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Photoacoustic imaging (PAI) is a successful clinical imaging platform for management of cancer and other health conditions that has seen significant progress in the past decade. However, clinical translation of PAI based methods are still under scrutiny as the imaging quality and clinical information derived from PA images are not on par with other imaging methods. Hence, to improve PAI, exogenous contrast agents, in the form of nanomaterials, are being used to achieve better image with less side effects, lower accumulation, and improved target specificity. Nanomedicine has become inevitable in cancer management, as it contributes at every stage from diagnosis to therapy, surgery, and even in the postoperative care and surveillance for recurrence. Nanocontrast agents for PAI have been developed and are being explored for early and improved cancer diagnosis. The systemic stability and target specificity of the nanomaterials to render its theranostic property depends on various influencing factors such as the administration route and physico-chemical responsiveness. The recent focus in PAI is on targeting the lymphatic system and nodes for cancer diagnosis, as they play a vital role in cancer progression and metastasis. This review aims to discuss the clinical advancements of PAI using nanoparticles as exogenous contrast agents for cancer theranostics with emphasis on PAI of lymphatic system for diagnosis, cancer progression, metastasis, PAI guided tumor resection, and finally PAI guided drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. Methods: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. Results: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. Conclusion: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping. [ABSTRACT FROM AUTHOR]

Dysfunctions in the lymphatic system can cause primary or secondary lymphedema, derived from chronic edema, when the lymphatic system is unable to adequately drain lymph from the tissues, resulting in swelling and pain. Through a cross-sectional experimental clinical study, we sought to evaluate the effect of the Adapted Lymphatic Protocol of Medicinal Biomagnetism on pain in the lower limbs of patients with peripheral edema of lymphatic origin. Medicinal Biomagnetism is a therapeutic system developed in 1988 by Dr. Isaac Goiz Durán that uses static magnetic fields generated by medium intensity magnets. These magnets are applied in pairs, one with a north pole, with a calming effect, and the other with a south pole, which activates areas with organic deficiencies, known as Biomagnetic Pairs. Carried out on four female participants, the study applied the protocol in three sessions, spaced weekly. The results demonstrated a reduction in the measurements of the lower limbs, relief in the intensity of pain and discomfort in the legs, although the lymphedema did not disappear completely. It was concluded that Medicinal Biomagnetism proved to be a non-invasive, accessible approach with few side effects, with the potential to alleviate pain and improve quality of life in patients with peripheral edema of lymphatic origin. [ABSTRACT FROM AUTHOR]

The lymphatic system is an integral part of the circulatory system and plays an important role in the fluid homeostasis of the human body. Accumulating evidence has recently suggested the involvement of lymphatic dysfunction in the pathogenesis of cardio-reno-vascular (CRV) disease. However, how the sophisticated contractile machinery of lymphatic vessels is modulated and, possibly impaired in CRV disease, remains largely unknown. In particular, little attention has been paid to the effect of the renin-angiotensin-system (RAS) on lymphatics, despite the high concentration of RAS mediators that these tissue-draining vessels are exposed to and the established role of the RAS in the development of classic microvascular dysfunction and overt CRV disease. We herein review recent studies linking RAS to lymphatic function and/or plasticity and further highlight RAS-specific signaling pathways, previously shown to drive adverse arterial remodeling and CRV organ damage that have potential for direct modulation of the lymphatic system. [ABSTRACT FROM AUTHOR]

Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of 200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Treatment with nutritional optimization and management of the underlying etiology are the cornerstones of therapy. When conservative measures fail, other interventions such as octreotide/somatostatin analogues, surgical ligation, embolization and transjugular intrahepatic portosystemic shunt in patients with cirrhosis can be considered.

Copyright of China Journal of Oral & Maxillofacial Surgery is the property of Shanghai Jiao Tong University, College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Contractile function of the collecting lymphatic vessels depend on smooth muscle cells, one-way valves, surrounding tissues, and regulation by the autonomic nervous system. The potentially deleterious effects of the Fontan procedure and elevated central venous pressure on lymphatic function leading to life-threatening complications are described. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease. [ABSTRACT FROM AUTHOR]

Little progress has been made in modern lymphatic medicine since Dr. Kinmonth first described pedal lymphangiography in the 1950s. The clinical need for an effective treatment modality for managing lymphatic leakage greatly increased only after intranodal lymphangiography, which enabled the depiction of the exact location of the leakage. This review introduces five hypotheses that have been proposed while addressing various clinical scenarios involving lymphatic leakage: (1) various embolization techniques can be used to prevent lymphatic leakage; (2) lymph node embolization can treat postoperative pelvic lymphoceles that are refractory to sclerotherapy; (3) the technical success rate of thoracic duct cannulation can be improved by using retrograde thoracic duct access as a bail-out method; (4) non-traumatic chylothorax can be managed by understanding the underlying pathophysiology; and (5) chylous ascites can be managed by understanding the underlying pathophysiology. Five retrospective observational studies, one randomized prospective clinical trial, and two case reports (letters to the editor) were published after the hypotheses were validated. We provide a new systematic approach to lymphatic intervention by describing the process of the current comprehensive research.

