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[Anatomical variants of the lymphatic vessels connecting the inguinal lymph nodes].

The study of anatomical variants of lymphatic vessels connecting inguinal lymph nodes was carried out on 56 corpses of adult persons of both sex whose deaths were not connected with lesions in the lymphatic system of the pelvis and lower extremities. The inguinal lymph nodes and their afferent and efferent lymphatic vessels were detected by the method of intradermal injection and by the method of direct injection into the lymphatic vessels. It was stated that groups of the inguinal lymph nodes, as well as the nodes in every group determined, can serve as nodes of different stages for afferent lymphatic vessels running from different parts of the body and organs.

Female↗

[Tumors of the lymphatic vessel of the skin and soft tissue].

Tumours of lymphatic vessels comprise only a small group in the heterogeneous spectrum of vascular neoplasms of skin and soft tissues. However, this discrepancy between haemangiomas/angiosarcomas and lymphangiomas/lymphangiosarcomas probably represents the present inability to reliably differentiate between lymphatic and capillary vascular endothelium. Histologically, neoplastic lymphatic vessels tend to be lined by endothelial cells with plumper and more prominent, matchstick-like nuclei (in contrast to vascular spaces in haemangiomas that are lined by flat or epithelioid endothelial cells), often show variations in the thickness of the vessel walls and are not completely surrounded by actin-positive (myo)pericytes. Endothelial cells in lymphatic neoplasms tend to be negative for CD34 or stain only focally positive for this marker and an expression of lymphatic markers as vascular endothelial growth factor-C receptor (VEGRF-3), podoplanin and M2A oncofetal antigen has been reported most recently. In addition to "traditional" lymphatic neoplasms including lymphangioma circumscriptum, cavernous lymphangioma/cystic hygroma, benign lymphangioendothelioma, lymphangiomatosis and the rare lymphangiosarcoma, histological and immunohistochemical features of a group of vascular neoplasms with a hobnail cytomorphology (hobnail haemangioma, retiform haemangioendothelioma, papillary intralymphatic angioendothelioma, benign lymphangiomatous papule following radiotherapy) suggest that these lesions also belong to the spectrum of tumours of lymphatic vessels.

Diagnosis, Differential↗

[An experimental study on the regeneration of lymphatic vessels after replantation of the limb (author's transl)].

In order to determine the role of the lymphatic vessels in the subsidence of the edema after replantation of the amputated lim the stage of regeneration of lymphatic vessels was studied by 2 ways: lymphangiography and 198Au colloid scinti-scanning with the chronological measurement of the circumference at the thigh and legs of hind limbs from 15 adult dogs which were replanted after the complete amputation. As the results, edema gradually increased after the operation with the maximal rates on the seventh day at the thigh and on the sixth day at the leg. On the other hand, the earliest regeneration of lymphatic vessels at the proximal site of the transection was seen by the lymphangiography on the twelfth day. 198Au colloid scinti-scanning showed that the accumulation of 198Au at the proximal site of transection took place on the tenth day after the subcutaneous injection of 198Au at the distal site of transection. In spite of the fact that there appeared to be more available to find the earliest regeneration of lymphatic vessels by scinti-scanning than by lymphangiography, the former method failed to show any lymphatic drainage at the peak of edema. The lymphatic regeneation was demonstrated by scinti-scanning during the decreasing period of edema and, in consideration of limitation of experimental method, it was strongly suggested that the subsidence of edema depended on the regeneration of lymphatic vessels.

Animals↗

Identification of lymphatic vessels by using a monoclonal antibody specific for the human thoracic duct.

Light microscopic identification of lymphatic vessels of the human small intestine was studied immuno-histochemically with a monoclonal antibody specific for human thoracic duct (mAb-D) and rabbit anti-human laminin antibody (anti-L). Two types of vessels were observed with anti-L; one strongly reacted with regularly outlined vessels and the other weakly reacted with irregularly outlined vessels and thin walls. Immunoreactivity to mAb-D was strong in the weakly reacting vessels, and the strongly reacting vessels did not react to mAb-D. Immunoreactivity of lymphatic vessels to anti-L has been reported to be weaker than that of the blood vessels; only irregularly outlined vessels which were weakly immunostained with anti-L reacted to mAb-D and no cross-reaction to mAb-D was observed in the regularly outlined vessels. This indicates that the vessels strongly reacting with anti-L are blood vessels and the vessels immunostained with mAb-D must be lymphatics. The study shows that it is possible to identify lymphatic vessels light microscopically by mAb-D. This method will be useful in studying the fine distribution of lymphatic vessels in normal tissue and also in pathological tissue such as metastasis of malignant tumors.

