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At least 19 recordsLinked to original sources

PubMed1996

A study of the three-dimensional organization of the human diaphragmatic lymphatic lacunae and lymphatic drainage units.

The peritoneal stomata, lymphatic drainage units and subperitoneal terminal lymphatics, called lymphatic lacunae, form a specialized drainage system in the diaphragm, by which absorption of fluid in bulk, particles and cells is carried out in the peritoneal cavity. The aim of this study is to elucidate the three-dimensional organization and function of the subperitoneal lymphatic lacunae and lymphatic drainage units by using lymphatic casts in the scanning electron microscope (SEM), ODO (OsO4-DMSO-OsO4) freeze fracture, conventional SEM and the transmission electron microscope (TEM). The subperitoneal lymphatic lacuna is unique for its large size and its multiple morphology and can be recognized by its broad, flattened enlargement and the blind-ends of lymphatic vessels, from which extend numerous main lymphatic vessels and side branches. These lymphatic vessels communicate with each other and form a rich lymphatic plexus under the diaphragmatic peritoneum. Two layers of lymphatic networks, i.e. the subperitoneal plexus and the deeper plexus are found in the muscular portion. Only one layer is present in the tendinous portion of the human diaphragm. The lymphatic plexus is denser in the tendinous portion than that in the muscular portion. The lymphatic lacunae occur exclusively in the muscular portion of the human diaphragm. The lumina of lymphatic lacunae are separated from the peritoneal cavity by a barrier consisting of cuboidal mesothelial cells, endothelial cells of the lymphatic lacunae and intervening connective tissue forming a lymphatic drainage unit. All these three components of the lymphatic drainage unit abut upon each other, but are not linked by specialized junctions. The cuboidal mesothelial cells frequently extend valve-like cytoplasmic processes that bridge the subperitoneal channel and make give it a tortuous course. The fibrous layer of the connective tissue is arranged in fiber bundles and gives a three-dimensional network forming the floor of the peritoneal stomata and the roof of the lymphatic lacunae. Via the fibrous network, the cuboidal mesothelial cells and the endothelial cells of the lacunae come into close contact with each other and form short subperitoneal channels which connect the peritoneal cavity with the subperitoneal lymphatic lacunae. The lymphatic drainage units may regulate the material absorption of the peritoneal stomata from the peritoneal cavity. It is suggested that the peritoneal stomata together with the subperitoneal channels, lymphatic drainage units and lymphatic lacunae comprise an important diaphragmatic lymphatic drainage system which plays an important role in the absorption of materials from the peritoneal cavity.

Diaphragm↗

PubMed2006

Renal lymphatics, and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases.

Although renal sinus vein invasion is the most common site of extrarenal involvement in clear cell renal cell carcinoma (CC), CC also spreads by lymphatics. As cortical lymphatics drain into the sinus, some involved sinus structures may be lymphatics, not veins. This possibility was investigated with podoplanin, a specific lymphatic endothelial marker, in 40 CC with sinus vein invasion. Ten blocks of uninvolved kidney, serving as controls, showed lymphatics within the adventitia of midcortical intralobular arteries. Lymphatics became more numerous and enlarged with progression towards the medulla. No lymphatics were among glomeruli or within the medulla unless associated with inflammation. The largest lymphatics occurred within the sinus, and were also noted within pelvic muscularis, and media of large veins. Intralymphatic tumor was observed and divided into two Groups. Group 1 (four cases) involved lymphatics within the invasive edge of tumors lacking a pseudocapsule. The lymphatics were small (0.045-0.19 mm), irregularly shaped, often incomplete, and contained single cells or small clusters of tumor cells. Group 2 (four cases) involved sinus lymphatics separate from tumor. One case each also involved adventitial lymphatics of an intralobular artery, the muscularis of the renal pelvis, and media of a muscular vein. The intralymphatic tumor in Group 2 often appeared discohesive, not endothelial cell invested, and larger than in Group 1 (0.4-0.5 mm). Conversely, tumor within muscular veins was cohesive, contained a capillary plexis, and was endothelial cell invested. In conclusion, intralymphatic tumor can be demonstrated in CC. Lymphatic involvement is less frequent than venous involvement and involves smaller structures. The potential for lymphatic spread may not be equal among involved lymphatics. Small peritumoral lymphatics may be destined for destruction by tumor growth. However, involved lymphatics within sinus and associated with renal pelvis, are likely sources for lymphatic spread and lymph node metastases.

