A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-induced ROCK2/JAM-A complex.

Impaired lymphatic drainage and lymphedema are major morbidities whose mechanisms have remained obscure. To study lymphatic drainage and its impairment, we engineered a microfluidic culture model of lymphatic vessels draining interstitial fluid. This lymphatic drainage-on-chip revealed that inflammatory cytokines that are known to disrupt blood vessel junctions instead tightened lymphatic cell-cell junctions and impeded lymphatic drainage. This opposing response was further demonstrated when inhibition of rho-associated protein kinase (ROCK) was found to normalize fluid drainage under cytokine challenge by simultaneously loosening lymphatic junctions and tightening blood vessel junctions. Studies also revealed a previously undescribed shift in ROCK isoforms in lymphatic endothelial cells, wherein a ROCK2/junctional adhesion molecule-A (JAM-A) complex emerges that is responsible for the cytokine-induced lymphatic junction zippering. To validate these in vitro findings, we further demonstrated in a genetic mouse model that lymphatic-specific knockout of ROCK2 reversed lymphedema in vivo. These studies provide a unique platform to generate interstitial fluid pressure and measure the drainage of interstitial fluid into lymphatics and reveal a previously unappreciated ROCK2-mediated mechanism in regulating lymphatic drainage.

Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and Triggering DECR1-Mediated Mitochondrial Bioenergetics.

BACKGROUND: BMP9 (bone morphogenetic protein 9) is a member of the TGF-ß (transforming growth factor ß) family of cytokines with pleiotropic effects on glucose metabolism, fibrosis, and lymphatic development. However, the role of BMP9 in myocardial infarction (MI) remains elusive. METHODS: The expressional profiles of BMP9 in cardiac tissues and plasma samples of subjects with MI were determined by immunoassay or immunoblot. The role of BMP9 in MI was determined by evaluating the impact of BMP9 deficiency and replenishment with adeno-associated virus-mediated BMP9 expression or recombinant human BMP9 protein in mice. RESULTS: We show that circulating BMP9 and its cardiac levels are markedly increased in humans and mice with MI and are negatively associated with cardiac function. It is important to note that BMP9 deficiency exacerbates left ventricular dysfunction, increases infarct size, and augments cardiac fibrosis in mice with MI. In contrast, replenishment of BMP9 significantly attenuates these adverse effects. We further demonstrate that BMP9 improves lymphatic drainage function, thereby leading to a decrease of cardiac edema. In addition, BMP9 increases the expression of mitochondrial DECR1 (2,4-dienoyl-CoA reductase 1), a rate-limiting enzyme involved in ß-oxidation, which, in turn, promotes cardiac mitochondrial bioenergetics and mitigates MI-induced cardiomyocyte injury. Moreover, DECR1 deficiency exacerbates MI-induced cardiac damage in mice, whereas this adverse effect is restored by the treatment of adeno-associated virus-mediated DECR1. Consistently, DECR1 deletion abrogates the beneficial effect of BMP9 against MI-induced cardiomyopathy and cardiac damage in mice. CONCLUSIONS: These results suggest that BMP9 protects against MI by fine-tuning the multiorgan cross-talk among the liver, lymph, and the heart.

Cerebrospinal fluid markers of neuroinflammation and coagulation in severe cerebral edema and chronic hydrocephalus after subarachnoid hemorrhage: a prospective study.

BACKGROUND: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. METHODS: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. RESULTS: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1ß, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. CONCLUSIONS: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction.

The cerebral lymphatic drainage system and its implications in epilepsy.

The central nervous system has long been thought to lack a clearance system similar to the peripheral lymphatic system. Therefore, the clearance of metabolic waste in the central nervous system has been a subject of great interest in neuroscience. Recently, the cerebral lymphatic drainage system, including the parenchymal clearance system and the meningeal lymphatic network, has attracted considerable attention. It has been extensively studied in various neurological disorders. Solute accumulation and neuroinflammation after epilepsy impair the blood-brain barrier, affecting the exchange and clearance between cerebrospinal fluid and interstitial fluid. Restoring their normal function may improve the prognosis of epilepsy. However, few studies have focused on providing a comprehensive overview of the brain clearance system and its significance in epilepsy. Therefore, this review addressed the structural composition, functions, and methods used to assess the cerebral lymphatic system, as well as the neglected association with epilepsy, and provided a theoretical basis for therapeutic approaches in epilepsy.

Patterns of forearm lymphatic drainage to the epitrochlear lymph nodes in 1400 cutaneous melanoma patients.