Aged↗

Prognostic significance of parenchymal lymphatic vessel and blood vessel invasion in carcinoma of the lung.

In a series of 685 men who had undergone a microscopically curative resection of a carcinoma of the lung admitted to a prospective randomized adjuvant chemotherapy trial, a review of the data relative to the prognostic implication of either parenchymal lymphatic vessel or blood vessel invasion as determined by routine histologic examination was carried out. In the patients without parenchymal lymphatic vessel invasion and without lymph node metastasis, the three year survival rate was 61.0 per cent. In those without lymphatic vessel invasion but with lymph node metastasis, the three year survival rate was 34.5 per cent. In the patients with lymphatic vessel invasion and no lymph node metastasis, the three year survival rate was 41.7 per cent and when lymph node metastasis was present, it was 33.8 per cent. In the patients without blood vessel invasion and with neither lymph node metastasis nor lymphatic vessel invasion, the survival rate was 61.9 per cent at three years. When either or one, or both, of the latter were present, the survival rate was 35.6 per cent. In the patients with blood vessel invasion, the three year survival rate in those without lymph node invasion or lymphatic vessel invasion was 58.0 per cent, and in those with either one or both, the survival rate was 34.9 per cent. It is concluded that parenchymal lymphatic vessel invasion in itself is an indication of a poor prognosis. However, blood vessel invasion when identified by routine histologic examination was found to provide little, if any, additional predictive information.

Blood Vessels↗

Histochemical demonstration of mucin in lymphatic vessels of human middle ear cholesteatoma.

We investigated the possible existence of mucin in lymphatic vessels in cholesteatoma perimatrix using the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method. Histochemical staining distinguished two types of lymphatic vessels, one of which contained PA-TCH-SP reacting substance showing a loose mesh-like appearance. Connective tissue was edematous around this vessel and was infiltrated by abundant round cells. The second type of lymphatic vessel did not contain PA-TCH-SP reacting substance and few round cells were seen infiltrating tissue around this vessel. Gland-like structures of mucous epithelium in the perimatrix were heavily stained by the PA-TCH-SP method. Secretory granules of the mucous epithelium and its luminal content had a loose mesh-like appearance. Since contents of the gland-like structures may leak through the chinks of epithelial cells into subepidermal connective tissues, the resultant inflow of mucin into the lymphatic vessels may then cause inflammation of the cholesteatoma perimatrix.

Cell Nucleus↗

Origins and pathways of fluid entering sublobular lymphatic vessels in cat livers.

The liver, which produces a large volume of lymph, has a lymphatic system which can be classified into three categories: portal, sublobular, and superficial lymphatic vessels. As little is known about the origin and pathways of sublobular lymph, this study demonstrates pathways of interstitial fluid flowing into sublobular lymphatic vessels. Livers from cats whose thoracic ducts were either ligated or non-ligated were examined by light-, transmission electron- and scanning electron-microscopy (SEM). Complete ligation of the thoracic duct caused significant dilation of the hepatic sinusoids, the space of Disse, and channels passing through the limiting plate. Sublobular interstitial space and sublobular lymphatic vessels were also expanded. The channels between hepatocytes forming the limiting plate contained collagen fibers, and connected the space of Disse with a sublobular interstitial space. The alkali-water maceration/SEM confirmed that collagen fibers traversing the layer of the limiting plate independently of blood vessels connected collagen fibers in the space of Disse with those in the sublobular space. Complete ligation of the thoracic duct also showed an accumulation of mast cells and plasma cells in the sublobular interstitial space. Our data suggest that fluid in the space of Disse flows along collagen fibers in channels traversing the limiting plate as well as those along the sinusoids and central veins that drain into sublobular veins, and enters the sublobular interstitial space to finally lead into sublobular lymphatic vessels. Our study has also shown that hepatic lymphostasis causes the accumulation of mast cells and plasma cells in the sublobular interstitial space, which may be involved in lymphangiogenesis and fibrogenesis.

Animals↗

Lymphatic vessel density, nodal metastases, and prognosis in patients with head and neck cancer.

