Lymphatic Research and Biology

We aimed to assess the sleep quality and the relationship between sleep and fatigue and quality of life in female lipedema patients.

A total of 52 patients with lipedema (Group 1) and 40 healthy control subjects (Group 2) were enrolled. The type and stage of lipedema were recorded for Group 1. The quality of sleep was assessed by using the Pittsburgh Sleep Quality Index (PSQI). The Fatigue Severity Scale (FSS) was used for assessing fatigue. Quality of life was assessed with the World Health Organization Quality of Life. The mean age of the patient group was 45.26 ± 9.81, whereas it was 42.10 ± 6.36 years in the control group (p > 0.05). The mean body mass index was 30.23 ± 4.70 in Group 1 and 28.55 ± 4.14 in Group 2 (p > 0.05). The total PSQI score was 10 (range: 7–12.75) in Group 1 and 8 (range: 5–10) in Group 2 (p < 0.05). There was no difference between the groups in terms of FSS. In the assessment of quality of life, only the physical function domain was significantly poorer in Group 1 than in Group 2 (p < 0.05). Physical function was correlated with subjective sleep quality, sleep disorder, and daytime dysfunction; fatigue was correlated with sleep disorder, daytime dysfunction, and use of sleep medications (p < 0.05). There was a correlation between the total PSQI score and physical functioning and fatigue (p < 0.05).

Female patients with lipedema have poor sleep quality and decreased quality of life. Sleep disturbance is associated with both physical function and fatigue. Quality of sleep should be questioned in every assessment of patients with lipedema.

The incidence of lymphedema may be as high as 65% among breast cancer patients, varying according to the diagnostic method and locoregional treatment. Therefore, investigations of preventive methods are highly welcomed. Our goal was to conduct a systematic review of the literature about the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We hypothesized that identification of arm-draining lymph nodes may decrease the incidence of lymphedema.

On October 7, 2019, we conducted a systematic review of studies in PubMed, Cochrane Clinical Answers, and Cochrane Central Register of Controlled Trials, without time frame or language limitations, on the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We excluded articles that investigated other uses of lymphoscintigraphy, such as lymphedema diagnosis or treatment evaluation.

Of 104 potential articles found in the literature, 5 studies fulfilled the eligibility criteria. A total of 501 patients were included. Reverse mapping was done with radiography or single-photon emission computed tomography/computed tomography. Moreover, the examination was applied with different treatments, such as axillary lymph node dissection or radiotherapy, allowing preservation of noncompromised lymph nodes. Axillary reverse mapping also had prognostic value and was used with sentinel lymph node biopsy to identify patients at higher risk for lymphedema. Only one study compared the incidence of lymphedema between patients who received standard care or reverse mapping, showing significant benefits of its use.

Use of axillary reverse mapping to prevent lymphedema is feasible and seems to provide valuable information for breast cancer treatment. Future studies that compare reverse mapping and standard care are still necessary.

Lymph flow measurements can assist in attaining a better understanding of the lymphatic system’s function and its diseases. However, in vivo assessment of lymph flow has been challenging. Transit-time ultrasound technique (TTUT) provides direct quantitative lymph flow values and has been used to successfully measure lymph flow in patients with secondary lymphedema. Currently, no measurements using TTUT in healthy subjects have been reported. The aim of this study is to measure lymph flow in healthy subjects using the TTUT.

Twenty consecutive patients who had an indication for a free radial forearm flap (FRFF) reconstruction were included in the study. Patients with scars on their arms, a history of extremity lymphedema, metastatic disease, or axillary node dissection were excluded. The Transonic® Microvascular Flow Probe was used to measure lymph flow during FRFF reconstruction in accordance with the Transonic® protocol for Quantitative Patency Assessment. The subdermal superficial lymphatic collecting vessels had a mean diameter of 0.40 ± 0.10 mm (range: 0.3–0.5 mm) and a mean lymph flow velocity of 0.45 ± 0.48 mL/min (range: 0.08–1.68 mL/min). Neighboring subdermal veins measured had a mean diameter of 0.48 ± 0.11 mm (range: 0.03–0.7 mm) and a mean blood flow velocity of 0.96 ± 1.73 mL/min (range: 0.07–7.40 mL/min).

The TTUT is a viable method to measure real-time lymph flow velocities in healthy subjects. Future studies with a larger sample size are required to validate the TTUT measurement accuracy and establish clinical correlations.

Lymphedema is a common but distressing sequela after cancer treatment. A cure is not yet available; thus, prevention is essential in its management.

