Chronic edema, which has multiple etiologies, is predicted to be a significant underlying cause of lymphedema, potentially leading to serious complications. Elephantiasis, characterized by massive swelling of any body part, is a rare but debilitating condition often associated with lymphatic obstruction or anomalies in the lymphatic system. Lymphedema can predispose a patient to cellulitis, an infectious condition with multiple risk factors. This case study presents a 45-year-old male with a history of chronic lymphatic obstruction due to elephantiasis and recurrent cellulitis in his lower limb. Despite receiving multiple courses of antibiotics, the patient continued to experience multiple episodes of cellulitis, along with worsening lymphedema and functional impairment of the limb. The mainstay of treatment for this condition includes compression stockings and surgery, but addressing the root cause of the disease is crucial. Typically, a multidisciplinary approach is required, involving antibiotics, lymph drainage, and compression therapy. This case highlights the challenges faced in managing elephantiasis and its related complications and emphasizes the need for preventive strategies.

Cancer dissemination to lymph nodes (LN) is associated with a worse prognosis, increased incidence of distant metastases and reduced response to therapy. The LN microenvironment puts selective pressure on cancer cells, creating cells that can survive in LN as well as providing survival advantages for distant metastatic spread. Additionally, the presence of cancer cells leads to an immunosuppressive LN microenvironment, favoring the evasion of anti-cancer immune surveillance. However, recent studies have also characterized previously unrecognized roles for tumor-draining lymph nodes (TDLNs) in cancer immunotherapy response, including acting as a reservoir for pre-exhausted CD8+ T cells and stem-like CD8+ T cells. In this review, we will discuss the spread of cancer cells through the lymphatic system, the roles of TDLNs in metastasis and anti-cancer immune responses, and the therapeutic opportunities and challenges in targeting LN metastasis.

The human gastrointestinal tract, boasting the most diverse microbial community, harbors approximately 100 trillion microorganisms comprising viruses, bacteria, fungi, and archaea. The profound genetic and metabolic capabilities of the gut microbiome underlie its involvement in nearly every facet of human biology, from health maintenance and development to aging and disease. Recent recognition of microbiota - gut - brain axis, referring to the bidirectional communication network between gut microbes and their host, has led to a surge in interdisciplinary research. This review begins with an overview of the current understandings regarding the influence of gut microbes on intestinal and blood-brain barrier integrity. Subsequently, we discuss the mechanisms of the microbiota - gut - brain axis, examining the role of gut microbiota-related neural transmission, metabolites, gut hormones and immunity. We propose the concept of microbiota-mediated multi-barrier modulation in the potential treatment in gastrointestinal and neurological disorders. Furthermore, the role of lymphatic network in the development and maintenance of barrier function is discussed, providing insights into lesser-known conduits of communication between the microbial ecosystem within the gut and the brain. In the final section, we conclude by describing the ongoing frontiers in understanding of the microbiota - gut - brain axis\'s impact on human health and disease.

The purpose of this study was to present a protocol for visualizing lymphatic flow in patients with heart failure (HF) by using indocyanine green fluorescence lymphography. We studied 37 subjects: 20 patients with acute heart failure (AHF) and lower limb edema, 7 patients with chronic heart failure (CHF) without lower limb edema, and 10 control subjects (no HF, no limb edema). All subjects were assessed at rest, and 11 subjects (6 control and 5 with CHF) were assessed again after a 10-minute walk. The lymph flow was visualized in all selected patients without complications. At rest, there was either no lymph flow or minimal lymph flow in all control subjects and patients with CHF, whereas the majority of patients with AHF demonstrated significant lymph flow. This study describes a new method to visualize/assess lymphatic flow in patients with HF, allowing for continuous, real-time tracking of lymphatic flow in the lower extremity.

Mesenteric cystic lymphangiomas are a rare benign abdominal malformation of lymphatic vessels, with an estimated incidence of 1 per 250,000. Clinical presentation ranges from asymptomatic masses to acute abdominal pain. Diagnostic investigation includes ultrasound, abdominal computed tomography, or magnetic resonance imaging. Complete surgical excision is the recommended treatment. We present an 11-year-old female with abdominal cramps, and a 6-month history of gradually developing distension, constipation, and polyuria, without the occurrence of vomiting. Clinical examination revealed a soft, movable, painless abdominal mass with dullness on palpation. Ultrasound showed multi-cavity cystic masses in the abdomen, and a contrast-enhanced computed tomography scan revealed a large multi-cavity cystic mass involving most of the abdomen. A complete surgical excision was performed, and microscopic examination confirmed the diagnosis of mesenteric cystic lymphangioma. This case underscores the importance of considering mesenteric cystic lymphangiomas in the differential diagnosis of abdominal masses in pediatric patients, even in rarer age groups. Imaging aids in diagnosis and surgery planning. Complete excision curbs the risk of infection and recurrences.

