Number Of Lymphatic Vessels Research Articles

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis.

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.

Quantifying Lymphatic Vessel Density in Human Tissue Samples.

The development of new blood and lymphatic vessels, through the process of angiogenesis and lymphangiogenesis, respectively, is critical to the development and growth of tumors, and integral to the process of metastasis. Lymphatic vessel density can be assessed as a surrogate measure of lymphangiogenesis in human tissue samples. Lymphatic vessel density has been shown to be associated with lymph node metastasis and patient survival in various solid tumor types. Here we describe a method for quantifying the number of lymphatic vessels within tumor tissue that can also be used to assess lymphatic vessel invasion, and compare with blood vessel density and invasion.

Abstract 12751: Diallyl Trisulfide Augments Lymphangiogenesis via an Akt-Dependent Mechanism and Ameliorates Lymphedema

Background: Secondary lymphedema is one of the serious clinical problems that can often occur after surgical resection of malignant tumors. However, no effective treatment options exist at present. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil that liberates H2S under physiological conditions. We previously demonstrated that DATS augmented reparative angiogenesis and improved blood perfusion recovery in the HLI model. Here, we investigated the effects of DATS on lymphatic vessel growth and lymphedema in a mouse model and assessed its potential mechanism. Methods and Results: A mouse model of lymphedema was created by ablation of a tail surface lymphatic network, and the tail diameter was measured to estimate lymphedema at day 28 after induction of lymphedema. Lymphatic vessels were detected by immunohistochemical staining as LYVE-1 and podoplanin double-positive cells. The DATS group was intraperitoneally injected with DATS for up to 10 days following lymphedema induction. DATS treated mice (n=10) showed a smaller tail thickness compared with control wild-type (WT) mice (n=11) (p&lt;0.001) which was accompanied by a greater number of lymphatic vessels in the injured tails (p&lt;0.05). Interestingly, the distal lymphatic lumen area was dilated in the control group, whereas the DATS treatment group improve dilated lymphatic area at the distal site of the injured point (p&lt;0.001). In vitro experiments revealed that treatment with DATS promoted the differentiation of human lymphatic endothelial cells (LECs) into tube-like structures (p&lt;0.001) in a dose-dependent manner, when cultured on Matrigel matrix. DATS also stimulated the phosphorylation of Akt in LECs. Furthermore, blockade of Akt activation canceled the DATS-stimulated increase in LEC differentiation. Conclusions: Our data clearly demonstrate that DATS promotes reparative lymphatic vessel growth and ameliorates secondary lymphedema, at least in part, through activation of the Akt pathway within lymphatic endothelial cells.

Morphometric study of lymphangiogenesis in different lesions of psoriasis vulgaris with correlation to disease activity.

In the last decades, attention to the role of lymphangiogenesis in psoriasis has been paid. Our study was conducted to evaluate podoplanin-stained lymphatic vessels and the level of lymphangiogenesis in papular psoriatic lesions and psoriatic plaques and ascertain if podoplanin provides any additional prognostic information. Number of lymphatic vessels and total lymphatic vessel area were morphometrically analyzed in podoplanin-stained sections, using anti-D2-40, together with the immunohistochemical study of epidermal Ki-67 in psoriasis vulgaris (n=20) (papules=7 and plaques=13) and control skin specimens (n=20). The number of lymphatic vessels and total lymphatic vessel area were higher in psoriasis cases compared with normal skin (p=0.01, p=0.01 respectively). In psoriatic plaques, the number of lymphatic vessels, total lymphatic vessel area, and epidermal Ki-67 immunoreactivity were higher than in papular lesions (p=0.002, p=0.008, and p=0.01, respectively). Psoriasis vulgaris is found to be a lymphangiogenesis-dependent disease, and the lymphatic vascular network is in remodeling and expanding process. Podoplanin may be implicated in the pathogenesis of psoriasis and could be used as a prognostic biomarker for disease severity and progression.

CD147 Promotes Tumor Lymphangiogenesis in Melanoma via PROX-1.

