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Sample records for lymphatic metastasis based

  1. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

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    Metcalfe Chris

    2010-05-01

    Full Text Available Abstract Background Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB, which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group. Methods Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators. Results The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis was also effective when combined into the Shields index in a cohort of 24 patients. Conclusions These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.

  2. Prediction of lymphatic metastasis based on gene expression profile analysis after brachytherapy for early-stage oral tongue carcinoma

    International Nuclear Information System (INIS)

    Watanabe, Hiroshi; Mogushi, Kaoru; Miura, Masahiko; Yoshimura, Ryo-ichi; Kurabayashi, Tohru; Shibuya, Hitoshi; Tanaka, Hiroshi; Noda, Shuhei; Iwakawa, Mayumi; Imai, Takashi

    2008-01-01

    Background and purpose: The management of lymphatic metastasis of early-stage oral tongue carcinoma patients is crucial for its prognosis. The purpose of this study was to evaluate the predictive ability of lymphatic metastasis after brachytherapy (BRT) for early-stage tongue carcinoma based on gene expression profiling. Patients and methods: Pre-therapeutic biopsies from 39 patients with T1 or T2 tongue cancer were analyzed for gene expression signatures using Codelink Uniset Human 20K Bioarray. All patients were treated with low dose-rate BRT for their primary lesions and underwent strict follow-up under a wait-and-see policy for cervical lymphatic metastasis. Candidate genes were selected for predicting lymph-node status in the reference group by the permutation test. Predictive accuracy was further evaluated by the prediction strength (PS) scoring system using an independent validation group. Results: We selected a set of 19 genes whose expression differed significantly between classes with or without lymphatic metastasis in the reference group. The lymph-node status in the validation group was predicted by the PS scoring system with an accuracy of 76%. Conclusions: Gene expression profiling using 19 genes in primary tumor tissues may allow prediction of lymphatic metastasis after BRT for early-stage oral tongue carcinoma

  3. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

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    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and

  4. Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

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    Christianson, Dawn R; Dobroff, Andrey S; Proneth, Bettina; Zurita, Amado J; Salameh, Ahmad; Dondossola, Eleonora; Makino, Jun; Bologa, Cristian G; Smith, Tracey L; Yao, Virginia J; Calderone, Tiffany L; O'Connell, David J; Oprea, Tudor I; Kataoka, Kazunori; Cahill, Dolores J; Gershenwald, Jeffrey E; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2015-02-24

    Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

  5. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

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    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  6. An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery.

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    Chen, Qian; Liang, Chao; Wang, Xin; He, Jingkang; Li, Yonggang; Liu, Zhuang

    2014-11-01

    A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a 'photothermal ablation assisted surgery' strategy, promising for future clinical cancer treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

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    Cao, R.H.; Bjorndahl, M.A.; Religa, P.

    2006-01-01

    This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

  8. Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

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    Kim Wun-Jae

    2011-04-01

    Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

  9. [Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

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    Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

    2018-02-09

    Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( Psquamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

  10. Treatment of lymphatic nodes metastasis in advanced cancer with interventional chemotherapy combined radiotherapy

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    Xia Shian; Guo Weijian; Wu Guohua; Lin Qing; Jiang Mawei; Yao Yuan

    2000-01-01

    Objective: To evaluate the clinical effects of treatment with interventional chemotherapy combined radiotherapy for lymphatic nodes metastasis in advanced cancer. Methods: Treated with interventional chemotherapy for 27 cases of lymphatic rode metastasis once a month with average 2-3 times totally. Simultaneously treated with linear accelerator radiotherapy with average dose of 40-50 Gy/20-25 times/4-5 weeks. Results: To evaluate the clinical effects after finished the whole treatment program two months later. CR + PR reached 77.8% (24/27). All patients showed tolerance to accept the treatment. Conclusion: Treatment for lymphatic node metastasis in advanced cancer with interventional chemotherapy combined radiation therapy seems to be a valuable way

  11. Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles.

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    Zhuang, Zhang; Jian, Pan; Longjiang, Li; Bo, Han; Wenlin, Xiao

    2010-02-01

    Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients. We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray-based expression profiles between them were also compared, and a panel of differential genes was validated using real-time-PCR. In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary-like structures. Moreover, microarray-based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells. These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis-related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.

  12. Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

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    Rui-Cheng Ji

    2016-12-01

    Full Text Available The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs. Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs. Several molecules, e.g., S1P, CCR7-CCL19/CCL21, CXCL12/CXCR4, IL-7, IFN-γ, TGF-β, and integrin α4β1 play an important role in controlling the activity of LN stromal cells including LECs, fibroblastic reticular cells (FRCs and follicular dendritic cells (DCs. The functional stromal cells are critical for reconstruction and remodeling of the LN that creates a unique microenvironment of tumor cells and LECs for cancer metastasis. LN metastasis is a major determinant for the prognosis of most human cancers and clinical management. Ongoing work to elucidate the function and molecular regulation of LN lymphatic sinuses will provide insight into cancer development mechanisms and improve therapeutic approaches for human malignancy.

  13. Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis

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    Aula Ammar

    2011-01-01

    Full Text Available Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1 in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC, CD209 (immature DC, iDC and CD68 (macrophage, M&phis;. in vitro expression of CLEVER-1 on lymphatic (LEC and blood endothelial cells (BEC was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples, lymphatic vessels (LV, 18.2% of samples and in M&phis;/DCs (82.4% of samples. However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027 and with M&phis; indices (p = 0.021. Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049. The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001 and LV (p = 0.004. Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.

  14. Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma

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    Hongming Teng

    2015-06-01

    Full Text Available Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways.

  15. Human Papilloma Virus: Prevalence, distribution and predictive value to lymphatic metastasis in penile carcinoma

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    Aluizio Goncalves da Fonseca

    2013-07-01

    Full Text Available Objectives To evaluate the prevalence, distribution and association of HPV with histological pattern of worse prognosis of penile cancer, in order to evaluate its predictive value of inguinal metastasis, as well as evaluation of other previous reported prognostic factors. Material and Methods Tumor samples of 82 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR. HPV status was correlated to histopathological factors and the presence of inguinal mestastasis. The influence of several histological characteristics was also correlated to inguinal disease-free survival. Results Follow-up varied from 1 to 71 months (median 22 months. HPV DNA was identified in 60.9% of sample, with higher prevalence of types 11 and 6 (64% and 32%, respectively. There was no significant correlation of the histological characteristics of worse prognosis of penile cancer with HPV status. Inguinal disease-free survival in 5 years did also not show HPV status influence (p = 0.45. The only independent pathologic factors of inguinal metastasis were: stage T ≥ T1b-T4 (p = 0.02, lymphovascular invasion (p = 0.04 and infiltrative invasion (p = 0.03. conclusions HPV status and distribution had shown no correlation with worse prognosis of histological aspects, or predictive value for lymphatic metastasis in penile carcinoma.

  16. The clinical application of ultrasonography-guided percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent for the treatment of hilar lymphatic metastasis

    International Nuclear Information System (INIS)

    Zhao Guangsheng; Zhang Yuewei; Yang Xiaohong; Li Chuang; Zhao Mu; Wang Wenqing; Wang Ruoyu

    2010-01-01

    Objective: To discuss the technique and the clinical effect of ultrasonography-guided percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent for the treatment of hepatic hilar lymphatic metastasis. Methods: Under ultrasonographic guidance,percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent, so-called chemo-ablation, into the diseased lymph nodes was performed in thirteen patients with hepatic hilar lymphatic metastasis. The therapeutic results were evaluated based on the post-operative imaging examinations as well as the alleviation of the clinical symptoms. Results: Percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent into the diseased lymph nodes was successfully carried out in all thirteen patients. After the procedure,the patients were followed up for a mean period of 13.5 months. The therapeutic effectiveness was 100%, while the regression rate of the lesions was 76.9%. No operation-related complications occurred. Conclusion: Percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent into the diseased lymph nodes under ultrasonographic guidance is an effective and safe treatment for hepatic hilar lymphatic metastasis with reliable effectiveness. (authors)

  17. Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification.

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    Mermod, Maxime; Bongiovanni, Massimo; Petrova, Tatiana V; Dubikovskaya, Elena A; Simon, Christian; Tolstonog, Genrich; Monnier, Yan

    2016-09-01

    The use of lymphatic vessel density as a predictor of occult lymph node metastasis (OLNM) in head and neck squamous cell carcinoma (HNSCC) has never been reported. Staining of the specific lymphatic endothelial cells nuclear marker, PROX1, as an indicator of lymphatic vessel density was determined by counting the number of positive cells in squamous cell carcinomas (SCCs) of the oral cavity and the oropharynx with clinically negative necks. Correlation with histopathological data was established. Peritumoral PROX1 lymphatic nuclear count significantly correlated with the detection of OLNM in multivariate analysis (p oral cavity and the oropharynx allows accurate prediction of occult lymph node metastasis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1407-1415, 2016. © 2016 Wiley Periodicals, Inc.

  18. Z-100, an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma.

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    Horii, Takayuki; Yoshinaga, Koji; Kobayashi, Nobuyoshi; Seto, Koichi; Orikawa, Yuki; Okamoto, Masahiro; Eta, Runa; Ohira, Yuta; Katsunuma, Kokichi; Hori, Yuko; Tanaka, Takao; Takei, Mineo

    2014-01-01

    Lymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan. Here, we investigated the inhibitory effect of Z-100 on spontaneous lymphatic metastasis. C57BL/6N mice injected subcutaneously with B16-BL6 melanoma cells in the right hind footpad were administered Z-100 subcutaneously in the right inguinal region on a daily basis. On day twenty-one after the injection, the right inguinal lymph nodes were excised, and the extent of metastasis, the number of immune cells, and the amount of granzyme B protein in the lymph nodes were examined. We also investigated the combined effect of Z-100 and irradiation in this model. Results showed that Z-100 reduced number of animals with metastasis, with respective metastasis rates of 85.7%, 42.9%, 7.1% and 0.0% in saline, 0.1 mg/kg Z-100, 1 mg/kg Z-100 and 10 mg/kg Z-100 group. Further, mice that had been given Z-100 were found to have more immune cells and granzyme B protein in the lymph nodes than control mice. The combination of low dose Z-100 and irradiation also inhibited spontaneous lymph node metastases. These findings suggest that Z-100 may be beneficial in preventing lymphatic metastasis by enhancing the immune response.

