The history of anatomical research of lymphatics - From the ancient times to the end of the European Renaissance.

Very often, descriptions of the scientific discovery of the lymphatic system start with Gaspare Aselli, probably because of his so captivating account. Nevertheless, there was prior and even very old evidence of the lymphatic vessels, which was of course known to Aselli himself, as he cited most of these antique references. In fact, the first insights were contributed by the Hippocratic School. The Alexandrian School added quite a lot but unfortunately most of that knowledge is not extant and can only be appreciated by translations or citations by other authors such as Galen. The 'dark' middle ages did not add to the anatomical knowledge of the lymphatics, and only the rise of the Renaissance brought new insights. Even at that time, Aselli was not the first to identify at least some components of the lymphatic system, but he was actually the first to present a proper account in a book dedicated to the "lacteal veins". Afterwards the interest rose enormously and cumulated in one of the first priority - or plagiarism - disputes, the Rudbeck-Bartholin feud. Surprisingly, William Harvey, the discoverer of the systemic blood circulation, ignored, at least in part, the progress of the discoveries in lymphatic circulation. This narrative review tries to summarize the major contributions to the anatomical knowledge of the lymphatic system from the ancient times up to the end of the European Renaissance.

Putative Primo-Vascular System in Rabbit Placenta.

The primo vascular system (PVS) is a very important topic of study nowadays because of their role in transport and regeneration of tissue and in cell migration and cancer metastasis. The PVS was detected in different organs of the rabbit but not in the placenta. In this work, we observe the PVS inside the blood vessels of the placenta for the first time. The main characteristic features of the primo vessels (PVs) from the rabbit placenta were in agreement with the PVS in different organs of animals, including the rod-shaped nuclei and their arrangement.

Primo Vascular System: A Unique Biological System Shifting a Medical Paradigm.

The primo vascular system has a specific anatomical and immunohistochemical signature that sets it apart from the arteriovenous and lymphatic systems. With immune and endocrine functions, the primo vascular system has been found to play a large role in biological processes, including tissue regeneration, inflammation, and cancer metastases. Although scientifically confirmed in 2002, the original discovery was made in the early 1960s by Bong-Han Kim, a North Korean scientist. It would take nearly 40 years after that discovery for scientists to revisit Kim's research to confirm the early findings. The presence of primo vessels in and around blood and lymph vessels, nerves, viscera, and fascia, as well as in the brain and spinal cord, reveals a common link that could potentially open novel possibilities of integration with cranial, lymphatic, visceral, and fascial approaches in manual medicine.

Dynamic contrast-enhanced MR lymphangiography: feasibility study in swine.

PURPOSE: To demonstrate the feasibility of dynamic four-dimensional ( 4D four-dimensional ) intranodal contrast material-enhanced magnetic resonance (MR) lymphangiography with inguinal lymph node injection of gadopentetate dimeglumine. MATERIALS AND METHODS: All procedures were performed in accordance with the guidelines on the use of animals in research and were approved by the animal care and use committee. Five swine underwent nonenhanced MR lymphangiography with a heavily T2-weighted MR sequence, bilateral inguinal lymph node injection of 2 mL of undiluted gadopentetate at a rate of 1 mL/min, and 60 minutes of MR imaging with T1-weighted high-spatial- and high-temporal-resolution MR angiography. Images were reviewed by a radiologist with expertise in lymphatic imaging and a pediatric cardiac MR imaging specialist for visualization of the thoracic duct ( TD thoracic duct ). Categorical variables were compared by using the exact conditional McNemar test. A difference with a P value less than .05 was considered significant. RESULTS: The TD thoracic duct was visualized in three of the five animals (60%) on T2-weighted images. In contrast, the TD thoracic duct was visualized in all five of the animals (100%) after contrast agent injection (P = .25). The median time for flow of the contrast agent through the lymphatic system to the TD thoracic duct outlet was 244 seconds (range, 201-387 seconds). Enhancement was seen in the TD thoracic duct up to 1 hour after injection. All animals survived without any complications. CONCLUSION: Dynamic 4D four-dimensional contrast-enhanced MR lymphangiography with intranodal injection of gadopentetate dimeglumine is feasible, produces good images of the central lymphatic system, and demonstrates the time course of flow of contrast agent up the central lymphatic ducts. On the basis of the results of this initial animal experiment, it appears that dynamic 4D four-dimensional contrast-enhanced MR lymphangiography is potentially feasible and safe with commercially available contrast agents.