The lymphatic system plays a crucial, yet often overlooked, role in maintaining fluid homeostasis, and its dysregulation is a key feature of heart failure (HF). Lymphatic dysregulation in patients with HF typically results from a combination of self-perpetuating congestive mechanisms, such as increased fluid filtration, decreased lymph drainage into the central venous system, impaired lymph vessel integrity, dysfunctional lymphatic valves, and dysfunctional renal lymphatic system. These pathomechanisms collectively overwhelm the lymphatic system and hinder its ability to decongest the interstitial space with subsequent manifestation and progression of clinical congestion. Targeting the lymphatic system to counteract these congestive pathomechanisms and facilitate interstitial fluid removal represents a novel pathway to treat congestion in HF. In this study, we discuss the physiological roles of the lymphatic system in fluid homeostasis and the pathophysiological alteration of these roles in HF. We also discuss innovative technologies that aim to use the lymphatic system pathway to treat congestion in HF and provide future directions related to these approaches.

Background: The thoracic duct (TD) and the cisterna chyli (CC) exhibit a high degree of variability in their topographical and morphometric properties. Materials and Methods: PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to identify all studies that included information regarding the morphometric and topographical characteristics of the TD and CC. Results: The most frequent location of the TD termination was the left venous angle, with a pooled prevalence of 45.29% (95% CI: 25.51-65.81%). Moreover, the TD terminated most commonly as a single vessel (pooled prevalence = 78.41%; 95% CI: 70.91-85.09%). However, it divides into two or more terminating branches in approximately a quarter of the cases. The pooled prevalence of the CC was found to be 55.49% (95% CI: 26.79-82.53%). Conclusions: Our meta-analysis reveals significant variability in the anatomy of the TD and CC, particularly regarding TD termination patterns. Despite the predominance of single-vessel terminations, almost a quarter of cases exhibit branching, highlighting the complexity of the anatomy of the TD. These findings demonstrate the importance of detailed anatomical knowledge for surgeons to minimize the risk of accidental injury during head and neck, as well as thoracic surgeries. Our study provides essential insights that can enhance surgical safety and efficacy, ultimately improving patient outcomes.

UNASSIGNED: Lymphatic valves are specialized structures in collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves. Conventionally, in many cell types, AKT is phosphorylated at Ser473 by the mTORC2 (mammalian target of rapamycin complex 2). However, mTORC2 has not yet been implicated in lymphatic valve formation.
UNASSIGNED: In vivo and in vitro techniques were used to investigate the role of Rictor, a critical component of mTORC2, in lymphatic endothelium.
UNASSIGNED: Here, we showed that embryonic and postnatal lymphatic deletion of Rictor, a critical component of mTORC2, led to a significant decrease in lymphatic valves and prevented the maturation of collecting lymphatic vessels. RICTOR knockdown in human dermal lymphatic endothelial cells not only reduced the level of activated AKT and the expression of valve-forming genes under no-flow conditions but also abolished the upregulation of AKT activity and valve-forming genes in response to oscillatory shear stress. We further showed that the AKT target, FOXO1 (forkhead box protein O1), a repressor of lymphatic valve formation, had increased nuclear activity in Rictor knockout mesenteric lymphatic endothelial cells in vivo. Deletion of Foxo1 in Rictor knockout mice restored the number of valves to control levels in lymphatic vessels of the ear and mesentery.
UNASSIGNED: Our work identifies a novel role for RICTOR in the mechanotransduction signaling pathway, wherein it activates AKT and prevents the nuclear accumulation of the valve repressor, FOXO1, which ultimately enables the formation and maintenance of lymphatic valves.

Lymphoscintigraphy is a nuclear medicine procedure that uses a small quantity of radioactive particles for visualizing the lymphatic system. Traditionally, the radiotracer was injected subcutaneously, but the quality of lymphatic path imaging was scarce due to high background. Intradermal radiotracer injection is considered the modern-day intralymphatic injection. We propose rest/stress intradermal lymphoscintigraphy for the diagnosis, staging and surgical planning of lymphedema. Major and minor findings were described in primary and secondary lymphedema. Based on the in-depth information of the lymphatic pathways, physiotherapists and microsurgeons can obtain important functional information in patients\' selection to treat with physical treatments and/or undergo microsurgery.

Currently, there is unavailability of disease-modifying medication for Alzheimer\'s disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aβ) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aβ. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system\'s function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.