  19. EVALUATION OF LYMPHATIC SPREAD, VISCERAL METASTASIS AND TUMORAL LOCAL INVASION IN ESOPHAGEAL CARCINOMAS.

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    Tustumi, Francisco; Kimura, Cintia Mayumi Sakurai; Takeda, Flavio Roberto; Sallum, Rubens Antônio Aissar; Ribeiro-Junior, Ulysses; Cecconello, Ivan

    2016-01-01

    Knowing esophageal tumors behavior in relationship to lymph node involvement, distant metastases and local tumor invasion is of paramount importance for the best esophageal tumors management. To describe lymph node involvement, distant metastases, and local tumor invasion in esophageal carcinoma, according to tumor topography and histology. A total of 444 patients with esophageal squamous cell carcinoma and 105 adenocarcinoma were retrospectively analyzed. They were divided into four groups: adenocarcinoma and squamous cell carcinoma in the three esophageal segments: cervical, middle, and distal. They were compared based on their CT scans at the time of the diagnosis. Nodal metastasis showed great relationship with of primary tumor site. Lymph nodes of hepatogastric, perigastric and peripancreatic ligaments were mainly affected in distal tumors. Periaortic, interaortocaval and portocaval nodes were more commonly found in distal squamous carcinoma; subcarinal, paratracheal and subaortic nodes in middle; neck chains were more affected in cervical squamous carcinoma. Adenocarcinoma had a higher frequency of peritoneal involvement (11.8%) and liver (24.5%) than squamous cell carcinoma. Considering the local tumor invasion, the more cranial neoplasia, more common squamous invasion of airways, reaching 64.7% in the incidence of cervical tumors. Middle esophageal tumors invade more often aorta (27.6%) and distal esophageal tumors, the pericardium and the right atrium (10.4%). Esophageal adenocarcinoma and squamous cell carcinoma in different topographies present peculiarities in lymph node involvement, distant metastasis and local tumor invasion. These differences must be taken into account in esophageal cancer patients' care. Conhecer o comportamento das neoplasias esofágicas em relação à disseminação linfonodal, distribuição de metástases e invasão local do tumor, pode auxiliar o manejo dos pacientes. Descrever o envolvimento linfonodal, disseminação metast

  20. Nuclear medicine in breast cancer diagnostics: Primary tumor and lymphatic metastasis

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    Sinilkin, I.; Medvedeva, A.; Chernov, V.; Slonimskaya, E.; Zelchan, R.; Bragina, O.

    2017-09-01

    The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer.

  1. RIP1 regulates TNF-α-mediated lymphangiogenesis and lymphatic metastasis in gallbladder cancer by modulating the NF-κB-VEGF-C pathway.

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    Li, Cheng-Zong; Jiang, Xiao-Jie; Lin, Bin; Hong, Hai-Jie; Zhu, Si-Yuan; Jiang, Lei; Wang, Xiao-Qian; Tang, Nan-Hong; She, Fei-Fei; Chen, Yan-Ling

    2018-01-01

    Tumor necrosis factor alpha (TNF-α) enhances lymphangiogenesis in gallbladder carcinoma (GBC) via activation of nuclear factor (NF-κB)-dependent vascular endothelial growth factor-C (VEGF-C). Receptor-interacting protein 1 (RIP1) is a multifunctional protein in the TNF-α signaling pathway and is highly expressed in GBC. However, whether RIP1 participates in the signaling pathway of TNF-α-mediated VEGF-C expression that enhances lymphangiogenesis in GBC remains unclear. The RIP1 protein levels in the GBC-SD and NOZ cells upon stimulation with increasing concentrations of TNF-α as indicated was examined using Western blot. Lentiviral RIP1 shRNA and siIκBα were constructed and transduced respectively them into NOZ and GBC-SD cells, and then PcDNA3.1-RIP1 vectors was transduced into siRIP1 cell lines to reverse RIP1 expression. The protein expression of RIP1, inhibitor of NF-κB alpha (IκBα), p-IκBα, TAK1, NF-κB essential modulator were examined through immunoblotting or immunoprecipitation. Moreover, VEGF-C mRNA levels were measured by quantitative real-time polymerase chain reaction, VEGF-C protein levels were measured by immunoblotting and enzyme-linked immunosorbent assay, and VEGF-C promoter and NF-κB activities were quantified using a dual luciferase reporter assay. The association of NF-κB with the VEGF-C promoter was analysed by chromatin immunoprecipitation assay. A three-dimensional coculture method and orthotopic transplantation nude mice model were used to evaluate lymphatic tube-forming and metastasis ability in GBC cells. The expression of RIP1 protein, TNF-α protein and lymphatic vessels in human GBC tissues was examined by immunohistochemistry, and the dependence between RIP1 protein with TNF-α protein and lymphatic vessel density was analysed. TNF-α dose- and time-dependently increased RIP1 protein expression in the GBC-SD and NOZ cells of GBC, and the strongest effect was observed with a concentration of 50 ng/ml. RIP1 is fundamental

  2. Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer

    International Nuclear Information System (INIS)

    Wu, Qiu-Wan; She, Hong-Qiang; Liang, Jing; Huang, Yu-Fan; Yang, Qing-Mo; Yang, Qiao-Lu; Zhang, Zhi-Ming

    2012-01-01

    metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer

  3. Hypoxia preconditioning of mesenchymal stromal cells enhances PC3 cell lymphatic metastasis accompanied by VEGFR-3/CCR7 activation.

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    Huang, Xin; Su, Kunkai; Zhou, Limin; Shen, Guofang; Dong, Qi; Lou, Yijia; Zheng, Shu

    2013-12-01

    Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastases through the secretion of chemokines. MSCs have been reported to home toward the hypoxic tumor microenvironment in vivo. In this study, we investigated prostate cancer PC3 cell behavior under the influence of hypoxia preconditioned MSCs and explored the related mechanism of prostate cancer lymphatic metastases in mice. Transwell assays revealed that VEGF-C receptor, VEGFR-3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs. Knock-in Ccr7 in PC3 cells also improved cell migration in vitro. Furthermore, when PC3 cells were labeled using the hrGfp-lentiviral vector, and were combined with hypoxia preconditioned MSCs for xenografting, it resulted in an enhancement of lymph node metastases accompanied by up-regulation of VEGFR-3 and CCR7 in primary tumors. Both PI3K/Akt/IκBα and JAK2/STAT3 signaling pathways were activated in xenografts in the presence of hypoxia-preconditioned MSCs. Unexpectedly, the p-VEGFR-2/VEGFR-2 ratio was attenuated accompanied by decreased JAK1 expression, indicating a switching-off of potential vascular signal within xenografts in the presence of hypoxia-preconditioned MSCs. Unlike results from other studies, VEGF-C maintained a stable expression in both conditions, which indicated that hypoxia preconditioning of MSCs did not influence VEGF-C secretion. Our results provide the new insights into the functional molecular events and signalings influencing prostate tumor metastases, suggesting a hopeful diagnosis and treatment in new approaches. © 2013 Wiley Periodicals, Inc.

  4. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    International Nuclear Information System (INIS)

    Ran, Sophia; Montgomery, Kyle E.

    2012-01-01

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  5. Photoacoustic imaging of lymphatic pumping

    Science.gov (United States)

    Forbrich, Alex; Heinmiller, Andrew; Zemp, Roger J.

    2017-10-01

    The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system.

  6. A study of the area of paraaortic lymph nodes dissection in gastric cancer based on lymphatic flow of the stomach using radioactive isotope

    Energy Technology Data Exchange (ETDEWEB)

    Sasagawa, Tsuyoshi (Tokyo Women' s Medical Coll. (Japan))

    1992-04-01

    In gastric cancer patients, I subdivided paraaortic lymph nodes (No.16) into 4 zones. Using RI lymphography I analyzed the lymphatic flow from the cardiac and pyloric region to the No.16. Also, based on these results as well as studies of clinical lymph node metastasis, I elucidate the rational No.16 area in extended lymph node dissection. The lymphatic flows to the No.16 by RI lymphography showed the following routes. The route from the cardiac region was: (1) along the left gastric artery heading towards lymph node around the celiac artery and into the left/right No.16; (2) along the posterior gastric artery and splenic artery from lymph node around the splenic artery directly to the left No.16; (3) along the inferior phrenic artery from left cardiac lymph node and lymph node at the splenic hilus directly to the left upper No.16. The route from the pyloric region was: (1) along the common hepatic artery heading towards lymph node around the celiac artery to the left/right No.16; (2) from infrapyloric lymph node along the gastrocolic trunc flowing to lymph node at the root of the mesenterium and No.16. In upper gastric cancer, there was a high rate of metastasis to lymph node along the lesser curvature and right cardial lymph node, and lymph node along the left gastric artery and splenic artery. There were 3 cases in which metastasis was positive only to cardial lymph node and upper left No.16. In lower gastric cancer, there was a high rate of metastasis to infrapyloric lymph node, lymph node along the lesser curvature, lymph node along the left gastric artery and the common hepatic artery. In all cases which metastasized in group 4, the No.16 metastasis rate was significantly higher in the upper left No.16, being 84.8%. Given the above, the area of paraaortic lymph node dissection in extended lymph node dissection, irrespective of whether it is upper or lower gastric cancer, must be done in the 4 zones, and especially, the upper left No.16 is important. (author).

  7. An evidence-based analysis of epidemiologic associations between lymphatic and hematopoietic cancers and occupational exposure to gasoline.

    Science.gov (United States)

    Keenan, J J; Gaffney, S; Gross, S A; Ronk, C J; Paustenbach, D J; Galbraith, D; Kerger, B D

    2013-10-01

    The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough understanding of this issue is important. The current study utilizes an evidence-based approach to examine whether or not the available epidemiologic studies demonstrate a strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers. Among 67 epidemiologic studies initially identified, 54 were ranked according to specific criteria relating to the relevance and robustness of each study for answering the research question. The 30 highest-ranked studies were sorted into three tiers of evidence and were analyzed for strength, specificity, consistency, temporality, dose-response trends and coherence. Meta statistics were also calculated for each general and specific lymphatic/hematopoietic cancer category with adequate data. The evidence-based analysis did not confirm any strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers based on the epidemiologic studies available to date. These epidemiologic findings, combined with the evidence showing relatively low occupational benzene vapor exposures associated with gasoline formulations during the last three decades, suggest that current motor gasoline formulations are not associated with increased lymphatic/hematopoietic cancer risks related to benzene.