Actins↗

PubMed1997

Lymphatic system of the mouse diaphragm: morphology and function of the lymphatic sieve.

BACKGROUND: The diaphragm has a unique system that collects peritoneal fluid and carries it into the lymphatic system. However, our understanding of the morphology and function of this system is still incomplete. METHODS: Twelve C57BL/6 mice of 13 to 25 weeks of age were used without regard to sex. In one series of experiments, the diaphragm was isolated and fixed 10-15 minutes after injection of india ink into the peritoneal cavity and then the peritoneal mesothelium was peeled off from the submesothelial connective tissue. The lymphatic vessels attached to the mesothelial strip were examined by scanning electron microscopy. The diaphragm was also observed in plastic-embedded semithin and ultrathin sections. In another series of experiments, the diaphragm was stained by 5'-nucleotidase histochemistry (Wachstein and Meizel, 1957a. Am. J. Clin. Pathol., 27:13-23), and several microdrops of india ink were placed on the peritoneal or pleural surface to reveal the profile of the lymphatic vessels. RESULTS: The lymphatic vessels on the peritoneal side of the diaphragm were flattened. They usually ranged from several to 100 microns in width and from close to zero to a few micrometers in thickness. In other words, they formed extremely flat lumina, differing from the more usual tubular lymphatic vessels. Several lymphatic vessels extended radially and parallel to one another from the central tendon to the thoracic wall, with numerous connecting branches, forming an area of lymphatic vessels. The india ink that had been injected intraperitoneally and the staining with 5'-nucleotidase revealed that there were seven to nine such lymphatic areas in one hemisphere of the diaphragm. The lymphatic areas spread in parallel with the peritoneal surface of the diaphragm and all the areas together appeared to occupy more than half the surface area of the sternocostal part of the diaphragm. Each area was a relatively distinct functional unit with respect to the draining of india ink. Microdrops of india ink placed on the pleural surface did not enter the lymphatic vessels, while those placed on the peritoneal surface immediately entered the peritoneal lymphatic vessels and migrated to the pleural lymphatic vessels via the transmuscular lymphatic branches. CONCLUSIONS: The peritoneal lymphatic vessels of the diaphragm have extremely flat lumina that spread in parallel with the peritoneal surface of the diaphragm and form a lymphatic sieve that covers approximately half or more of the surface area of the sternocostal region for drainage of fluid and particulate matter from the peritoneal cavity. The lymphatic system has been characterized by the presence of openings (= stomata) to the peritoneal cavity and the amplitude of the lumina (= lacunae). However, the fundamental characteristic of the system is the extremely flat lumen (= vadum), which facilitates the formation of the lymphatic sieve.

Animals↗

PubMed1996

Distribution of lymphatics in human palatine tonsils: a study by enzyme-histochemistry and scanning electron microscopy of lymphatic corrosion casts.

The distribution of lymphatics in human palatine tonsils was studied by enzyme-histochemistry for 5'-nucleotidase (5'-Nase) and scanning electron microscopy (SEM) of lymphatic corrosion casts. The palatine tonsils were found to possess lymphatics in the parafollicular area (i.e., interfollicular, interfolliculo-septal, and folliculo-septal area), in the connective tissue septa, and in the capsules, but not in the subepithelial area between the follicles and the follicle-associated epithelia or within the follicles. The tubular lymphatics originated some 200-300 microns below the epithelium and formed a three-dimensional network in the parafollicular area. Some lymphatics around the lower part of the follicle were flat, wide, and irregular in shape, and thus appeared to be lymphatic sinuses, referred to as perifollicular lymphatic sinuses. The lymphatics in the parafollicular area drained into the septal lymphatics, which ran rather straight in the connective tissue septa. The septal lymphatics finally gathered into the broader capsular lymphatics. Most of the septal and capsular lymphatics were endowed with valves. Our results indicate that lymphocytes and fluid from the follicles and the subepithelial region enter the perifollicular lymphatic sinuses and/or the interfollicular lymphatics, pass through the interfolliculo- and folliculo-septal lymphatics, and finally enter the septal and capsular lymphatics to leave the tonsil.