BACKGROUND: Variations of hand and forearm lymphatic drainage to upper-arm lymphatic pathways may impact the route of melanoma metastasis. This study compared rates of lymphatic drainage to epitrochlear nodes between anatomic divisions of the hand and forearm to determine whether the anatomic distribution of hand and forearm melanomas affects the likelihood of drainage to epitrochlear lymph nodes. METHODS: Using a single-institution lymphoscintigraphy database, we identified all patients with cutaneous melanoma on the hand and forearm. A body-map two-dimensional coordinate system was used to classify cutaneous melanoma sites between radial-ulnar and dorsal-volar divisions. Sentinel lymph nodes (SLNs) visualized on lymphoscintigraphy were recorded. Proportions of patients with epitrochlear SLNs were compared between anatomic divisions using χ2 analysis. RESULTS: Of 3628 upper extremity cutaneous melanoma patients who underwent lymphatic mapping with lymphoscintigraphy, 1400 met inclusion criteria. Twenty-one percent of patients demonstrated epitrochlear SLNs. Epitrochlear SLNs were observed in 27% of dorsal forearm melanomas and 15% of volar forearm melanomas (p < 0.001). Epitrochlear SLNs were observed in 31% of ulnar forearm melanomas and 17% of radial forearm melanomas (p < 0.001). CONCLUSIONS: Higher proportions of dorsal and ulnar forearm melanomas have epitrochlear SLNs. Metastasis to epitrochlear SLNs may be more likely from melanomas in these respective forearm regions.

Lymphatic drainage patterns of malignant skin tumors in the head and neck region: a single-center retrospective study.

BACKGROUND: This study aimed to clarify the relationship between primary site and lymphatic drainage pattern for malignant skin tumors in the head and neck region. Malignant melanoma and squamous cell carcinoma in the head and neck region are known to have poor prognosis because of lymph node metastasis. Nevertheless, numerous aspects of lymphatic drainage patterns remain elusive. METHODS: We statistically analyzed data of 47 patients with malignant skin tumors in the head and neck region. Information was collected on the patients' clinical characteristics, primary tumor site, and lymphatic drainage patterns. RESULTS: The parotid lymph nodes drained the greatest amount of lymph from skin tumors of the head and neck. Important lymphatic drainage pathways were the superficial cervical nodes for primary tumors in the buccal/nasal region, level IA and level IB nodes for primary tumors in the lip region, the occipital nodes, posterior auricular nodes, and level VA nodes in the parietal/occipital region, and the preauricular nodes in the auricular region. CONCLUSION: These findings have considerable significance in terms of understanding lymphatic drainage patterns for malignant skin tumors in the head and neck and may be useful for clinical decision-making and when planning treatment. Further research and clinical applications are expected to contribute to an improved prognosis in patients with cutaneous head and neck malignancies.

The Impact of Lymphatic Drainage and Nerve Mobilization Techniques on Nerve Morphology in Mild-to-Moderate Carpal Tunnel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To investigate whether nerve mobilization related to nerve mobility or the removal of edema using lymphatic drainage affects the cross-sectional area of the nerve, hand function, and symptom severity in carpal tunnel syndrome. DESIGN: The study is a prospective randomized controlled trial. Data were analyzed between groups using ANOVA, Chi-squared test, and Kruskal-Wallis test. SETTING: Treatment lasted 4 weeks. Splint group wore the splint daily. Splint+manual lymphatic drainage received lymphatic drainage 5 days a week. Splint+nerve mobilization performed neuromobilization exercises as home exercises 5 days a week. Evaluations were conducted before and after 4 weeks of treatment. PARTICIPANTS: The study included 80 patients with mild-to-moderate carpal tunnel syndrome. INTERVENTIONS: The patients were randomly divided into three groups: splint (n = 27), splint+manual lymphatic drainage (n = 27), or the splint+nerve mobilization (n = 26). MAIN OUTCOME MEASURES: The main outcome measures were ultrasound assessments and the Boston Carpal Tunnel Questionnaire (Symptom Severity Scale and Boston Functional Status Scale). RESULTS: Compared to the other groups, the nerve cross-sectional area decreased at both the carpal tunnel (p = 0.003) and mid-forearm (p = 0.014) levels in the drainage group. Nerve mobilization did not result in a significant change in the nerve cross-sectional area. All groups showed significant improvements in both symptom severity and functional status scores (p < 0.001). CONCLUSION: The reduction of edema through lymphatic drainage contributes to a decrease in the cross-sectional area of the median nerve. Additionally, all three methods appear to positively impact the functional capacity of the hand and alleviate symptoms.

