ICG-L staging of BCRL was superior to clinical staging in forecasting BCRL excess arm volume, fat mass, and lean mass. However, there was a high degree of variance in excess arm volume, fat mass, and lean mass within each staging system, and neither the ICG-L nor clinical staging forecasted perfectly.

Upper limb sensory evaluations and ultrasonographic skin measurements in breast cancer-related lymphedema receiving complex decongestive physiotherapy.

PURPOSE: The aims of this study were to investigate if/how the presence of lymphedema affects the sensation of the upper limb and to assess whether complex decongestive physiotherapy (CDP) has a favorable impact on sensory testing. METHODS: A total of 27 patients with unilateral stage 2 breast cancer-related lymphedema (BCRL) were included in the study. Bilateral circumferential measurements were taken with a tape measure at different levels. Based on these measurements, limb volumes were determined by summing segment volumes derived from the truncated cone formula. Circumferential measurements and ultrasonographic evaluations (epidermis, dermis, and subcutaneous fat thicknesses) were performed at 10 cm distal to the elbow crease. The Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination, pressure pain threshold (PPT), and tactile localization tests were also applied at the same site. After an initial evaluation, all patients underwent CDP phase 1 program. All the evaluations were repeated at the end of the treatment period. RESULTS: Before CDP, affected sides had significantly higher values than the unaffected sides in terms of SWM (p < 0.001), static (p = 0.002) and moving (p = 0.011) two-point discrimination, PPT (p = 0.001), and tactile localization (p < 0.001) values. After CDP, SWM (p = 0.002), static (p = 0.009) and moving (p = 0.024) two-point discrimination, PPT (p = 0.014), and tactile localization (p < 0.001) values decreased significantly on the affected sides. CONCLUSION: BCRL seems to reduce light touch, static and moving two-point discrimination, PPT, and tactile localization sensations, whereas CDP seems to improve these sensory perceptions in women with BCRL. Ultrasonographic measurements also appear to be promising for prompt and convenient follow-up in the management of BCRL. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04296929 (date of registration: March 5, 2020).

Diagnostic Contribution of Ultrasonography in Breast Cancer-Related Lymphedema.

Background: Many assessments have been reported and used in evaluating lymphedema. The aim of this study was to investigate the diagnostic contribution of ultrasonography in unilateral breast cancer-related lymphedema. Methods and Results: Upper extremity circumferences were measured with a measuring tape from ulnar styloid at the wrist to the axilla at 4 cm intervals. The point with the highest difference between the upper extremities and the control point with no difference between the lower extremities were marked. Skin and subcutaneous thicknesses were measured from four quadrants (volar medial-lateral and dorsal medial-lateral) at the marked points and also subcutaneous tissue changes were graded according to the subcutaneous echogenicity grade (SEG) scale ultrasonographically. The correlations between circumferential and ultrasonographic measurements were investigated. Receiver operating characteristic curve analysis was made to estimate the diagnostic accuracy of the difference in ultrasonographic subcutaneous thickness measurements between the two arms. The study was completed with 34 female patients. Circumferential and subcutaneous tissue thickness measurements were moderately positively correlated in the volar quadrants and strongly positively correlated in the dorsal quadrants of the affected extremity. In the unaffected extremity, a strong positive correlation was identified in all quadrants. The clinical stages of lymphedema and SEG were weakly positively correlated in the volar medial quadrant. The difference between the two upper extremities was found to have a high (0.83%) sensitivity, and an acceptable (0.75%) specificity in the differentiation of Grade II and Grade III lymphedema. Conclusion: A correlation was established between circumferential measurements and ultrasonographic measurements. Ultrasonography can be used complementary to circumferential measurements in diagnosing lymphedema. Clinical trial registration number: NCT04213001.

The role of ultrasonography in follow-up of effectiveness of Complex Decongestive Therapy (CDT) in different subgroups of patients with breast cancer-related lymphoedema.

OBJECTIVE: To determine the role of ultrasonography in the follow-up of effectiveness of complex decongestive therapy (CDT) in different subgroups of patients with breast cancer-related lymphoedema (BCRL). METHODS: Forty-seven patients with unilateral upper BCRL were enrolled in the study. The patient group was divided into two subgroups according to body mass index (BMI) as obese and non-obese and three subgroups according to International Society of Lymphology staging. All patients underwent CDT, the circumference measurements and ultrasonographic soft tissue thicknesses evaluations were performed at two anatomic sites, and upper extremity limb volumes were calculated using the truncated cone formula before and after CDT. RESULTS: There were significant decreases in both circumferential measurements and ultrasonographic soft tissue thicknesses in non-obese patients and stage 2 lymphoedema patients after 15 sessions of CDT. The ultrasonographic soft tissue thickness values were correlated with the upper arm and forearm circumference values before (r = 0.491, p < .001, r = 0.841, p < .001, respectively) and after (r = 0.535, p < .001, r = 0.714, p < .001, respectively) CDT. CONCLUSIONS: Ultrasonography presents as a reliable method to measure the soft tissue thickness and treatment efficacy after CDT in only non-obese and stage 2 patients with BCRL.