5'-Nucleotidase↗

PubMed2001

Phylogeny and ontogeny of the lymphatic stomata connecting the pleural and peritoneal cavities with the lymphatic system--a review.

This paper reviews the phylogeny and ontogeny of "lymphatic stomata" through which fluids and cells in the pleural and peritoneal cavities enter the lymphatic system. In amphibians, the pleuroperitoneal cavity is connected through numerous pores with the wide subvertebral lymphatic sinus corresponding to the thoracic duct in mammals. In reptiles, direct connections of the pleural and peritoneal cavities with the lymphatic system have been reported. In mammals, the pleural and peritoneal cavities are directly connected with lymphatics through lymphatic stomata. How do lymphatic stomata develop in mammals? In the rat, distinct lymphatics are noted in the subpleural space of the diaphragm periphery in 16 days old embryo. With age, the supleural lymphatics increase and form a polygonal network. They show a tubular appearance and possess many valves. Some of them become endowed with smooth muscle cells. In 19 days old embryos, some lymphatics appear in the subperitoneal space of the diaphragm. They extend centripetally and form many lateral projections that later elongate and connect with those from adjacent lymphatics, thus forming a lattice-like network or "lymphatic lacunae". During early postnatal days, the lymphatic lacunae project many bulges that subsequently come into contact with the pores among mesothelial cells lining the diaphragmatic peritoneum, thus forming lymphatic stomata. They increase until postnatal week 10. The lymphatic stomata in the costal pleura also develop during early postnatal days.

Aging↗

PubMed2005

Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40: a new selective immunohistochemical marker of lymphatic endothelium.

OBJECTIVES: To identify the presence of lymphatic invasion in primary cutaneous melanoma using monoclonal antibody D2-40, a marker of lymphatic endothelium, and to correlate the presence of lymphatic invasion with other clinicopathologic characteristics of the tumors. DESIGN: Retrospective melanoma case series study comparing conventional hematoxylin-eosin staining with D2-40 immunostaining for detection of lymphatic invasion. SETTING: Departments of Pathology and Dermatology, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, Ontario. Patients Forty-four consecutive cases of primary cutaneous melanoma with a tumor thickness greater than 0.75 mm were examined for presence of lymphatic invasion. RESULTS: Seven (16%) of 44 melanomas showed the presence of lymphatic invasion under immunostaining with D2-40. In 2 cases, subepidermal lymphatic involvement was present; in 5 cases lymphatic invasion was noted within the tumor, including 1 case of additional lymphatic invasion at the invasive edge of the tumor. Lymphatic invasion was not detected on routine hematoxylin-eosin staining. We observed a trend in the association between lymphatic invasion and 2 markers of tumor aggressiveness, namely, a deeper Clark level and increased frequency of ulceration, which suggests that lymphatic invasion detected with D2-40 may indicate a poor prognosis. CONCLUSIONS: Immunostaining with D2-40 increases the frequency of detection of lymphatic invasion relative to conventional hematoxylin-eosin staining in primary melanoma. Future outcome data will determine the prognostic significance of lymphatic invasion detected by D2-40 immunostaining.

Adult↗

PubMed2006

Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: New insights into intratumoral and peritumoral lymphatics.

Lymphatic metastasis of tumor cells represents a series of extremely complex and sequential processes that include dissemination and invasion into surrounding stromal tissues from primary tumors, penetration into lymphatic walls and implantation in regional lymph nodes, and extravasation or proliferation in parenchyma of target organs. Recent developments in lymphatic biology and research, especially the application of unique molecular markers specific for lymphatic endothelial cells (LECs), LYVE-1, Prox-1 and podoplanin have provided exciting new insights into the tumor microenvironment and LEC-tumor cell interface. To date, established factors for determining the behavior and prognosis of primary tumors have been emphasized morphologically and physiologically, i.e., lymphatic impairment and vessel density, dysfunction of lymphatic valves, interstitial fluid pressure, as well as a series of lymphangiogenic growth factors including VEGF-C/-D, and other cytokines and chemokines. Increasing knowledge of the tumor biological significance in lymphatics within the tumors (intratumoral lymphatics, ITLs) and at the tumor periphery (peritumoral lymphatics, PTLs) has greatly promoted understanding of tumor access into the lymphatic system by inducing lymphangiogenesis or by co-opting preexisting lymphatics. Therefore, the targeting PTLs and ITLs, which have been proposed as an important route for antimetastatic approach, are deemed worthy of further study in various animal tumor models and human tumors.

