Lymphatic Distribution Research Articles

The human renal lymphatics under normal and pathological conditions

Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Soh S & Ishii T (2006) Histopathology 49, 265–273The human renal lymphatics under normal and pathological conditionsAimsThe renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody.Methods and resultsNormal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney.ConclusionsLymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics.

Lymphatic vessel density and distribution in benign and malignant lesions of thyroid

Lymphatic vessel density and distribution in benign and malignant lesions of thyroid

The effect of methoxy-PEG chain length and molecular architecture on lymph node targeting of immuno-PEG liposomes

The rate of drainage and lymphatic distribution of subcutaneously injected liposomes is controlled by inclusion of methoxypoly(ethyleneglycol), mPEG-phospholipid into the liposomal bilayer. The effect is most dramatic with liposomes containing 15 mol% mPEG-lipid, with an average PEG molecular mass of 350 Da. These vesicles are drained rapidly from the injection site into the initial lymphatics when compared to unmodified liposomes, and are retained more favourably by the scavengers of the regional lymph node. Liposomes decorated with longer surface mPEG chains (6.7 mol% of mPEG 2000-lipid) exhibit faster drainage rates than vesicles having 15 mol% mPEG 350-lipid in their lipid bilayer, but their lymph node retention is very poor. The lymph node retention of rapidly drained PEG-bearing vesicles was increased dramatically following conjugation of a non-specific IgG to the distal end of PEG, using a functionalized PEG 2000 lipid. Adjusting the molecular architecture of surface mPEG and IgG-PEG chains to a “nearly overlapped mushroom” regime further enhanced target recognition of immuno-PEG 2000 liposomes without compromising their drainage rate from the interstitium. The lymph node retention of these vesicles was further optimized by enriching their lipid bilayer with 20 mol% phosphatidylserine. These approaches have established important compositional and structural variables that control lymphatic targeting of immuno-PEG liposomes and their application in experimental medicine and biology is discussed.

The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status

Background: Sentinel node (SN) status is the most important prognostic indicator in patients with cutaneous melanoma without clinically evident metastatic spread, but the procedure is associated with considerable morbidity. The...

A Case of Sarcoidosis with Cavitation

Sarcoidosis is a rare systemic disorder with unknown cause that is characterized pathologically by non-caseating granuloma. The lung and mediastinal lymph nodes are almost always involved, and most patients experience acute or insidious respiratory symptom. Because sarcoidosis is an interstitial lung disorder involving the alveoli and bronchioles, the most common radiological finding is a reticularnodular lesion with lymphatic distribution. However, cavitation is quite rare. Sarcoidosis is also a major cause of hepatic granuloma in Western countries, accounting for 12% to 30% of cases. In most patients, the course of hepatic sarcoidosis is benign. However, chronic intrahepatic cholestasis or portal hypertension may develop in some patients. We report a case of sarcoidosis with cavitation and hepatic involvement.

Vaginal lymphatic channel location and its implication for intracavitary brachytherapy radiation treatment

Purpose In vaginal intracavitary brachytherapy using cylindrical applicators, it is common to prescribe dose to a depth of 0.5 cm to cover the lymphatic channels. However, the actual depth of the lymphatics within the vaginal wall has never been determined. In this study, we examined the depth distribution of lymphatics lying beneath the mucosal surface of the vagina. Methods and materials Between January 24, 1996 and October 27, 2003, 31 patients underwent full-thickness vaginal biopsy or partial resection for both benign and malignant disease. In addition, in February 2004, vaginal samples from two autopsy specimens were stretched and pinned for formalin fixation and slide production. Forty-five slides of both stretched and nonstretched vaginal tissue were stained with D2-40 monoclonal antibody lymphatic endothelium marker. The percentages of lymphatics located within 1, 1–2, 2–3, and 3–4 mm were calculated for all slides. Results For the nonstretched samples, the percentages of lymphatics located within 1, 1–2, 2–3, and 3–4 mm were 50.5%, 30.7%, 11.9%, and 6.9%, respectively. For the stretched samples, the percentages of lymphatics located within 1, 1–2, 2–3, and 3–4 mm were 44.0%, 33.8%, 18.8%, and 3.4%, respectively. The differences of lymphatic percentages within and superficial to 1 mm ( p = 0.60), 1–2 mm ( p = 0.85), 2–3 mm ( p = 0.89), and 3–4 mm ( p = 0.99) were not statistically significant between the stretched and nonstretched states. Conclusions Our results show that approximately 95% of vaginal lymphatic channels are located within a 3 mm depth from the vaginal surface. This suggests that dose prescribed to a depth less than 0.5 cm may be adequate and could permit treatment with less normal tissue toxicity in certain clinical situations.