Here, we used a mouse hindlimb model to demonstrate the effects of exercise performed before lymph node resection and irradiation on the development of lymphedema. BALB/c mice trained on a treadmill at moderate intensity, 30 minutes/day, 5 times/week for 4 weeks, were compared to a no-exercise group (n = 7/group). Weekly limb measurements and indocyanine green (ICG) lymphangiography were performed to assess lymphedema severity. Pre-injury exercise mice consistently showed a lower percentage excess in ankle diameter, reflecting a lesser degree of swelling. Moreover, most of them exhibited the mild “splash” pattern on ICG lymphangiography, while some reverted to the normal linear pattern on the 3rd week. Meanwhile, most of the no-exercise mice displayed the moderate “stardust” and severe “diffuse” patterns throughout the observation period. Histopathological analysis revealed a lesser increase in skin thickness and a greater density of lymphatic vessels of the exercise mice.

Taken together, results showed that pre-injury exercise attenuated the development of lymphedema in our mouse hindlimb model. This provides preliminary evidence on the potential preventive role of exercise in secondary lymphedema.

The number of lymph nodes (LNs) excised during extended pelvic LN dissections (ePLND) in prostate cancer (PCa) is related to complications including lymphoceles (up to 15%) and lymphedema (up to 14%). Approaches that reduce the resection of LNs related to healthy anatomies may help reduce the complication rate. The aim of this study was to unravel the complexity of the pelvic lymphatics by researching to what extent the lymphatics draining the abdominal wall overlap with the ePLND template and the lymphatic metastatic spread of primary PCa lesions.

This prospective (NCT05120973), single-center study included 10 patients who underwent robot-assisted radical prostatectomy with ePLND. To visualize the lymphatic drainage of the abdominal wall, indocyanine green was injected intradermally at four sites distributed over the lower abdomen. In vivo fluorescence imaging was performed using the robot-integrated fluorescence endoscope. Harvested LNs were assessed for fluorescence and tumor content.

In total, 195 LNs were removed (average 20/patient); 56% of these nodes were fluorescent (average 11.5/patient). Three patients were positive pathological N stage (pN1), yielding 6 positive nodes, of which in two patients the tumor-positive nodes were also found to be fluorescent (3 nodes in total [50%]). Indicating overlapping patterns.

Within the ePLND template there is a 56% overlap, on a nodal level, with the lymphatic drainage from the abdominal wall. Three fluorescent LNs also contained metastases, indicating that the lymphatic drainage of healthy tissues directly converges with the drainage of the primary PCa.

Cancer-related lymphedema is a common, lifelong, and disabling condition resulting from oncologic treatments. Although multidisciplinary collaboration enhances patient outcomes, a framework for research and therapeutic priorities for prevention and treatment is lacking. This study utilizes group concept mapping (GCM), a participatory research methodology, to highlight clinical and scholarly priorities.

Providers and researchers involved in lymphedema care at The Ohio State University, a Lymphatic Education & Research Network (LE&RN) Center of Excellence, participated in a GCM study between November 2024 and January 2025. The groupwisdom® web-platform was used to (1) generate ideas for clinical/academic priorities for multidisciplinary collaboration, (2) sort priorities into categories, and (3) rate priorities on (a) the basis of their contribution to value-based care and (b) likelihood to secure research funding. Hierarchical cluster analysis yielded two-dimensional representations of conceptual similarity between items. Ratings were synthesized into GoZone plots demonstrating priorities most likely to secure funding and contribute to high-value care.

Thirty-five participants identified 74 priority areas. Cluster domains included: (1) identification/validation of patient-reported outcome metrics, (2) optimizing prospective surveillance, (3) surgical prevention/management of lymphedema, (4) diagnosis of lymphedema and downstream sequelae, (5) identifying risk factors/prediction tools, (6) basic/translational research, and (7) access to care/resource utilization. Improving access to care and mitigating resource barriers were deemed most impactful for delivering high-value care and ability to secure research funding.

Priorities identified at our LE&RN Lymphedema Center of Excellence provide a framework for multidisciplinary collaboration to improve care delivery and patient outcomes for those with and at-risk for cancer-related lymphedema.

This study aimed to examine the effects of aerobic exercise added to manual lymphatic drainage (MLD) on venous hemodynamics, inflammatory–vascularization markers, local tissue water percentages (LTW%), calf muscle endurance, exercise capacity, and quality of life (QoL) in patients with chronic venous insufficiency (CVI).