Microsurgery for management of primary and secondary lymphedema.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of lymphaticovenular anastomosis (LVA) in patients with lymphedema. METHODS: A retrospective analysis was conducted of 70 patients suffering from primary or secondary lymphedema who underwent LVA surgery with indocyanine green fluorescence lymphangiography. Postoperative evaluation included qualitative and quantitative volumetric assessment and analysis. Limb volume was measured by circumferential tape measurement volumetric method, in which the limb is subdivided into five segments and each segment's circumference is measured. RESULTS: LVA was performed in 70 patients, 22 with primary lymphedema and 48 with secondary lymphedema. The difference in preoperative upper limb volume was 35% with mean postoperative follow-up of 9 months. The mean number of lymphovenous bypasses was 3.9. The reduction in limb volume at 3, 6, and 12 months was 40.4%, 41%, and 45%, respectively. Patients with early-stage lymphedema had significantly higher volume reductions than patients with late-stage lymphedema at 3, 6, and 12 months (48% vs 18%, 49% vs 22%, and 65% vs 31%; P < .001). For lower extremity lymphedema, the preoperative volume differential was 25.5%. The mean postoperative follow-up was 9 months. The reduction in limb volume at 3, 6, and 12 months was 28%, 37%, and 39%, respectively. CONCLUSIONS: LVA surgery is a safe and effective method of reducing lymphedema severity, especially in upper extremity lymphedema at an earlier disease stage.

The Correlation Between Fluid Distribution and Swelling or Subjective Symptoms of the Trunk in Lymphedema Patients: A Preliminary Observational Study.

Background: Manual lymph drainage (MLD) is one of the common treatments for breast cancer-related lymphedema (BCRL). Although the primary goal of MLD is to drain the excessive fluid accumulated in the affected upper limb and trunk to an area of the body that drains usually, the use of MLD is decided based on swelling and subjective symptoms, without assessing whether there is fluid accumulated in the affected region. The purpose of this study was to examine truncal fluid distribution in a sample of BCRL patients and investigate any correlation between such fluid distribution and swelling or subjective symptoms. Methods and Results: An observational study was conducted with 13 women who had unilateral, upper extremity BCRL. Fluid distribution was evaluated by using two magnetic resonance imaging (MRI) sequences: half-Fourier acquisition single-shot turbo spin echo and three-dimensional double-echo steady-state. The presence of swelling was determined by lymphedema therapists, and subjective symptoms were measured by using a visual analog scale. On MRI, no participants had any free water signals in the trunk. However, seven had swelling and all 13 had some kind of subjective symptoms on the affected side of their trunk. Conclusions: These results suggest that swelling and subjective symptoms do not correlate with the presence of truncal fluid. For such cases, a different approach than MLD may be needed to address truncal swelling and related subjective symptoms. Checking for the presence of fluid in the truncal region may help MLD be used more appropriately.

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.

Magnetic resonance imaging and bioimpedance evaluation of lymphatic abnormalities in patients with breast cancer treatment-related lymphedema.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) evaluation is frequently performed using portable measures of limb volume and bioimpedance asymmetry. Here quantitative magnetic resonance imaging (MRI) is applied to evaluate deep and superficial tissue impairment, in both surgical and contralateral quadrants, to test the hypothesis that BCRL impairment is frequently bilateral and extends beyond regions commonly evaluated with portable external devices. METHODS: 3-T MRI was applied to investigate BCRL topographical impairment. Female BCRL (n = 33; age = 54.1 ± 11.2 years; stage = 1.5 ± 0.8) and healthy (n = 33; age = 49.4 ± 11.0 years) participants underwent quantitative upper limb MRI relaxometry (T2), bioimpedance asymmetry, arm volume asymmetry, and physical evaluation. Parametric tests were applied to evaluate study measurements (i) between BCRL and healthy participants, (ii) between surgical and contralateral limbs, and (iii) in relation to clinical indicators of disease severity. Two-sided p-value < 0.05 was required for significance. RESULTS: Bioimpedance asymmetry was significantly correlated with MRI-measured water relaxation (T2) in superficial tissue. Deep muscle (T2 = 37.6 ± 3.5 ms) and superficial tissue (T2 = 49.8 ± 13.2 ms) relaxation times were symmetric in healthy participants. In the surgical limbs of BCRL participants, deep muscle (T2 = 40.5 ± 4.9 ms) and superficial tissue (T2 = 56.0 ± 14.8 ms) relaxation times were elevated compared to healthy participants, consistent with an edematous micro-environment. This elevation was also observed in contralateral limbs of BCRL participants (deep muscle T2 = 40.3 ± 5.7 ms; superficial T2 = 56.6 ± 13.8 ms). CONCLUSIONS: Regional MRI measures substantiate a growing literature speculating that superficial and deep tissue, in surgical and contralateral quadrants, is affected in BCRL. The implications of these findings in the context of titrating treatment regimens and understanding malignancy recurrence are discussed.