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Simple lymphatic drainage (SLD) is a self-administered technique for managing lymphedema; however, its efficacy in preventing lower limb lymphedema (LLE) following pelvic lymphadenectomy remains unclear. This prospective study evaluated the preventive effects of SLD at a single institution. A total of 224 patients were enrolled who underwent gynecological cancer surgery with pelvic lymphadenectomy between April 2011 and May 2012. After excluding patients with deep vein thrombosis, age ≥ 80 years, refusal to participate, and those with uncertain malignancy, 190 patients remained. A subset of 87 patients without adjuvant therapy was divided into two groups based on their preference: 24 in the SLD group and 63 in the control group. SLD group patients performed daily SLD for one year, and a 5-year follow-up was conducted. No significant differences were observed between groups in the change ratio of the lower limb circumference and the impedance method for the extracellular water: total body water ratio. The 5-year cumulative incidence of lymphedema (ISL stage I or more) was 37.5% in the SLD group and 23.5% in the control group, with no significant difference between the two groups. SLD does not contribute to the prevention of LLE following gynecological cancer surgery with pelvic lymphadenectomy.

PurposeBreast 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.FindingsRisk 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.ConclusionProgress 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.

Background Breast cancer is the most common cancer, and the leading cause of cancer-related deaths, among females world-wide. Recent research suggests that extracellular vesicles (EVs) play a major role in the development of breast cancer metastasis. Axillary lymph node dissection (ALND) is a procedure in patients with known lymph node metastases, and after surgery large amounts of serous fluid are produced from the axilla. The overall aim was to isolate and characterize EVs from axillary serous fluid, and more specifically to determine if potential breast cancer biomarkers could be identified. Methods Lymphatic drain fluid was collected from 7 patients with breast cancer the day after ALND. EVs were isolated using size exclusion chromatography, quantified and detected by nanoparticle tracking analysis, electron microscopy, nano flow cytometry and western blot. The expression of 37 EV surface proteins was evaluated by flow cytometry using the MACSPlex Exosome kit. Results Lymphatic drainage exudate retrieved after surgery from all 7 patients contained EVs. The isolated EVs were positive for the typical EV markers CD9, CD63, CD81 and Flotillin-1 while albumin was absent, indicating low contamination from blood proteins. In total, 24 different EV surface proteins were detected. Eleven of those proteins were detected in all patients, including the common EV markers CD9, CD63 and CD81, cancer-related markers CD24, CD29, CD44 and CD146, platelet markers CD41b, CD42a and CD62p as well as HLA-DR/DP/DQ. Furthermore, CD29 and CD146 were enriched in Her2+ patients compared to patients with Her2- tumors. Conclusions Lymphatic drainage exudate retrieved from breast cancer patients after surgery contains EVs that can be isolated using SEC isolation. The EVs have several cancer-related markers including CD24, CD29, CD44 and CD146, proteins of potential interest as biomarkers as well as to increase the understanding of the mechanisms of cancer biology.

PurposeManual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This systematic review aims to examine the methodologies used in recent research and evaluate the effectiveness of MLD for those at-risk of or living with lymphedema.MethodsThe electronic databases Embase, PubMed, CINAHL Complete and Cochrane Central Register of Controlled Trials were searched using relevant terms. Studies comparing MLD with another intervention or control in patients at-risk of or with lymphedema were included. Studies were critically appraised with the PEDro scale.ResultsSeventeen studies with a total of 867 female and two male participants were included. Only studies examining breast cancer-related lymphedema were identified. Some studies reported positive effects of MLD on volume reduction, quality of life and symptom-related outcomes compared with other treatments, while other studies reported no additional benefit of MLD as a component of complex decongestive therapy. In patients at-risk, MLD was reported to reduce incidence of lymphedema in some studies, while others reported no such benefits.ConclusionsThe reviewed articles reported conflicting findings and were often limited by methodological issues. This review highlights the need for further experimental studies on the effectiveness of MLD in lymphedema.Implications for Cancer SurvivorsThere is some evidence that MLD in early stages following breast cancer surgery may help prevent progression to clinical lymphedema. MLD may also provide additional benefits in volume reduction for mild lymphedema. However, in moderate to severe lymphedema, MLD may not provide additional benefit when combined with complex decongestive therapy.