Participants were randomly assigned to one of two groups: (1) MLD group, which received MLD 5 days per week, and (2) MLD + aerobic exercise group, which received the same MLD plus aerobic exercise (30-minute walking sessions, three times per week) for 6 weeks. Venous hemodynamics was evaluated using Doppler ultrasonography. Inflammatory–vascularization markers, such as interleukin-6, vascular endothelial growth factor-A (VEGF-A), and some blood values were examined. LTW%, calf muscle endurance, exercise capacity, and QoL were evaluated with MoistureMeterD device, heel-rise test, 6-minute walk test (6MWT), and Venous Insufficiency Epidemiological and Economic Study on Quality-of-Life Questionnaire/Symptoms (VEINES-QOL/Sym), respectively.

There was a significant increase in venous blood flow in the right great saphenous vein (GSV), VEGF-A, and QoL and a significant decrease in the diameter of the right GSV, monocytes, and LTW% in both groups. However, there was no superiority between groups. There was a significant increase in calf muscle endurance and exercise capacity in the group that added aerobic exercise compared to the MLD group (p < 0.05).

Since positive effects of MLD on venous flow, edema, and QoL have been found, MLD can be used in physiotherapy programs for CVI. Adding aerobic exercise to MLD is an effective treatment for CVI by increasing calf muscle endurance and exercise capacity, in addition to these positive effects.

Cartilage thickness has been evaluated in many diseases, and its relationship with osteoarthritis has been investigated. However, the effect of lower extremity lymphedema on knee joint cartilage has not been well investigated. This study aimed to evaluate the distal femoral cartilage thickness ultrasonographically in patients with unilateral lower extremity lymphedema and to investigate its relationship with clinical features.

This cross-sectional study included 27 patients (mean age: 49.56 ± 12.06 years; 92.6% female) with unilateral lower extremity lymphedema. Distal femoral cartilage thickness of both knees was measured at the medial condyle, lateral condyle, and intercondylar notch by using ultrasound. Functional status and quality of life were assessed with the Lower Extremity Functional Scale and Lymphedema Quality of Life Questionnaire, respectively. The mean intercondylar notch cartilage was significantly thinner on the lymphedema side compared to the contralateral side (2.03 ± 0.41 mm vs. 2.24 ± 0.58 mm, p < 0.05). Although the medial (1.96 ± 0.36 mm vs. 2.04 ± 0.42 mm) and lateral (1.90 ± 0.37 mm vs. 2.03 ± 0.41 mm) condyles were also thinner on the affected side, they were not statistically significant (p > 0.05). No significant correlations were identified between distal femoral cartilage thickness at the intercondylar notch and clinical features, functionality, and quality of life (p > 0.05).

This study showed that distal femoral cartilage thickness, particularly at the intercondylar notch, is thinner in the affected limbs of patients with unilateral lower extremity lymphedema. These findings suggest that knee joint cartilage integrity may be affected in patients with lower extremity lymphedema and that ultrasonographic evaluation may be useful in this regard.

To investigate the diagnostic value of computed tomography lymphangiography (CTL) and nonenhanced magnetic resonance lymphangiography (MRL) for central conducting lymphatic anomaly (CCLA).

Clinical and laboratory examinations and imaging data of patients with CCLA diagnosed by lymphangiography between January 2017 and July 2023 were retrospectively analyzed. CTL and nonenhanced MRL were performed for all patients. And the evaluation indices of CTL and nonenhanced MRL included lymphatic ducts and trunks. The differences in the presence of any imaging abnormality between CTL and nonenhanced MRL were statistically analyzed, and p < 0.05 was considered to indicate statistical significance.

Forty-three patients had a greater percentage of nonenhanced MRL than CTL for the main trunk of the thoracic duct, the end of the thoracic duct, the main trunk of the right lymphatic duct, the end of the right lymphatic duct, the double subclavian trunk, and the iliac lymphatic vessels and a greater CTL display rate than did MRL for the intestinal trunk. Nonenhanced MRL in all CCLA patients revealed a tortuous and dilated thoracic duct trunk. Moreover, the end of the thoracic duct dilatation, increased number of branches, and cystic degeneration nonenhanced MRL were better than CTL. Right lymphatic duct dilatation nonenhanced MRL showed better than CTL, CTL showed intestinal trunk reflux better than nonenhanced MRL.

CTL and nonenhanced MRL can be used to image the central lymphatic system. Nonenhanced MRL showing tortuous, and dilated thoracic duct trunk is one of the main diagnostic criteria for CCLA.