Over sixty years, laser technologies have undergone a technological revolution and become one of the main tools in biomedicine, particularly in neuroscience, neurodegenerative diseases and brain tumors. Glioblastoma is the most lethal form of brain cancer, with very limited treatment options and a poor prognosis. In this study on rats, we demonstrate that glioblastoma (GBM) growth can be suppressed by photosensitizer-free laser treatment (PS-free-LT) using a quantum-dot-based 1267 nm laser diode. This wavelength, highly absorbed by oxygen, is capable of turning triplet oxygen to singlet form. Applying 1267 nm laser irradiation for a 4 week course with a total dose of 12.7 kJ/cm2 firmly suppresses GBM growth and increases survival rate from 34% to 64%, presumably via LT-activated apoptosis, inhibition of the proliferation of tumor cells, a reduction in intracranial pressure and stimulation of the lymphatic drainage and clearing functions. PS-free-LT is a promising breakthrough technology in non- or minimally invasive therapy for superficial GBMs in infants as well as in adult patients with high photosensitivity or an allergic reaction to PSs. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) are small, cell-derived particles with sizes of approximately 100 nm. Since these particles include cargos such as host cell-derived proteins, messenger RNAs, and micro RNAs, they serve as mediators of cell-cell communication. While the analysis of the pharmacokinetic of sEVs after the intravenous injection have been reported, the lymphatic transport of sEVs remains unclear. The objective of this study was to provide insights into the intra-lymphatic trafficking and distribution of sEVs when they are injected into an interstitial space both in normal skin tissue and in cancerous tissue. When sEVs were Subcutaneously administered into the tail base and the tumor tissue, they preferably accumulated in the lymph nodes (LNs), rather than in the liver and the spleen. The findings reported herein show that the lymphatic transport of sEVs was drastically changed in model mice, in which a surgical treatment was used to modify to allow the dominant lymphatic flow from the footpad directly to the axillary LN via the inguinal LN. Based on the results, we conclude that when sEVs are injected into the subcutis space, they are preferably delivered to the LN via the lymphatic system. Further, the extent of accumulation of sEVs in the LN after subcutaneous injection was reduced when they were preliminarily incubated with Proteinase K. These results suggest that the lymphatic drainage of sEVs in normal skin tissue is regulated by membrane proteins on their surface. This reduction, however, was not observed in the case of cancer tissue. This discrepancy can be attributed to the presence of highly permeable lymphatic vessels in the tumor tissue. Further, the major cell subtypes that captured sEVs in the LN were LN-resident medullary sinus macrophages. These collective findings indicate that the lymphatic drainage of sEVs are mediated by proteins and, that they may appear to contribute to the control of the function of immune-responsive cells in the LNs. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Mersin University School of Medicine Lokman Hekim Journal of History of Medicine & Folk Medicine is the property of Mersin University School of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Despite being rarely discussed, perinephric lymphatics are involved in many pathological and benign processes. The lymphatic system in the kidneys has a harmonious dynamic with ureteral and venous outflow, which can result in pathology when this dynamic is disturbed. Although limited by the small size of lymphatics, multiple established and emerging imaging techniques are available to visualize perinephric lymphatics. Manifestations of perirenal pathology may be in the form of dilation of perirenal lymphatics, as with peripelvic cysts and lymphangiectasia. Lymphatic collections may also occur, either congenital or as a sequela of renal surgery or transplantation. The perirenal lymphatics are also intimately involved in lymphoproliferative disorders, such as lymphoma as well as the malignant spread of disease. Although these pathologic entities often have overlapping imaging features, some have distinguishing characteristics that can suggest the diagnosis when paired with the clinical history. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Imaging of the lymphatic system has always encountered difficulties, such as high costs, timeconsuming procedures, and low-resolution images. Each method of imaging provides its own challenges. The use of high-resolution ultrasonography (HR-US) and microvascular flow imaging (MVFI) may prove to be the most effective method for visualizing the superficial lymphatic vessels. This study investigated the utilization of HR-US and MVFI in imaging inguinal lymph nodes and vessels, as well as the innovative use of an intranodal saline injection that acted as a contrast agent. This technical note aims to demonstrate that HR-US and MVFI, in combination with an intranodal saline injection, are applicable to the dynamic imaging of superficial inguinal lymph nodes and vessels. [ABSTRACT FROM AUTHOR]

