A novel therapy for fracture healing by increasing lymphatic drainage.

Background: The musculoskeletal system contains an extensive network of lymphatic vessels. Decreased lymph flow of the draining collecting lymphatics usually occurs in clinic after traumatic fractures. However, whether defects in lymphatic drainage can affect fracture healing is unclear. Methods: To investigate the effect of lymphatic dysfunction on fracture healing, we used a selective VEGFR3 tyrosine kinase inhibitor to treat tibial fractured mice for 5 weeks versus a vehicle-treated control. To ensure successfully establishing deceased lymphatic drainage model for fractured mice, we measured lymphatic clearance by near infrared indocyanine green lymphatic imaging (NIR-ICG) and the volume of the draining popliteal lymph nodes (PLNs) by ultrasound at the whole phases of fracture healing. In addition, hindlimb edema from day 0 to day 7 post-fracture, pain sensation by Hargreaves test at day 1 post-fracture, bone histomorphometry by micro-CT and callus composition by Alcian Blue-Hematoxylin/Orange G staining at day 14 post-fracture, and bone quality by biomechanical testing at day 35 post-fracture were applied to evaluate fracture healing. To promote fracture healing via increasing lymphatic drainage, we then treated fractured mice with anti-mouse podoplanin (PDPN) neutralizing antibody or isotype IgG antibody for 1 week to observe lymphatic drainage function and assess bone repair as methods described above. Results: Compared to vehicle-treated group, SAR-treatment group significantly decreased lymphatic clearance and the volume of draining PLNs. SAR-treatment group significantly increased soft tissue swelling, and reduced bone volume (BV)/tissue volume (TV), trabecular number (Tb.N), woven bone and biomechanical properties of fracture callus. In addition, anti-PDPN treated group significantly reduced the number of CD41+ platelets in PLNs and increased the number of pulsatile lymphatic vessels, lymphatic clearance and the volume of PLNs. Moreover, anti-PDPN treated group significantly reduced hindlimb edema and pain sensation and increased BV/TV, trabecular number (Tb.Th), woven bone and biomechanical properties of fracture callus. Conclusions: Inhibition of proper lymphatic drainage function delayed fracture healing. Use of a anti-PDPN neutralizing antibody reduced lymphatic platelet thrombosis (LPT), increased lymphatic drainage and improved fracture healing. The translational potential of this article: (1) We demonstrated lymphatic drainage function is crucial for fracture healing. (2) To unblock the lymphatic drainage and prevent the risk of bleeding and mortality by blood thinner, we demonstrated PDPN neutralizing antibody is a novel and safe way forward in the treatment of bone fracture healing by eliminating LPT and increasing lymphatic drainage.

Manual lymphatic drainage: the evidence behind the efficacy.

Manual lymphatic drainage (MLD), a specific type of massage performed by specialists that aims to enhance the filling and emptying of lymph vessels, is often recommended as an essential part of a successful management strategy for lymphoedema. However, the literature on its efficacy is often contradictory, and its addition may not always be necessary. To ensure optimal understanding of practitioners and benefit to patients, Francesca Ramadan summarises the evidence-based advantages and limitations of MLD.

Is the Absence of Manual Lymphatic Drainage-Based Treatment in Lymphedema after Breast Cancer Harmful? A Randomized Crossover Study.

(1) Background: Manual lymphatic drainage (MLD), included within the complex decongestive therapy, as a therapy for the treatment of lymphedema has raised controversy about its benefits for lymphedema after breast cancer. The aim of this research is to test the effects of MLD on lymphedema after breast cancer during the treatment maintenance phase. (2) Methods: A randomized, single-blinded, controlled crossover trial was conducted to analyze the effects of a manual lymphatic drainage intervention compared to a control group without MLD intervention for the treatment of lymphedema. Arm volume measured by circumference measurement, subcutaneous tissue thickness measured by ultrasound, and the sensation of pain, heaviness, and swelling were evaluated as outcome measures. (3) Results: For the control group, an increase in volume was found in some of the circumference and subcutaneous tissue thickness measurements, in addition to a worsening of arm pain, swelling and heaviness. (4) Conclusion: The absence of treatment based on MLD in lymphedema after breast cancer worsens volume measurements, as well as arm heaviness. Therefore, it would be advisable to carry out this type of therapy as part of the maintenance treatment for lymphedema in breast cancer.