Simple SummaryMelanoma is one of the most aggressive skin cancers, characterized by metastasis to the lymph nodes and a high capacity to develop drug resistance. There is a lack of knowledge on the mechanisms contributing to lymphatic vessel formation and metastasis regulation in malignant melanoma. We previously reported the involvement of CD147, a transmembrane glycoprotein overexpressed in melanoma, in the regulation of the tumor microenvironment and angiogenesis. The aim of our study was to further determine how CD147 is involved in lymphangiogenesis regulation. Our results revealed that high CD147 expression is correlated with the number of lymphatic vessels in the human melanoma lymph nodes and that paracrine CD147 upregulates lymphangiogenesis through lymphangiogenic mediators in vitro and in vivo, suggesting that CD147 could be a promising target for melanoma-associated lymphangiogenesis inhibition.Malignant melanoma is one of the most aggressive skin cancers and is characterized by early lymph node metastasis and the capacity to develop resistance to therapies. Hence, understanding the regulation of lymphangiogenesis through mechanisms contributing to lymphatic vessel formation represents a treatment strategy for metastatic cancer. We have previously shown that CD147, a transmembrane glycoprotein overexpressed in melanoma, regulates the angiogenic process in endothelial cells. In this study, we show a correlation between high CD147 expression levels and the number of lymphatic vessels expressing LYVE-1, Podoplanin, and VEGFR-3 in human melanoma lymph nodes. CD147 upregulates in vitro lymphangiogenesis and its related mediators through the PROX-1 transcription factor. In vivo studies in a melanoma model confirmed that CD147 is involved in metastasis through a similar mechanism as in vitro. This study, demonstrating the paracrine role of CD147 in the lymphangiogenesis process, suggests that CD147 could be a promising target for the inhibition of melanoma-associated lymphangiogenesis.

Morphological and biochemical changes of lymphatic vessels in the soleus muscle of mice after hindlimb unloading.

Lymphatic vessels are responsible for the removal of metabolic waste from body tissues. They also play a crucial role in skeletal muscle functioning thorough their high-energy metabolism. In this study we investigated whether disuse muscle atrophy induced by hindlimb unloading is associated with an alteration in the number of lymphatic vessels and differential expression of lymphangiogenic factors in the soleus muscle. Male C57BL/6 mice were subjected to tail suspension (TS) for 2 or 4 weeks to induce soleus muscle atrophy. After TS, lymphatic and blood capillaries in the soleus muscle were visualized and counted by double staining with LYVE-1 and CD31. The protein and mRNA levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor-3 were measured by Western blotting and real-time reverse transcript polymerase chain reaction, respectively. TS for 2 weeks resulted in a significant decrease in the number of blood capillaries compared with controls. However, there was no significant change in the number of lymphatic capillaries. By contrast, TS for 4 weeks resulted in a significant decrease in the number of lymphatic and blood capillaries. We observed a significant decrease in the mRNA levels of VEGF-C and VEGF-D in mice subjected to TS for 4 weeks. The decrease of intramuscular lymphatic vessels may a crucial role in the process of muscle atrophy.

Prokineticin-1 induces normal lymphangiogenic activity and is involved in lymphangiogenesis and lymph node metastasis in colorectal cancer.

Background: Prokineticin family correlates with important roles in several biological processes, including homeostasis. We discovered novel functions of prokineticin1 (PROK1) in lymphangiogenesis and lymphnode metastasis in colorectal cancer.Materials and Methods: We examined changes in the number of lymphatic endothelial cells after PROK1 stimulation. PROK1 protein was stimulated with subcutaneously implanted in mice. Also a high-PROK1-expressing colorectal cancer cell line and anti-PROK1 antibody(Ab) were subcutaneously implanted in mice, and then examine lymphangiogenesis. PROK1 expression and the number of lymph vessels were examined in the primary lesion of 391 patients whose colorectal tumors had been resected.Results: When PROK1 was used as a stimulus, the number of lymphatic cells increased compared to unstimulated cells. And the number of lymph vessels in the skin of mice increased compared to mice implanted without PROK1. The number of lymph vessels in the primary tumor tissue increased when PROK1 was highly expressed compared to cases with non-detectable PROK1 expression. When PROK1 was expressed in human colorectal tumors, the rate of lymphnode metastasis was significantly higher than that in cases with non-detectable PROK1 expression.Conclusions: PROK1 is a lymphangiogenic factor involved in the formation of new lymph vessels and lymphnode metastasis in human colorectal cancer.

Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review.

Chylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

Role of the Cadaver Lab in Lymphatic Microsurgery Education: Validation of a New Training Model

Background Microsurgical transplantation of vascularized lymph nodes (VLNT) or lymphatic vessels (VLVT) alongside derivative lymphaticovenous procedures are promising approaches for treatment of lymphedema. However, clinically relevant training models for mastering these techniques are still lacking. Here we describe a new training model in human cadaver and validate its use as training tool for microsurgical lymphatic reconstruction. Methods 10 surgeons with previous exposure to microsurgery were trained in a controlled environment. Lymphatic vessel mapping and dissection in 4 relevant body regions, harvesting of five different VLNTs and one VLVT were performed in 5 fresh-frozen cadavers. The number of lymphatic vessels and lymph nodes for each VLNT were recorded. Finally, the efficacy of this model as training tool was validated using the Dundee Ready Education Environment Measure (DREEM). Results The average cumulative DREEM score over each category was 30,75 (max = 40) while individual scoring for each relevant category revealed highly positive ratings from the perspective of teaching (39,3), training 40,5 (max = 48) and self perception of the training 30,5 (max = 32) from all participants. The groin revealed the highest number of lymphatic vessels (3.2 ± 0.29) as all other regions on the upper extremity, while the gastroepiploic VLNT had the highest number of lymph nodes (4.2 ± 0.37). Conclusions This human cadaver model represents a new, reproducible “all-in-one” tool for effective training in lymphatic microsurgery. Its unique diligence in accurately reproducing human lymphatic anatomy, should make this model worth considering for each microsurgeon willing to approach lymphatic reconstruction.

Esophageal carcinoma cell-excreted exosomal uc.189 promotes lymphatic metastasis.

Most cancers are old age-related diseases. Patients with lymphatic metastasis have an extremely poor prognosis in esophageal cancers (ECs). Previous studies showed ultraconserved RNAs are involved in tumorigenesis and ultraconserved RNA 189 (uc.189) served as an oncogene in cervical cancer, but the effect of exosomal uc.189 in esophageal squamous cell carcinoma (ESCC) remains undefined. This study revealed that uc.189 is closely correlated with lymph node (LN) metastasis and the number of lymphatic vessels in ESCC. ESCC-secreted exosomal uc.189 is transferred into human lymphatic endothelial cells (HLECs) to promote its proliferation, migration and tube formation to facilitate lymph node metastasis. Mechanistically, uc.189 regulated EPHA2 expression by directly binding to its 3’UTR region through dual-luciferase reporter assay. Over-expression and knockdown of EPHA2 could respectively rescue and simulate the effects induced by exosomal uc.189. Especially, the uc.189-EPHA2 axis activates the P38MAPK/VEGF-C pathway in HLECs. Finally, ESCC-secreted exosomal of uc.189 promotes HLECs sprouting in vitro, migration, and lymphangiogenesis. Thus, these findings suggested that exosomal uc.189 targets the EPHA2 of HLECs to promote lymphangiogenesis, and may represent a novel marker of diagnosis and treatment for ESCC patients in early stages.

Use of photoacoustic imaging to determine the effects of aging on lower extremity lymphatic vessel function

ObjectiveAging is one of the causes of primary lymphedema. However, the effects of aging on the lymphatic system are still not completely understood. We investigated the effects of aging on the lymphatic vessels in the lower extremities of healthy volunteers using photoacoustic imaging. MethodsHealthy volunteers who underwent photoacoustic lymphangiography between March 2018 and January 2019 were enrolled. To visualize lymphatics, indocyanine green (ICG, 5.0 mg/mL) was injected subcutaneously into the first and fourth web spaces of the foot and under the lateral malleolus. Subsequently, near-infrared fluorescence lymphography was performed to confirm good ICG flow, and photoacoustic lymphangiography was performed on the medial side of the lower leg. Ti sapphire laser irradiation at 797 and 835 nm, the optimal wavelengths for visualizing ICG and blood, was applied. The number of lymphatic vessels shown at areas 10 cm (L10) and 20 cm (L20) cranially from the internal malleolus was counted. ResultsNineteen healthy volunteers (4 males and 15 females) were enrolled in the study. Their mean age was 42.9 ± 12.8 years. One volunteer was bilaterally imaged; 15 left lower limbs and 5 right lower limbs were imaged. The number of lymphatic vessels visualized increased with age. There were strong positive correlations between age and L10 (R = 0.729, P < .001) and between age and L20 (R = 0.570, P = .009). ConclusionsPhotoacoustic imaging indicates that the number of lymphatic vessels increases with age. Lymphatic stasis resulted in visualization of not only normal drainage pathways but also nonfunctional lymphatic pathways.