  8. Data base management system for lymphatic filariasis--a neglected tropical disease.

    Science.gov (United States)

    Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Kadiri, Madhusudhan Rao; Kumaraswamy, Sriram; Nelaturu, Sarat Chandra Babu

    2012-01-01

    Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. This database application is developed using Model View Controller (MVC) architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

  9. Lymphatics and Lymphangiogenesis in the Eye

    Directory of Open Access Journals (Sweden)

    Shintaro Nakao

    2012-01-01

    Full Text Available Lymphatic is a prerequisite for the maintenance of tissue fluid balance and immunity in the body. A body of evidence also shows that lymphangiogenesis plays important roles in the pathogenesis of diseases such as tumor metastasis and inflammation. The eye was thought to lack lymphatic vessels except for the conjunctiva; however, advances in the field, including the identification of lymphatic endothelial markers (e.g., LYVE-1 or podoplanin and lymphangiogenic factors (e.g., VEGF-C, have revealed the exsitence and possible roles of lymphatics and lymphangiogenesis in the eye. Recent studies have shown that corneal limbus, ciliary body, lacrimal gland, orbital meninges, and extraocular muscles contain lymphatic vessels and that the choroid might have a lymphatic-like system. There is no known lymphatic outflow from the eye. However, several lymphatic channels including uveolymphatic pathway might serve the ocular fluid homeostasis. Furthermore, lymphangiogenesis plays important roles in pathological conditions in the eye including corneal transplant rejection and ocular tumor progression. Yet, the role of lymphangiogenesis in most eye diseases, especially inflammatory disease or edema, remains unknown. A better understanding of lymphatic and lymphangiogenesis in the eye will open new therapeutic opportunities to prevent vision loss in ocular diseases.

  10. Lymphatic Education & Research Network

    Science.gov (United States)

    Lymphatic Education & Research Network Donate Now Become a Supporting Member X Living with LYMPHEDEMA AND Lymphatic Disease FAQs About ... December 8, 2017 11.08.2017 The Lymphatic Education & Research Network… Read More > ASRM LE&RN Combined ...

  11. Data base management system for lymphatic filariasis--a neglected tropical disease.

    Directory of Open Access Journals (Sweden)

    Suryanaryana Murty Upadhyayula

    Full Text Available BACKGROUND: Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. METHODS: This database application is developed using Model View Controller (MVC architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. CONCLUSION: The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

  12. Lymphatic drainage and efficiency of computed tomography in the detection of lymph node metastasis in NO stage patients with squamous cell carcinoma of the mouth and oropharynx

    International Nuclear Information System (INIS)

    Freire, Addah Regina da Silva; Kowalski, Luiz Paulo

    2002-01-01

    Clinical examination alone is not sufficient to precisely evaluated lymph node involvement in head and neck cancer. The results of computed tomography on the neck and lymphoscintigraphy were evaluated in 21 patients with carcinoma of the mouth and oropharynx staged NO. Nine patients were treated by homolateral and 12 by bilateral neck dissection. Sensitivity and specificity of computed tomography were 16% and 73% for homolateral side and 0% and 90% for contralateral side, respectively. Lymphatic drainage was observed in 76.2% of the cases. No-migration was associated with cases involving the retromollar region and tonsillar fossa, where injection of the 99m Tc-Dextran 500 is more difficult. Bilateral migration occurred only in carcinomas of the floor of the mouth, with involvement of the midline. From these results it was concluded that computed tomography was less efficient than clinical examination. Nevertheless it must be considered that conventional computed tomography was used. We are currently undertaking similar studies with helical computed tomography. Lymphoscintigraphy showed promising results, and the same method to evaluated sentinel lymph nodes in patients with carcinoma of the mouth is being used. (author)

  13. [Pleural lymphatics and effusions].

    Science.gov (United States)

    Mordant, P; Arame, A; Legras, A; Le Pimpec Barthes, F; Riquet, M

    2013-06-01

    The pleural lymphatic system has a great absorption capacity. Its most known function is fluid resorption. The pleura which cover the lungs (visceral pleura), the mediastinum, diaphragm and thoracic wall (parietal pleura) are formed by a mesothelial cell layer (mesothelium). This permeable layer is in direct contact with the vascular endothelium. The mesothelium is based over a connective tissue (interstitium) containing the blood and lymphatic vessels. The primary lymphatic vessels drain interstitium but are also in direct contact with pleural space by the stoma or openings, situated in the lower parts of parietal pleura, i.e: diaphragm, over lower ribs and mediastinum but not existing in the adjacent visceral pleura. In addition, a part of interstitial pulmonary fluid entered in the pleural cavity by passing the visceral pleura would be absorbed by these openings. The resorption process is active and directly related to the function of smooth muscles of lymphatic vessels. Besides resorption, we must emphasize that this "pumping" activity is permanent and the origin of negative pressure (the pleural void) in pleural cavity, a unique property. The other resorbed elements are molecules, bacterial and cellular debris, cells, red blood and cancer cells. Copyright © 2013. Published by Elsevier Masson SAS.

  14. Imaging of the interaction of cancer cells and the lymphatic system.

    Science.gov (United States)

    Tran Cao, Hop S; McElroy, Michele; Kaushal, Sharmeela; Hoffman, Robert M; Bouvet, Michael

    2011-09-10

    A thorough understanding of the lymphatic system and its interaction with cancer cells is crucial to our ability to fight cancer metastasis. Efforts to study the lymphatic system had previously been limited by the inability to visualize the lymphatic system in vivo in real time. Fluorescence imaging can address these limitations and allow for visualization of lymphatic delivery and trafficking of cancer cells and potentially therapeutic agents as well. Here, we review recent articles in which antibody-fluorophore conjugates are used to label the lymphatic network and fluorescent proteins to label cancer cells in the evaluation of lymphatic delivery and imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro

    International Nuclear Information System (INIS)

    Vigl, Benjamin; Zgraggen, Claudia; Rehman, Nadia; Banziger-Tobler, Nadia E.; Detmar, Michael; Halin, Cornelia

    2009-01-01

    Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity

  16. Lymphatic vessels assessment in feline mammary tumours

    International Nuclear Information System (INIS)

    Sarli, Giuseppe; Sassi, Francesco; Brunetti, Barbara; Rizzo, Antonio; Diracca, Laura; Benazzi, Cinzia

    2007-01-01

    and extramammary stroma was significantly higher than intratumoral and intramammary fields respectively in the NMG, BT and MT. This suggests a scant biological importance of intratumoral lymphatics while their higher number is due to the concentration of existing vessels following compression of the extratumoral stroma in spite of a non demonstrable increase from NMG to MT. The tumour model employed provided no evidence of lymphangiogenesis, and metastasis in the regional lymph node develops following the spread through the pre-existing lymphatic network

  17. Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

    International Nuclear Information System (INIS)

    Matsuno, Akira; Murakami, Mineko; Hoya, Katsumi; Yamada, Shoko M.; Miyamoto, Shinya; Yamada, So; Son, Jae-Hyun; Nishido, Hajime; Ide, Fuyuaki; Nagashima, Hiroshi; Sugaya, Mutsumi; Hirohata, Toshio; Mizutani, Akiko; Okinaga, Hiroko; Ishii, Yudo; Tahara, Shigeyuki; Teramoto, Akira; Osamura, R. Yoshiyuki; Yamazaki, Kazuto; Ishida, Yasuo

    2013-01-01

    Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma

  18. Impact of Education Campaign on Community-Based Vector Control in Hastening the Process of Elimination of Lymphatic Filariasis in Tamil Nadu, South India

    Science.gov (United States)

    Nandha, B.; Krishnamoorthy, K.

    2012-01-01

    Globally mosquito-borne lymphatic filariasis (LF) is targeted for elimination by 2020. Towards this goal, the scope of community-based vector control as a supplementary strategy to mass drug administration (MDA) was assessed through an intensive education campaign and evaluated using pre- and post-educational surveys in an intervention and…

  19. C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.

    Science.gov (United States)

    Kawamata, Futoshi; Homma, Shigenori; Kamachi, Hirofumi; Einama, Takahiro; Kato, Yasutaka; Tsuda, Masumi; Tanaka, Shinya; Maeda, Masahiro; Kajino, Kazunori; Hino, Okio; Takahashi, Norihiko; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru

    2014-01-01

    Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

  20. The prognostic significance of lymphatics in colorectal liver metastases.

    Science.gov (United States)

    Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

    2014-01-01

    Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  1. The Prognostic Significance of Lymphatics in Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Vijayaragavan Muralidharan

    2014-01-01

    Full Text Available Background. Colorectal Cancer (CRC is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%–60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM and surrounding host tissue. Lymphatic vessel density (LVD was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P=0.01, P>0.01, and P=0.05, resp.. Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P=0.05. Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  2. Lymphatic filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Kisinza, William N.

    2013-01-01

    Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA...

  3. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs...

  4. Bone metastasis pattern in initial metastatic breast cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Xiong Z

    2018-02-01

    Full Text Available Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%. Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of

  5. Estimation of lymphatic conductance. A model based on protein-kinetic studies and haemodynamic measurements in patients with cirrhosis of the liver and in pigs

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    1985-01-01

    A model of lymphatic conductivity (i.e. flow rate per unit pressure difference = conductance) based on protein-kinetic and haemodynamic measurements is described. The model is applied to data from patients with cirrhosis and from pigs with different haemodynamic abnormalities in the hepatosplanch......A model of lymphatic conductivity (i.e. flow rate per unit pressure difference = conductance) based on protein-kinetic and haemodynamic measurements is described. The model is applied to data from patients with cirrhosis and from pigs with different haemodynamic abnormalities...... compatible with increased sinusoidal wall tightening and fibrosis in the interstitial space of the liver. The model presented supports the so-called 'lymph-imbalance' theory of ascites formation according to which a relatively insufficient lymph drainage is important in the pathogenesis of hepatic ascites....