Effects of manual lymphatic drainage on total knee replacement: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total knee joint replacement (TKR) is an effective method for the treatment of severe knee osteoarthritis. With an increasing number of surgeries, complications such as lower limb edema, pain, and limited mobility have caused a heavy burden. Manual lymphatic drainage (MLD) may be a solution to solve the problem. The study aims to evaluate the efficacy of MLD in reducing knee edema, pain, and improving range of motion (ROM) in patients after TKR. METHODS: A search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIPs, WanFang database, and Google Scholar from inception to June 2023. Only randomized controlled trials (RCTs) that compared the effects of MLD and non-MLD (or another physiotherapy) on improving knee edema, pain, and ROM after TKR were included. Stata 16.0 was used for meta-analysis. GRADE was used to assess the quality of evidence. RESULTS: In total, 7 RCTs with 285 patients were identified. There were no significant differences found in the ROM of knee flexion (standardized mean difference (SMD) = 0.03, 95% confidence interval (CI): -0.22, 0.28, P = 0.812) and the ROM of knee extension (SMD= -0.30, 95%CI: -0.64, 0.04, P = 0.084). No differences were observed in the lower extremity circumference after TKR (SMD= -0.09, 95%CI: -0.27, 0.09, P = 0.324). For postoperative pain, there was no significant advantage between the MLD and non-MLD groups (SMD= -0.33, 95%CI: -0.71, 0.04, P = 0.083). CONCLUSIONS: Based on the current evidence from RCTs, manual lymphatic drainage is not recommended for the rehabilitation of patients following total knee replacement.

Application of complete decongestive therapy after lymphaticovenular anastomosis of the lower limb combined with liposuction-A retrospective study research.

BACKGROUND: Complete decongestive therapy (CDT) is a conservative treatment for lymphedema that combines interventions and lifestyle changes. We evaluated the application of CDT after lymphaticovenular anastomosis (LVA) of the lower limb combined with liposuction. METHODS: A total of 55 patients who underwent LVA of the lower limb combined with liposuction from January 2021 to July 2022 were enrolled in the study. The patients were divided into groups A (n = 24) and B (n = 31) according to whether they adhered to CDT treatment during the 12-month follow-up. Group A was the non-adherence CDT group and Group B was the adherence CDT group. Lower Extremity Lymphedema Index (LELI) and Lymphoedema Functioning, Disability, and Health Questionnaire for Lower Limb Lymphoedema (Lymph-ICF-LL) were used as prognostic indicators to observe the remission of postoperative lymphedema symptoms in the two groups. RESULTS: At 6-month and 12-month follow-up, LELI and the score of Lymph-ICF-LL in group B and group A were lower than before the operation (p < .05). The circumference of the affected limb was reduced, and the quality of life was improved in both groups after the operation. The reduction of LELI and Lymph-ICF-LL in group B was higher than in group A, and the difference was statistically significant (p < .05). CONCLUSION: This study preliminarily proves the effectiveness of CDT after LVA of the lower limb combined with liposuction, which can maintain and strengthen the surgical effect. Further, CDT treatment is still needed after the operation, which is necessary to reduce the circumference of the affected limb and improve patients' quality of life.

Effectiveness of manual lymphatic drainage in intensive phase I therapy of breast cancer-related lymphedema-a retrospective analysis.

