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Lymphoscintigraphy showing right pelvic lymph node obstruction: (A) anterior (40 minutes, alpha value of 30%), (B) posterior (alpha value of 30%), (C) anterior (40 minutes), and (D) posterior.
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Lymphedema, a chronic disease that lowers patients’ quality of life, is categorized as primary or secondary. Secondary lymphedema can be improved by treating the underlying cause. However, in many cases, efforts are not made to identify the primary cause of lymphedema and treatment is targeted at the edema itself, resulting in misdiagnosis. Here, w...
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... and stair-climbing. His D-dimer levels and lower-extremity computed tomography (CT) results did not confirm deep vein thrombosis; thus, additional tests were performed for lymphedema. On lymphoscintigraphy, right inguinal lymph node (LN) activity was observed in the early and delayed phases, with delayed lymphatic drainage in the right lower leg (Fig. 1). On indocyanine green (ICG) lymphography, a mixed stardust and diffuse pattern was observed below the knee; a linear lymphatic pattern was observed above the knee, correlated with his clinical symptoms of prominent leg edema below the knee ( Fig. 2A). Although these tests confirmed the presence of lymphedema, its cause remained ...
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Background
In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer.
Methods
A systematic review of electronic databases including PubM...
Background
Near-infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatic flow and reveals not only the spatial distribution of drainage (static analysis), but also information on the lymphatic contrac...
Background: Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer.
Methods: From January 2018 through June 2020, seven cancer patients (three...
Introduction
Hepatic lymphorrhea (HL) is an uncommon but potentially life-threatening type of postoperative lymphatic leakage, especially following pancreaticoduodenectomy.
Case presentation
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Treatment outcomes for lower extremity lymphedema (LEL) using multiple lymphaticovenular anastomoses (LVA) are still uncertain. Classification of progression of lymphedema by disease staging is a potential preoperative predictor of the efficacy of treatment, but it is difficult to judge progression of lymphedema objectively. Recent studies have ind...
Citations
... 7 Gut lymphangiogenesis compensates for lymphatic insufficiency in patients with inflammatory bowel disease (IBD). 8,9 During cirrhosis, the production of abdominal lymph increases 30-fold, and there is a positive correlation between increased lymph flow and portal pressures (PPs). 10,11 In carbon tetrachloride (CCl 4 )-induced cirrhosis models and patients with cirrhosis, previous studies reported that gut LVs show an impaired phenotype and reduced contractility. ...
Background & aims:
Lymphatic vessels (LVs) are crucial for maintaining abdominal fluid homoeostasis and immunity. In cirrhosis, mesenteric LVs (mLVs) are dilated and dysfunctional. Given the established role of vascular endothelial growth factor-C (VEGF-C) in improving LVs, we hypothesised that VEGF-C treatment could ameliorate the functions of mLVs in cirrhosis.
Methods:
In this study, we developed a nanoformulation comprising LV-specific growth factor, recombinant human VEGF-C (Cys156Ser) protein (E-VEGF-C) and delivered it orally in different models of rat cirrhosis to target mLVs. Cirrhotic rats were given nanoformulation without VEGF-C served as vehicles. Drainage of mLVs was analysed using tracer dye. Portal and systemic physiological assessments and computed tomography were performed to measure portal pressures and ascites. Gene expression and permeability of primary mesenteric lymphatic endothelial cells (LyECs) was studied. Immune cells in mesenteric lymph nodes (MLNs) were quantified by flow cytometry. Endogenous and exogenous gut bacterial translocation to MLNs was examined.
Results:
In cirrhotic rats, mLVs were dilated and leaky with impaired drainage. Treatment with E-VEGF-C induced proliferation of mLVs, reduced their diameter, and improved functional drainage. Ascites and portal pressures were significantly reduced in E-VEGF-C rats compared with vehicle rats. In MLNs of E-VEGF-C animals, CD8+CD134+ T cells were increased, whereas CD25+ regulatory T cells were decreased. Both endogenous and exogenous bacterial translocation were limited to MLNs in E-VEGF-C rats with reduced levels of endotoxins in ascites and blood in comparison with those in vehicle rats. E-VEGF-C treatment upregulated the expression of vascular endothelial-cadherin in LyECs and functionally improved the permeability of these cells.