  6. Water-stable NaLuF4-based upconversion nanophosphors with long-term validity for multimodal lymphatic imaging.

    Science.gov (United States)

    Zhou, Jing; Zhu, Xingjun; Chen, Min; Sun, Yun; Li, Fuyou

    2012-09-01

    Multimodal imaging is rapidly becoming an important tool for biomedical applications because it can compensate for the deficiencies of individual imaging modalities. Herein, multifunctional NaLuF(4)-based upconversion nanoparticles (Lu-UCNPs) were synthesized though a facile one-step microemulsion method under ambient condition. The doping of lanthanide ions (Gd(3+), Yb(3+) and Er(3+)/Tm(3+)) endows the Lu-UCNPs with high T(1)-enhancement, bright upconversion luminescence (UCL) emissions, and excellent X-ray absorption coefficient. Moreover, the as-prepared Lu-UCNPs are stable in water for more than six months, due to the protection of sodium glutamate and diethylene triamine pentacetate acid (DTPA) coordinating ligands on the surface. Lu-UCNPs have been successfully applied to the trimodal CT/MR/UCL lymphatic imaging on the modal of small animals. It is worth noting that Lu-UCNPs could be used for imaging even after preserving for over six months. In vitro transmission electron microscope (TEM), methyl thiazolyl tetrazolium (MTT) assay and histological analysis demonstrated that Lu-UCNPs exhibited low toxicity on living systems. Therefore, Lu-UCNPs could be multimodal agents for CT/MR/UCL imaging, and the concept can be served as a platform technology for the next-generation of probes for multimodal imaging. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. A Risk Prediction Model Based on Lymph-Node Metastasis in Poorly Differentiated-Type Intramucosal Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Jeung Hui Pyo

    Full Text Available Endoscopic submucosal dissection (ESD for undifferentiated type early gastric cancer is regarded as an investigational treatment. Few studies have tried to identify the risk factors that predict lymph-node metastasis (LNM in intramucosal poorly differentiated adenocarcinomas (PDC. This study was designed to develop a risk scoring system (RSS for predicting LNM in intramucosal PDC.From January 2002 to July 2015, patients diagnosed with mucosa-confined PDC, among those who underwent curative gastrectomy with lymph node dissection were reviewed. A risk model based on independent predicting factors of LNM was developed, and its performance was internally validated using a split sample approach.Overall, LNM was observed in 5.2% (61 of 1169 patients. Four risk factors [Female sex, tumor size ≥ 3.2 cm, muscularis mucosa (M3 invasion, and lymphatic-vascular involvement] were significantly associated with LNM, which were incorporated into the RSS. The area under the receiver operating characteristic curve for predicting LNM after internal validation was 0.69 [95% confidence interval (CI, 0.59-0.79]. A total score of 2 points corresponded to the optimal RSS threshold with a discrimination of 0.75 (95% CI 0.69-0.81. The LNM rates were 1.6% for low risk (<2 points and 8.9% for high-risk (≥2 points patients, with a negative predictive value of 98.6% (95% CI 0.98-1.00.A RSS could be useful in clinical practice to determine which patients with intramucosal PDC have low risk of LNM.

  8. The effect of lymphatic valve morphology on fluid transport

    Science.gov (United States)

    Alexeev, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon

    2016-11-01

    The lymphatic vasculature is present in nearly all invertebrate tissue, and is essential in the transport of fluid and particles such as immune cells, antigens, proteins and lipids from the tissue to lymph nodes and to the venous circulation. Lymphatic vessels are made of up a series of contractile units that work together in harmony as "micro hearts" to pump fluid against a pressure gradient. Lymphatic valves are critical to this functionality, as they open and close with the oscillating pressure gradients from contractions, thus allowing flow in only one direction and leading to a net pumping effect. We use a hybrid lattice-Boltzmann lattice spring model which captures fluid-solid interactions through two-way coupling between a viscous fluid and lymphatic valves in a section of a lymphatic vessel to study the dynamics of lymphatic valves and their effect on fluid transport. Further, we investigate the effect of variations in valve geometry and material properties on fluid pumping. This work helps to increase our understanding of the mechanisms of lymphatic fluid transport, which has implications in a variety of pathologies, including cancer metastasis, autoimmunity, atherosclerosis and obesity. Support from NSF CMMI 1635133 is gratefully acknowledged.

  9. Impact of community-based lymphedema management on perceived disability among patients with lymphatic filariasis in Orissa State, India.

    Directory of Open Access Journals (Sweden)

    Philip J Budge

    Full Text Available Lymphatic filariasis (LF infects approximately 120 million people worldwide. As many as 40 million have symptoms of LF disease, including lymphedema, elephantiasis, and hydrocele. India constitutes approximately 45% of the world's burden of LF. The Indian NGO Church's Auxiliary for Social Action (CASA has been conducting a community-based lymphedema management program in Orissa State since 2007 that aims to reduce the morbidity associated with lymphedema and elephantiasis. The objective of this analysis is to evaluate the effects of this program on lymphedema patients' perceived disability.For this prospective cohort study, 370 patients ≥14 years of age, who reported lymphedema lasting more than three months in one or both legs, were recruited from villages in the Bolagarh sub-district, Khurda District, Orissa, India. The World Health Organization Disability Assessment Schedule II was administered to participants at baseline (July, 2009, and then at regular intervals through 24 months (July, 2011, to assess patients' perceived disability. Disability scores decreased significantly (p<0.0001 from baseline to 24 months. Multivariable analysis using mixed effects modeling found that employment and time in the program were significantly associated with lower disability scores after two years of program involvement. Older age, female gender, the presence of other chronic health conditions, moderate (Stage 3 or advanced (Stage 4-7 lymphedema, reporting an adenolymphangitis (ADL episode during the previous 30 days, and the presence of inter-digital lesions were associated with higher disability scores. Patients with moderate or advanced lymphedema experienced greater improvements in perceived disability over time. Patients participating in the program for at least 12 months also reported losing 2.5 fewer work days per month (p<0.001 due to their lymphedema, compared to baseline.These results indicate that community-based lymphedema management programs

  10. Correlation between theoretical anatomical patterns of lymphatic drainage and lymphoscintigraphy findings during sentinel node detection in head and neck melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Monica; Ruiz, Diana Milena [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Vidal-Sicart, Sergi; Paredes, Pilar; Pons, Francesca [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Institut d' Investigacions Biomediques Agusti Pi i Sunyer (IDIBAPS), Barcelona (Spain); Torres, Ferran [Hospital Clinic Barcelona, Statistical of Biostatistics and Data Management Core Facility, IDIBAPS, Barcelona (Spain); Universitat Autonoma de Barcelona, Biostatistics Unit, Faculty of Medicine, Barcelona (Spain)

    2016-04-15

    In the diagnosis of head and neck melanoma, lymphatic drainage is complex and highly variable. As regional lymph node metastasis is one of the most important prognostic factors, lymphoscintigraphy can help map individual drainage patterns. The aim of this study was to compare the results of lymphoscintigraphy and sentinel lymph node (SLN) detection with theoretical anatomical patterns of lymphatic drainage based on the location of the primary tumour lesion in patients with head and neck melanoma. We also determined the percentage of discrepancies between our lymphoscintigraphy and the theoretical location of nodal drainage predicted by a large lymphoscintigraphic database, in order to explain recurrence and false-negative SLN biopsies. In this retrospective study of 152 patients with head and neck melanoma, the locations of the SLNs on lymphoscintigraphy and detected intraoperatively were compared with the lymphatic drainage predicted by on-line software based on a large melanoma database. All patients showed lymphatic drainage and in all patients at least one SLN was identified by lymphoscintigraphy. Of the 152 patients, 4 had a primary lesion in areas that were not described in the Sydney Melanoma Unit database, so agreement could only be evaluated in 148 patients. Agreement between lymphoscintigraphic findings and the theoretical lymphatic drainage predicted by the software was completely concordant in 119 of the 148 patients (80.4 %, 95 % CI 73.3 - 86 %). However, this concordance was partial (some concordant nodes and others not) in 18 patients (12.2 %, 95 % CI 7.8 - 18.4 %). Discordance was complete in 11 patients (7.4 %, 95 % CI 4.2 - 12.8 %). In melanoma of the head and neck there is a high correlation between lymphatic drainage found by lymphoscintigraphy and the predicted drainage pattern and basins provided by a large reference database. Due to unpredictable drainage, preoperative lymphoscintigraphy is essential to accurately detect the SLNs in head and

  11. Tris-base buffer: a promising new inhibitor for cancer progression and metastasis.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Abrahams, Dominique; Enriquez-Navas, Pedro M; Luddy, Kim; Gatenby, Robert A; Gillies, Robert J

    2017-07-01

    Neutralizing tumor external acidity with oral buffers has proven effective for the prevention and inhibition of metastasis in several cancer mouse models. Solid tumors are highly acidic as a result of high glycolysis combined with an inadequate blood supply. Our prior work has shown that sodium bicarbonate, imidazole, and free-base (but not protonated) lysine are effective in reducing tumor progression and metastasis. However, a concern in translating these results to clinic has been the presence of counter ions and their potential undesirable side effects (e.g., hypernatremia). In this work, we investigate tris(hydroxymethyl)aminomethane, (THAM or Tris), a primary amine with no counter ion, for its effects on metastasis and progression in prostate and pancreatic cancer in vivo models using MRI and bioluminescence imaging. At an ad lib concentration of 200 mmol/L, Tris effectively inhibited metastasis in both models and furthermore led to a decrease in the expression of the major glucose transporter, GLUT-1. Our results also showed that Tris-base buffer (pH 8.4) had no overt toxicity to C3H mice even at higher doses (400 mmol/L). In conclusion, we have developed a novel therapeutic approach to manipulate tumor extracellular pH (pHe) that could be readily adapted to a clinical trial. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. Systematic review of efficacy for manual lymphatic drainage techniques in sports medicine and rehabilitation: an evidence-based practice approach.