BACKGROUND: The standard therapy for lymphedema of any origin is complex physical decongestive therapy (CDT). It comprises manual lymph drainage (MLD), compression therapy (CT), exercise therapy (ET), skincare, and patient education. Additionally, intermittent pneumatic compression (IPC) can be applied. However, the contribution of MLD to decongestion is repeatedly questioned. PATIENTS AND METHODS: This study re-analyzes a previous study during a 3-week decongestion period, comparing two different types of compression bandaging at the weekend. Sixty-one patients with unilateral breast cancer-related lymphedema were included. The patients received the same therapy (CDT + IPC) except for the different weekend compression bandaging. MLD was performed twice a day on weekdays. The volume of the affected arm was measured on days 1, 5, 8, 12, 15, 19, and 22. For the analysis, the data of both study groups were pooled. RESULTS: During the week, the patients showed a significant volume reduction (- 155.23 mL (week 1), - 101.02 mL (week 2), - 61.69 mL (week 3), respectively; p < 0.001 each) with a high effect size. On the weekends without MLD, they showed a slight, but also significant increase (12.08 mL (weekend 1), 8.36 mL (weekend 2), 4.33 mL (weekend 3), respectively; p < 0.001 each) with a medium effect size. CONCLUSIONS: We showed a strong effect of MLD on volume reduction. Differences from other studies are the larger study population and the more intensive application of MLD. If applied intensively, MLD is strongly decongestive during a 3-week decongestion therapy for breast cancer-related lymphedema.

Therapeutic Ultrasound Alone and Associated with Lymphatic Drainage in Women with Breast Engorgement: A Clinical Trial.

Introduction: Breast engorgement (BE) is a problem that affects many women, especially in the first days of breastfeeding, producing inflammatory symptoms. Nonpharmacological therapies are inexpensive, safe, and can produce symptom relief. Objective: This study aims to analyze the safety of therapeutic ultrasound regarding possible risks of overheating and the effects of its use alone and associated with lymphatic drainage (LD) in women. Material and Methods: Effectiveness is measured through thermography, visual analog scale, and six-point scale of BE. This is a nonrandomized clinical trial with a sample of 34 in the ultrasound group (G1), 28 in the ultrasound and LD group (G2), and 37 in the control group (G3). Results: The mean reduction for engorgement was 1.3 ± 0.8 to G1, 1.4 ± 1.0 to G2, and 1.2 ± 0.9 to G3 according to the six-point scale. The mean reduction for pain level was 3.6 ± 2.1 to G1, 4.0 ± 3.1 to G2, and 4.0 ± 2.2 to G3 according to the visual analogue scale. Conclusion: It was observed that all therapies were effective in reducing the level of engorgement, according to the six-point scale. However, combined ultrasound and LD therapy has been shown to be more effective in reducing the level of pain. Brazilian Registry of Clinical Trials (RBR-6btb6zz).

Comparative effects of lymphatic drainage and soft tissue mobilization on pain threshold, shoulder mobility and quality of life in patients with axillary web syndrome after mastectomy.

PURPOSE: The purpose was to compare the effects of manual lymphatic drainage and soft tissue mobilization on pain threshold, shoulder mobility and quality of life in patients with axillary web syndrome. METHODS: This randomized clinical trial was conducted on 36 breast cancer patients with developed axillary web; participants were randomly divided into two groups. One group was treated with manual lymphatic drainage; the other group was treated with soft tissue mobilizations in addition to therapeutic exercises, i.e., stretching, strengthening and range of motion (ROM) exercises. The duration of treatment was four weeks (5 sessions/week), with therapeutic exercises as a common treatment protocol. Outcome measures were Breast-Cancer specific quality of life questionnaires, Disabilities of the Arm, Shoulder and Hand (DASH), Numeric Pain Rating Scale (NPRS), Patient Specific Functional Scale (PSFS), Dynamometer and Goniometer. All outcome measure readings were recorded at baseline and the end (4th week) of the treatment. RESULTS: The compliance of the variable distribution with normal distribution was verified using the Shaphiro-Wilk test. Parametric tests were applied, and both groups showed significant effects (p < 0.05) in pairwise comparison (paired t-test). The comparison group analysis (independent t-test) showed that there was no significant difference in pain, upper limb strength, range of motions and fatigue component of quality of life questionnaire parameters (p > 0.05). Two parameters (DASH, PSFS) and one component of the quality of life questionnaire (global health) showed a significant difference (p < 0.05). CONCLUSION: Manual lymphatic drainage showed more improvement in functional movements. It was concluded that both groups, manual lymphatic drainage and soft tissue mobilization groups were clinically equally effective. TRIAL REGISTRATION NUMBER: This trial is registered at ClinicalTrial.gov PRS under trial number NCT05463185 on date 18/07/2022.