Meninges that surround the CNS consist of an outer fibrous sheet of dura mater (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura are the arachnoid and pia mater (leptomeninges) that form the boundaries of the subarachnoid space. In this review we (1) examine the development of leptomeninges and their role as barriers and facilitators in the foetal CNS. There are two separate CSF systems during early foetal life, inner CSF in the ventricles and outer CSF in the subarachnoid space. As the foramina of Magendi and Luschka develop, one continuous CSF system evolves. Due to the lack of arachnoid granulations during foetal life, it is most likely that CSF is eliminated by lymphatic drainage pathways passing through the cribriform plate and nasal submucosa. (2) We then review the fine structure of the adult human and rodent leptomeninges to establish their roles as barriers and facilitators for the movement of fluid, cells and pathogens. Leptomeningeal cells line CSF spaces, including arachnoid granulations and lymphatic drainage pathways, and separate elements of extracellular matrix from the CSF. The leptomeningeal lining facilitates the traffic of inflammatory cells within CSF but also allows attachment of bacteria such as Neisseria meningitidis and of tumour cells as CSF metastases. Single layers of leptomeningeal cells extend into the brain closely associated with the walls of arteries so that there are no perivascular spaces around arteries in the cerebral cortex. Perivascular spaces surrounding arteries in the white matter and basal ganglia relate to their two encompassing layers of leptomeninges. (3) Finally we examine the roles of ligands expressed by leptomeningeal cells for the attachment of inflammatory cells, bacteria and tumour cells as understanding these roles may aid the design of therapeutic strategies to manage developmental, autoimmune, infectious and neoplastic diseases relating to the CSF, the leptomeninges and the associated CNS.

Background Breast cancer related lymphoedema (BCRL) is a common side effect of cancer treatment. Recently indocyanine green (ICG) fluorescent lymphography has become a popular method for imaging the lymphatics, however there are no standard protocols nor imaging criteria. We have developed a prospective protocol to aid in the diagnosis and therapeutic management of BCRL. Methods Lymphatic imaging procedures were conducted in three phases. Following initial observation of spontaneous movement of ICG in phase one, manual lymphatic drainage (MLD) massage was applied to facilitate ICG transit via the lymphatics in phase two. All imaging data was collected in phase three. Continuous lymphatic imaging of the upper limb was conducted for approximately an hour and lymphatic drainage pathways were determined. Correlations between the drainage pathway and MD Anderson Cancer Centre (MDACC) ICG lymphoedema stage were investigated. Results One hundred and three upper limbs with BCRL were assessed with this new protocol. Despite most of the patients having undergone axillary node dissection, the ipsilateral axilla drainage pathway was the most common (67% of upper limbs). We found drainage to the ipsilateral axilla decreased as MDACC stage increased. Our results suggest that the axillary pathway remained patent for over two-thirds of patients, rather than completely obstructed as conventionally thought to be the case for BCRL. Conclusions We developed a new ICG lymphography protocol for diagnosing BCRL focusing on identification of an individual patient’s lymphatic drainage pathway after lymph node surgery. The new ICG lymphography protocol will allow a personalised approach to manual lymphatic drainage massage and potentially surgery.