Animals↗

PubMed2005

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↗

PubMed2005

Development of lymphatic vessels: tumour lymphangiogenesis and lymphatic invasion.

In human solid cancer, the lymph node status is the most important prognostic indicator for the clinical outcome of patients. Follow-up data has shown that about 80% of metastasis follows an orderly pattern of progression via the lymphatic network while about 20% systemic metastasis occurs, bypassing the lymphatic system. Over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumour-induced lymphangiogenesis, and the majority of studies point out to a positive correlation between tumour-induced lymphangiogenesis and lymphatic metastasis. However, the impact of intra- and peritumoural lymphatics on the tumour biology and the first steps of lymphatic metastasis, i.e. the invasion of tumour cells into the lymphatic vessels, are not well understood. We will give an outline of i. the physiological process of lymphangiogenesis, ii. tumour-induced lymphangiogenesis and lymphatic metastasis, iii. lymphatic invasion and the common pathways of tumour-lymphangiogenesis and lymphatic invasion. The growing interest in this topic has brought up a number of new molecular players in the field, which may provide the basis for a rational therapy against the process of lymphatic dissemination of tumour cells.

Animals↗

PubMed2001

Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer.

Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease.

Adult↗

PubMed2006

[Clinical significance of detection on lymphatic microvessel, lymphatic microvessel density and vascular endothelial growth factor-C in patients with colorectal carcinoma].

OBJECTIVE: To evaluate the clinical significance of detection on lymphatic microvessel, lymphatic microvessel density (LMVD) and vascular endothelial growth factor-C (VEGF-C) in patients with colorectal carcinoma. METHODS: Eighty tissue specimens of the colorectal carcinoma and the peritumoral tissue and thirty of adjacent normal bowel tissue were collected. The lymphatic microvessel and LMVD were determined by 5'-nucleotidase histochemical staining. The expression of VEGF-C protein and VEGF-C mRNA in specimens of colorectal carcinoma and normal colorectal tissues were studied by RT-PCR and immunohistochemical methods utilizing strept-avidin-biotin complex. Clinicopathological data and survival of each patient were obtained and analyzed. RESULTS: (1) The brown or filemot stained lymphatic microvessels were observed in specimens from the colorectal carcinoma, the peritumoral tissue and the normal bowel. Collapsed, nonfunctional lymphatic vessels were observed in the intratumoral tissue, and plenty of lymphatic vessels with large lumen referred as functional lymphatic vessels were observed in the peritumoral tissue. (2) The mean value of LMVD in the peritumoral tissue was significantly higher than that in the normal bowel tissue (9.76+/-2.85 vs. 5.49+/-1.43, t=8.220, P<0.01) and tumor tissue (9.76+/-2.85 vs. 2.13+/-0.96, t=15.118, P<0.001). (3) The positive rate (48.8% vs. 0, P<0.01) and mean value (1.09+/-1.20 vs. 0, P<0.01) of the VEGF-C protein expression in colorectal carcinoma specimens were significantly higher than that of the normal bowel tissue. The expression of VEGF-C protein was consistent with the expression of VEGF-C mRNA. The VEGF-C expression in intratumoral tissue demonstrated significant correlation with LMVD in the peritumoral tissue of colorectal carcinoma. (4) Both LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue correlated significantly with Dukes' stage (P<0.0001 and P=0.0234), lymph node metastasis (P<0.0001 and P=0.0059), and survival (P<0.0001 and P<0.0001), but not with age, sex, location and dimension of lesion, gross and histological type. Also, there was a positive significant correlation of LMVD in the peritumoral tissue with degree of differentiation (P=0.0168) and metastasis to the liver or the lung (P=0.0088). CONCLUSIONS: Lymphatic microvessels in the peritumoral tissue are functional. The functional lymphatic microvessels, increased LMVD in the peritumoral tissue and the expression of VEGF-C in the intratumoral tissue may act as the morphological features and the molecular phenotype of lymphangiogenesis in colorectal carcinoma, and also as important predictive markers for evaluating lymphatic metastasis and prognosis in patients with colorectal carcinoma.