Effectiveness of manual lymphatic drainage and intermittent pneumatic compression in lymphedema maintenance therapy.

Background: To compare the effectiveness of intermittent pneumatic compression (IPC) and/or manual lymphatic drainage (MLD) associated to compression stockings in the maintenance treatment of lymphedema. Patients and methods: Patients in the maintenance phase of lymphedema therapy with MLD and compression since more than a year with stable values for weight and circumferences of ankle and calf were asked to participate in a study: Compression had to be worn daily, (1) 4 weeks IPC+MLD, (2) 4 weeks MLD alone, (3) 4 Weeks IPC alone (Order 1 and 3 was randomized). At the beginning and after each 4 weeks, circumference measurements (by hand and by machine: BT600®, Bauerfeind) were documented, pain and discomfort were assessed, and quality-of-life questionnaires were completed. Results: Of 20 participants, 18 (14 female, 4 male), mean age 59.6 years (48-89) could be evaluated. 11 subjects had bilateral, 7 unilateral, 5 primary, 13 secondary lymphedema since 2-20 years (mean 7.7), the subjects had received MLD and compression for 2-14 years (mean 6.4), 1-3 times per week (mean 1.5). The BMI ranged between 21 and 47 (mean 33.7). No differences between any phases were found for: Calf and thigh volume, circumference of calf. Only the ankle circumference was significant less (-0.22 cm) when using "both" (IPC+MLD). Compared to before the study, quality of life was better in all three phases, but with a significantly higher improvement in the phases with IPC than in the phases without. Conclusions: There were no differences in objective measurement between MLD alone, IPC alone or both, excepting the minimal significant difference in ankle circumference after IPC+MLD. QOL favored IPC application. Considering the economic consequences of these results, a change of maintenance therapy with MLD weekly over years in favor of permanent care with IPC and few appointments of MLD per year should be considered and further investigated.

Does manual lymphatic drainage improve upper extremity functionality in female patients diagnosed with rheumatoid arthritis? A randomized controlled study.

OBJECTIVE: To demonstrate the effect of manual lymphatic drainage (MLD) on upper extremity functionality in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Thirty-nine female patients diagnosed with RA who were in remission were included in the study. The study group included 19 participants (mean age 50.63 ± 9.83 years), the control group included 20 participants (mean age 55.05 ± 5.89 years). The patients were randomized into two groups as home exercise program plus MLD and home exercise program alone. Both groups received treatment for 4 weeks. The primary outcome measure was pressure pain threshold (PPT). The patients were evaluated using the PPT, visual analog scale (VAS), hand-wrist joint range of motion examination, hand dynamometer and pinchmeter measurements, and the Rheumatoid Arthritis Quality of Life Scale before the interventention and at the end of the 4th week. RESULTS: The PPT evaluated at the thumbnail, wrist, and trapezius significantly increased in the study group after treatment (p < .001, p = .001, and p < .001, respectively). MLD was found to significantly increase the PPT at the thumbnail compared with home exercise program (p = .047). The VAS score significantly decreased in the study group (p = .011). The level of increase in radial deviation was statistically higher in the study group (p = .004). CONCLUSION: Manual lymphatic drainage had a positive effect on pain, PPT, and range of motion in RA patients in remission. MLD can be added to medical and other conservative treatments in RA patients.

Three-month work-related musculoskeletal disorders assessment during manual lymphatic drainage in physiotherapists using Generic Postures notion.