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.

Contribution of the cadaveric recirculation system in the anatomical study of lymphatic drainage of the ovary: applications in the management of ovarian cancer.

PURPOSE: The present knowledge about lymphatic drainage of the ovary is based on carcinological studies, but it has only rarely been studied under physiological conditions. However, it is one of the preferential routes of dissemination in ovarian cancer, and understanding it is therefore vital for optimal carcinological management.Our purpose was to evaluate the feasibility of an innovative technique to study the lymphatic drainage territories of the ovary using a recirculation module on the cadaveric model. METHODS: We injected patent blue into the cortex of twenty "revascularised" cadaver ovaries with the Simlife recirculation model. We observed the migration of the dye live and described the drainage territories of each ovary. RESULTS: We observed a staining of the lymphatic vessels and migration of the dye in all the subjects, systematically ipsilateral to the injected ovary. We identified a staining of the lumbo-aortic territory in 65% of cases, with a preferential lateral-caval involvement (60%) for the right ovary and lateral-aortic territory (40%) for the left ovary. A common iliac involvement was observed in only 10% of cases. In 57% of cases, the staining of the lumbo-aortic territory was associated with a staining of the suspensory ligament. The pelvic territory was involved in 50% of cases, with an external iliac staining in 25% of cases and internal in 20%. CONCLUSION: Our study provides for a better understanding of lymphatic drainage of the ovary using a new detection method, and allows the possibility of improving the teaching for operators with a realistic model. Continuation of this work could lead to considering more targeted and thus less morbid lymph node sampling for lymph node staging in early-stage ovarian cancer.

An overview of manual lymphatic drainage.

Manual lymphatic drainage is an advanced therapy that enhances the movement of lymph via a gentle form of massage. In this article, Sarah Jane Palmer provides an overview of manual lymphatic drainage as a treatment for lymphoedema, and summarises the latest research in the area.

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.

Use of simple lymphatic drainage on truncal lymphoedema for a patient with diabetes and peripheral arterial disease.

Lymphoedema is the gradual, abnormal build-up of lymph fluid in the tissues resulting from a failure of the lymphatic system. The swelling impedes movement and is painful. Compression garments are contraindicated and not tolerated by patients with extensive peripheral arterial disease. In this case study, simple lymphatic drainage was therefore considered a safer treatment option to reduce oedema and to encourage proactive self-management for a patient with bilateral amputations, diabetes and peripheral arterial disease.

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.

Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

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.

Lymphatic Drainage System and Lymphatic Metastasis of Cancer Cells in the Mouse Esophagus.

BACKGROUND: Lymphatic metastasis is commonly seen in patients with esophageal squamous cell carcinoma (ESCC). Both lymphatic metastasis and the number of involved nodes are prognostic for post-operative survival. To better understand lymphatic metastasis of ESCC, there is a need to develop proper animal models. AIMS: This study is aimed to characterize the morphology and function of the lymphatic drainage system in the mouse esophagus. METHODS: Immunostaining and fluorescence imaging were used to visualize the lymphatic drainage system in the mouse esophagus. Tracers and cancer cells were orthotopically inoculated into the submucosa of the mouse esophagus to mimic lymphatic metastasis of T1 ESCC. RESULTS: Using immunostaining of a lymphatic vessel marker (LYVE1), we found that lymphatic vessels were located in the submucosa and muscularis propria of the mouse esophagus, similar to the human esophagus. In the esophagus of ProxTom mice expressing tdTomato in the lymphatic vessels, we discovered a microscopic meshwork of lymphatic vessels. Functionally, orthotopically inoculated tracers (Indian ink and FITC-dextran) were drained from the submucosa into peri-esophageal lymph nodes via lymphatic vessels. Orthotopically inoculated mouse cancer cells (LLC-eGFP, MOC2) metastasized from the submucosa to lymphatic vessels, peri-esophageal lymph nodes, and distant organs (liver and lung) in immunocompetent mice. Similarly, in immunodeficient mice, orthotopically inoculated human ESCC cells (KYSE450-eGFP-Luc) metastasized via the same route. CONCLUSION: We have characterized the morphology and function of the lymphatic drainage system of the mouse esophagus. These observations lay a foundation for mechanistic and therapeutic studies on lymphatic metastasis of T1 ESCC.

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.

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.

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.