Photoacoustic lymphangiography before and after lymphaticovenular anastomosis.

BackgroundLymphaticovenular anastomosis (LVA) is a minimally invasive surgical procedure used to treat lymphedema. Volumetric measurements and quality-of-life assessments are often performed to assess the effectiveness of LVA, but there is no method that provides information regarding postoperative morphological changes in lymphatic vessels and veins after LVA. Photoacoustic lymphangiography (PAL) is an optical imaging technique that visualizes the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and provides three-dimensional images of superficial lymphatic vessels and the venous system simultaneously. In this study, we performed PAL in lymphedema patients before and after LVA and compared the images to evaluate the effect of LVA.MethodsPAL was performed using the PAI-05 system in three patients (one man, two women) with lymphedema, including one primary case and two secondary cases, before LVA. ICG fluorescence lymphography was performed in all cases before PAL. Follow-up PAL was performed between 5 days and 5 months after LVA.ResultsPAL enabled the simultaneous visualization of clear lymphatic vessels that could not be accurately seen with ICG fluorescence lymphography and veins. We were also able to observe and analyze morphological changes such as the width and the number of lymphatic vessels and veins during the follow-up PAL after LVA.ConclusionsBy comparing preoperative and postoperative PAL images, it was possible to analyze the morphological changes in lymphatic vessels and veins that occurred after LVA. Our study suggests that PAL would be useful when assessing the effect of LVA surgery.

Negative regulation of lymphangiogenesis by tenascin‐C controls the resolution of inflammation

<Introduction> It has become apparent that the lymphangiogenic factors such as VEGF-C promote lymphangiogenesis during inflammation to resolve inflammatory responses. On the other hand, the anti-lymphangiogenic factors themselves or their roles during inflammation remain unclear. We herein investigated the functional role of anti-lymphangiogenic factors during inflammation and the molecular mechanisms of anti-lymphangiogenesis. <Methods> To clarify the relationships between anti-lymphangiogenic factors and lymphatic vessels during inflammation, we used several mouse models of inflammatory diseases in vivo. To clarify the molecular signaling associated with anti-lymphangiogenesis, we used human dermal lymphatic endothelial cells (HDLEC) in vitro. <Results> Tenascin-C (TNC) is an extracellular matrix protein that is transiently expressed during the early phase of inflammation. In a mouse model of lymphedema or auto-immune myocarditis, the number of lymphatic vessels increased in TNC-negative area or after the expression of TNC decreased. The genetic deletion of TNC promoted lymphangiogenesis and accelerated the resolution of inflammation in a model of lymphedema or auto-immune myocarditis, while its exogenous addition inhibited lymphangiogenesis and prolonged inflammation in a model of lymphedema. Furthermore, genetic deletion of TNC promoted lymphangiogenesis in a model of peritonitis and exogenous addition of TNC inhibited lymphangiogenesis in mouse ear sponge assay. These results confirmed that TNC directly inhibited the growth of lymphatic vessels and prolonged inflammatory responses in various tissues and in adapted as well as innate immunity. We also demonstrated that genetic deletion of TNC unaffected the density of lymphatic vessels in various tissues under normal condition. Thus, the negative regulation of lymphangiogenesis by TNC was limited to pathological conditions. We further explored the molecular mechanisms of anti-lymphangiogenesis by TNC. In lymphatic endothelial cells, TNC inhibited proliferation, promoted apoptosis, and disturbed tube formation via p38 MAPK and ATF2 signaling in vitro. TNC bound to integrin αv and increased the expression of integrin αvβ1 heterodimer, which phosphorylates FAK and SRC. Furthermore, TNC induced clustering of TGF-β receptor type II and integrin β1 to activate p38 MAPK via TAK1, known as non-canonical TGF-β signaling. <Conclusion> In conclusion, the present study confirmed that TNC, as a negative regulator, inhibits lymphangiogenesis in the early phase of inflammation. The p38 MAPK/ ATF-2 pathway is involved in mediating the negative effects of TNC on lymphatic endothelial cells, and clustering of TGF-β receptors and integrin β1 by TNC was required for the activation of p38 MAPK via TAK1. TNC may restrict the growth of lymphatic vessels in active inflammatory lesions to induce the accumulation of immune cells or fluid containing growth factors.