    Science.gov (United States)

    Vairo, Giampietro L; Miller, Sayers John; McBrier, Nicole M; Buckley, William E

    2009-01-01

    Manual therapists question integrating manual lymphatic drainage techniques (MLDTs) into conventional treatments for athletic injuries due to the scarcity of literature concerning musculoskeletal applications and established orthopaedic clinical practice guidelines. The purpose of this systematic review is to provide manual therapy clinicians with pertinent information regarding progression of MLDTs as well as to critique the evidence for efficacy of this method in sports medicine. We surveyed English-language publications from 1998 to 2008 by searching PubMed, PEDro, CINAHL, the Cochrane Library, and SPORTDiscus databases using the terms lymphatic system, lymph drainage, lymphatic therapy, manual lymph drainage, and lymphatic pump techniques. We selected articles investigating the effects of MLDTs on orthopaedic and athletic injury outcomes. Nine articles met inclusion criteria, of which 3 were randomized controlled trials (RCTs). We evaluated the 3 RCTs using a validity score (PEDro scale). Due to differences in experimental design, data could not be collapsed for meta-analysis. Animal model experiments reinforce theoretical principles for application of MLDTs. When combined with concomitant musculoskeletal therapy, pilot and case studies demonstrate MLDT effectiveness. The best evidence suggests that efficacy of MLDT in sports medicine and rehabilitation is specific to resolution of enzyme serum levels associated with acute skeletal muscle cell damage as well as reduction of edema following acute ankle joint sprain and radial wrist fracture. Currently, there is limited high-ranking evidence available. Well-designed RCTs assessing outcome variables following implementation of MLDTs in treating athletic injuries may provide conclusive evidence for establishing applicable clinical practice guidelines in sports medicine and rehabilitation.

  13. Lymphatic System Flows

    Science.gov (United States)

    Moore, James E., Jr.; Bertram, Christopher D.

    2018-01-01

    The supply of oxygen and nutrients to tissues is performed by the blood system and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH2O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls. Passive vessel squeezing causes further pumping. The dynamics of lymphatic pumping have been investigated experimentally and mathematically, revealing complex behaviors that indicate that the system performance is robust against minor perturbations in pressure and flow. More serious disruptions can lead to incurable swelling of tissues called lymphedema.

  14. Spleen and Lymphatic System

    Science.gov (United States)

    ... Wrong Print en español El bazo y el sistema linfático The lymphatic system is an extensive drainage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  15. Pleural function and lymphatics.

    Science.gov (United States)

    Negrini, D; Moriondo, A

    2013-02-01

    The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  16. Chapter 20. Lymphatic system

    International Nuclear Information System (INIS)

    Meyniel, G.; Plagne, R.; Veyre, A.

    1975-01-01

    It is recalled than in isotopic lymphography the tracer may be introduced into the lymphatic system by two methods: direct lymphography when the product is injected directly into a lymphatic vessel or lymph node, indirect lymphography when the product is injected into interstitial tissues, taken up by the lymph flow and fixed by the glands. The disadvantages of the direct method at present restrict the radioisotopic exploration of the lymphatic system to indirect lymphography. This technique, whereby the lymphatic draining of the tracer injection zone may be followed, is described. The use of metallic colloids (Au-198, In-111, Tc-99m) fixed by the glands gives a sharp and lasting contrast, but also possesses disadvantages. The conditions required of a selective tracer are examined and the possibilities of various types of molecules for this study estimated. In spite of undeniable disadvantages the colloids of technetium-99m are being used more and more because of the quality of the images obtained. The results are interpreted and the chief indications of the method defined. The therapeutic possibilities of isotopic lymphography are also shown [fr

  17. Isolated hypoglossal nerve palsy due to skull base metastasis from breast cancer

    International Nuclear Information System (INIS)

    Pavithran, K.; Doval, D.C.; Hukku, S.; Jena, A.

    2001-01-01

    We describe a 44-year-old woman who presented with an isolated unilateral hypoglossal nerve paralysis caused by a skull base metastasis from breast cancer. The patient had a modified radical mastectomy followed by local radiotherapy and adjuvant chemotherapy. Fourteen months later she presented with difficulty in speaking. Physical examination revealed an isolated left hypoglossal nerve paralysis. The MRI scan showed a mass lesion involving the left occipital condyle extending into hypoglossal canal. Copyright (2001) Blackwell Science Pty Ltd

  18. Micelle System Based on Molecular Economy Principle for Overcoming Multidrug Resistance and Inhibiting Metastasis.

    Science.gov (United States)

    Qi, Yan; Qin, Xianya; Yang, Conglian; Wu, Tingting; Qiao, Qi; Song, Qingle; Zhang, Zhiping

    2018-03-05

    The high mortality of cancer is mainly attributed to multidrug resistance (MDR) and metastasis. A simple micelle system was constructed here to codeliver doxorubicin (DOX), adjudin (ADD), and nitric oxide (NO) for overcoming MDR and inhibiting metastasis. It was devised based on the "molecular economy" principle as the micelle system was easy to fabricate and exhibited high drug loading efficiency, and importantly, each component of the micelles would exert one or more active functions. DOX acted as the main cell killing agent supplemented with ADD, NO, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). MDR was overcome by synergistic effects of mitochondria inhibition agents, TPGS and ADD. A TPGS-based NO donor can be used as a drug carrier, and it can release NO to enhance drug accumulation and penetration in tumor, resulting in a positive cycle of drug delivery. This DOX-ADD conjugate self-assembly system demonstrated controlled drug release, increased cellular uptake and cytotoxicity, enhanced accumulation at tumor site, and improved in vivo metastasis inhibition of breast cancer. The micelles can fully take advantage of the functions of each component, and they provide a potential strategy for nanomedicine design and clinical cancer treatment.

  19. Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

    2011-11-19

    Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

  20. Imagery of the abdominal reticulo-histiocytary system [lymphatic nodes

    International Nuclear Information System (INIS)

    Ruel, Y.; Begon, D.

    1996-01-01

    Radiography and ultrasonography used together provide useful help in the clinical exploration of spleen and of abdominal lymphatic node abnormalities. These organs are difficult to examine by other techniques. Examination by radiography and ultrasonography often allows the abnormality to be localized and described, to visualize its spread and to observe its extension to other organs. Although these examinations do not allow this aspect they are invaluable in effective diagnosis. The information provided by these studies should avoid some exploratory laparotomies, to prepare for future surgical operations, to help in the prognostic (observation of metastasis,..), even to complete direct visual pre-operation examination (intra-hepatic metastasis)

  1. Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Koji; Sasaki, Tomoaki; Nabaa, Basim; Aburano, Tamio (Department of Radiology, Asahikawa Medical University and Hospital, Asahikawa (Japan)), Email: taka1019@asahikawa-med.ac.jp; Beek, Edwin Jr. von (Clinical Research Imaging Centre, Queen' s Medical Research Institute, University of Edinburgh, Edinburgh (United Kingdom)); Stanford, William (Department of Radiology, University of Iowa College of Medicine, Iowa City (United States))

    2012-03-15

    Background. In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity. Purpose. To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery. Material and Methods. We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups. Results. Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = -0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter (P <0.01). Conclusion. Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent

  2. Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis

    International Nuclear Information System (INIS)

    Takahashi, Koji; Sasaki, Tomoaki; Nabaa, Basim; Aburano, Tamio; Beek, Edwin Jr. von; Stanford, William

    2012-01-01

    Background. In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity. Purpose. To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery. Material and Methods. We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups. Results. Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = -0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter (P <0.01). Conclusion. Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent

  3. Pulmonary lymphatics and radiation

    International Nuclear Information System (INIS)

    Leeds, S.E.

    1976-01-01

    Knowledge of the anatomy and physiology of the respiratory system has been more difficult to acquire than that of other organ systems owing to the complexity of the respiratory function of the lungs and to the technical difficulties involved. This is especially true of the lymphatics of the lung and is illustrated by the fact that the first measurement of pulmonary lymph flow was in 1942 by Warren and Drinker. A review of the literature reveals that few experiments have been designed to study the pulmonary lymphatics per se in relation to the effects of external radiation or after the inhalation of radioactive particles. However, the documented involvement of hilar lymph nodes implies that the lung lymphatics have a role in transporting particles from the alveoli or malignant cells from the parenchyma. Information from clinical and experimental sources, though scattered, is fairly abundant and of value in assessing the role of the pulmonary lymphatics. Our method for collecting pulmonary lymph is presented. Studies on the pulmonary lymph flow in normal dogs and in dogs with experimental congestive heart failure are described. We irradiated (4000 to 5000 R) the medial one-third of both lungs of a series of dogs. The lymph flow of the lungs was measured immediately after the course of irradiation and after a period of about 5 months. Although lung biopsies showed characteristic radiation pneumonitis in many areas, alterations in the lung parenchyma were not quantitatively reflected in the pulmonary lymph flow either in the acute stage or after fibrosis had time to develop

  4. The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

    Science.gov (United States)

    Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

  5. A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

    Science.gov (United States)

    Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

    2015-08-01

    of the penis and folded at the abdominal wall to the outside, and finally merged into the inguinal lymph nodes. The changes in distribution, number and diameter of the lymphatic vessels in the penis were observed by MRI. MIP and MIMICS reconstructions directly revealed the anatomical features of penile lymphatic vessels such as spatial distribution, overall alignment, and the relations to adjacent structures, drainage and reflux. The study will provide the anatomical basis for penile surgery, penile lymphatic reflux disorders caused by trauma or lymphatic vessels obstruction, and lymph node metastasis in penile cancer. © 2014 Wiley Periodicals, Inc.

  6. Lymphatic malformations: a proposed management algorithm.

    LENUS (Irish Health Repository)

    Oosthuizen, J C

    2012-02-01

    OBJECTIVE: The aim of this study was to develop a management algorithm for cervicofacial lymphatic malformations, based on the authors\\' experience in managing these lesions as well as current literature on the subject. STUDY DESIGN AND METHODS: A retrospective medical record review of all the patients treated for lymphatic malformations at our institution during a 10-year period (1998-2008) was performed. DATA COLLECTED: age at diagnosis, location and type of lesion, radiologic investigation performed, presenting symptoms, treatment modality used, complications and results achieved. RESULTS: 14 patients were identified. Eight (57%) male and six (43%) female. There was an equal distribution between the left and right sides. The majority (71%) of cases were diagnosed within the first year of life. The majority of lesions were located in the suprahyoid region. The predominant reason for referral was an asymptomatic mass in 7 cases (50%) followed by airway compromise (36%) and dysphagia (14%). Management options employed included: observation, OK-432 injection, surgical excision and laser therapy. In 5 cases (36%) a combination of these were used. CONCLUSION: Historically surgical excision has been the management option of choice for lymphatic malformations. However due to the morbidity and high complication rate associated this is increasingly being questioned. Recent advances in sclerotherapy e.g. OK-432 injection have also shown significant promise. Based on experience in managing these lesions as well as current literature the authors of this paper have developed an algorithm for the management of cervicofacial lymphatic malformations.