Gut ischemia/reperfusion (I/R) injury is a common clinical problem associated with significant mortality and morbidities that result from systemic inflammation and remote organ dysfunction, typically acute lung injury. The mechanisms underlying the dissemination of gut-derived harmful mediators into the circulation are poorly understood. The objective of our study was to determine the role of mesenteric lymphatic circulation in the systemic and pulmonary inflammatory response to gut I/R. Using a murine intestinal I/R model, we evaluated whether and how blocking mesenteric lymph flow affects the inflammatory response in local tissues (gut) and remote organs (lungs). We further explored the mechanisms of post-I/R lymph-induced systemic inflammation by examining neutrophil activity and interaction with endothelial cells in vitro. Mice subjected to intestinal I/R displayed a significant inflammatory response in local tissues, evidenced by neutrophil infiltration into mucosal areas, as well as lung inflammation, evidenced by increased myeloperoxidase levels, neutrophil infiltration, and elevated microvascular permeability in the lungs. Mesenteric lymph duct ligation (MLDL) had no effect on gut injury per se, but effectively attenuated lung injury following gut I/R. Cell experiments showed that lymph fluid from post-I/R animals, but not pre-I/R, increased neutrophil surface CD11b expression and their ability to migrate across vascular endothelial monolayers. Moreover, post-I/R lymph upregulated neutrophil expression of pro-inflammatory cytokines and chemokines, which was mediated by a mechanism involving nuclear factor (NF)-κB signaling. Consistently, gut I/R activated NF-κB in lung neutrophils, which was alleviated by MLDL. In conclusion, all these data indicate that mesenteric lymph circulation contributes to neutrophil activation and lung inflammation following gut I/R injury partly through activating NF-κB.

The adrenergic innervation of the thoracic lymphatic duct was studied in young, mature and old animals. Adrenergic innervation of lymphatic system in postnatal ontogenesis, especially in its late period, was not thoroughly studied. The purpose of this study was to determine the state of adrenergic innervation of TLD in young, mature, and senile animals. The study shows that the adrenergic apparatus in the TLD tissues of rats continues its formation and complication from the first days after birth and is entirely formed by Day 25–30 after birth. From the age of one month, the adrenergic innervation represents fully formed plexuses in all areas which function throughout life. These are brightly fluorescent nerve fibers that form plexuses with regularly located multiple sites of varicose dilation. In senile animals, the dilations remain frequent and numerous in all parts of the lymph node, but their brightness decreases; the fibers in the plexuses become discontinuous, the varicose thickenings become less frequent or disappear. The adrenergic vasomotor innervation in the walls of the TLD affects its function. The formed adrenergic innervation is presented across all periods of postnatal ontogenesis of the TLD and affects its functioning, and age-related changes in the course of development and aging of the organism can be considered as adaptation to new conditions. This study promotes understanding of the sympathetic regulation. The trial does not involve people and the trial registration is not required.

Objective: to investigate the effectiveness of a new mechanized lymphatic drainage method in acute decompensated heart failure (ADHF) modeling through local reduction in venous pressure in the site of lymphatic drainage from the thoracic duct.Materials and methods. Main components of the device are a catheter with built-in inlet and outlet mechanical valves designed for insertion into the left brachiocephalic vein through the left internal jugular vein. It comes with an extracorporeal drive system made as a valveless pulsator pump with a 10 ml shock discharge and a controller ensuring preset frequency and pressure/rarefaction duty cycle. The operating principle of the device is based on local reduction of venous pressure in the site of lymphatic drainage from the thoracic duct (in the junction of the left internal jugular and subclavian veins).Results. When modeling hydrodynamics under ADHF conditions on a hydrodynamic test bench, the upper venous flow through the left brachiocephalic vein was 0.4 l/min, the pressure in the site of lymphatic drainage from the thoracic duct, was decreased from 20–25 mmHg to 0–5 mmHg due to operation of the mechanized drainage device with suction/injection phase duration ratio 0.2/0.8 and pulsator pump operating frequency from 30 to 60 beats/min.