Increased secretion of VEGF-C from SiO2-induced pulmonary macrophages promotes lymphangiogenesis through the Src/eNOS pathway in silicosis

Silicosis, a type of lung inflammation and fibrosis caused by long-term inhalation of SiO2 particles, lacks effective treatment currently. Based on the results of our previous animal experiments, in lungs of SiO2-induced silicosis rats, a large number of lymphatic vessels are generated in the early stage of inflammation, which is of great significance for the removal of dust and inflammatory mediators. Here, the molecular mechanism of lymphangiogenesis is further studied. Vascular endothelial growth factor (VEGF-C) is a key pro-lymphangiogenic factor, and its elevated expression is closely related to lymphangiogenesis. In this investigation, we demonstrated that the protein level of VEGF-C was differentially expressed in bronchoalveolar lavage fluid (BALF) and alveolar macrophages (AM) in silicosis patients and healthy controls. We further stimulated human monocyte-macrophage line U937 with SiO2, collected the culture supernatants as conditioned medium (CM) for culturing lymphatic endothelial cells (LECs) in vitro, and observed the expression of VEGF-C in the supernatant and its effect on LEC tube formation. The results showed that both CM and single VEGF-C recombinant protein stimulation significantly enhanced LEC proliferation [(1.80 ± 0.18), (1.73 ± 0.16)], chemotaxis [chemotactic cell number (101.40 ± 13.83), (93.40 ± 9.61)], and tube formation [tube number (32.20 ± 7.26), (25.00 ± 6.25); branch number (77.20 ± 6.80), (84.60 ± 7.90)], whereas CM treated with VEGF-CmAb inhibited the proliferation (1.37 ± 0.17), chemotaxis [chemotactic cell number (57.40 ± 8.62)], and tube formation [tube number (7.40 ± 1.85); branch number (47.20 ± 13.44)] of LECs. In addition, CM and VEGF-C can promote the expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in LECs, which may further mediate lymphangiogenesis by up-regulating the Src/eNOS downstream signaling molecular pathway. This study is the first to clarify the molecular mechanism of pulmonary lymphangiogenesis in silicosis and may point in the direction of eventual treatments, surveillance, and regulation at a molecular level.

Effects of inhibition of lymphangiogenesis by the vascular endothelial growth factor receptor 3 (VEGFR-3) inhibitor, MAZ51 on full thickness wounds in mice

We herein used MAZ51 to inhibit lymphangiogenesis and aimed to clarify the effect of inhibition of lymphangiogenesis on wound healing. BALB/c male mice were divided into two groups: the control group which was injected the dimethyl sulfoxide (DMSO), the experiment group was injected MAZ51 in the DMSO. All wounds were observed for 15 days and the wound areas were measured. Tissue samples were harvested on day 3, 7, 9, 11, 13 and 15, and subjected to immunostaining of blood vessels and lymphatic vessels. There are no significant differences between two groups in the wound area, the number of blood vessels and lymphatic vessels. The number of blood vessels peaked on day 7 in both groups as with previous studies, while the number of lymphatic vessels peaked on 13 or 15 in both groups. This result revealed delayed lymphangiogenesis in comparison with previous studies. The wound healing process in the control and experiment groups were similar, but both groups seemed delayed lymphangiogenesis comparing with previous studies. Injections of MAZ51 or/and DMSO did not affect angiogenesis, while they may affect lymphangiogenesis.