Conclusions:
E-VEGF-C treatment ameliorates mesenteric lymph drainage and portal pressure and strengthens cytotoxic T-cell immunity in MLNs in experimental cirrhosis. It may thus serve as a promising therapy to manage ascites and reduce pathogenic gut bacterial translocation in cirrhosis.
Impact and implications:
A human recombinant pro-lymphangiogenic growth factor, VEGF-C, was encapsulated in nanolipocarriers (E-VEGF-C) and orally delivered in different models of rat liver cirrhosis to facilitate its gut lymphatic vessel uptake. E-VEGF-C administration significantly increased mesenteric lymphatic vessel proliferation and improved lymph drainage, attenuating abdominal ascites and portal pressures in the animal models. E-VEGF-C treatment limited bacterial translocation to MLNs only with reduced gut bacterial load and ascitic endotoxins. E-VEGF-C therapy thus holds the potential to manage ascites and portal pressure and reduce gut bacterial translocation in patients with cirrhosis.
... Unlike primary lymphedema, which is a clinical manifestation of insufficient lymphatic transport, acquired lymphedema is a consequence of traumatic perturbation of the lymphatic system, mainly due to malignancy, inflammation, and infections (Rutkowski et al., 2006;Padera et al., 2016;Borman, 2018;Hong et al., 2019;Bertelli et al., 2020). Acquired lymphedema constitutes more than 90% cases of lymphedema worldwide (Greene and Goss, 2018/04). ...
... Interestingly, a recent case report by Hong et al. (2019) established a causative association between bacterial infection and lymphedema in the lower extremities of a patient with intestinal tuberculosis in Korea. Although an extremely rare case, it can broaden our horizon that lymphedema is not solely attributed to the adverse effects of anticancer regimens. ...
Lymphedema is a debilitating chronic disease that mostly develops as an adverse reaction to cancer treatment modalities such as chemotherapy, surgery, and radiotherapy. Lymphedema also appears to be a deteriorating consequence of roundworm infections, as best represented by filariasis. According to its origin, lymphedema is classified as primary lymphedema and acquired lymphedema. The latter is an acquired condition that, hitherto, received a considerably low attention owing to the less number of fatal cases been reported. Notably, despite the low mortality rate in lymphedema, it has been widely reported to reduce the disease-free survival and thus the quality of life of affected patients. Hence, in this review, we focused on acquired lymphedema and orchestration of molecular interplays associated with either stimulation or inhibition of lymphedema development that were, in vast majority, clearly depicted in animal models with their specific and distinct technical approaches. We also discussed some recent progress made in phytochemical-based anti-lymphedema intervention strategies and the specific mechanisms underlying their anti-lymphedema properties. This review is crucial to understand not only the comprehensive aspects of the disease but also the future directions of the intervention strategies that can address the quality of life of affected patients rather than alleviating apparent symptoms only.
Gut lymphatic vessels (LVs) are crucial for maintaining gut immunity and abdominal fluid homeostasis. In experimental liver cirrhosis with ascites, gut LVs are dilated and dysfunctional with impaired gut immune response. Therapy with pro-lymphangiogenic factor, vascular endothelial growth factor-C (VEGF-C) promotes functional LVs growth and attenuates inflammation. However, therapeutic role of VEGF-C in cirrhosis has not been explored. Here we developed a nanoformulation comprising of recombinant human VEGF-C loaded reverse micelles (E-VEGF-C) and delivered it orally in rat models of liver cirrhosis to specifically target mesenteric LVs (mLVs). E-VEGF-C treated cirrhotic rats displayed an increased density of gut LVs, improved functional drainage and reduced abdominal fluid/ascites and portal pressures without any adverse events. E-VEGF-C also enhanced the proliferation of LVs in the mesenteric lymph nodes, triggering active immune responses, which helped to contain the spreading of bacteria to other organs preventing systemic infection. At molecular level, E- VEGF-C treatment upregulated the expression of cell adhesion and permeability markers, VE-cadherin and VCAM1 in the mesenteric lymphatic endothelial cells. Collectively, oral delivery of E-VEGF-C in cirrhotic rats ameliorates drainage of gut LVs, ascites formation and immunity and thus represents a potential treatment to manage ascites and immune dysfunction in cirrhosis.