Anatomies of the vascular and lymphatic systems have been vital research topics in reconstructive surgery. Harvey was a pioneer who provided the earliest descriptions of the cutaneous vasculature in the 17th century. The concept of vascular territories of the skin was first described by Manchot. The radiographic injection method in cadavers was developed by Salman, who defined more than 80 vascular territories. The arterial system has been thoroughly investigated with the development of regional and free flaps. The concept of axial and random pattern flaps was introduced by McGregor and Morgan. Manchot's vascular territories were refined by Taylor and Palmer as the angiosome concept. Detailed information about the venous circulation is essential for reconstructive surgeries. The concept of intrinsic and extrinsic venocutaneous vascular systems was introduced by Nakajima and led to the development of the venoadipofascial flap. The importance of venous augmentation in flap survival was emphasized by Chang. The lymphatic system was discovered much later than the arterial and venous systems. Aselli was credited for discovering the lacteal vessels in the 17th century; mercury was popularly used as a contrast agent to distinguish lymphatic vessels for the next three centuries. A radiographic method in cadavers was developed by Suami. Lymphatic imaging devices are constantly upgrading, and photoacoustic imaging was recently introduced for three-dimensional visualization of architecture of superficial layers of the lymphatic and venous systems.

Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling. [ABSTRACT FROM AUTHOR]

Purpose: Ankle swelling (AS) is one of the main complaints in athletes with a lateral ankle sprain (LAS) in the acute phase. Reducing AS may help the athlete to return to training faster. The purpose of this study was to evaluate the efficacy of Kinesio Taping® (KT) and neuromuscular electrical stimulation (NMES) in reducing AS in athletes with a LAS. Methods: Thirty-one athletes with a unilateral ankle sprain from various sports were allocated to either KT (N = 16; mean age of 24.1 years) or NMES (N = 15; mean age of 26.4 years) groups. KT was applied over the medial and lateral ankle surfaces in the Fan cut pattern for five consecutive days; however, NMES was applied to the tibialis anterior and gastrocnemius muscles for 30 min. Outcome measures to assess the extent of AS included volumetry, perimetry, relative volumetry, and the difference in both ankles' volumetry and perimetry at baseline, after the interventions, and 15 days following the treatment completion. Results: The results of the mixed model repeated measures ANOVA demonstrated no significant difference between the two groups in mean changes in outcomes over pre- and post-interventions as well as follow-up periods (P > 0.05). Conclusions: None of the KT and NMES methods could reduce acute AS in athletes with LAS. Further studies are needed in this area of research that consider changes in treatment protocol given the variety of NMES approaches and KT applications that can be used in recovery from an ankle sprain. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an important role in the development and progression of hematological malignancies. In recent years, studies have focused on understanding how tumor cells communicate within the TME. In addition to several factors, such as growth factors, cytokines, extracellular matrix (ECM) molecules, etc., a growing body of evidence has indicated that extracellular vesicles (EVs) play a crucial role in the communication of tumor cells within the TME, thereby contributing to the pathogenesis of hematological malignancies. The present review focuses on how EVs derived from tumor cells interact with the cells in the TME, such as immune cells, stromal cells, endothelial cells, and ECM components, and vice versa, in the context of various hematological malignancies. EVs recovered from the body fluids of cancer patients often carry the bioactive molecules of the originating cells and hence can be considered new predictive biomarkers for specific types of cancer, thereby also acting as potential therapeutic targets. Here, we discuss how EVs influence hematological tumor progression via tumor–host crosstalk and their use as biomarkers for hematological malignancies, thereby benefiting the development of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The lymphatic system has been poorly understood and its importance neglected for decades. Growing understanding of lymphatic flow pathophysiology through peripheral and central lymphatic flow imaging has improved diagnosis and treatment options in children with lymphatic diseases. Flow dynamics can now be visualized by different means including dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL), the current standard technique to depict central lymphatics. Novel imaging modalities including intranodal, intrahepatic and intramesenteric DCMRL are quickly evolving and have shown important advances in the understanding and guidance of interventional procedures in children with intestinal lymphatic leaks. Lymphatic imaging is gaining importance in the radiologic and clinical fields and new techniques are emerging to overcome its limitations. [ABSTRACT FROM AUTHOR]

Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000–September 2022. Inclusion criteria were studies investigating parameters related to contraction frequency, fluid velocity, and lymphatic pressure in vivo and ex vivo in human lymphatic vessels. The search returned 2885 papers of which 28 met the inclusion criteria. In vivo vessels revealed baseline contraction frequencies between 0.2 ± 0.2 and 1.8 ± 0.1 min1, velocities between 0.008 ± 0.002 and 2.3 ± 0.3 cm/s, and pressures between 4.5 (range 0.5–9.2) and 60.3 ± 2.8 mm Hg. Gravitational forces, hyperthermia, and treatment with nifedipine caused increases in contraction frequency. Ex vivo lymphatic vessels displayed contraction frequencies between 1.2 ± 0.1 and 5.5 ± 1.2 min−1. Exposure to agents affecting cation and anion channels, adrenoceptors, HCN channels, and changes in diameter‐tension properties all resulted in changes in functional parameters as known from the blood vascular system. We find that the lymphatic system is dynamic and adaptable. Different investigative methods yields alternating results. Systematic approaches, consensus on investigative methods, and larger studies are needed to fully understand lymphatic transport and apply this in a clinical context. [ABSTRACT FROM AUTHOR]