Multi-segment lymphatic vessel model based on lattice Boltzmann method

The lymphatic system plays an important part in the body’s immunity and cell’s internal environment homeostasis. Like a blood circulatory system, the lymphatic system is a piping system throughout the body, which is composed mainly of lymphatic fluid and lymphatic vessels. The spontaneous contraction of the lymphatic vessels drives the flow of lymphatic fluid in the vessels. The spontaneous contraction-relaxation mechanism of lymphatic vessels is determined by the oscillating feedback of Ca&lt;sup&gt;2+&lt;/sup&gt; concentration and NO concentration. The distribution of NO in the vessels plays an important role in the contraction cycle of lymphatic vessels. The shear force acting on the lymphatic valves due to the flow of fluid is the main source of NO. In a real system, the distribution of NO in a certain section of lymphatic vessel will be affected by other lymphanion connected to it, especially the upstream connecting fragments. Through the lattice Boltzmann method, a multi-segment lymphatic vessel model with valve structure is established, which reproduces the feedback mechanism of Ca&lt;sup&gt;2+&lt;/sup&gt; and NO, valve change and fluid flow. There are three types of lymphatic vessels in the model, namely the initial lymphatic vessel, the collecting lymphatic vessel, and the outlet lymphatic vessel. The number of lymphatic vessels can be unlimited and inputted by the parameters. The number of lymphatic vessels is 3－5, and there are two pairs of valves in each lymphatic vessel. In this paper studied are the distribution of NO and pressure in multi-segment lymphatic vessel, and the change in the flow of each vessel in the three-segment vessel model over time.

Magnetic resonance lymphography as three-dimensional navigation for lymphaticovenular anastomosis in patients with leg lymphedema

Precise mapping of functional lymphatic vessels is essential for successful lymphaticovenular anastomosis (LVA). This study aimed to clarify the precision of magnetic resonance lymphography (MRL) in detecting lymphatic vessels prior to LVA. Eighteen patients with leg lymphedema were recruited for this prospective study. All patients underwent MRL before LVA to obtain three-dimensional coordinates of lymphatic vessels from MRL images. The precision of MRL for detecting lymphatic vessels was evaluated and compared with those of other contrast techniques. Twenty legs from 18 patients were analyzed. A total of 40 skin incisions were made, 32 of which were determined by MRL. The precision of MRL to detect lymphatic vessels was 94%. With the addition of MRL, the number of lymphatic vessels identified preoperatively was increased as compared with indocyanine green lymphography (ICG-L) alone. Assuming a detection sensitivity of MRL for lymphatic vessels of 1, those of other contrast techniques were 0.90 for ICG-L under microscopy, 0.73 for patent blue staining, and 0.43 for ICG-L before incision. Whereas ICG-L before incision could not detect lymphatic vessels at depths greater than 17.0 mm, all deeper anastomosed lymphatic vessels were identified by MRL. Lymphatic vessels enhanced on MRL can be reliably identified intraoperatively. MRL is a promising preoperative examination in LVA that can selectively depict suitable lymphatic vessels even in deep tissue layers.

Detection and prognostic value of intratumoral and peritumoral lymphangiogenesis in colorectal cancer.

BackgroundColorectal cancer (CRC) with lymphatic invasion is one of the critical prognostic factors in lymph node metastasis. Lymphangiogenesis has a significant effect on lymphatic metastasis and tumor progression. However, the significance of intratumoral and peritumoral lymphangiogenesis has been controversial in CRC. The aim of this study is to investigate the different role of introtumoral and peritumoral lymphangiogenesis in CRC progression and prognosis.MethodsLymphangiogenesis of 120 CRC specimens, as measured by lymphatic vessel density (LVD), was examined by immunostaining for podoplanin, a lymphatic vessel-specific marker. The mean number of lymphatic vessels of three hotspots was measured in intratumoral and peritumoral areas as intratumoral LVD (LVDit) and peritumoral LVD (LVDpt), respectively. The association of LVDit and LVDpt with the clinicopathological findings and prognosis was investigated.ResultsCompared to the peritumoral lymphatics, the intratumoral lymphatics were small, collapsed and irregular. The mean LVDpt was higher than the mean LVDit (P<0.001). LVDit was positively correlated with tumor size (P=0.009), tumor histologic grade (P=0.023), and overall survival (P=0.036). LVDpt was correlated with lymph node metastasis (P<0.001), tumor stage (P=0.004), and overall survival (P=0.016).ConclusionsLVDpt plays a prominent role in lymph node metastasis, whereas LVDit is more closely correlated with tumor growth and histopathological differentiation. Both LVDpt and LVDit contribute to CRC progression and prognosis.