  7. A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

    Science.gov (United States)

    Ryan, Gemma M; Bischof, Robert J; Enkhbaatar, Perenlei; McLeod, Victoria M; Chan, Linda J; Jones, Seth A; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

    2016-02-01

    Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

  8. A community-based study of factors associated with continuing transmission of lymphatic filariasis in Leogane, Haiti.

    Directory of Open Access Journals (Sweden)

    Alexis Boyd

    Full Text Available Seven rounds of mass drug administration (MDA have been administered in Leogane, Haiti, an area hyperendemic for lymphatic filariasis (LF. Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15.5%, suggesting that transmission had been reduced. A separate 30-cluster survey of 2- to 4-year-old children was conducted to determine if MDA interrupted transmission. Antigen and antifilarial antibody prevalence were 14.3% and 19.7%, respectively. Follow-up surveys were done in 6 villages, including those selected for the cluster survey, to assess risk factors related to continued LF transmission and to pinpoint hotspots of transmission. One hundred houses were mapped in each village using GPS-enabled PDAs, and then 30 houses and 10 alternates were chosen for testing. All individuals in selected houses were asked to participate in a short survey about participation in MDA, history of residence in Leogane and general knowledge of LF. Survey teams returned to the houses at night to collect blood for antigen testing, microfilaremia and Bm14 antibody testing and collected mosquitoes from these communities in parallel. Antigen prevalence was highly variable among the 6 villages, with the highest being 38.2% (Dampus and the lowest being 2.9% (Corail Lemaire; overall antigen prevalence was 18.5%. Initial cluster surveys of 2- to 4-year-old children were not related to community antigen prevalence. Nearest neighbor analysis found evidence of clustering of infection suggesting that LF infection was focal in distribution. Antigen prevalence among individuals who were systematically noncompliant with the MDAs, i.e. they had never participated, was significantly higher than among compliant individuals (p<0.05. A logistic regression model found that of the factors examined for association with infection, only noncompliance was significantly associated with infection. Thus, continuing transmission of LF seems

  9. The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Stocks, Meredith E; Freeman, Matthew C; Addiss, David G

    2015-10-01

    Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis (LF), with an estimated 14 million persons affected worldwide. The twin goals of the World Health Organization's Global Program to Eliminate Lymphatic Filariasis include interrupting transmission of the parasitic worms that cause LF and providing care to persons who suffer from its clinical manifestations, including lymphedema-so-called morbidity management and disability prevention (MMDP). Scaling up of MMDP has been slow, in part because of a lack of consensus about the effectiveness of recommended hygiene-based interventions for clinical lymphedema. We conducted a systemic review and meta-analyses to estimate the effectiveness of hygiene-based interventions on LF-related lymphedema. We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases through March 23, 2015 with no restriction on year of publication. Studies were eligible for inclusion if they (1) were conducted in an area endemic for LF, (2) involved hygiene-based interventions to manage lymphedema, and (3) assessed lymphedema-related morbidity. For clinical outcomes for which three or more studies assessed comparable interventions for lymphedema, we conducted random-effects meta-analyses. Twenty-two studies met the inclusion criteria and two meta-analyses were possible. To evaluate study quality, we developed a set of criteria derived from the GRADE methodology. Publication bias was assessed using funnel plots. Participation in hygiene-based lymphedema management was associated with a lower incidence of acute dermatolymphagioadenitis (ADLA), (Odds Ratio 0.32, 95% CI 0.25-0.40), as well as with a decreased percentage of patients reporting at least one episode of ADLA during follow-up (OR 0.29, 95% CI 0.12-0.47). Limitations included high heterogeneity across studies

  10. The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis.

    Directory of Open Access Journals (Sweden)

    Meredith E Stocks

    2015-10-01

    Full Text Available Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis (LF, with an estimated 14 million persons affected worldwide. The twin goals of the World Health Organization's Global Program to Eliminate Lymphatic Filariasis include interrupting transmission of the parasitic worms that cause LF and providing care to persons who suffer from its clinical manifestations, including lymphedema-so-called morbidity management and disability prevention (MMDP. Scaling up of MMDP has been slow, in part because of a lack of consensus about the effectiveness of recommended hygiene-based interventions for clinical lymphedema.We conducted a systemic review and meta-analyses to estimate the effectiveness of hygiene-based interventions on LF-related lymphedema. We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases through March 23, 2015 with no restriction on year of publication. Studies were eligible for inclusion if they (1 were conducted in an area endemic for LF, (2 involved hygiene-based interventions to manage lymphedema, and (3 assessed lymphedema-related morbidity. For clinical outcomes for which three or more studies assessed comparable interventions for lymphedema, we conducted random-effects meta-analyses. Twenty-two studies met the inclusion criteria and two meta-analyses were possible. To evaluate study quality, we developed a set of criteria derived from the GRADE methodology. Publication bias was assessed using funnel plots. Participation in hygiene-based lymphedema management was associated with a lower incidence of acute dermatolymphagioadenitis (ADLA, (Odds Ratio 0.32, 95% CI 0.25-0.40, as well as with a decreased percentage of patients reporting at least one episode of ADLA during follow-up (OR 0.29, 95% CI 0.12-0.47. Limitations included high heterogeneity

  11. Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

    Science.gov (United States)

    Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

    2015-01-01

    Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

  12. Omics-based profiling of carcinoma of the breast and matched regional lymph node metastasis

    DEFF Research Database (Denmark)

    Li, J.; Gromov, P.; Gromova, I.

    2008-01-01

    Axillary lymph node (ALN) status is currently used as an important clinical indicator of breast cancer prognosis. However, the molecular mechanisms underlying lymph node metastasis are poorly understood and the relationship between ALN metastasis and the primary tumor remains unclear. In an effor...

  13. Predictive value of the time-intensity curves on dynamic contrast-enhanced magnetic resonance imaging for lymphatic spreading in breast cancer

    International Nuclear Information System (INIS)

    Komatsu, Shuhei; Lee, Chol Joo; Ichikawa, Daisuke

    2005-01-01

    Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a promising diagnostic modality in various breast cancer treatments. However, little is known about the correlation between the pattern of time to signal intensity curves (TIC) on the CE-MRI and clinicopathologic features. This study was designed to investigate these correlations and evaluate the predictive value of TIC on CE-MRI in order to identify high-risk patients. Between 2001 and 2003, 101 lesions were evaluated to detect malignancy on CE-MRI in 101 women who were suspected of having breast tumors based on either clinical findings or conventional imaging studies. Moreover, the clinicopathologic findings were compared with the pattern of TIC for the 69 surgically treated malignant lesions. In detecting malignancy, the sensitivity, specificity, and accuracy were 78.7%, 88.5%, and 81.2%, respectively, in the 101 breast lesions. Especially for the 69 surgically treated malignant lesions, in comparison with breast cancer tumors with the benign pattern of TIC, the breast cancer tumors with a malignant pattern were found more frequently in lymphatic invasion (P<0.01) and lymph node metastasis (P<0.005), although no statistical correlation regarding the histological type, tumor size, vascular invasion, extensive intraductal component, hormone receptor status, or pathological stage was noted between the two groups. According to a logistic regression model, lymph node metastasis was found to be a significant independent variable. The pattern of TIC could be used to predict lymphatic spreading associated with lymph node metastasis prior to surgery as well as to detect malignancy. Therefore, a more detailed evaluation should be made to identify the presence of lymphatic spreading in patients with a malignant pattern of TIC. (author)

  14. Risk of lymph node metastasis associated with deeper invasion by early adenocarcinoma of the esophagus and cardia: study based on endoscopic resection specimens

    NARCIS (Netherlands)

    Alvarez Herrero, L.; Pouw, R. E.; van Vilsteren, F. G.; ten Kate, F. J.; Visser, M.; van Berge Henegouwen, M. I.; Weusten, B. L.; Bergman, J. J.

    2010-01-01

    Background: Most risk estimations for lymph node metastasis in adenocarcinoma of the esophagus and cardia (AEC) with invasion into the muscularis mucosae (m3) or submucosa are based on surgical series. This study aimed to correlate the lymph node metastasis rate with m3 and submucosal infiltration

  15. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.

    Science.gov (United States)

    Absinta, Martina; Ha, Seung-Kwon; Nair, Govind; Sati, Pascal; Luciano, Nicholas J; Palisoc, Maryknoll; Louveau, Antoine; Zaghloul, Kareem A; Pittaluga, Stefania; Kipnis, Jonathan; Reich, Daniel S

    2017-10-03

    Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

  16. Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ali Esfahani

    2016-01-01

    Full Text Available Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS. Then a score was defined as prealbumin/CRP based prognostic score (PCPS to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n=43 and those with nonmetastatic (n=28 gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P=0.005. Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted.

  17. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    2011-02-01

    Full Text Available Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.

  18. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads

    International Nuclear Information System (INIS)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-01-01

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes

  19. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

    Science.gov (United States)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-05-21

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

  20. RNA-Based TWIST1 Inhibition via Dendrimer Complex to Reduce Breast Cancer Cell Metastasis

    Directory of Open Access Journals (Sweden)

    James Finlay

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer-related deaths among women in the United States, and survival rates are lower for patients with metastases and/or triple-negative breast cancer (TNBC; ER, PR, and Her2 negative. Understanding the mechanisms of cancer metastasis is therefore crucial to identify new therapeutic targets and develop novel treatments to improve patient outcomes. A potential target is the TWIST1 transcription factor, which is often overexpressed in aggressive breast cancers and is a master regulator of cellular migration through epithelial-mesenchymal transition (EMT. Here, we demonstrate an siRNA-based TWIST1 silencing approach with delivery using a modified poly(amidoamine (PAMAM dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT-related target genes. Knockdown lasts up to one week after transfection and leads to a reduction in migration and invasion, as determined by wound healing and transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least four hours after treatment. These results suggest that further development of dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable adjunctive therapy for patients with TNBC.