Background: The axillary web syndrome (AWS) is a surgical breast cancer sequel that limits the functionality of the patient and delays the protocol times of application of cancer treatments. This implies a long period of discomfort and limitations for the user. Objective: To investigate the different physiotherapy treatments for the AWS and how effective they are. Methods: A systematic review based on PRISMA protocol and registered in PROSPERO (CRD42021281354) was conducted. The research was performed using PubMed, Scopus, CINAHL, PEDro, and Web of Science databases during January 2022 and March 2022. All randomized controlled trials and controlled clinical trials were included in this review. Results: A total of 188 articles were identified, with 9 studies selected for the systematic review. These studies basically propose treatments based on exercises and stretching, manual therapy, and the combination of manual therapy and exercises. Conclusions: Exercise and stretching are the most effective therapies within the field of physiotherapy for the rehabilitation of axillary web syndrome. They restore range of motion faster, reduce pain, improve quality of life, and reduce disabilities. Manual therapy, scar massage, and myofascial release could help improve outcomes but with worse results. The meta-analysis conclusion is that pain is the only outcome with a significant reduction after the application of physiotherapy treatments − 0.82 [− 1.67; 0.03]. This conclusion is drawn from the only three studies with small sample sizes. [ABSTRACT FROM AUTHOR]

Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic, or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries, CA is classified according to portal and non-portal etiology. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of > 200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Treatment with nutritional optimization and management of the underlying etiology are the cornerstones of therapy. When conservative measures fail, other interventions such as octreotide/somatostatin analogues, surgical ligation, embolization, and transjugular intrahepatic portosystemic shunt in patients with cirrhosis can be considered. [ABSTRACT FROM AUTHOR]

Background: Secondary upper extremity lymphedema occurs after an insult such as surgery. One theory suggests underlying lymphatic dysfunction predisposing certain patients into developing secondary lymphedema. We aim to determine the rate of incidental edema in the contralateral upper extremity of patients with secondary unilateral lymphedema. Methods and Results: MRI of the upper extremities were obtained in patients with lymphedema who were referred by a lymphedema clinic from 2017 to 2019. Axial short-tau inversion recovery MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded. Interobserver agreement was calculated. Indocyanine green (ICG) lymphography was compared against MRI stage in symptomatic and contralateral. Age, symptom duration, body mass index (BMI), and history of chemotherapy were compared between patients with and without contralateral limb lymphedema. ICG severity was compared against MRI stage. Seventy-eight patients were analyzed. The MRI stages of symptomatic versus contralateral arms were 1.7 ± 1.1 versus 0.1 ± 0.4 (p < 0.00001). Interobserver agreement was 0.86 (0.79–0.94). Of the patients with MRI Stage 1 or above in the symptomatic arm (n = 64), 55 (82.1%) patients demonstrated no abnormality in the contralateral arm. Nine patients (14.1%) demonstrated asymptomatic edema (MRI Stage 1). The mean ICG lymphography stage of symptomatic versus contralateral arms was 1.83 ± 0.96 versus 0.04 ± 0.25 (p < 0.00001). There was no difference in the age, symptom duration, BMI, or history of chemotherapy between patients with or without edema in the contralateral arm. Conclusion: Asymptomatic contralateral edema was detected in 14.1% of patients with unilateral secondary upper extremity lymphedema using MRI modality. [ABSTRACT FROM AUTHOR]

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

The article presents a general description of the lymphatic system and detailed characteristics of the structure of the terminal thoracic duct (TD) and lymphovenous junction (LVJ): their clinical and anatomical features, the role of LVJ in regulating lymph flow, and the separating two systems (circulatory and lymphatic). The presented data expand the concept of the structural and functional characteristics of the left central LVJ, its valves, and TD, and also provides information about the anatomical heterogeneity of the studied tissue complex. The morphological and functional characteristics of LVJ will help to better understand the logistics of the lymph flow and the mechanism of the LVJ valves’ work.

Abstract Background Cystic hygromas (lymphangiomas) are rarely reported in various animal species, humans included. A hygroma is a benign congenital malformation of the lymphatic drainage system, presenting itself as a mass consisting of multiple cysts of various sizes with a watery content. Case presentation This report describes clinical, ultrasonographic, and post-mortem findings of a cystic hygroma in a suckling pig. The mass was characterized by a few thin-walled cysts, containing clear yellow serous fluid. Histologically, the central cavity was lined by a single layer of squamous cells, supported by a thick fibrous stroma. On immunohistochemistry, scattered lining cells were weakly positive for Factor-VIII, suggesting their possible endothelial origin. Conclusions This case report contributes to raising awareness on this condition in pigs allowing early identification in life so that appropriate care can be provided. The case report attributes to science on hygromas in general, as better understanding of pathologic features, the aetiology and appropriate treatment are needed.