Alveolar rhabdomyosarcoma of the extremity and nodal metastasis: Is the in-transit lymphatic system at risk?

Alveolar rhabdomyosarcoma (RMS) of the extremity is not infrequently associated with regional node metastasis. Knowledge of lymphatic drainage of extremity RMSs is important to determine radiotherapy fields. In this report we describe two patients with alveolar RMS of the lower extremity with inguinal metastasis at presentation. Both the distal lower extremity and inguinal region received local therapy consisting of surgery and postoperative radiotherapy. Both patients later developed in-transit lymphatic metastasis outside of the irradiated field. The in-transit lymphatics can be a site of failure in children with alveolar RMS of the extremity and nodal involvement.

The lymph drainage pattern of the mammary glands in the cat: a lymphographic and computerized tomography lymphographic study.

Seventy-three clinically normal, lactating cats were used to investigate the lymph drainage of 73 mammary glands. In 50 cats of the first group, the number of lymphatic vessels emerging from the examined mammary gland, their course and the lymph nodes into which they are drained were studied by indirect lymphography (IL) after intramammary injection of an oily contrast medium. In 23 cats of the second group, the lymph drainage of the mammary glands was studied by computerized tomography indirect lymphography (CT-IL) after intramammary injection of a water soluble contrast medium. The following day, the lymph drainage of the mammary gland examined by CT-IL was studied by IL, as it was described in the first group, for comparison purposes. The main conclusions drawn after this study were as follows: lymph drains from the first and second mammary glands with one or rarely two or three lymphatic vessels to the accessory axillary lymph nodes. Lymph drains from the third mammary gland with one or two and rarely three lymphatic vessels usually to the accessory inguinal lymph nodes or to the accessory axillary lymph nodes. In some cases, it drains to both lymph nodes simultaneously or it may rarely drain only to the medial iliac lymph nodes. The fourth mammary gland with one or two and rarely three lymphatic vessels usually drains to the accessory inguinal lymph nodes. It may rarely drain only to the medial iliac lymph nodes. Mammary lymphatic vessels that cross the midline and lymphatic connection between the mammary glands were not demonstrated. No differences in the mammary lymph drainage pattern between IL and CT-IL were found.

In vivo real-time, multicolor, quantum dot lymphatic imaging.

The lymphatic network is complex and difficult to visualize in real-time in vivo. Moreover, the direction of flow within lymphatic networks is often unpredictable especially in areas with well-developed "watershed" or overlapping lymphatics. Herein, we report a method of in vivo real-time multicolor lymphatic imaging using cadmium-selenium quantum dots (Qdots) with a fluorescence imaging system that enables the simultaneous visualization of up to five distinct lymphatic basins in real-time. Five visually well-distinguishable carboxyl-Qdots (Qdot 545, 565, 585, 605, and 655) were selected and injected subdermally into mice at five different sites, and serially imaged in vivo or in situ under surgery with real-time multicolor lymphatic imaging. In all seven mice, in vivo lymphatic images successfully distinguished all five lymphatic basins with different colors in real-time. These visualizations of lymph node lasted up to at least 7 days. This method could have a considerable potential in lymphatic research for studying the anatomy and flow within the lymphatic system as well as in some limited clinical settings where real-time visible fluorescence could facilitate procedures under surgery or endoscopy.

Structure and function of the lymphatic system: an overview.

The lymphatic system is often overlooked, but is a vital part both of the circulation and the immune system. This article provides a basic overview of the structure and function of the lymphatic system as a grounding for understanding the development of chronic oedemas, notably lymphoedema.

The perineurial vessel: a possible candidate for the structural basis of the meridian (Jing-Luo) in Chinese medicine.

A new concept is proposed of the 'perineurial vessel' as another vascular system of the body. The effects of acupuncture and moxibustion are explained as mechanical or thermal stimulation of intraperineurial cerebrospinal fluid (CSF). Fenestrated venous capillaries of circumventricular organs, including the choroid plexus, instead of arachnoid granulations, are shown to be the main site of CSF absorption. A new concept is also presented of a double circulatory system of the body, namely, in addition to the cardiovascular system, a lympho-liquid system with complete fluid circulation throughout the entire body.

Visualization of normal and interrupted lymphatic drainage in dog legs with interstitial MR lymphography using an extracellular MR contrast agent, gadopentetate dimeglumine.