OBJECTIVES: The aim of this work was to quantify the postures and to assess the musculoskeletal disorders (MSDs) risk in physiotherapists repeating a manual lymphatic drainage (MLD) over a three-month period. The underlying hypothesis was that there would be Generic Postures (GP) that would be repeated and could be used to more simply describe repetitive and long-duration complex activities. METHODS: The posture of five physiotherapists performing five 20-min MLD at their workplace was captured by two cameras. From the recordings, the adopted postures were extracted every 5 s and quantified through 13 joint angles, that is, 6594 analyzed postures. Rapid Upper Limb (RULA) and Rapid Entire Body Assessment (REBA) were used to assess MSDs risks. A hierarchical analysis was used to define GP. RESULTS: Seven GP were identified through mean values and standard deviation. GP ergonomic assessment showed a low to moderate MSD risk (RULA between 3 and 6 and REBA between 2 and 7). High neck (>20°) and trunk (>15°) flexion were observed for all GP. High shoulder abduction and flexion (>40°) were evidenced for GP3 to GP5. GP1 was the most used (34%) and presented the lowest ergonomic scores (RULA: 4.46 ± 0.84; REBA: 5.06 ± 1.75). GP3 to GP6 had frequency of between 10 and 20%. GP5, GP6, and GP7 obtained the highest ergonomic scores (RULA>5; REBA>7). All physiotherapists use different GP combinations to perform MLD. CONCLUSION: MLD could be described as a combination of GP. Ergonomic analysis showed that MLD exposes physiotherapists to low at moderate MSD risks.

Meningeal lymphatics and their role in CNS disorder treatment: moving past misconceptions.

The central nervous system (CNS) was previously thought to lack lymphatics and shielded from the free diffusion of molecular and cellular components by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB). However, recent findings have redefined the roles played by meningeal lymphatic vessels in the recruitment and drainage of lymphocytes from the periphery into the brain and the potentiation of an immune response. Emerging knowledge surrounding the importance of meningeal lymphatics has the potential to transform the treatment of CNS disorders. This review details the most recent understanding of the CNS-lymphatic network and its immunologic implications in both the healthy and diseased brain. Moreover, the review provides in-depth coverage of several exciting avenues for future therapeutic treatments that involve the meningeal lymphatic system. These therapeutic avenues will have potential implications in many treatment paradigms in the coming years.

Postoperative swelling after elbow surgery: influence of a negative pressure application in comparison to manual lymphatic drainage-a randomized controlled trial.

PURPOSE: Postoperative soft tissue swelling is a significant factor influencing outcomes after elbow surgery. It can crucially affect important parameters such as postoperative mobilization, pain, and subsequently the range of motion (ROM) of the affected limb. Furthermore, lymphedema is considered a significant risk factor for numerous postoperative complications. Manual lymphatic drainage is nowadays part of the standardized post-treatment concept, basing on the concept of activating the lymphatic tissue to absorb stagnated fluid from the tissue into the lymphatic system. This prospective study aims to investigate the influence of technical device-assisted negative pressure therapy (NP) on early functional outcomes after elbow surgery. NP was therefore compared to manual lymphatic drainage (MLD). Is a technical device-based NP suitable for treatment of lymphedema after elbow surgery? METHODS: A total of 50 consecutive patients undergoing elbow surgery were enrolled. The patients were randomized into 2 groups. 25 participants per group were either treated by conventional MLD or NP. The primary outcome parameter was defined as the circumference of the affected limb in cm postoperative up to seven days postoperatively. The secondary outcome parameter was a subjective perception of pain (measured via visual analogue scale, VAS). All parameters were measured on each day of postoperative inpatient care. RESULTS AND CONCLUSION: NP showed an overall equivalent influence compared to MLD in reducing upper limb swelling after surgery. Moreover, the application of NP showed a significant decrease in overall pain perception compared to manual lymphatic drainage on days 2, 4 and 5 after surgery (p < 0.05). CONCLUSION: Our findings show that NP could be a useful supplementary device in clinical routine treating postoperative swelling after elbow surgery. Its application is easy, effective and comfortable for the patient. Especially due to the shortage of healthcare workers and physical therapists, there is a need for supportive measures which NP could be.

The Sentinel Lymph Node in Treatment Planning: A Narrative Review of Lymph-Flow-Guided Radiotherapy.