ABSTRACT Chronic Progressive Lymphoedema (CPL) is a disabling disease of draft horses that affects lymphatic system function typically in the distal limbs. Deformities of distal limbs, especially of the pastern, with fibrosis and skin nodular lesions are consequences of disease progression. A 15-year-old Friesian stallion presented for evaluation with history of forelimb enlargement and nodule formations distal to the carpus for four years. Simple radiographs showed soft tissue nodular lesions and venous contrasted radiography showed intense enlargement of II common digital palmar vein of both forelimbs. Tissue culture tests revealed Streptococcus equi and Proteus mirabilis isolation and skin scraping test identified Chorioptes bovis mites. Histological examination revealed perivasculitis and lymph vessels distention. History, clinical and histological findings, and complementary exams suggested CPL diagnosis. We were unable to find previously published cases describing this disease in Brazil, where the increasing number of draft horses requires attention to this problem. The correct and early diagnosis substantially delays disease progression. Therefore, we highlight the need for nationwide propagation of these data to ensure better diagnosis and early treatment of future CPL cases.

Abstract Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000–September 2022. Inclusion criteria were studies investigating parameters related to contraction frequency, fluid velocity, and lymphatic pressure in vivo and ex vivo in human lymphatic vessels. The search returned 2885 papers of which 28 met the inclusion criteria. In vivo vessels revealed baseline contraction frequencies between 0.2 ± 0.2 and 1.8 ± 0.1 min1, velocities between 0.008 ± 0.002 and 2.3 ± 0.3 cm/s, and pressures between 4.5 (range 0.5–9.2) and 60.3 ± 2.8 mm Hg. Gravitational forces, hyperthermia, and treatment with nifedipine caused increases in contraction frequency. Ex vivo lymphatic vessels displayed contraction frequencies between 1.2 ± 0.1 and 5.5 ± 1.2 min−1. Exposure to agents affecting cation and anion channels, adrenoceptors, HCN channels, and changes in diameter‐tension properties all resulted in changes in functional parameters as known from the blood vascular system. We find that the lymphatic system is dynamic and adaptable. Different investigative methods yields alternating results. Systematic approaches, consensus on investigative methods, and larger studies are needed to fully understand lymphatic transport and apply this in a clinical context.

BackgroundFluid overload remains a vexing problem in management of heart failure. The lymphatic system that plays the central role in fluid homeostasis has recently been explored as a potential target to counteract tissue fluid overload. The goal of the study was to evaluate the preliminary effects of exercises in activating lymphatic system on fluid overload symptoms, abnormal weight gains, and physical functions for patients with heart failure.Methods and resultsA pilot, pre- and post-test, randomized clinical trial was conducted to recruit a total of 66 patients who were randomized to receive either a 4-week The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF) program or usual care alone. The primary outcome was the prevalence and burden of the fluid overload symptoms. Findings of the trial showed that the TOLF-HF intervention was effective in reducing the prevalence or burden of the majority of fluid overload symptoms. TOLF-HF intervention also demonstrated significant improvement in the outcomes of abnormal weight gains (MD: −0.82; 95% CI: −1.43 to −0.21; P = 0.010) and physical functions (F = 13.792, P

Introduction: Lipedema is a bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat. Recent studies using lymphoscintigraphy documented that lipedema associates with lymphatic alterations. It is still not known, whether non-lipedema obesity also leads to similar lymphoscintigraphic changes within lower legs. Clinically, both, lipedema and obesity may progress to secondary lymphedema. The aim of the study was to evaluate lymphoscintigraphy of lower limbs in women with lipedema in comparison to overweight/obese women. Methods: 51 women (in the mean age of 43.3 ± 13.56) with the diagnosis of lipedema and 31 women (in the mean age of 44.7 ± 13.48) with overweight/obesity were enrolled into the study. Women in both study groups had no clinical signs of lymphedema. The groups were matched by mean volume of their legs, calculated using the formula for a truncated cone. Lymphoscintigraphy was evaluated in every women qualitatively. Body composition parameters were assessed using bioelectric impedance analysis (BIA).Results: Lymphoscintigraphic alterations within lower extremities were similar in both, lipedema and overweight/obese groups and were present in majority of women in both study groups. The most common lymphoscintigraphic alteration in both groups were additional lymphatic vessels (in the lipedema group observed in 76.5% of patients and in the overweight/obesity group – in 93.5%). Visualization of popliteal lymph nodes and dermal backflow were observed respectively in 33% and in 5.9% in the group with lipedema and in 45.2% and in 9.7% in the overweight/obesity group. There were significant relationships between severity of lymphoscintigraphic alterations and weight, lean body mass (LBM), total body water (TBW), volume of both legs and thigh circumference in the lipedema group. Such relationships were absent in the overweight/obesity group. Discussion: Our study indicates that lymphatic alterations are present before development to clinically visible secondary lymphedema in both conditions, lipedema and overweight/obesity. In majority of women from both study groups they indicate rather an overload of the lymphatic system than insufficiency. Lymphoscintigraphic alterations are similar in both groups, therefore, lymphoscintigraphy is not a diagnostic tool that might distinguish lipedema from overweight/obesity.

Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging oflymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of «1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding ofthe morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future. [ABSTRACT FROM AUTHOR]

Recently, the superficial fascia has been recognized as a specific anatomical structure between the two adipose layers—the superficial adipose tissue (SAT) and the deep adipose tissue (DAT). The evaluation of specific characteristics of cells, fibers, blood circulation, and innervation has shown that the superficial fascia has a clear and distinct anatomical identity, but knowledge about lymphatic vessels in relation to the superficial fascia has not been described. The aim of this study was to evaluate the presence of lymphatic vessels in the hypodermis, with a specific focus on the superficial fascia and in relation to the layered subdivision of the subcutaneous tissue into SAT and DAT. Tissue specimens were harvested from three adult volunteer patients during abdominoplasty and stained with D2-40 antibody for the lymphatic endothelium. In the papillary dermis, a huge presence of lymphatic vessels was highlighted, parallel to the skin surface and embedded in the loose connective tissue. In the superficial adipose tissue, thin lymphatic vessels (mean diameter of 11.6 ± 7.71 µm) were found, close to the fibrous septa connecting the dermis to the deeper layers. The deep adipose tissue showed a comparable overall content of lymphatic vessels with respect to the superficial layer; they followed the blood vessel and had a larger diameter. In the superficial fascia, the lymphatic vessels showed higher density and a larger diameter, in both the longitudinal and transverse directions along the fibers, as well as vessels that intertwined with one another, forming a rich network of vessels. This study demonstrated a different distribution of the lymphatic vessels in the various subcutaneous layers, especially in the superficial fascia, and the demonstration of the variable gauge of the vessels leads us to believe that they play different functional roles in the collection and transport of interstitial fluid—important factors in various surgical and rehabilitation fields. [ABSTRACT FROM AUTHOR]

Simple Summary: This multicentre randomised controlled trial investigated the added value of fluoroscopy-guided manual lymph drainage (MLD) (compared to traditional or placebo MLD) as part of the decongestive lymphatic therapy (DLT) for superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). No differences between the three groups were found regarding the change in the number of efferent superficial lymphatic vessels leaving the dermal backflow region in the total dermal backflow score, and in the number of superficial lymph nodes. As a consequence, this trial was not able to demonstrate the beneficial value of MLD for the other components of DLT on superficial lymphatic architecture in patients with chronic mild to moderate BCRL. The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL. [ABSTRACT FROM AUTHOR]

Animal models of diseases, particularly mice, are considered to be the cornerstone for translational research in immunology. The aim of the present study is to model the geometry and analyze the network structure of the murine lymphatic system (LS). The algorithm for building the graph model of the LS makes use of anatomical data. To identify the edge directions of the graph model, a mass balance approach to lymph dynamics based on the Hagen–Poiseuille equation is applied. It is the first study in which a geometric model of the murine LS has been developed and characterized in terms of its structural organization and the lymph transfer function. Our study meets the demand for quantitative mechanistic approaches in the growing field of immunoengineering to utilize or exploit the lymphatic system for immunotherapy. [ABSTRACT FROM AUTHOR]

The lymphatic system not only plays an important role as a drainage eliminating metabolic wastes and toxins from tissues, but also represents an arena for the unfolding of immune response scenarios aimed at protecting the organism from bacteria and viruses. In the central nervous system (CNS), drainage processes proceed with the same intensity as in peripheral tissues. The brain actively exchanges nutrients with the blood and excretes metabolic waste products through the drainage routes closely related to the peripheral lymphatic system. The same routes allow the traffic of immune cells and antibodies to the CNS, thus providing a communication between the peripheral and central immune systems. Over the bicentennial history of brain drainage studies, a lot of facts have been accumulated to suggest indirectly the presence of lymphatic vessels in the CNS. However, even with the advent of high-tech imaging of brain structures and a rediscovery of the meningeal lymphatic vessels (MLVs), which was a watershed in neuroscience, scientists have not advanced beyond confirming the already existing dogma that the lymphatic network is present exclusively in the brain meninges, but not in brain tissues. In fact, however, the rediscovery of MLVs by American scientists was not a "true revelation", as they were first described by the Italian anatomist Mascagni two centuries earlier, and his results were confirmed later on in many other studies performed on the meninges in humans, macaques, rodents, dogs, rabbits and zebrafish. As a result, the scientific community did not recognize the "forgotten" MLVs as a new discovery. This review highlights the turning points that occurred in neuroscience when a new player has entered the game and orchestrated innumerable efforts of scientists to explain how unnecessary molecules and toxins are removed from the brain, as well as how drainage and immunity are implemented in the CNS. This is an important informational and creative platform both for new fundamental knowledge about the lymphatic system in the brain, as well as for the development of innovative neurorehabilitation technologies based on the management of lymphatic drainage processes. [ABSTRACT FROM AUTHOR]