OBJECTIVE: To examine the relationship between intratumoral lymphatic vessel density and clinical and pathological variables in patients with head and neck squamous cell carcinoma. DESIGN: Archived paraffin-embedded biopsy specimens were sectioned and stained with hematoxylin-eosin and anti-LYVE-1 antibody, a highly specific marker for lymphatic endothelium. Tumor grade, infiltrating margin, inflammatory infiltrate, and percentage of tumor necrosis were noted and lymphatic vessel density measured using Chalkley point counting. SETTING: Tertiary care center at a university hospital. PATIENTS: A total of 168 previously untreated patients with advanced squamous cell carcinoma (73, larynx; 62, oropharynx; and 33, hypopharynx) treated with primary radiation (with or without planned neck dissection) and salvage surgery from 1992 to 1999. INTERVENTIONS: Measurement of intratumoral lymphatic vessel density in pretreatment tissue biopsy specimen. MAIN OUTCOME MEASURES: Disease-free and disease-specific survival, tumor occurrence, and nodal status. RESULTS: In patients with laryngeal carcinoma there was a significant relationship between the presence of intratumoral lymphatics and nodal metastases at presentation (P = .02) and poorly differentiated tumor grade (P = .02). Patients with high lymphatic vessel density also had a significantly worse disease-specific survival (P = .03). However, this difference was not significant with multivariate analysis. No significant relationship existed between the presence of intratumoral lymphatics and any of the clinical or pathological variables in oropharyngeal and hypopharyngeal carcinoma. CONCLUSIONS: In this patient sample, the development of intratumoral lymphatics in laryngeal carcinoma, but not in oropharyngeal or hypopharyngeal carcinoma, is associated with a spread of the tumor to regional lymph nodes. Detecting tumor lymphatic vessel proliferation is another step in the understanding of tumor biology, and the targeting of lymphatic growth may be of potential therapeutic benefit in selected patients with head and neck squamous cell carcinoma.

Aged↗

Finding an optimal method for imaging lymphatic vessels of the upper limb.

Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with (99m)Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id (99m)Tc-HIG was compared with sc (99m)Tc-HIG, in three id (99m)Tc-nanocolloid was compared with sc (99m)Tc-nanocolloid, in three id (99m)Tc-HIG was compared with id (99m)Tc-nanocolloid and in three sc (99m)Tc-HIG was compared with sc (99m)Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance ( k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, (99m)Tc-HIG gave images that were marginally but significantly better than those given by (99m)Tc-nanocolloid. Image quality correlated inversely with time after injection at which the best image was obtained, consistent with the notion that good vessel definition was dependent on a "narrow" bolus width. k was approximately three times higher after id injection than after sc injection but it was not significantly different between radiopharmaceuticals for either injection route. Intradermal (99m)Tc-HIG gave a cardiac blood pool signal that, over the first 60 min, increased about five times faster than that with sc (99m)Tc-HIG, but no clear difference was observed in the rate of increase in hepatic activity between id (99m)Tc-nanocolloid and sc (99m)Tc-nanocolloid. We conclude that id injection provides rapid access of radiotracers to lymphatic vessels, which is ideal for imaging lymphatic vessel morphology. (99m)Tc-HIG is marginally superior to nanocolloid for this purpose and, in drainage basins from which lymph nodes have been excised, is not handicapped by a potentially inferior ability, compared with radiocolloid, to image lymph nodes.

Female↗

[Lymphangiogenes and location of tumor lymphatic vessels induced by VEGF-C in primary breast carcer].

OBJECTIVE: To investigate the lymphangiogenesis and location of tumor lymphatic vessels induced by vascular endothelial growth factor C (VEGF-C) in primary breast cancer. METHODS: The expression of VEGF-C mRNA in 89 cases of primary breast cancer was detected by in situ hybridization, and lymphatic vessels with vascular endothelial growth factor receptor-3 (VEGFR-3) were labeled by immunohistochemistry SP method. RESULTS: VEGF-C mRNA expressed in 49 of all 89 cases of primary breast cancer, and the expression rate was 55.06%. The expression of VEGF-C mRNA was positively correlated with lymphatic vessel density (LVD) and axillary lymph node metastasis, LVD and the rate of axillary lymph node metastasis were significantly higher in VEGF-C mRNA positive group than those in the negative group (both P < 0.05). Different levels of lymphangiogenesis took place in all cases of breast cancer, but it was mainly located in tumor stroma, and apparently mature lymphatic vessels were not found in cancer nests. LVD was positive related with the clinical stage and axillary lymph node metastasis in breast cancer; the clinical stage, the LVD, the axillary lymph node metastasis in positive group were higher than those in the negative group (P < 0.05). CONCLUSION: The expression of VEGF-C mRNA is positively correlated with lymphangiogenesis and axillary lymph node metastasis in primary breast cancer. Lymphangiogenesis induced by VEGF-C predominantly takes place in the tumor stroma tissue, and mature lymphatic vessels are not found in cancer nests.

Adult↗

Lymphatic vessels of the human dental pulp in different conditions.