PURPOSE: The capability of the interstitial magnetic resonance lymphography (MR-LG) using a widely available extracellular contrast agent, gadopentetate dimeglumine, for the visualization of normal and interrupted lymphatic drainage was tested in dog legs. MATERIALS AND METHODS: With a 7-day interval, 1 mL and 2 mL undiluted gadopentetate dimeglumine were injected intradermally into the dorsal foot of both hind legs of 12 dogs. T1-weighted 3-dimensional (3D) spoiled gradient-echo (repetition time/echo time = 6.7/1.6 ms) and maximum intensity projection (MIP) images covering the legs and pelvic region were acquired at 1.5 T for 10 minutes after 30 seconds gentle massage at the injection sites. These dogs also underwent the MR-LG with 2 mL of this contrast agent 7 days after surgical ligation of the popliteal lymphatic vessels. RESULTS: In the normal dogs, the interstitial MR-LG quickly and consistently visualized the direct connection of the lymphatic vessels and lymph nodes draining from the injection sites up to the inguinal region, without any late adverse effects. The enhancement effect was significantly greater with a 2-mL dose than with a 1-mL dose. After lymphatic obstruction, the MR-LG clearly revealed the anatomic compromises of the lymphatics, such as poor enhancement of the affected lymphatic vessels and lymph nodes, collateral lymphatic vessels, abnormal soft-tissue enhancement, and delayed lymphatic migration of the contrast agent. The topographic 3D images provided a comprehensive anatomy of these normal and compromised lymphatic drainage. CONCLUSION: Although gadopentetate dimeglumine is not lymphotropic, the interstitial MR-LG using this T1-contrast agent appears to have potential for quick and sufficient mapping of the lymphatic drainage from the injection sites and for the characterization of interrupted lymph flow.

[The theory of lymphangion and current approaches to the pathogenesis, diagnosis and treatment of lymphedema of the lower extremities]. / Teoriia limfangiona i sovremennye podkhody k patogenezu, diagnostike i lecheniiu limfedemy nizhnikh konechnostei.

The paper describes the results of examination carried out by the Sankt-Peterburg school of lymphologists, pertaining to the structure, physiological properties and function of lymphangions responsible for active lymph transport. The problems of the pathogenesis, diagnosis and treatment of lymphedema of the lower extremities used in clinical practice are reviewed from the standpoint of the new theory. The data obtained as a result of the clinico-morphofunctional studies allowed to delineate the stages of lymphedema as dependent on the degree of lymphocytic structure and function integrity. Based on the aforesaid the new approaches to the diagnosis and selection of the treatment methods for lymphedema of the lower extremities have been formulated.

[Diseases of the pulmonary lymphatic system in children]. / Pathologies des lymphatiques pulmonaires chez l'enfant.

Diseases of the lymphatic system in children include a group of exceptional conditions difficult to manage. The anatomy of lymphatic system is complex in the lung. Variable from one subject to another, its complex physiology plays an important role in air-blood exchanges occurring in the lung. In the pulmonary interstitium and in the pleura, the lymphatic system acts like an overflow valve capable of regulating variations in interstitial fluid. The presence or development of dysplasic lymphatics causes leakage, dilatation, and reflux of the lymph through incontinent valves leading to chylothorax and/or fluid overload in the pulmonary interstitium. Symptomatic care is usually proposed, based on a fat-free diet supplemented with light-chain triglycerides and liposoluble vitamins. Other therapeutic options can be proposed. Medical options include cytotoxic agents, somatostatin, and interferon-alpha. Surgery may also be useful, but an assessment of therapeutic efficacy is very difficult due to partial effects and the small number of cases studied.

Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy.

