• Korean Journal of Radiology
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• v.24 no.2
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• pp.95-108
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• 2023

Recent advances in lymphatic imaging have provided novel insights into the lymphatic system. Interventional radiology has played a significant role in the development of lymphatic imaging techniques and modalities. Radiologists should be familiar with the basic physiology and anatomy of the lymphatic system to understand the imaging features of lymphatic disorders, which reflect their pathophysiology. This study comprehensively reviews the physiological and anatomical aspects of the human lymphatic system as well as the latest lymphatic imaging techniques.

• Korean Journal of Radiology
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• v.24 no.2
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• pp.109-132
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• 2023

Lymphatic disorders encompass a broad spectrum of diseases involving the lymphatic system, ranging from traumatic lymphatic leaks to lymphatic malformations. Lymphatic disorders can be categorized into traumatic and non-traumatic disorders according to their etiology. These two categories may be further divided into subgroups depending on the anatomical location of the lymphatic pathology and their association with clinical syndromes. Thoracic duct embolization was a milestone in the field of lymphatic intervention that encouraged the application of percutaneous embolization techniques to treat leaks and reflux disorders in the lymphatic system. Additional access routes for embolization, including retrograde thoracic duct and transhepatic lymphatic access, have also been developed. This article comprehensively reviews a variety of options for the treatment of lymphatic disorders, from conservative management to the most recent embolization techniques.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.75-82
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• 2010

Specific diseases like cancer and acquired immune deficiency syndrome (AIDS) occur at various organs including lymphatics and spread through lymphatic system. Thus, if therapeutic agents for such diseases are more distributed or targeted to lymphatic system, we can obtain several advantages like reduction of systemic side effect and increase of efficacy. For these reasons, much interest has been focused on the nature of lymphatics and a lot of studies for lymphatic delivery of drugs have been carried out. Because lymphatics consist of single layer endothelium and have high permeability compared with blood capillaries, especially, the studies using nano-sized carriers have been performed. Polymeric nano-particle, liposome, and lipid-based vehicle have been adopted for lymphatic delivery as carriers. According to the administration route and the kind of carrier, the extent of lymphatic delivery efficiency of nano-sized carriers has been changed and influenced by several factors such as size, charge, hydrophobicity and surface feature of carrier. In this review, we summarized the key factors which affect lymphatic uptake and the major features of carriers for achieving the lymphatic delivery. Lymphatic delivery of drug using nano-sized carriers has many fold improved ability of lymphatic delivery compared with that of conventional dosage forms, but it has not shown whole lymph selectivity yet. Even though nano-sized carriers still have the potential and worth to study as lymphatic drug delivery technology as before, full understanding of delivery mechanism and influencing factors, and setting of pharmacokinetic model are required for more ideal lymphatic delivery of drug.

• Archives of Plastic Surgery
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• v.49 no.1
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• pp.99-107
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• 2022

Background Dermal backflow (DBF), which refers to lymphatic reflux due to lymphatic valve insufficiency, is a diagnostic finding in lymphedema. However, the three-dimensional structure of DBF remains unknown. Photoacoustic lymphangiography (PAL) is a new technique that enables the visualization of the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and can provide three-dimensional images of superficial lymphatic vessels and the venous system. This study reports the use of PAL to visualize DBF structures in the extremities of patients with lymphedema after cancer surgery. Methods Patients with a clinical or lymphographic diagnosis of lymphedema who previously underwent surgery for cancer at one of two participating hospitals were included in this study. PAL was performed using the PAI-05 system. ICG was administered subcutaneously in the affected hand or foot, and ICG fluorescence lymphography was performed using a near-infrared camera system prior to PAL. Results Between April 2018 and January 2019, 21 patients were enrolled and examined using PAL. The DBF was composed of dense, interconnecting, three-dimensional lymphatic vessels. It was classified into three patterns according to the composition of the lymphatic vessels: a linear structure of lymphatic collectors (pattern 1), a network of lymphatic capillaries and lymphatic collectors in an underlying layer (pattern 2), and lymphatic capillaries and precollectors with no lymphatic collectors (pattern 3). Conclusions PAL showed the structure of DBF more precisely than ICG fluorescence lymphography. The use of PAL to visualize DBF assists in understanding the pathophysiology and assessing the severity of cancer-related lymphedema.

• Molecules and Cells
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• v.37 no.7
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• pp.503-510
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• 2014

Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical importance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in vertebrates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels.

• Archives of Plastic Surgery
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• v.49 no.6
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• pp.773-781
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• 2022

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.