This brief report demonstrates the diagnostic utility of cone-beam CT lymphangiography (CBCTL) with intranodal injection of water-soluble iodinated contrast agent for assessing lymphatic disorders in two infants who were contraindicated for MRI and oil-based contrast agent. Both infants had dextro-transposition of the great arteries (d-TGA) and presented with high-output chylothoraces that were recalcitrant to conservative medical therapy. Both infants were diagnosed with central lymphatic flow disorder based on the CBCTL findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of immunotherapy within the usual strategies for cancer treatment has meant an enormous advance in the survival of patients with very restrictive prognoses. However, a high percentage of patients still cannot benefit from it. The lack of response to immunotherapy is mainly due to resistance from the tumor stroma itself. The lymphatic endothelium constitutes a permeable vascular system from the stroma specially dedicated to balancing tissue homeostasis and leukocyte emigration. Most solid carcinomas present lymphatic microvasculature that participates in tumor progression ambivalently. On one hand, it facilitates the transit of immune cells toward the lymph nodes and therefore promotes the antitumor response; on the other hand, they constitute an accessible route through which tumor cells metastasize to the lymph nodes. Due to this double function, it is not easy to establish strategies that "educate" the lymphatic endothelium only in its antitumor function without compromising its participation in the immune response. In this review, we study how combinations of radiotherapy and immunotherapy can modulate lymphatic function to use them in therapeutic approaches. The study of lymphatic tumor vasculature has been gaining interest in the context of cancer immunotherapy. These vessels constitute conduits for immune cells' transit toward the lymph nodes, and they endow tumors with routes to metastasize to the lymph nodes and, from them, toward distant sites. In addition, this vasculature participates in the modulation of the immune response directly through the interaction with tumor-infiltrating leukocytes and indirectly through the secretion of cytokines and chemokines that attract leukocytes and tumor cells. Radiotherapy constitutes the therapeutic option for more than 50% of solid tumors. Besides impacting transformed cells, RT affects stromal cells such as endothelial and immune cells. Mature lymphatic endothelial cells are resistant to RT, but we do not know to what extent RT may affect tumor-aberrant lymphatics. RT compromises lymphatic integrity and functionality, and it is a risk factor to the onset of lymphedema, a condition characterized by deficient lymphatic drainage and compromised tissue homeostasis. This review aims to provide evidence of RT's effects on tumor vessels, particularly on lymphatic endothelial cell physiology and immune properties. We will also explore the therapeutic options available so far to modulate signaling through lymphatic endothelial cell receptors and their repercussions on tumor immune cells in the context of cancer. There is a need for careful consideration of the RT dosage to come to terms with the participation of the lymphatic vasculature in anti-tumor response. Here, we provide new approaches to enhance the contribution of the lymphatic endothelium to radioimmuno-oncology. [ABSTRACT FROM AUTHOR]

Vascular anomalies are classified by the International Society for the Study of Vascular Anomalies (ISSVA). They result from an abnormal embryonic development of vessels, and in most cases, they are present at birth. A minority of VAs manifest at a later stage. They grow along with the child and may enlarge spontaneously during an infection. They often create aesthetic flaws, pain, impaired quality of life and require challenging treatment options that frequently do not provide patients with desired results. Part of these anomalies are classified as lymphatic. Proper diagnosis is based on radiological tests, including ultrasonography, computed tomography and magnetic resonance. It is vital to establish a correct diagnosis that precedes the appropriate treatment. The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult lymphatic anomalies. This article presents the current use of sirolimus and its antiproliferative properties that enables mTOR pathway inhibition, leading directly to stopping, reversing or minimising the effects of development of vascular anomalies. So far, it has been proven that sirolimus has a measurable effect on lymphatic malformations, is well tolerated, manageable and rarely produces adverse effects. Still, there are no guidelines for sirolimus care in patients with vascular anomalies as we lack prospective clinical trials.