Abstract 377: The Role of Impaired Lymphatic Drainage in Cardiac Transplantation

Functional lymphatic drainage inherently modulates cardiac function by maintaining the immune response and tissue-fluid homeostasis. During cardiac transplantation, the lymphatic collecting vessels are severed at the time of heart excision and not surgically reconstructed in the recipient. The consequence resulting from impaired lymphatic drainage in transplanted hearts is unknown. We hypothesize disruption of lymphatic drainage potentiates chronic inflammation by impeding the egress of immune cells and pro-inflammatory cytokines out of the myocardium exacerbating transplant rejection. Methods: Banked human allograft biopsies were utilized to retrospectively evaluate lymphatic differences between patients that did and did not develop chronic transplant rejection from 1 week to 5 years after surgery. Immunofluorescence staining permitted quantification of normalized lymphatic vessel number and area throughout the lifespan of each cardiac allograft (n=24). Autopsy patients with non-cardiac related fatalities served as controls to delineate normal cardiac lymphatic distribution (n=6). Results: Patients without chronic rejection displayed an initial presence of lymphatic vasculature that steadily declined (n=12), while patients with chronic rejection exhibited a delayed increase in lymphatic development (n=12). Conclusions: These data show significant differences in lymphatic area between patients with and without chronic transplant rejection at critical timepoints, suggesting delayed lymphangiogenesis may correlate with rejection. Translational Impact: These preliminary human data support further investigation into lymphatic-modifying therapeutics to prolong the life of cardiac allografts.

Prevention of Prolonged Lymphorrhea in Minor Pectoral Myoplasty in Women after Breast Cancer Surgery: Anatomical and Physiological Aspects

Introduction. Surgery remains the main method of treatment for breast cancer patients. However, in surgery a large number of lymphatic vessels are crossed which inevitably leads to a lymph flow damage. The article discusses the problem of lymphorrhea in breast cancer patients after the radical mastectomy and radical resection. The aim of the study was to assess the effectiveness of minor pectoral myoplasty in the axillary region of the "dead space" for lymphorrhea prevention after radical mastectomy and radical resection.Methods. The case group included 30 patients who underwent 30 surgeries with myoplasty of pectoralis minor (Maddens radical mastectomy or radial resection) in the Tver Oncological Center at the Department of breast pathology from 2016 to 2017. The control group included 30 patients who underwent Maddens mastectomy or radical resection without myoplasty (conventional option).Results. In the case group, during the mastectomy, the patients with lymphorrhea had the drainage removed on the 5,31,2 day. The total amount of the drainage was around 235,43,6 ml. The average daily volume of the drained liquid was 47,12,7 ml. In the control group, during the radical mastectomy without myoplasty, the drainage was removed on the 12,71,4 day. The average total amount of the drained liquid was 1691,632,5 ml. The average daily drained volume was 130,32,5 ml.The patients after radical resection in the case group had the drainage removed on the 5,21,2 day. The total amount of the drained liquid in patients with lymphorrhea was 25 ml/day. The total amount of the drained liquid was 223,711,3 ml. The average daily drained volume was 44,62,3 ml. The patients after radical resection in the control group had the drainage removed on the 11,22,0 day. The average total volume of the drained liquid was 835,526,4 ml. The average daily drained volume was 69,92,2 ml.Conclusion. Application of A. Kh. Ismagilov intraoperative technique dead space closure in minor pectoral myoplasty (patent No. 2385673, issued April 10, 2010) with the simultaneous application of compression garments appears to be a simple and effective method for reducing postoperative lymphorrhea. Myoplasty was effective in reducing lymphorrhea regardless of the type of surgical intervention (radical mastectomy or radical resection). Lymphorrhea duration reduced in more than 2 times.