• The Journal of Korean Academy of Orthopedic Manual Physical Therapy
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• v.22 no.2
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• pp.35-39
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• 2016

Background: The superficial lymphatic system is divided into areas called lymphatic territories which are separated by watersheds. When the lymphatic system fails to remove its load either due to surgery, radiotherapy or some congenital malformation of it then the fluid and the proteins and wastes contained within it accumulates in that territory. Anastomotic connections exist across the watersheds and while they can work unaided manual lymph drainage (MLD) can significantly help drainage across them into unaffected lymphatic territories. The purpose of the study is to examine the effectiveness of a manual technique in moving fluids and softening hardened tissues using a tape measure and Patient-Specific Functional Scale. Methods: We examined the movement of fluids from the affected limbs of lymphedema patients who underwent a standardized 30-min treatment using the Dr. Vodder method of MLD. We chose a typical cross section of patients with secondary leg or secondary arm lymphedema. The lymphedema patient was also measured after the conclusion of treatment and underwent a follow-up control measurement, within 8 weeks. Both evaluation tools indicated a movement of fluid to different and unblocked lymphatic territories as well as a softening of tissues in some of the affected limbs. Results: MLD is an effective means of fluid clearance when it accumulates as a consequence of a failure of the lymphatic system. It seems likely that MLD has a systemic effect on the lymphatic system and that it can improve flow from otherwise normal tissues. Conclusions: It is hypothesized that a series of treatments would result in even more significant improvements.

• The Journal of Korean Medical History
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• v.23 no.1
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• pp.23-41
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• 2010

Greater yang disease(太陽病) is a syndrome induced by peripheral obstruction. One of them is "wind stroke(中風)" with the obstruction in lymphatic system. The other obstruction appearing on circulatory system is called "cold damage(傷寒)." Kyejitang(桂枝湯) is the formula prescribed for greater yang wind stroke pattern(太陽中風證) which is caused by peripheral lymphatic duct obstruction. Ramulus Cinamoni acts as a vasodilator and Radix Paeoniae relieves the abdominal tension. They make blood move to the internal organ and this can remove the retention of peripheral lymphatic system. Covering the patient with a blanket and getting him/her to have hot and thin rice gruel causes slight Diaphoresis, contributing to relieving the retention of lymphatic system. Disharmony between nutrient and defense(營衛不和) means that pressure becomes different between lymphatic system and vascular system. Kyejitang(桂枝湯) is called releasing muscles formula(解肌劑) because it can resolve such pressure difference. Diaphoresis is not a means to eliminate pathogenic qi(邪氣) from the body. That is the syndrome proving that the body fluid has moved around when disordered fluid distribution is corrected. Therefore, diaphoresis should be induced weakly all the time. If diaphoresis is induced excessively, body fluid will move more than desired and then illness cannot be cured. In Sanghanlun(傷寒論), dispersing drugs aim at addressing the retention in the exterior field, but it actually applies to the entire exterior and interior to make body fluid move. Therefore, diaphoresis does not just act on exterior field, and freeing the stool does not only apply to interior field. Distribution of body fluid changed by pathogenic qi(邪氣) influences the whole body because the human body has a closed circulatory system. Sanghanlun(傷寒論) has included treatments for pathogenic disease. However, its value should not be limited to pathogenic disease. It is because controlling blood flow by sending body fluid to the place a doctor wants is certainly worth using for treatment of non-exogenous disease or chronic illnesses.

• BMB Reports
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• v.49 no.8
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• pp.403-404
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• 2016

The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development.

• Archives of Plastic Surgery
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• v.49 no.2
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• pp.227-239
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• 2022

Complications experienced during lymphatic surgery have not been ubiquitously reported, and little has been described regarding how to prevent them. We present a review of complications reported during the surgical management of lymphedema and our experience with technical considerations to reduce morbidity from lymphatic surgery. A comprehensive search across different databases was conducted through November 2020. Based on the complications identified, we discussed the best approach for reducing the incidence of complications during lymphatic surgery based on our experience. The most common complications reported following lymphovenous anastomosis were re-exploration of the anastomosis, venous reflux, and surgical site infection. The most common complications using groin vascularized lymph node transfer (VLNT), submental VLNT, lateral thoracic VLNT, and supraclavicular VLNT included delayed wound healing, seroma and hematoma formation, lymphatic fluid leakage, iatrogenic lymphedema, soft-tissue infection, venous congestion, marginal nerve pseudoparalysis, and partial flap loss. Regarding intra-abdominal lymph node flaps, incisional hernia, hematoma, lymphatic fluid leakage, and postoperative ileus were commonly reported. Following suction-assisted lipectomy, significant blood loss and transient paresthesia were frequently reported. The reported complications of excisional procedures included soft-tissue infections, seroma and hematoma formation, skin-graft loss, significant blood loss, and minor skin flap necrosis. Evidently, lymphedema continues to represent a challenging condition; however, thorough patient selection, compliance with physiotherapy, and an experienced surgeon with adequate understanding of the lymphatic system can help maximize the safety of lymphatic surgery.