Identification Of Lymphatics Research Articles

Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms.

Glioblastoma (GBM) is the most typical and aggressive form of primary brain tumor in adults, with a poor prognosis. Successful glioma treatment is hampered by ineffective medication distribution across the blood-brain barrier (BBB) and the emergence of drug resistance. Although a few FDA-approved multimodal treatments are available for glioblastoma, most patients still have poor prognoses. Targeting epigenetic variables, immunotherapy, gene therapy, and different vaccine- and peptide-based treatments are some innovative approaches to improve anti-glioma treatment efficacy. Following the identification of lymphatics in the central nervous system, immunotherapy offers a potential method with the potency to permeate the blood-brain barrier. This review will discuss the rationale, tactics, benefits, and drawbacks of current glioma therapy options in clinical and preclinical investigations.

Bedside 3D Visualization of Lymphatic Vessels with a Handheld Multispectral Optoacoustic Tomography Device.

Identification of lymphatics by Indocyanine Green (ICG) lymphography in patients with severe lymphedema is limited due to the overlying dermal backflow. Nor can the method detect deep and/or small vessels. Multispectral optoacoustic tomography (MSOT), a real-time three- dimensional (3D) imaging modality which allows exact spatial identification of absorbers in tissue such as blood and injected dyes can overcome these hurdles. However, MSOT with a handheld probe has not been performed yet in lymphedema patients. We conducted a pilot study in 11 patients with primary and secondary lymphedema to test whether lymphatic vessels could be detected with a handheld MSOT device. In eight patients, we could not only identify lymphatics and veins but also visualize their position and contractility. Furthermore, deep lymphatic vessels not traceable by ICG lymphography and lymphatics covered by severe dermal backflow, could be clearly identified by MSOT. In three patients, two of which had advanced stage lymphedema, only veins but no lymphatic vessels could be identified. We found that MSOT can identify and image lymphatics and veins in real-time and beyond the limits of near-infrared technology during a single bedside examination. Given its easy use and high accuracy, the handheld MSOT device is a promising tool in lymphatic surgery.

Does BMI affect the detection of sentinel lymph nodes with indocyanine green in early breast cancer patients?

Sentinel node biopsy (SNB) has proved to be a useful and safe method for axillary staging in the surgical management of early breast cancer. Sentinel node (SN) detection rates with blue dye (patent blue) and radioisotopes (99m-Tc), either alone or particularly in combination, are high (95% to 100%). Even better detection rates were reported with fluorescent dyes like indocyanine green (ICG). This study was designed to show whether sentinel node detection and mapping of lymphatics with ICG might depend on the body mass index (BMI). Between February 2014 and April 2015, SNB with blue dye, 99m-Tc, and ICG navigation was conducted for 100 consecutive procedures in patients scheduled for surgery of early breast cancer. ICG injection, lymphatic mapping with the Photodynamic Eye (PDE; Hamamatsu Photonics, Hamamatsu, Japan), and identification of the sentinel nodes with blue dye and ICG were followed by a final search for more lymph nodes with a gamma probe. Data were collected prospectively. In all patients, up to six sentinel nodes (mean 2.49) were detected. No statistical correlation was found between the BMI and the identification of lymphatics or the detection of lymph nodes with ICG. Lymphatics were successfully identified preoperatively in no more than 79 cases. In 6 patients, a gamma probe was needed for detection. Adverse events or allergic reactions were absent throughout. SN detection and lymphatic mapping with ICG were not related to the BMI. Pending answers to as yet unsolved questions, the combined use of blue dye and 99m-Tc imaging should, however, be continued.

Identification of lymphatics in the ciliary body of the human eye: A novel “uveolymphatic” outflow pathway

Impaired aqueous humor flow from the eye may lead to elevated intraocular pressure and glaucoma. Drainage of aqueous fluid from the eye occurs through established routes that include conventional outflow via the trabecular meshwork, and an unconventional or uveoscleral outflow pathway involving the ciliary body. Based on the assumption that the eye lacks a lymphatic circulation, the possible role of lymphatics in the less well defined uveoscleral pathway has been largely ignored. Advances in lymphatic research have identified specific lymphatic markers such as podoplanin, a transmembrane mucin-type glycoprotein, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). Lymphatic channels were identified in the human ciliary body using immunofluorescence with D2-40 antibody for podoplanin, and LYVE-1 antibody. In keeping with the criteria for lymphatic vessels in conjunctiva used as positive control, D2-40 and LYVE-1-positive lymphatic channels in the ciliary body had a distinct lumen, were negative for blood vessel endothelial cell marker CD34, and were surrounded by either discontinuous or no collagen IV-positive basement membrane. Cryo-immunogold electron microscopy confirmed the presence D2-40-immunoreactivity in lymphatic endothelium in the human ciliary body. Fluorescent nanospheres injected into the anterior chamber of the sheep eye were detected in LYVE-1-positive channels of the ciliary body 15, 30, and 45 min following injection. Four hours following intracameral injection, Iodine-125 radio-labeled human serum albumin injected into the sheep eye (n = 5) was drained preferentially into cervical, retropharyngeal, submandibular and preauricular lymph nodes in the head and neck region compared to reference popliteal lymph nodes (P < 0.05). These findings collectively indicate the presence of distinct lymphatic channels in the human ciliary body, and that fluid and solutes flow at least partially through this system. The discovery of a uveolymphatic pathway in the eye is novel and highly relevant to studies of glaucoma and other eye diseases.