Modulation of lymphatic distribution of subcutaneously injected poloxamer 407-coated nanospheres: the effect of the ethylene oxide chain configuration

Lymphatic distribution of interstitially injected poloxamer 407-coated nanospheres (45 nm in diameter) is controlled by surface configuration of the ethylene oxide (EO) segments of the adsorbed copolymer. At low poloxamer surface coverage, EO tails spread laterally on a nanosphere surface and assume a ‘flat or mushroom-like’ configuration. Such entities drain rapidly from the subcutaneous site of injection into the initial lymphatic, when compared to uncoated nanospheres, and subsequently are captured by scavengers of the regional lymph nodes. In vitro experiments have also confirmed that such entities are prone to phagocytosis. When the equilibrium poloxamer concentration is at 75 μg/ml or greater the EO chains become more closely packed and project outward from the nanosphere surface. These surface-engineered nanospheres drain faster than those with EO chains in mushroom configurations into the initial lymphatic, escape clearance by lymph node macrophages, reach the systemic circulation, and remain in the blood for prolonged periods. These experiments provide a rational approach for the design and engineering of nano-vehicles for optimal lymphatic targeting and are discussed.

Computed Tomography of Benign Intrapulmonary Lymph Nodes: Retrospective Comparison With Sarcoma Metastases

To determine whether the computed tomographic (CT) characteristics of benign intrapulmonary lymph nodes and small sarcoma metastases are sufficiently characteristic to allow specific prospective identification. Preoperative chest CT scans of 41 patients with benign intrapulmonary lymph nodes and 33 patients with sarcoma metastases seen from 1991 through 1996 were retrospectively reviewed and correlated with pathologic findings. Fifty-seven benign intrapulmonary lymph nodes were found. Twenty-six (46%) were subpleural, 38 (67%) were oval, and 46 (81%) were located in the lower portions of the lungs; 43 (75%) had a lymphatic distribution on CT and 54 (95%) at pathologic review. Ninety-eight sarcoma metastases were found. Thirteen (13%) were subpleural, 15 (15%) were oval, and 56 (57%) were in the lower portions of the lungs; 29 (30%) had a lymphatic distribution on CT and 45 (46%) at pathologic review. Benign intrapulmonary lymph nodes were more likely than sarcoma metastases to be oval, to occur in a lymphatic distribution, and to be located subpleurally.

Anatomic distribution of intraprostatic lymphatics: Implications for the lymphatic spread of prostate cancer—A preliminary study

Anatomic distribution of intraprostatic lymphatics: Implications for the lymphatic spread of prostate cancer—A preliminary study

Anatomic distribution of intraprostatic lymphatics: Implications for the lymphatic spread of prostate cancer—A preliminary study

Anatomic distribution of intraprostatic lymphatics: Implications for the lymphatic spread of prostate cancer—A preliminary study

Anatomic distribution of intraprostatic lymphatics: implications for the lymphatic spread of prostate cancer-a preliminary study.