Carpal tunnel syndrome is the most common entrapment neuropathy in the upper extremity, making it essential to assess the effectiveness of various physiotherapy treatments. This study aimed to determine the clinical and electrodiagnostic improvement in mild-to-moderate carpal tunnel syndrome patients through manual lymphatic drainage (MLD) versus an orthosis alone. This is a prospective randomized controlled study. The sample consisted of a total of 36 patients who met the inclusion criteria. Experimental group received MLD and orthosis, and the control group received only orthosis. The patients were evaluated with electrodiagnostic tests, Visual Analog Scale, algometer measurements (pressure pain threshold), Boston Carpal Tunnel Syndrome Questionnaire before and after treatment. Evaluations were made before and after treatment (4 weeks later). Boston Carpal Tunnel Syndrome Questionnaire scores improved significantly with both treatment methods in both the experimental (p < 0.001, d = 2.0) and control groups (p < 0.001, d = 1.5). The pressure pain threshold significantly increased in the experimental group at the level of the transverse carpal ligament (p = 0.02, d = 0.86, 95% Confidence Interval (CI) = −0.08 to 1.2). At the distal radioulnar joint and extensor digitorum communis muscle levels, the pressure pain threshold similarly increased for two groups after treatment (p = 0.65, d = 0.31, 95% CI = −0.44 to 1.2), but the post-treatment increase in the experimental group was significant (p = 0.007, d = 0.31). In the experimental group, motor velocity (p = 0.001, d = 0.98), amplitude (p = 0.002, d = 1.5), and latency (p = 0.002, d = 0.60) and sensory velocity (p = 0.03, d = 0.91) and latency (p = 0.001, d = 1.2) significantly improved, while in the control group, there was a significant change only in motor velocity and amplitude (p = 0.047, d = 0.59). The post-treatment sensory improvement was significantly higher in the experimental group (p = 0.01, d = 0.81, 95% CI = −0.78 to −0.49). MLD significantly improved sensory conduction velocity, amplitude, and latency of the median nerve. Additionally, MLD and orthosis increased the pain pressure threshold and led to functional improvement. This is listed with study ID: NCT05394870 •Manual lymphatic drainage (MLD) significantly improved sensory conduction the median nerve.•MLD and orthosis increased the pain pressure threshold and functionality.•MLD can be a new option for conservative treatment in carpal tunnel syndrome.

BackgroundWe investigated the comparability of Complete Decongestive Therapy (CDT) including manual lymphatic drainage (MLD) vs. without MLD in the management of arm lymphoedema in patients with breast cancer.MethodsPatients randomised into either treatment including MLD (T+MLD) or treatment without MLD (T−MLD) received treatment 2×weekly for 4 weeks. The primary outcome was the volume reduction (%) of arm lymphoedema at 7-month follow-up. The secondary outcomes were volume reduction after the end of treatment, circumference of the arm, patient experience of heaviness and tension, and health status.ResultsDespite difficulties enrolling the planned number of patients (160), 77 were randomised and 73 (38 in T+MLD, 35 in T−MLD) completed the trial. In both groups, the volume of lymphoedema decreased significantly, with no difference between groups (1.0% [95% CI, −4.3;2.3%]): the precision in the 95% confidence interval indicates that the efficacy was comparable; the mean (SE) changes at month 7 were −6.8%(1.2) and −5.7% (1.2) in the T+MLD and T−MLD, respectively. There were no statistically significant differences with respect to any of the secondary outcomes. The results were robust and the conclusion was not sensitive even to various alternative assumptions or analytic approaches to data analysis.ConclusionManual lymphatic drainage adds no further volume reduction in breast cancer patients.

There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes. Cerebrospinal fluid drains via the cribriform plate and nasal mucosa to cervical lymph nodes in rats and sheep and to a lesser extent in humans. More significant for a range of human neurological disorders is the lymphatic drainage of interstitial fluid (ISF) and solutes from brain parenchyma along capillary and artery walls. Tracers injected into grey matter, drain out of the brain along basement membranes in the walls of capillaries and cerebral arteries. Lymphatic drainage of antigens from the brain by this route may play a significant role in the immune response in virus infections, experimental autoimmune encephalomyelitis and multiple sclerosis. Neither antigen-presenting cells nor lymphocytes drain to lymph nodes by the perivascular route and this may be a factor in immunological privilege of the brain. Vessel pulsations appear to be the driving force for the lymphatic drainage along artery walls, and as vessels stiffen with age, amyloid peptides deposit in the drainage pathways as cerebral amyloid angiopathy (CAA). Blockage of lymphatic drainage of ISF and solutes from the brain by CAA may result in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction and dementia. Facilitating perivascular lymphatic drainage of amyloid-β (Aβ) in the elderly may prevent the accumulation of Aβ in the brain, maintain homeostasis and provide a therapeutic strategy to help avert cognitive decline in Alzheimer’s disease.