Structural organization of lymphatics in the monkey esophagus as revealed by enzyme-histochemistry.

The fine structure and distribution of lymphatic vessels in the monkey esophageal wall were studied by light and electron microscopy using an enzyme-histochemical method. Identification of lymphatics was made by 5'-nucleotidase staining, whereas blood vessels were visualized by alkaline phosphatase staining. This technique revealed intramural lymphatic networks in the mucosa, submucosa, and myenteric layer of the esophagus. The organization of lymphatics in the esophagus basically conformed to that of the small intestine, although they showed certain distribution patterns peculiar to the esophagus. The lamina propria mucosae exhibited a double-layered lymphatic network, and lymphatic capillaries extended into its papillae. Despite their forming blind ends and being closed by endothelial cells, the lymphatics in the mucosal papillae were found to contain lymphocytes in their lumen. This suggests that free cells might penetrate the endothelium to enter these initial portions of the lymphatics.

Structure and function of lymphatics.

Lymphatics are large vessels with a lumen potentially ten times wider than blood vessels and have a mean mesh diameter in the upper dermis of approximately 504 +/- 88 microns. The plexus lies just deep to the subpapillary venous plexus and when functioning well it is difficult to identify because of the attenuated endothelium and collapsed lumen. The role of the lymphatic as a pathway for the Langerhans cell and as an exit for macromolecules such as lipid and protein make it an essential organ for normal skin biology. When this system fails, impaired immunity, fibrosis, and recurrent infections are inevitable. Even vasculitis may be a consequence of failure of clearance of immune complexes from the interstitium. The adipose tissue and deep dermis are especially vulnerable in this respect. Elastin fibers support cutaneous lymphatics and may be low resistance pathways through the connective tissues into the lymphatic. Identification of lymphatics by special markers is a concept that currently fails to take into account that changing roles in disease may be associated with a change in the specificity of markers. The anatomy of lymphatic vessels in the skin is described and the role of the lymphatic is emphasized.

Structure and Function of Lymphatics

Lymphatics are large vessels with a lumen potentially ten times wider than blood vessels and have a mean mesh diameter in the upper dermis of approximately 504 +/- 88 microns. The plexus lies just deep to the subpapillary venous plexus and when functioning well it is difficult to identify because of the attenuated endothelium and collapsed lumen. The role of the lymphatic as a pathway for the Langerhans cell and as an exit for macromolecules such as lipid and protein make it an essential organ for normal skin biology. When this system fails, impaired immunity, fibrosis, and recurrent infections are inevitable. Even vasculitis may be a consequence of failure of clearance of immune complexes from the interstitium. The adipose tissue and deep dermis are especially vulnerable in this respect. Elastin fibers support cutaneous lymphatics and may be low resistance pathways through the connective tissues into the lymphatic. Identification of lymphatics by special markers is a concept that currently fails to take into account that changing roles in disease may be associated with a change in the specificity of markers. The anatomy of lymphatic vessels in the skin is described and the role of the lymphatic is emphasized.

Radiographic-pathologic correlation in the interpretation of lymphangioadenograms.

Lymphangioadenography is the radiologic study of lymph vessels and lymph nodes. This method of examination (a) contributes to the detection and evaluation of the extension of lymph-node metastases; (b) aids in the differential diagnosis of intra-abdominal and pelvic masses; (c) assists in the evaluation of surgical, chemotherapeutic, and radiation treatment of malignant disease; (d) provides information as to the cause of obstructive edema, especially when combined with phlebography; (e) aids in the diagnosis and therapeutic control of lymphoma; (f) facilitates pelvic and peri-aortic lymphadenectomy by staining the lymphatics when the opaque medium is mixed with a green dye (chlorophyll). Difficulties of technic and interpretation account for the failure of lymphangioadenography to gain popularity and wide acceptance. New advances in the field of technic, such as the use of FDC Blue #1 Dye6 for the identification of the lymph vessels, large-bore catheters, and an automatic pressure-temperature controlled injector, solve most of the important technical problems. An adequate study can be performed in one to two and one-half hours. We have introduced the use of a green-stained opaque material which assists in the identification of lymphatics during pelvic and periaortic adenectomies. We have performed 253 successful lymphographic studies7 since June 1960 (Tables I and II). The cases have been reviewed in detail, and the various patterns of lymph-node architecture demonstrated on the radiographs have been correlated with the histologic findings. A. Normal Lymph Nodes The normal lymph nodes varied in number, size, and shape, and usually had a regular contour (Fig. 1). Anatomic variations in size and number were observed in relation to age, sex, and other conditions. Frequently, lymph nodes were larger when their number was reduced in a particular region. Reduction in both size and number was observed in senility and following external radiation therapy (nodes included in the radiation fields). In some instances, small foci of hypertrophic lymphoid tissue were found to be another effect of radiotherapy. The injected nodes were, in general, larger than noninjected ones. This was due to the marked distention of the sinusoids produced by the oily material. A hilar indentation of the node or a central filling defect was sometimes seen (Fig. 23, C). Normal nodes showed a homogeneous, dotted, or granular pattern (Fig. 2, A). The radiographic architecture was best observed on follow-up roentgenograms taken twenty-four to forty-eight hours after the injection, when the maximum filling of the node occurred. Most of the lymph vessels were devoid of opaque material, which tended to obscure the nodal contour (Fig. 1, B).