The characteristics of the lymphatic vessel endothelial wall have been investigated in human normal and inflamed dental pulps. In normal pulps the endothelial wall is characterized by the presence of micropinocytotic vesicles and intraparietal channels. In the inflamed pulpal tissue, where an increase in interstitial fluid pressure occurs, the distended endothelial wall presents open junctions between endothelial cells and the openings of the intraparietal channels. Moreover the micropinocytotic vesicles disappear. The cytoplasm of the endothelial cells is characterized by the presence of numerous Weibel-Palade bodies, which increase in number in the dilated vessels. In the fibrillar apparatus surrounding the lymphatic vessel wall collagen fibrils are the prevalent component, while elastic fibers are not present. The different morphological properties of the lymphatic vessels are compared and discussed with regard to the variation of the functional conditions of the tissue.

Adult↗

[Structure of lymphatic vessels in the rat thyroid gland].

The lymphatic bed of the thyroid gland has been studied in 24 intact rats. Three techniques facilitating to reveal lymphatic vessels in the organ have been used: preparation of semithin sections, injection of the blood bed with methyl methacrylate with a successive chemical extraction of the preparations, injection of the blood bed with liquid solution of methyl methacrylate with a consecutive study of the preparations in the scanning electron microscope. Methods of electron histochemistry (revealing horseradish peroxidase) and kryofractography have been applied. Construction of the thyroid lymphatic bed, structure of the wall are described, fibroblastic membrane (F-membrane) is revealed and the signs are presented, that allow to differentiate F-membrane from endothelium of the lymphatic capillaries. The pathways of lymph outflow in the rat thyroid gland consist of the following links: interstitial space in the interlobular spaces of the gland, into them the tissue liquor (lymph) is filtered ; plates of the F-membrane regulating direction of excessive albumin-containing liquor in the lymphatic capillaries, surrounding groups of 5-11 follicles, embracing the microlobule of the gland and situating in the interlobular spaces, deferent lymphatic vessels.

Animals↗

[Lymphatic vessel density in Dukes' B rectal carcinoma and its correlation to prognosis].

BACKGROUND & OBJECTIVE: The prognosis of patients diagnosed with Dukes' B rectal carcinoma varies largely. Micrometastasis via lymphatic vessel may have occurred in Dukes' B rectal carcinoma although no clinical pathologic evidence of lymph node metastasis was found. This study was to investigate the correlation of lymphatic vessel density (LVD) to the prognosis of Dukes' B rectal carcinoma. METHODS: Immunohistochemistry was used to display the lymphatic vessels with lymphatic endothelium-specific marker, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), in 54 specimens from Dukes' B rectal carcinoma. LVD in tumor, peri-tumor and normal tissues was calculated. All patients had complete clinical and follow-up data. RESULTS: Of the 54 specimens, 11 (20.4%) were LYVE-1-negative in tumor, peri-tumor, and normal tissues, 43 (79.6%) were LYVE-1-positive. LVD was significantly higher in peri-tumor than in tumor and normal tissues (6.05+/-5.61 vs. 0.89+/-0.66 and 4.11+/-3.29, P<0.05), and was significantly lower in tumor than in normal tissues (P<0.05). No significant correlation was found between LVD and recurrence rate (P>0.05), or overall survival (P>0.05). CONCLUSIONS: Lymphangiogenesis may occur in peri-tumor tissues. LVD may not be a prognostic factor of Dukes' B rectal carcinoma.

Adult↗

Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels.

Lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to promote lymphatic metastasis by inducing tumor-associated lymphangiogenesis. In this study, we have investigated how tumor cells gain access into lymphatic vessels and at what stage tumor cells initiate metastasis. We show that VEGF-C produced by tumor cells induced extensive lymphatic sprouting towards the tumor cells as well as dilation of the draining lymphatic vessels, suggesting an active role of lymphatic endothelial cells in lymphatic metastasis. A significant increase in lymphatic vessel growth occurred between 2 and 3 weeks after tumor xenotransplantation, and lymph node metastasis occurred at the same stage. These processes were blocked dose-dependently by inhibition of VEGF receptor 3 (VEGFR-3) signaling by systemic delivery of a soluble VEGFR-3-immunoglobulin (Ig) fusion protein via adenoviral or adeno-associated viral vectors. However, VEGFR-3-Ig did not suppress lymph node metastasis when the treatment was started at a later stage after the tumor cells had already spread out, suggesting that tumor cell entry into lymphatic vessels is a key step during tumor dissemination via the lymphatics. Whereas lymphangiogenesis and lymph node metastasis were significantly inhibited by VEGFR-3-Ig, some tumor cells were still detected in the lymph nodes in some of the treated mice. This indicates that complete blockade of lymphatic metastasis may require the targeting of both tumor lymphangiogenesis and tumor cell invasion.