Adult↗

PubMed1999

The lymphatic vessels and the so-called "lymphatic stomata" of the diaphragm: a morphologic ultrastructural and three-dimensional study.

We studied the absorbing peripheral lymphatic vessel with the light microscope, the transmission electron microscope, the scanning electron microscope, and three-dimensional models of the diaphragm of several rodents and insectivores under normal and experimental conditions (lymphatic stasis and dehydration). To clarify the delicate and complex mechanism that permits drainage of the abdominal cavity contents into the lymphatic circulatory system, we introduced Polystyrene latex spherules, China ink, and Trypan blue into the abdominal cavities. After anatomical comparisons of the superficial and deep networks of absorbing peripheral lymphatic vessels at the tendinous and muscular portions of the diaphragm and after classification of lymphatic vessels into absorbing and conducting functions, we examined the stomata, which, owing to morphologic and topographic findings, we defined as stable structures. Furthermore, we observed that the stomata and submesothelial connective channel are fundamental elements that facilitate the flow of the corpuscular and liquid contents of the peritoneal cavity to the submesothelial absorbing lymphatic vessel wall. Also, we underlined that the genesis of the connective channel depends on the secondary cytoplasm extensions of two distinct adjacent endothelial cells, which, to facilitate the flow of the absorbed abdominal contents, completely coat this channel. Additionally, our observations illustrate that the secondary cytoplasm extensions do not engage in continuous relationships with the basal lamina of the mesothelium and with the margins of the stoma, and, hence, the hypothesis of "lymphatic stomata" as an expression of the anchoring of the borders of the open interendothelial junctions to the orifice margins of the stoma cannot be confirmed. Moreover, we describe the presence and formation of intraendothelial channels in the lymphatic endothelial wall. We affirm that this morphological entity is a dynamic unit, because its numerical density varies according to different physiological and experimental conditions to degrees of hydrostatic and colloidal osmotic pressure and, perhaps, also to the particular characteristics of the substances that the connective channel liberates into the endothelial wall of the lymphatic vessel. In conclusion, we affirm that the absorbing peripheral lymphatic vessels of the diaphragm, by way of intraendothelial channel formations, membrane diffusion, and the vesicular path of the endothelial cells, constitute the fundamental draining elements for the corpuscular and liquid contents of the abdominal cavity.

Absorption↗

PubMed1998

[Locally advanced prostate carcinoma (T2b-T4 N0) without and with clinical evidence of local progression (Tx N+) with lymphatic metastasis. Is radiotherapy for pelvic lymphatic metastasis indicated or not?].

BACKGROUND: There is a greater controversy regarding the indication of radiotherapy of the pelvic lymphatics in patients with suspected lymph node metastases in locally advanced prostate cancer (T2b-4 N0) on the one hand and in patients with pathologically proven lymph node metastases in locoregional advanced prostate cancer (Tx pN+) on the other hand following definitive radiotherapy and radical prostatectomy. This paper investigates the possible indications for radiotherapy of the pelvic lymphatics in the light of data from the literature. PATIENTS AND METHODS: Because data from several retrospective studies concerning radiotherapy of the pelvic lymphatics indicated a better outcome, the RTOG conducted 2 prospective randomised studies (RTOG 75-06, 77-06) to address these questions. However, the results of these studies showed no better survival or cause specific survival for patients treated for the paraaortal or pelvic lymphatics and therefore, radiotherapy of the pelvic lymphatics was no more advocated. A reanalysis showed several problems of the study design and it was concluded that the studies couldn't prove the question of elective radiotherapy of the pelvic lymphatics. In RTOG 77-06 patients with T1b/T2 tumors were investigated. Therefore, there is no prospective study investigating the elective radiotherapy in patients with T3-tumors, who are at high risk of pelvic lymph node metastases. RESULTS: Today there is no indication for treating the paraaortal lymphatics in patients with locoregional advanced prostate cancer. Many radiotherapists perform the elective radiotherapy of pelvic lymphatics when the risk of metastases is above 15 to 20% because retrospective data indicate a better outcome. On the other hand, many others don't treat them because RTOG 75-06 and 77-06 didn't demonstrate a better outcome. Laparoscopic lymphadenectomy with low morbidity seems to be helpful as in pN0 patients radiotherapy is not necessary. Where performing laparoscopic pelvine lymphadenectomy is impossible the probability of the frequency of lymph node metastases can be estimated using the clinical tumor stage, the Gleason-score and the pretherapeutic PSA. In case of proven metastases (pN+) some retrospective data indicate that patients with micrometastasis could profit from aggressive treatment. In case of proven metastases and extirpation by lymphadenectomy it seems that patients with hormonal therapy and radiotherapy have a longer tumor-free interval. However, there are no data from randomized trials. CONCLUSIONS: Every radiotherapist has to make his own decision for radiotherapy of the pelvic lymphatics as there is no standard treatment. Two randomised studies are open and recruiting patients. These are one study of the ARO, investigating patients with histologically proven lymph node metastases and one study of the RTOG (RTOG 9413), investigating patients with an estimated risk of lymph node metastases > 15%. In case of radiotherapy of the pelvic lymphatics a dose of 45 Gy for suspected metastases and 50.4 Gy for proven metastases is recommended.