The sentinel lymph node technique is minimally invasive and used routinely by surgeons, reducing the need for morbid extensive lymph node dissections, which is a significant advantage for cancer staging and treatment decisions. The sentinel lymph node could also help radiation oncologists to identify tumor drainage for each of their patients, leading to a more personalized radiotherapy, instead of a probabilistic irradiation based on delineation atlases. The aim is both to avoid recurrence in unexpected areas and to limit the volume of irradiated healthy tissues. The aim of our study is to evaluate the impact of sentinel lymph node mapping for radiation oncologists. This concept, relying on sentinel lymph node mapping for treatment planning, is known as lymph-flow-guided radiotherapy. We present an up-to-date narrative literature review showing the potential applications of the sentinel lymph node technique for radiotherapy, as well as the limits that need to be addressed before its routine usage.

Effect of Manual Lymphatic Drainage on the Concentrations of Selected Adipokines, Cytokines, C-Reactive Protein and Parameters of Carbohydrate and Lipid Metabolism in Patients with Abnormal Body Mass Index: Focus on Markers of Obesity and Insulin Resistance.

The aim of the study was to assess the impact of manual lymphatic drainage (MLD) on the parameters of carbohydrate metabolism, lipid metabolism and the level of selected adipokines and cytokines in people with abnormal body mass index (BMI). In addition, an attempt was made to assess the optimal cut-off values of serum concentrations of the biochemical parameters studied in identifying the risk of obesity and insulin resistance (IR). The study included 60 subjects who underwent 10 and 30 min long MLD sessions three times a week. The study group included 15 patients with a normal body mass index (group I; n = 15), overweight patients (group II; n = 15) and obese patients (group III; n = 10). The control group was IV; n = 20 subjects not undergoing MLD. Biochemical tests were carried out on all subjects at stage 0' (before MLD therapy) and at stage 1' (one month after MLD therapy). In the control group, the time between the sample collection at stage 0' and stage 1' was the same as in the study group. Our results showed that 10 MLD sessions may have a positive effect on the selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR values in normal weight and overweight patients. In addition, in the study group, the highest AUCROC values in identifying the risk of obesity were found for leptin (AUCROC = 82.79%; cut-off = 17.7 ng/mL; p = 0.00004), insulin (AUCROC = 81.51%; cut-off = 9.5 µIU/mL; p = 0.00009) and C-peptide (AUCROC = 80.68%; cut-off = 2.3 ng/mL; p = 0.0001) concentrations as well as for HOMA-IR values (AUCROC = 79.97%; cut-off = 1.8; p = 0.0002). When considering the risk of IR, we observed the highest diagnostic value for insulin (AUCROC = 93.05%; cut-off = 1.8 ng/mL; p = 0.053), which was followed by C-peptide (AUCROC = 89.35%; cut-off = 17.7 ng/mL; p = 0.000001), leptin (AUCROC = 79.76%; cut-off = 17.6 ng/mL; p = 0.0002) and total cholesterol (AUCROC = 77.31%; cut-off = 198 mg/dL; p = 0.0008). Our results indicate that MLD may have a positive effect on selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR, in normal weight and overweight patients. In addition, we successfully established optimal cut-off values for leptin in the assessment of obesity and insulin in the assessment of insulin resistance in patients with abnormal body mass index. Based on our findings, we hypothesize that MLD, when combined with caloric restriction and physical activity, may serve as an effective preventive intervention against the development of obesity and insulin resistance.

The Effect of Craniofacial Manual Lymphatic Drainage after Moderate Traumatic Brain Injury.

Previous studies suggest that craniofacial manual lymphatic drainage (MLD) facilitates brain fluids clearance, reducing intracranial pressure and reabsorbing chronic subdural hematoma. This study aimed to explore the effect of craniofacial MLD in combination with pharmacological treatment for improving cranial pain intensity, vital signs, and cerebral edema (Hounsfield units, HUs) in moderate traumatic brain injury (mTBI). Patient 1 received pharmacological therapy, while patient 2 received both pharmacological and craniocervical MLD treatment. Patient 2 showed decreased cranial pain intensity and systolic blood pressure (66%-11.11%, respectively) after two 30 min daily sessions of treatment for three days. HUs in the caudate nucleus of both hemispheres (left 24.64%-right 28.72%) and in the left temporal cortical gray matter increased (17.8%). An increase in HU suggests a reduction in cerebral edema and vice versa. For patient 1, there were no changes in cranial pain intensity, but a slight increase in the systolic blood pressure was observed (0%-3.27%, respectively). HUs decreased in the temporal cortical (14.98%) and caudate nucleus gray matter (9.77%) of the left and right cerebral hemispheres (11.96%-16.74%, respectively). This case study suggests that craniofacial MLD combined with pharmacological treatment could reduce cerebral edema, decrease head pain intensity, and maintain vital signs in normal physiologic values in patients with mTBI.