Adenoviridae↗

Lymphatic vessels of the mammalian heart.

An in situ heart lung preparation was developed to label lymphatics of the actively beating dog heart with subsequent fixation by vascular perfusion. Immediately after interstitial injections of trypan blue and colloidal carbon, a rich plexus of lymphatic vessels was visualized in the epicardium of the actively beating heart. With this method of fixation, tissue preservation is generally excellent and uniform throughout the heart. In thin sections examined with the electron microscope, lymphatic vessels are easily recognized by the content of plasma proteins which is preserved as an electron dense precipitate that is evenly dispersed throughout the lumen. An extensive plexus of thin walled lymphatic vessels is observed throughout the epicardial, myocardial and subendocardial regions. Numerous anchoring filaments are observed closely apposed to the abluminal endothelial surface which extend into the surrounding connective tissue. The distribution and ultrastructure of the cardiac lymphatic vessels are discussed in relation to their role in the removal of interstitial fluid from the heart.

Animals↗

Lymphatic vessels in the healthy human dental pulp.

The lymphatic vessels of the dental pulp have been studied in non-carious teeth of young people. A network of lymphatic vessels drains the pulpal tissue. The lymphatic capillaries are characterized by a thin wall with an irregular profile. Cellular projections rise from the endothelial cells. Micropinocytotic vesicles and intercellular adjoining structures are the main mechanisms for the lymph formation. Multivesicular structures, Weibel-Palade bodies and paracrystalline inclusions have been observed.

Child↗

Relation between lymphatic vessel diameter and clinicopathologic parameters in squamous cell carcinomas of the oral region.

BACKGROUND: In an attempt to determine the mechanism of cervical lymph node metastases, the authors studied the relation between lymphatic vessels in or around tumor tissue and lymph node metastases in patients with primary squamous cell carcinoma (SCC) of the oral region by enzyme histochemistry using 5'nucleotidase-alkaline phosphatase. METHODS: The subjects were 23 patients who had biopsy proven oral SCC. After enzyme histochemical staining, the cross-sectional dimension (referred to as diameter) of the lymphatic vessels were measured and analyzed in relation to the T classification of the tumor, degree of tumor differentiation, and mode of invasion. RESULTS: The average diameter of the lymphatic vessels in or around tumor tissue was significantly greater than that in tumor free tissue (P < 0.01). The mode of invasion correlated significantly with the lymphatic vessel diameter (P < 0.01). The diameter did not correlate significantly with the T classification (P range, 0.135-0.254) or tumor differentiation (P = 0.274). The following relation was found between the incidence of cervical lymph node metastases and the mode of invasion: 40.0% of Grade 2 tumors were positive for metastases, 71.4% of Grade 3 tumors were positive, and 75.0% of Grade 4 tumors were positive (grading was according to Jakobsson's classification). CONCLUSIONS: Of the factors evaluated in this study, only the mode of invasion correlated significantly with the diameter of the lymphatic vessels. Although other studies have shown that tumor thickness and perhaps even perineural and blood vessel invasion may be equally important, the findings of the current study suggest that both lymphatic vessel diameter and the mode of invasion may be important factors in the prediction of cervical lymph node metastases.

5'-Nucleotidase↗

Novel threadlike structures (Bonghan ducts) inside lymphatic vessels of rabbits visualized with a Janus Green B staining method.

A staining method has been developed for in situ and in vivo observation of a threadlike tissue afloat inside the lymphatic vessels of rabbits without adherence to the vessel wall. The existence of this novel structure was not noticed previously because it is extremely difficult to detect it by microscopic inspection of lymphatic vessels. We have found a method that utilizes Janus Green B (JGB), which stained heavily the novel structure. The tissue was studied by confocal laser scanning microscopy (CLSM), light microscopy, and cryoscanning electron microscopy (cryo-SEM). The CLSM image obtained by acridine orange staining of the novel tissue revealed its characteristic nuclei distribution: rod-shaped nuclei of 10-20 microm length aligned in a broken-line/striped fashion. Hematoxylin and eosin staining revealed the threadlike structure passing through a lymphatic valve as histologically distinct from lymphatic vessels and valves. The cryo-SEM image showed the threadlike structure inside a collapsed lymphatic vessel. There were spherical globular structures observable inside sinuses in a rapidly frozen sample, which suggests liquid flowing through the longitudinal ductules in the threadlike structure. The specific staining of the JGB suggests that these threadlike structures inside lymphatic vessels have a high density of mitochondria in their cells and/or nerve-like properties, either of which may provide important clues to their physiological function.

Animals↗