Although prostate cancer metastasizes primarily into the lymphatic system, the anatomic distribution of intraprostatic lymphatics has not been elucidated. The aim of this study was to clarify the distribution of lymphatics in the human prostate by immunohistochemical techniques, using an anti-desmoplakin antibody. Whole-mount cryostatic sections were serially cut from the noncarcinomatous prostates of adult men with bladder carcinoma who underwent cystoprostatectomy. Each section was stained either with a monoclonal antibody specific for desmoplakin or with hematoxylin and eosin. Lymphatics were detected in all components of the prostate. In the glandular prostate, lymphatics were distributed evenly in the peripheral, transitional, and central zones. The lymphatic density was significantly high in the midbase region surrounding ejaculatory ducts. These results may indicate the importance of the midbase region as a route of lymphatic spread of prostate cancer.

Homing of negatively charged albumins to the lymphatic system: General implications for drug targeting to peripheral tissues and viral reservoirs

The present study shows the lymphatic distribution of the negatively charged anti-HIV-1 agents succinylated or aconytilated human serum albumins (HSAs) in rats. Quantitation of blood and lymphatic concentrations of these proteins was performed through fluorescence detection of the fluorescein isothiocyanate (FITC)-labeled proteins. At several time points after i.v. injection, samples were taken from the cannulated thoracic duct and the carotid artery. Distribution of the negatively charged albumins (NCAs) to lymph was much more rapid than that of albumin itself and was dependent on the total net negative charge added to the protein: the half-life times of lymphatic equilibration were 15, 30, and 120 min for FITC-labeled aconytilated HSA, FITC-labeled succinylated HSA, and FITC-labeled HSA, respectively. Lymph to blood concentration ratios of the studied compounds obtained at steady state approached unity. In addition, the fluorescence in both body fluids was shown to represent unchanged labeled proteins. It was therefore inferred that the NCAs efficiently passed the endothelial barrier from blood to the interstitial compartment. Subsequently, we studied whether a specialized process was involved in the endothelial passage of the NCAs to the lymph. The following observations supported such a mechanism: a) preinjection of the scavenger receptor blockers polyinosinic- and formaldehyde-treated HSA reduced the transport from blood to the lymphatic compartment of FITC-labeled aconytilated HSA by more than 90%; b) the rate of lymphatic distribution was largely reduced when the body temperature of the rat was lowered to 28°; and c) pre-administration of chloroquine resulted in a significant reduction in the lymphatic distribution of the NCAs. These data collectively indicate that a scavenger receptor-mediated process is involved in the transendothelial transport of NCAs. In situ localization in lymph nodes of the rat showed that FITC-labeled aconytilated and succinylated HSA are mainly present in the germinal center and parafollicular zones. The efficient distribution of these anionized proteins to the lymphatic system is of particular interest for HIV therapy, taking into account that replication of HIV mainly takes place in the lymphoid system. The observation that macromolecules, through charge modification, can extravasate through a receptor-mediated transcytotic process is potentially of major importance for the delivery of drugs with macromolecular carriers to cells not directly in contact with the blood.

Pulmonary pathology in Gaucher's disease

Gaucher's disease is a familial storage disease caused by a deficiency of the enzyme glucocerebrosidase. Pulmonary involvement is considered rare in Gaucher's disease, especially type I. Sporadic case reports have shown various types of lung involvement, but the spectrum of pulmonary pathology in Gaucher's disease has not been described. Nine cases of Gaucher's disease were retrieved from the autopsy file of Hadassah Medical Center, Jerusalem, Israel. There were six cases with type I Gaucher's disease and three cases with type II. Lung sections were evaluated, and special stains were employed, including immunohistochemical stains for CD68, cytokeratin, and CD34. Gaucher cells were found in the lungs in all nine cases. The involvement was considered pathologically significant in five of nine cases and clinically significant in three of nine cases. Four distinct patterns of pulmonary involvement by Gaucher cells emerged: intracapillary (9 of 9), patchy interstitial infiltrates in a lymphatic distribution (2 of 9), massive interstitial thickening of alveolar septa (1 of 9), and intra-alveolar infiltrates (2 of 9). The universal involvement of pulmonary capillaries indicates that this is probably systemic in nature and not intrinsic to the lungs. Pulmonary involvement in Gaucher's disease is commoner than previously recognized. Immunocytochemical stains help to identify isolated Gaucher cells and distinguish them from native alveolar macrophages.

Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease.

Erdheim-Chester disease is a clinicopathologic entity defined by a characteristic pattern of symmetric osteosclerosis caused by an infiltrate of mononuclear cells that include prominent numbers of foamy histiocytes. About half of patients have extraskeletal manifestations, including involvement of the hypothalamus/posterior pituitary, orbit, retroperitoneum, skin, lung, and heart. Pulmonary involvement is an uncommon but important manifestation of Erdheim-Chester disease because it causes significant morbidity and mortality. A review of the Mayo Clinic files produced four patients with confirmed Erdheim-Chester disease in whom lung biopsy had been performed. One additional patient was included from the University of Pittsburgh. Four patients were women. The mean age was 53.6 years (range 25-70 years). All patients had bilateral and symmetric sclerotic bone lesions characteristic of Erdheim-Chester disease, although in three the skeletal abnormalities were discovered only after lung biopsy. Four patients had dyspnea, and one also had a dry cough. One patient died 17 months after diagnosis. Chest radiographs showed diffuse interstitial infiltrates in all patients, with an upper zone predominance in three. Thoracic computed tomography (CT) scans showed thickening of the visceral pleura and interlobular septa with patchy associated fine reticular and centrilobular opacities and ground glass attenuation. Lung biopsy specimens showed an infiltrate of foamy histiocytes, lymphocytes, and scattered Touton giant cells with associated fibrosis in a striking lymphatic distribution. The infiltrate involved visceral pleura, interlobular septa, and bronchovascular bundles. Immunohistochemical stains were positive for CD68 in all cases and S-100 protein in four cases. Stains for CD1a were consistently negative. Ultrastructural studies in one case showed no Birbeck granules. Although in bone the histologic features of Erdheim-Chester disease may overlap with Langerhans' cell histiocytosis, its expression in the lung is distinct. Lung involvement in Erdheim-Chester disease has emerged as a unique radiographic and histologic entity.

Relationship between nodal stage and the number of dissected perigastric nodes in gastric cancer.

To evaluate the rationality of the current nodal staging system in gastric cancer, we retrospectively analyzed 152 patients with perigastric node involvement localized to a single station, in whom the route of metastasis to distant nodes was limited. No significant differences in pathology or survival were observed between patients with stage n1 and those with stage n2-3 nodal involvement, but the mean (standard deviation) number of perigastric nodes dissected was 22.6 (12.6) in those with stage nl involvement and 18.5 (9.5) in those with stage n2-3 involvement (P = 0.04). When perigastric node involvement was localized to station 3, the mean number of dissected station 3 nodes was 7.7 (4.2) in nl patients and 5.3 (2.8) in n2-3 patients (P = 0.04). This tendency was also observed in patients with perigastric node involvement limited to either station 1 (P = 0.08) or station 6 (P = 0.11). Thus, patients with fewer perigastric nodes may have more lymphatics that bypass perigastric nodes and empty directly into distant nodes, increasing the likelihood of skip metastases. The number of positive nodes, affected to a lesser degree by lymphatic distribution than the location of positive nodes, should be incorporated into the staging criteria.

Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with special reference to the distribution of the epidural lymphatics.

The structural organization of the epidural lymphatics and lymphatic drainage of the cerebrospinal fluid from spinal meninges was studied in Japanese monkeys (Macaca fuscata) by an enzyme-histochemical method. The spinal meninges were examined at various intervals from 1 to 48 h, as well as at 30 days, following an injection of ultrafine carbon particles into the subarachnoidal space (cisterna magna). Lymphatics were differentiated from blood capillaries by the 5'-nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) double staining method (KATO et al. 1991, 1993) both in the whole-mount preparations and tissue sections. Carbon-filled collecting lymphatics and lymph nodes constantly appeared in the cervical and thoracic regions but only rarely in the lumbo-sacral region after carbon injection. Networks of 5'-Nase-positive lymphatics in the epidural connective tissues were seen in a large area on the dorsal surface around each spinal nerve root in the cervical and upper thoracic regions, especially at a level corresponding to the brachial plexus (C5-Th1). Carbon particles were often found within the 5'-Nase-positive lymphatics. In the lower thoracic and lumbo-sacral regions, on the other hand, the epidural lymphatic network covered only a small area around each spinal nerve root. These findings suggest that the epidural lymphatics are well developed on the dorsal side of the lower cervical spinal dura mater and may function as an absorptive pathway for the cerebrospinal fluid from the subarachnoidal space.