Lymphoscintigraphy as a Therapeutic Guidance Tool Can Improve Manual Lymphatic Drainage for the Physical Treatment of Patients with Upper Limb Lymphedema: Randomized Clinical Trial.

Background: The purpose of this study was to measure the effects of lymphoscintigraphically guided manual lymphatic drainage (LG-MLD) and to compare it with standardized manual lymphatic drainage (St-MLD). Materials and Methods: Fifty-two patients with lymphedema of the upper limb who underwent lymphoscintigraphy were randomly allocated into two groups. Following the phase of physical activity, the control group underwent two phases of St-MLD as the experimental group underwent a first phase of St-MLD followed by a second phase of LG-MLD. Areas of interest were then selected [in particular, dermal backflow (DBF) and axillary lymph nodes (LN)], radioactive activities were quantified for each of these areas. Results: If a first phase of St-MLD increased the LN activity by 28% on average, the findings indicated that for the second phase of DLM, LG-MLD was 19% more efficient than St-MLD in increasing LN activity. If a period of rest does not influence the lymph charge of DBF areas, physical activity leads to an average activity increase of 17%, whereas LG-MLD and St-MLD lead to an activity decrease of 11%. Conclusions: For patients with lymphedema, the findings indicate that MLD can increase the lymphatic flow toward the lymphatic nodes by 28% on average and can decrease the charge in the areas of DBF by 11% on average. Moreover, lymphoscintigraphy can be an important therapeutic tool because LG-MLD significantly increases lymphatic flow by 19% more than St-MLD. Concerning the areas of DBF, the LG-MLD and St-MLD decrease the charge in these areas with the same intensity.

rTMS treatment for abrogating intracerebral hemorrhage-induced brain parenchymal metabolite clearance dysfunction in male mice by regulating intracranial lymphatic drainage.

BACKGROUND: The discovery of the glymphatic system and meningeal lymphatic vessels challenged the traditional view regarding the lack of a lymphatic system in the central nervous system. It is now known that the intracranial lymphatic system plays an important role in fluid transport, macromolecule uptake, and immune cell trafficking. Studies have also shown that the function of the intracranial lymphatic system is significantly associated with neurological diseases; for example, an impaired intracranial lymphatic system can lead to Tau deposition and an increased lymphocyte count in the brain tissue of mice with subarachnoid hemorrhage. METHODS: In this study, we assessed the changes in the intracranial lymphatic system after intracerebral hemorrhage and the regulatory effects of repeated transcranial magnetic stimulation on the glymphatic system and meningeal lymphatic vessels in an intracerebral hemorrhage (ICH) model of male mice. Experimental mice were divided into three groups: Sham, ICH, and ICH + repeated transcranial magnetic stimulation (rTMS). Three days after ICH, mice in the ICH+rTMS group were subjected to rTMS daily for 7 days. Thereafter, the function of the intracranial lymphatic system, clearance of RITC-dextran and FITC-dextran, and neurological functions were evaluated. RESULTS: Compared with the Sham group, the ICH group had an impaired glymphatic system. Importantly, rTMS treatment could improve intracranial lymphatic system function as well as behavioral functions and enhance the clearance of parenchymal RITC-dextran and FITC-dextran after ICH. CONCLUSION: Our results indicate that rTMS can abrogate ICH-induced brain parenchymal metabolite clearance dysfunction by regulating intracranial lymphatic drainage.

Advances in the prevention and treatment of breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies. FINDINGS: Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful. CONCLUSION: Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.

The Prevalence of the Axillo-Inguinal Lymphatic Pathway in Lymphedema of the Extremities and Potential Therapeutic Implications.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.