  1. Lymphographic criteria of lymphatic edema of the limbs in terms of microsurgery

    International Nuclear Information System (INIS)

    Rabkin, I.Kh.; Krylov, V.S.; Milanov, N.O.; Lein, A.P.; Ermakov, N.P.

    1980-01-01

    Based on the assessment of the results of 126 lymphographic studies, performed on patients with lymphatic edema of the limbs of various genesis, an important role has been assigned to lymphography as the criterion for establishing indications and contra-indications for microsurgical lymphovenous anastomosis. A special technique of pre-operation lymphophlebographic examination of patients with lymphatic edema of the limbds has been developed. A working scheme of primary lymphatic edemas, as well as the detailed interpretation of lymphographic appearance of primary and secondary lymphatic edemas are also provided

  2. Investigation of intratumoural and peritumoural lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours

    Science.gov (United States)

    Ji, RC; Eshita, Y; Kato, S

    2007-01-01

    Tumour-associated lymphatics contribute to a key component of metastatic spread, however, the biological interaction of tumour cells with intratumoural and peritumoural lymphatics (ITLs and PTLs) has remained unclear. To address this important issue, we have focused on the morphological and molecular aspects of newly formed lymphatics (lymphangiogenesis) and pre-existing lymphatics in the intratumoural and peritumoural tissues by using a hybridoma-induced tumour model. In the present study, ITLs with very high vessel density within the tumour mass showed small and flattened contours that varied from non-solid-to-solid tumours, whereas PTLs were relatively disorganized and tortuous, and packed with a cluster of tumour cells at the tumour periphery. Lymphatic endothelial cells (LECs) both in ITLs and PTLs were expressed with LYVE-1 and podoplanin in various tumour tissues, in which initial lymphatics were extremely extended and dilated. The tumour cells were frequently detected adhering to or penetrating lymphatic walls, especially near the open junctions. In the metastatic tissues, lymphangiogenic vasculatures occurred within the tumour matrix, and collecting PTLs represented abnormal twisty valve leaflets. The Western blot and RT-PCR analysis showed local variations of LEC proliferating potentials and lymphatic involvement in metastasis by a distinct profile of the protein and mRNA expression by LYVE-1, podoplanin, Prox-1 and vascular endothelial growth factor-3 (VEGFR-3). These findings indicated that both ITLs and PTLs, including enlarged pre-existing and newly formed lymphatics, may play a crucial role in metastasis with an active tumour cell adhesion, invasion, migration and implantation. PMID:17696907

  3. Supplementary oxygen and risk of childhood lymphatic leukaemia.

    Science.gov (United States)

    Naumburg, E; Bellocco, R; Cnattingius, S; Jonzon, A; Ekbom, A

    2002-01-01

    Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population-based case-control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth-related factors. Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Down's syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression. Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% Cl 1.21-6.82). The oxygen-related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16-10.80). Low Apgar scores at 1 and 5 min were associated with a non-significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth-related factors. Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.

  4. Hypophyseal metastasis

    International Nuclear Information System (INIS)

    Yanes Quesada, Miguel Angel; Yanes Quesada, Marelys; Lopez Arbolay, Omar; Lima Perez, Mayte; Hernandez Yero, Arturo

    2009-01-01

    Metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. We describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. (Author)

  5. Community-based field implementation scenarios of a short message service reporting tool for lymphatic filariasis case estimates in Africa and Asia.

    Science.gov (United States)

    Mableson, Hayley E; Martindale, Sarah; Stanton, Michelle C; Mackenzie, Charles; Kelly-Hope, Louise A

    2017-01-01

    Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted for global elimination by 2020. Currently there is considerable international effort to scale-up morbidity management activities in endemic countries, however there remains a need for rapid, cost-effective methods and adaptable tools for obtaining estimates of people presenting with clinical manifestations of LF, namely lymphoedema and hydrocele. The mHealth tool ' MeasureSMS-Morbidity ' allows health workers in endemic areas to use their own mobile phones to send clinical information in a simple format using short message service (SMS). The experience gained through programmatic use of the tool in five endemic countries across a diversity of settings in Africa and Asia is used here to present implementation scenarios that are suitable for adapting the tool for use in a range of different programmatic, endemic, demographic and health system settings. A checklist of five key factors and sub-questions was used to determine and define specific community-based field implementation scenarios for using the MeasureSMS-Morbidity tool in a range of settings. These factors included: (I) tool feasibility (acceptability; community access and ownership); (II) LF endemicity (high; low prevalence); (III) population demography (urban; rural); (IV) health system structure (human resources; community access); and (V) integration with other diseases (co-endemicity). Based on experiences in Bangladesh, Ethiopia, Malawi, Nepal and Tanzania, four implementation scenarios were identified as suitable for using the MeasureSMS-Morbidity tool for searching and reporting LF clinical case data across a range of programmatic, endemic, demographic and health system settings. These include: (I) urban, high endemic setting with two-tier reporting; (II) rural, high endemic setting with one-tier reporting; (III) rural, high endemic setting with two-tier reporting; and (IV) low-endemic, urban and rural setting with one

  6. Metastasis in the base of the cranium: initial manifestation of a hepato carcinoma. Findings in the CT and MRI; Metastasis en la base del carneo: manifestacion inicial de un hepatocarcinoma. Hallazgos en TC y RM

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, M T; Saiz, A; Cardenal, A; Oruezabal, M [Hospital Clinico San Carlos. Madrid (Spain)

    2000-07-01

    We present a case of hepato carcinoma (HC) whose first clinical manifestation was diplopia. The imaging methods showed a sold mass in the base of the cranium with meningioma characteristics. The histological study showed the existence of hepatocytes, which confirmed the diagnosis of metastasis of the HC: We present the X-ray findings in the CT and MRI of this case and the differential diagnosis with other tumors that affect the cranium base. We also perform a bibliographic review of this clinical manifestation with such an unusual X-ray. (Author) 19 refs.

  7. Successful Control of Soil-Transmitted Helminthiasis in School Age Children in Burkina Faso and an Example of Community-Based Assessment via Lymphatic Filariasis Transmission Assessment Survey.

    Directory of Open Access Journals (Sweden)

    François Drabo

    2016-05-01

    Full Text Available Burkina Faso is endemic with soil-transmitted helminth infections. Over a decade of preventive chemotherapy has been implemented through annual lymphatic filariasis (LF mass drug administration (MDA for population aged five years and over, biennial treatment of school age children with albendazole together with schistosomiasis MDA and biannual treatment of pre-school age children through Child Health Days. Assessments were conducted to evaluate the current situation and to determine the treatment strategy for the future.A cross-sectional assessment was conducted in 22 sentinel sites across the country in 2013. In total, 3,514 school age children (1,748 boys and 1,766 girls were examined by the Kato-Katz method. Overall, soil-transmitted helminth prevalence was 1.3% (95% CI: 1.0-1.8% in children examined. Hookworm was the main species detected, with prevalence of 1.2% (95% CI: 0.9-1.6% and mean egg counts of 2.1 epg (95% CI: 0-4.2 epg. Among regions, the Centre Ouest region had the highest hookworm prevalence of 3.4% (95% CI: 1.9-6.1% and mean egg counts of 14.9 epg (95% CI: 3.3-26.6 epg. A separate assessment was conducted in the Centre Nord region in 2014 using community-based cluster survey design during an LF transmission assessment survey (TAS. In this assessment, 351 children aged 6-7 years and 345 children aged 10-14 years were examined, with two cases (0.6% (95% CI: 0.2-2.1% and seven cases (2.0% (95% CI: 1.0-4.1% of hookworm infection was identified respectively. The results using both age groups categorized the region to be 2% to <10% in STH prevalence according to the pre-defined cut-off values.Through large-scale preventive chemotherapy, Burkina Faso has effectively controlled STH in school age children in the country. Research should be conducted on future strategies to consolidate the gain and to interrupt STH transmission in Burkina Faso. It is also demonstrated that LF TAS provides one feasible and efficient platform to assess the

  8. Metastasis in the base of the cranium: initial manifestation of a hepato carcinoma. Findings in the CT and MRI

    International Nuclear Information System (INIS)

    Fernandez, M. T.; Saiz, A.; Cardenal, A.; Oruezabal, M.

    2000-01-01

    We present a case of hepato carcinoma (HC) whose first clinical manifestation was diplopia. The imaging methods showed a sold mass in the base of the cranium with meningioma characteristics. The histological study showed the existence of hepatocytes, which confirmed the diagnosis of metastasis of the HC: We present the X-ray findings in the CT and MRI of this case and the differential diagnosis with other tumors that affect the cranium base. We also perform a bibliographic review of this clinical manifestation with such an unusual X-ray. (Author) 19 refs

  9. Correspondence model-based 4D VMAT dose simulation for analysis of local metastasis recurrence after extracranial SBRT

    Science.gov (United States)

    Sothmann, T.; Gauer, T.; Wilms, M.; Werner, R.

    2017-12-01

    The purpose of this study is to introduce a novel approach to incorporate patient-specific breathing variability information into 4D dose simulation of volumetric arc therapy (VMAT)-based stereotactic body radiotherapy (SBRT) of extracranial metastases. Feasibility of the approach is illustrated by application to treatment planning and motion data of lung and liver metastasis patients. The novel 4D dose simulation approach makes use of a regression-based correspondence model that allows representing patient motion variability by breathing signal-steered interpolation and extrapolation of deformable image registration motion fields. To predict the internal patient motion during treatment with only external breathing signal measurements being available, the patients’ internal motion information and external breathing signals acquired during 4D CT imaging were correlated. Combining the correspondence model, patient-specific breathing signal measurements during treatment and time-resolved information about dose delivery, reconstruction of a motion variability-affected dose becomes possible. As a proof of concept, the proposed approach is illustrated by a retrospective 4D simulation of VMAT-based SBRT treatment of ten patients with 15 treated lung and liver metastases and known clinical endpoints for the individual metastases (local metastasis recurrence yes/no). Resulting 4D-simulated dose distributions were compared to motion-affected dose distributions estimated by standard 4D CT-only dose accumulation and the originally (i.e. statically) planned dose distributions by means of GTV D98 indices (dose to 98% of the GTV volume). A potential linkage of metastasis-specific endpoints to differences between GTV D98 indices of planned and 4D-simulated dose distributions was analyzed.

  10. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  11. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis.