Carcinoma↗

PubMed1992

Structure of lymphatics in rat cecum with special reference to submucosal collecting lymphatics endowed with smooth muscle cells and valves. I. A scanning electron microscopic study.

The three-dimensional structure of lymphatic vessels in the rat cecum was studied by KOH-collagenase digestion/scanning electron microscopy (SEM), and corrosion casting/SEM. Abluminal surfaces of the lymphatic vessels show flat elliptical nuclear regions and flat cytoplasmic processes interdigitated with adjacent ones. The lymphatic capillaries closed by interdigitations of flat endothelial processes at their initial portion begin at the various levels of the mucosa. They descend and pass through the muscularis mucosa to connect with the lymphatic vessels in the submucosa. They form polygonal meshwork, the distances between intersections being about 0.2-0.5 mm. They also have valves, the distances between adjacent valves being about 0.1-0.6 mm. Most of the submucosal lymphatic vessels are surrounded by either periendothelial cells or typical smooth muscle cells. The polygonal meshworks made up of stellate periendothelial cells with many irregular processes embrace the initial segment of the collecting lymphatics. As they proceed proximally, the periendothelial cells become elongated and branch out by threes or fours, thus presenting the appearance of smooth muscle cells. These branches are connected side by side and run obliquely along the vessels, thus forming polygonal meshworks around the vessels. The more proximal collecting lymphatic vessels are surrounded by circularly oriented smooth muscle cells. Our results indicate that most of the lymphatic vessels in the submucosa are collecting ones and possess smooth muscle cells as well as valves. This suggests that the lymphatic vessels in the submucosa actively contract and propel the lymph towards the mesenteric lymphatic vessels.

Animals↗

PubMed1994

Three-dimensional structure of two different lymphatic spaces in rat testis, and the route of flow fluxes of their lymphatic fluids.

In addition to the collecting vessels, two initial lymphatic spaces were observed with light and electron microscopes. In the deep parenchyma, the peritubular lymphatic spaces surrounding the tubules were observed as polygonal piles after a corrosion casting to the testis. They were joined to the adjacent piles through fenestrae to form a loose spongiform structure. In the superficial parenchyma, the peritubular lymphatic spaces communicated to the subtunical lymphatic space on one side. The subtunical lymphatic spaces anastomosed to each other through small bypasses to form a rich network. Near the mediastinum, the peritubular lymphatic spaces bifurcated and narrowed on another side. Microradiography demonstrated two fluxes of the intratesticular lymphatic fluids; fast and slow flows. The fast flow was observed as a shaded line running into the subtunical lymphatic spaces immediately after injection of the contrast media. It remained 1 or 2 minutes and then disappeared. In contrast, the slow flux was observed as a spongiform shade shifting from the anteroposterial quadrant to the posterosuperior portion of the testis. Seven to 15 minutes were needed for the contrast media to reach near the mediastinum. Both lymphatic spaces are functionally discussed with relation to the two different fluxes of the lymphatic fluids.

Animals↗

PubMed2004

Ultrastructural study of pleural lymphatic drainage unit and effect of nitric oxide on the drainage capacity of pleural lymphatic stomata in the rat.