Three-dimensional structure of lymphatics in rabbit stomach.

Recently, the stomach lymphatics have been studied, but there are different opinions on the lymphatic distribution of the stomach layers[1-6]. There has been no reported in China. Discribing the three-dimensional organization of the stomach lymphatics and revealing the correlation of the three-dimensional and the two-dimensional and organization. In our study in the rabbit with the lymphatic corrosion cast with Mercox and semithin section methods we investigated the relationship of the three-dimensional organization with the drainage of the stomach lymphatics, which may provide the evidences of lymphology, pathology and the clinical medicine.

Lymphatic Targeting of Anti-Human Immunodeficiency Virus Nucleosides: Pharmacokinetics of G′-Deoxy-2′,3′-Didehydrothymidine after Intravenous and Oral Administration of Dipalmitoylphosphatidyl Prodrug to Mice

The lymphatic system is a primary target for early anti-human immunodeficiency virus drug therapy. Strategies are currently being sought to enhance the delivery of nucleoside analogues such as 3′-deoxy-2′,3′-didehydrothymidine (stavudine; d4T) toward the lymph and lymph nodes. The purpose of this study was to synthesize dipalmitoylphosphatidyl-d4T (DPP-d4T) as a lipophilic prodrug of d4T and to evaluate the lymphatic distribution of d4T following administration of d4T and DPP-d4T to mice. The pharmacokinetics of d4T were characterized following administration of a single intravenous or oral dose of 50 mg kg−1d4T and an equimolar dose (214 mg kg−1) of DPP-d4T. Concentrations of d4T in serum and lymph nodes were determined by HPLC. Following administration of d4T, the distribution of d4T into lymph nodes was rapid with maximum concentrations observed within 5 min after dosing. The AUC and half-life values of d4T in three groups of lymph nodes were similar to those in serum. Administration of DPP-d4T resulted in significantly lower concentrations of d4T in serum and lymph nodes. Approximately 67% of the intravenously administered DPP-d4T was biotransformed to parent compound. The apparent oral bioavailability of DPP-d4T was low. While the phospholipid prodrug did not increase d4T concentrations in the lymph nodes, it did provide an extended release of the parent nucleoside, resulting in sustained concentrations of d4T.

Lymph node localisation of biodegradable nanospheres surface modified with poloxamer and poloxamine block co-polymers

Studies were performed to develop a sub-100 nm biodegradable colloidal system for the efficient delivery of drugs and diagnostic agents to the lymphatic system. Nanospheres of poly(lactide-co-glycolide) were prepared by interfacial polymer deposition. The nanospheres were coated with block co-polymers in order to modify their surface characteristics. Radiolabelling of the nanospheres for in vivo tracing was achieved by the incorporation of the lipophilic complex 111In-oxine during nanosphere preparation. In vitro stability of the radiolabelled nanospheres was determined in rat serum at 37°C. The lymphatic distribution of the nanospheres was determined after subcutaneous administration to the rat. Lymphatic uptake of all coated systems was enhanced compared to the uncoated nanospheres, and a maximal uptake of 17% of the administered dose in the regional lymph nodes was achieved. These observations suggest that the nanospheres are suitable for diagnostic and therapeutic applications in clinical and experimental medicine.

Metabolic Fate of a New Dihydropyridine Calcium Antagonist, AE0047. (II): Lymphatic Absorption and Distribution of AE0047 in Rats.

Metabolic Fate of a New Dihydropyridine Calcium Antagonist, AE0047. (II): Lymphatic Absorption and Distribution of AE0047 in Rats.