Knowledge of the anatomy and physiology of the lymphatic system is helpful when considering a particular sentinel node biopsy technique. The delicate balance between internal and external pressures in a lymphatic channel can be influenced by the injection volume and by massage in a negative or positive way. The narrow openings in the interendothelial junctions determine the speed of clearance of particles with a certain size, and this has implications for the timing of lymphoscintigraphy and surgery. Tracer uptake and lymph flow are highly variable and depend on a number of factors, some of which are beyond our control. The lymphatic anatomy is not completely understood despite numerous studies since the end of the 18th century. Several topics have been elucidated in more recent studies and through experience with sentinel node biopsy. First, although axillary drainage is the principal lymphatic path of the breast, any drainage pattern from any quadrant of the breast can occur. Second, most lymph from the breast flows to the nodal basins with a direct course, not passing through the subareolar plexus. Another relevant point is that gentle massage encourages lymph flow and facilitates sentinel node detection. What problems do we still face in clinical practice? The optimum size and number of labeled colloid particles remain to be established. The optimum volume of the tracer also remains to be determined. But the main controversy concerns the injection site. Although the intradermal injection technique has attractive practical features, there is currently insufficient certainty that drainage of tracer injected anywhere in or underneath the skin of the breast reflects drainage from the cancer. Connections between collecting lymphatic vessels from the tumor site and the collecting vessels from the skin and subdermal lymphatics can explain the concordance between intraparenchymal and superficial injections in most patients. To determine the technique that yields the best sentinel node identification rate with the lowest possible false-negative rate would require a large randomized trial with all patients undergoing a complete lymph node dissection and evaluation of all other axillary lymph nodes with serial sections and immunohistochemistry. Current knowledge about sensitivity is based on examination of the other axillary nodes with hematoxylin and eosin staining and not with immunohistochemistry, with the exception of two studies. (33,76) In addition, a complete level I to III dissection may not have been done in all patients, and it is not certain that pathologists removed and examined all the nodes from the specimens. The proposed study seems impossible now that routine axillary node dissection has been abandoned by the larger centers around the world. Choosing the most attractive approach requires determining the aim of lymphatic mapping. A superficial injection technique may be adequate when the purpose is to spare patients without lymph node metastases in the axilla an unnecessary axillary node dissection. An intraparenchymal injection technique should be used when the additional purpose is to determine the stage as accurately as possible and to identify sentinel nodes elsewhere.

Improvement of macromolecular clearance via lymph flow in hamster gingiva by topical warming and massage.

The lymphatic system is very important for macromolecular clearance in various tissues, especially in the gingiva. However, the kinetics of macromolecular clearance via the lymph flow in the gingiva are poorly understood. The aim of this study was to investigate whether thermal or mechanical stimulation affects macromolecular clearance via the lymph flow in the gingiva. Carbon black suspension was injected into the mandibular gingiva of anesthetized hamsters and its drainage into cervical lymph nodes was examined. Clearance of 14C-methylated bovine albumin and tritiated water from the gingiva and their drainage into submandibular lymph nodes and blood was quantified. The effect of topical warming or massage on clearance of 14C-methylated albumin from the gingiva during a 15 min period was examined. In addition, the influence of neurochemical antagonists on the stimulatory effect of topical warming on albumin clearance was investigated. Submandibular lymph nodes were clearly delineated by carbon black 10 min after the injection. More radiolabeled albumin appeared in submandibular lymph nodes than in serum, while more tritiated water appeared in serum. Topical warming (45 degrees C, 2 min) and warming plus massage (with a silicon rubber brush, 20 s) decreased the radiolabeled albumin in the gingiva 15 min after the injection. There was less radiolabeled albumin in the gingiva after gingival warming plus massage than after warming. Previous injection of HOE140 or propranolol into the gingiva diminished the stimulatory effect of topical warming on albumin clearance. It was concluded that topical warming plus massage improves macromolecular clearance via the lymph flow in hamster gingiva.

[Observation on the microstructure of sanyinjiao acupoint].

METHOD: Fresh adult limbs were divided into acupoint and control group. (1) H. E stain; (2) Cajal-Fauordky stain; (3) Lymph perfusion and section. RESULT: the sensery organs are multiple structures of nerves, blood and lymph etc. in the acupoint. There isn't significant difference (P > 0.05) for innervation of nerve, blood and lymph between the acupoint and other part. But there are some big nerve trunk in the tissues of the acupoint that play a different role in the reaction of human body.

[Healing effects of several ecological exposure factors on the lymphatic system]. / Sanogennoe vliianie nekotorykh faktorov ékologicheskikh vozdeistvii na limfaticheskuiu sistemu.

The structural and functional responses of lymph nodes to environmental influences have common stereotypic features; however, they can vary with the nature of an influencing factor and the functional specialization of the lymph node. In this view, the morphological and functional status of lymph nodes can be regarded as markers of environmental impact on the lymphatic system. Approaches to correcting blood and lymph circulation have been developed via combined exposure of the body's internal environment to sorbent therapy, balneological procedures at the Siberian resorts, biological flavonoids, and derivatives of Siberian raw plant materials.