The objective of this study was twofold: first to investigate the ultrastructure of the lymphatic drainage unit on the costal pleura of rats by electron microscopy, and secondly to examine the effect of nitric oxide on the pleural lymphatic stomata and fluid absorption from the pleural cavity. The lymphatic drainage unit of the rat costal pleura is composed of three special components: the lymphatic stomata between the mesothelial cells, the initial part of the lymphatic vessels and the underlying connective tissue containing many foramina. The unit is the main passage to drainage fluid, particles and cells in the pleural space. To investigate the regulator of the lymph drainage, nitric oxide synthase inhibitor and nitric oxide donor were injected into the peritoneal cavity of the rats, respectively. Trypan blue was used as tracer. The ultrastructural changes of pleural lymphatic stomata were observed under scanning electron microscope and analyzed by a computer image processing system. It turned out that the area and density of the pleural lymphatic stomata were positively correlated with the nitric oxide quantity (p < 0.05). After the tracer was injected into the pleural cavity, the nitric oxide donor group exhibited a higher trypan blue concentration than the control group (p < 0.05). The ability of the pleura to absorb trypan blue was enhanced because of the larger opening of the lymphatic stomata (p < 0.05). It is suggested that nitric oxide can increase lymphatic absorption of the pleura by opening pleural lymphatic stomata.

Animals↗

PubMed2004

Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1).

PURPOSE: Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa. MATERIALS AND METHODS: LYVE-1 lymphatics (LVD) and CD34 blood vessels were assessed in 20 paraffin sections of BPH and 50 of PCa tissue by immunohistochemistry in a standardized experimental setting. The regions of PCa, periphery of the tumor and nontumorous regions of the PCa specimens, and BPH tissue were evaluated. Double staining was done (LYVE-1/CD34). Acquired data were interrelated and compared to the pathological parameters of the specimens. RESULTS: Double staining revealed numerous CD34 blood vessels but only a few LYVE-1 lymphatic vessels in BPH and PCa sections. Mean LVD +/- SD was distinctly lower (0.55 +/- 0.93) in PCa tissue than in tumor periphery (2.45 +/- 1.93) and nontumorous (3.16 +/- 2.23) tissue (p <0.0001). Maximum LVD was observed in BPH (7.17 +/- 3.61), which differed markedly from nontumorous areas of PCa specimens (p <0.001). In contrast to LVD, significantly more blood vessels were found in PCa (116.00 +/- 39.25) than in BPH (60.30 +/- 19.34) tissue (p <0.001). CONCLUSIONS: LYVE-1 is a specific lymphatic endothelial marker in benign and malignant prostate tissues. It is a useful new marker for the investigation of lymphatics. To our knowledge we report the immunohistochemical visualization and quantification of lymphatic vessels in prostatic tissue for the first time. In contrast to the stimulated angiogenesis of blood vessels in PCa, the destruction of lymphatic vessels occurs rather than lymphangiogenesis.

Antigens, CD34↗

PubMed2006

Lymphatic vascular endothelial hyaluronan receptor (LYVE)-1- and CCL21-positive lymphatic compartments in the diabetic thymus.

To explore the biological significance of the lymphatics in the autoimmune process, the thymus from non-obese diabetic (NOD) mice was evaluated by histochemistry and western blot analysis. Thymic lymphatic endothelial cells showed suggestive expression patterns of the functional molecules lymphatic vascular endothelial hyaluronan receptor (LYVE)-1, CCL21, CD31 and podoplanin. With increasing age, the expression of CCL21 was reduced in the medullary epithelial cells and lymphatics. Of note, LYVE-1-expressing lymphatics, filled with a cluster of thymocytes, increased in number and size and extended from the corticomedullary boundary into the medulla as the insulitis progressed. The development of lymphatic compartments was occasionally accompanied by a regional disappearance between the cortex and medulla. The CD4- and CD8-positive T cells frequently penetrated through the slender lymphatic walls. The epithelial reticular cell layer lining the perivascular spaces was extensively stained with cytokeratin, but the expression of cytokeratin showed an age-dependent decrease. These findings indicate that the occurrence of LYVE-1-expressing lymphatic compartments and the alteration of CCL21 expression in the lymphatics may be involved in defective thymocyte differentiation and migration, and play a significant role in insulitic and diabetic processes.

Aging↗