The bright future of nanotechnology in lymphatic system imaging and imaging-guided surgery

Lymphatic system is identified the second vascular system after the blood circulation in mammalian species, however the research on lymphatic system has long been hampered by the lack of comprehensive imaging modality. Nanomaterials have shown the potential to enhance the quality of lymphatic imaging due to the unparalleled advantages such as the specific passive targeting and efficient co-delivery of cocktail to peripheral lymphatic system, ease molecular engineering for precise active targeting and prolonged retention in the lymphatic system of interest. Multimodal lymphatic imaging based on nanotechnology provides a complementary means to understand the kinetics of lymphoid tissues and quantify its function. In this review, we introduce the established approaches of lymphatic imaging used in clinic and summarize their strengths and weaknesses, and list the critical influence factors on lymphatic imaging. Meanwhile, the recent developments in the field of pre-clinical lymphatic imaging are discussed to shed new lights on the design of new imaging agents, the improvement of delivery methods and imaging-guided surgery strategies. Graphical Abstract

Lymphedema as a Meteoropathic Disease Based on a Retrospective Study in a Single Institute: a Preliminary Report

Since cellulitis is one of the most important factors for the prognosis of lymphedema, the prevention and prediction of cellulitis are considered to be critical in controlling lymphedema. We hypothesized that patients with lymphedema might show meteoropathy, as abdominal aortic aneurysm ruptures are considered to be influenced by climatic conditions, and the lymphatic system is one of the circulation systems. Thus, we aimed to determine if the onset of cellulitis in limbs affected by lymphedema is related to climatic conditions. We reviewed the clinical records of patients with lymphedema admitted for cellulitis at our institute between January 2007 and December 2017. We identified 40 patients, 25 of whom lived in the same area. We examined the association between the number of patient admissions according to season and meteorological data obtained from the Japan Meteorological Agency database. Thirteen of 25 patients were admitted in summer, whereas only one patient was admitted in winter. Both higher temperature and lower atmospheric pressure around the day of admission were associated with the occurrence of cellulitis. Lymphedema may be regarded as a meteoropathic disease, as climatic conditions were shown to be associated with cellulitis in limbs affected by lymphedema.

Design of an Auxiliary Artificial Lymphatic Vessel in Treatment of Secondary Lymphedema Due to Breast Cancer

Breast cancer is the most common malignant tumor that affects women in the United States, Europe, and Mexico. As an adverse effect when performing treatments for this condition, secondary lymphedema associated with breast cancer occurs in some cases. This complication occurs due to the interruption of lymphatic flow in the upper extremities in conjunction with other factors such as radiation, sedentary lifestyle, removal of lymph nodes, damage to lymphatic vessels, and others. This article reviews breast cancer incidence, mortality, and survival patterns, confirming that, specifically, lymphedema has high health, social, and economic impacts. Research demonstrates that it fundamentally affects women at an early age. In approximately a third of the cases, it becomes a chronic disease. Therefore, physical therapy is essential for a better quality of life in patients who survive this disease. Surgeries and manual and pharmacological treatments are the current procedures done to reduce to reduce the alterations suffered by patients with lymphedema; however, the success of the treatments depends on each patient’s characteristics. To face this problem, the design of a lymphatic vessel has been proposed to assist the mechanical failure of the damaged lymphatic system. In this work, the design methodology used for the blueprint of the lymphatic vessel is presented, as well as the computer analysis of fluid simulation and the selection of the proposed material, resulting in the production of a micrometric design. In the future, it is expected that a surgeon will be able to implant the design of the vessel to restore lymph flow through the lymphatic system, thus helping to combat lymphedema.

Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing

Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a CellTag system-based single-cell lineage tracing approach to show the metastasis rate and route of breast cancer cells and their interactions with the tumour microenvironment (TME) during metastasis. The results indicate that only a small fraction of cells can intravasate from the primary site into the blood circulation, whereas more cells disseminate through the lymphatic system to different organs. Tumour cells derived from the same progenitor cell exhibit different gene expression patterns in different soils, and the cancer cell-TME communication paradigm varies significantly between primary and metastatic tumours. Furthermore, metastable cells require a prewired IL-2 expression ability to migrate in vivo. In summary, leveraging a single-cell lineage tracing system, we demonstrate that the crosstalk between tumour cells and the TME is the driving force controlling the preferential metastatic fate of cancer cells through the lymphatic system and that this metastasis can be suppressed by knockdown of IL-2.

Bacterial Lymphatic Metastasis in Infection and Immunity

Lymphatic vessels permeate tissues around the body, returning fluid from interstitial spaces back to the blood after passage through the lymph nodes, which are important sites for adaptive responses to all types of pathogens. Involvement of the lymphatics in the pathogenesis of bacterial infections is not well studied. Despite offering an obvious conduit for pathogen spread, the lymphatic system has long been regarded to bar the onward progression of most bacteria. There is little direct data on live virulent bacteria, instead understanding is largely inferred from studies investigating immune responses to viruses or antigens in lymph nodes. Recently, we have demonstrated that extracellular bacterial lymphatic metastasis of virulent strains of Streptococcus pyogenes drives systemic infection. Accordingly, it is timely to reconsider the role of lymph nodes as absolute barriers to bacterial dissemination in the lymphatics. Here, we summarise the routes and mechanisms by which an increasing variety of bacteria are acknowledged to transit through the lymphatic system, including those that do not necessarily require internalisation by host cells. We discuss the anatomy of the lymphatics and other factors that influence bacterial dissemination, as well as the consequences of underappreciated bacterial lymphatic metastasis on disease and immunity.

Lymphatic self-massage for enhancing immunity during a pandemic

The article is devoted to the problem of improving immunity during the COVID-19 pandemic and the related effect of lymphatic self-massage.The article analyzes the general concepts of the lymphatic system and its functions, as well as lymphatic self-massage and its effect on cardiovascular and lymphatic systems.It is noted that the lymph flow stimulation through movements activates and normalizes the most important body functions. Using Skype, the authors surveyed medical students about knowledge on benefits and techniques of lymphatic selfmassage.Further, a master class was held on the technique of lymphatic self-massage. The authors studied the awareness of students about the benefits of lymphatic selfmassage, revealed a tendency to chronic diseases and assessed the benefits after the procedure.Based on the data obtained, it was revealed that viral infections, namely COVID-19, provoke one of the most common diseases — autoimmune thyroiditis. So, 64% of the respondents noted about it.Using lymphatic self-massage, the manifestations of this pathology decreases, the facial muscles relax and the blood and lymph outflow improves.Thus, there is an undoubted benefit of lymphatic self-massage for the prevention of diseases with immune involvement, including COVID-19.