    Science.gov (United States)

    Secchin, Pedro; Trope, Beatriz Moritz; Fernandes, Larissa Araujo; Barreiros, Glória; Ramos-E-Silva, Marcia

    2017-01-01

    Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis), it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  12. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-12-07

    To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

  13. Patterns of lymph node metastasis identified following bilateral mandibular and medial retropharyngeal lymphadenectomy in 31 dogs with malignancies of the head.

    Science.gov (United States)

    Skinner, Owen T; Boston, Sarah E; Souza, Carlos H de M

    2017-09-01

    Variable pathways of lymphatic drainage have been described in the dog head and neck. The aim of this study was to retrospectively assess the patterns of lymph node metastasis in dogs with malignancies of the head following bilateral mandibular and medial retropharyngeal lymphadenectomy. Thirty-one dogs were included. Median age at surgery was 10 years (range: 5 months to 14 years) and mean bodyweight was 21.4 ± 11.9 kg. Lymph node metastasis occurred in 14 dogs (45%), with spread to mandibular lymph nodes in 14 dogs and medial retropharyngeal metastasis in 11 dogs. Eight of 13 dogs (62%) with lymphatic metastasis and a lateralised lesion showed contralateral dissemination, while 12/13 (92%) showed ipsilateral metastasis. Of 13 dogs with oral malignant melanoma, four showed metastasis to all four lymph centres. Contralateral metastasis may occur in dogs with malignancies of the head and should be considered during staging and management. © 2016 John Wiley & Sons Ltd.

  14. Lymphatic Vessel Density as Prognostic Factor in Breast Carcinoma: Relation to Clinico pathologic Parameters

    International Nuclear Information System (INIS)

    El-Gendi, S.; Abdel-Hadi, M.

    2009-01-01

    Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic micro vessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immuno stained for D2-40, CD31 and VEGF. Median lymphatic and blood micro vessel densities, as well as VEGF expression, were related to each other and to clinico pathologic parameters including lymph node (Ln) status. The efficacy of haematoxylin and eosin (H and E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H and E. VEGF was expressed in 85% of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H and E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis

  15. Lymphatic imaging in unsedated infants and children

    Science.gov (United States)

    Rasmussen, John C.; Balaguru, Duraisamy; Douglas, William I.; Breinholt, John P.; Greives, Matthew R.; Aldrich, Melissa B.; Sevick-Muraca, Eva M.

    2017-02-01

    Primary lymphedema and lymphatic malformations in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the underlying anatomy and function of the lymphatic system. Diagnostics for the lymphatic vasculature are limited, consisting of lymphoscintigraphy or invasive lymphangiography, both of which require sedation that can restrict use in infants and children. As a result, therapeutic protocols for pediatric patients with lymphatic disorders remain sparse and with little evidence to support them. Because near-infrared fluorescence (NIRF) imaging enables image acquisition on the order of tenths of seconds with trace administration of fluorescent dye, sedation is not necessary. The lack of harmful radiation and radioactive contrast agents further facilitates imaging. Herein we summarize our experiences in imaging infants and children who are suspected to have disorders of the lymphatic vascular system using indocyanine green (ICG) and who have developed chylothorax following surgery for congenital heart defects. The results show both anatomical as well as functional lymphatic deficits in children with congenital disease. In the future, NIRF lymphatic imaging could provide new opportunities to tailor effective therapies and monitor responses. The opportunity to use expand NIRF imaging for pediatric diagnostics beyond the lymphatic vasculature is also afforded by the rapid acquisition following trace administration of NIRF contrast agent.

  16. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Souheil El-Chemaly

    2012-09-01

    Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

  17. Endothelial ERK signaling controls lymphatic fate specification

    Science.gov (United States)

    Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

    2013-01-01

    Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

  18. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    Science.gov (United States)

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  19. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

    Science.gov (United States)

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. © 2015 Aspelund et al.

  20. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

    Directory of Open Access Journals (Sweden)

    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  1. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis

    DEFF Research Database (Denmark)

    Cao, Renhai; Ji, Hong; Feng, Ninghan

    2012-01-01

    Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading...... endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting...

  2. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2.Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  3. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Pedro Secchin

    2017-08-01

    Full Text Available Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis, it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  4. Prediction of Metastasis and Recurrence in Colorectal Cancer Based on Gene Expression Analysis: Ready for the Clinic?

    International Nuclear Information System (INIS)

    Shibayama, Masaki; Maak, Matthias; Nitsche, Ulrich; Gotoh, Kengo; Rosenberg, Robert; Janssen, Klaus-Peter

    2011-01-01

    Cancers of the colon and rectum, which rank among the most frequent human tumors, are currently treated by surgical resection in locally restricted tumor stages. However, disease recurrence and formation of local and distant metastasis frequently occur even in cases with successful curative resection of the primary tumor (R0). Recent technological advances in molecular diagnostic analysis have led to a wealth of knowledge about the changes in gene transcription in all stages of colorectal tumors. Differential gene expression, or transcriptome analysis, has been proposed by many groups to predict disease recurrence, clinical outcome, and also response to therapy, in addition to the well-established clinico-pathological factors. However, the clinical usability of gene expression profiling as a reliable and robust prognostic tool that allows evidence-based clinical decisions is currently under debate. In this review, we will discuss the most recent data on the prognostic significance and potential clinical application of genome wide expression analysis in colorectal cancer

  5. Prediction of Metastasis and Recurrence in Colorectal Cancer Based on Gene Expression Analysis: Ready for the Clinic?

    Energy Technology Data Exchange (ETDEWEB)

    Shibayama, Masaki [Sysmex Corporation, Central Research Laboratories, Kobe 651-2271 (Japan); Maak, Matthias; Nitsche, Ulrich [Chirurgische Klinik, Klinikum Rechts der Isar der TUM, München 81657 (Germany); Gotoh, Kengo [Sysmex Corporation, Central Research Laboratories, Kobe 651-2271 (Japan); Rosenberg, Robert; Janssen, Klaus-Peter, E-mail: klaus-peter.janssen@lrz.tum.de [Chirurgische Klinik, Klinikum Rechts der Isar der TUM, München 81657 (Germany)

    2011-07-07

    Cancers of the colon and rectum, which rank among the most frequent human tumors, are currently treated by surgical resection in locally restricted tumor stages. However, disease recurrence and formation of local and distant metastasis frequently occur even in cases with successful curative resection of the primary tumor (R0). Recent technological advances in molecular diagnostic analysis have led to a wealth of knowledge about the changes in gene transcription in all stages of colorectal tumors. Differential gene expression, or transcriptome analysis, has been proposed by many groups to predict disease recurrence, clinical outcome, and also response to therapy, in addition to the well-established clinico-pathological factors. However, the clinical usability of gene expression profiling as a reliable and robust prognostic tool that allows evidence-based clinical decisions is currently under debate. In this review, we will discuss the most recent data on the prognostic significance and potential clinical application of genome wide expression analysis in colorectal cancer.

  6. Proposing the lymphatic target volume for elective radiation therapy for pancreatic cancer: a pooled analysis of clinical evidence

    Directory of Open Access Journals (Sweden)

    Lu Jiade J

    2010-04-01

    lymph nodes (Group 16, 16.44%, and inferior body lymph nodes (Group 18, 24.66%. The probability of metastasis in other lymph nodal regions were Conclusions Pancreatic cancer has a high propensity of regional lymphatic metastases; however, clear patterns including the site and probability of metastasis can be identified and used as a guide of treatment in patients with resectable pancreatic cancer. Further clinical investigation is needed to study the efficacy of elective treatment to CTV defined based on these patterns using high-dose conformal or intensity-modulated radiation therapy.

  7. THE CHOICE OF TREATMENT OF SINGLE BRAIN METASTASIS SHOULD BE BASED ON EXTRACRANIAL TUMOR-ACTIVITY AND AGE

    NARCIS (Netherlands)

    NOORDIJK, EM; VECHT, CJ; HAAXMAREICHE, H; PADBERG, GW; VOORMOLEN, JHC; HOEKSTRA, FH; TANS, JTJ; LAMBOOIJ, N; METSAARS, JAL; WATTENDORFF, AR; BRAND, R; HERMANS, J

    1994-01-01

    Purpose: To determine if in patients with single brain metastasis the addition of neurosurgery to radiotherapy leads to lengthening of survival or to better quality of life. Methods and Materials: From 1985 to 1990, 66 patients with single brain metastasis from a solid tumor were entered in a

  8. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    DEFF Research Database (Denmark)

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria

    2009-01-01

    and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO...

  9. Prediction of axillary lymph node metastasis in primary breast cancer patients using a decision tree-based model

    Directory of Open Access Journals (Sweden)

    Takada Masahiro

    2012-06-01

    Full Text Available Abstract Background The aim of this study was to develop a new data-mining model to predict axillary lymph node (AxLN metastasis in primary breast cancer. To achieve this, we used a decision tree-based prediction method—the alternating decision tree (ADTree. Methods Clinical datasets for primary breast cancer patients who underwent sentinel lymph node biopsy or AxLN dissection without prior treatment were collected from three institutes (institute A, n = 148; institute B, n = 143; institute C, n = 174 and were used for variable selection, model training and external validation, respectively. The models were evaluated using area under the receiver operating characteristics (ROC curve analysis to discriminate node-positive patients from node-negative patients. Results The ADTree model selected 15 of 24 clinicopathological variables in the variable selection dataset. The resulting area under the ROC curve values were 0.770 [95% confidence interval (CI, 0.689–0.850] for the model training dataset and 0.772 (95% CI: 0.689–0.856 for the validation dataset, demonstrating high accuracy and generalization ability of the model. The bootstrap value of the validation dataset was 0.768 (95% CI: 0.763–0.774. Conclusions Our prediction model showed high accuracy for predicting nodal metastasis in patients with breast cancer using commonly recorded clinical variables. Therefore, our model might help oncologists in the decision-making process for primary breast cancer patients before starting treatment.

  10. A Population-based Study of the Fractionation of Palliative Radiotherapy for Bone Metastasis in Ontario

    International Nuclear Information System (INIS)

    Kong, Weidong; Zhang-Salomons, Jina; Hanna, Timothy P.; Mackillop, William J.

    2007-01-01

    Purpose: To describe the use of palliative radiotherapy (PRT) for bone metastases in Ontario between 1984 and 2001 and identify factors associated with the choice of fractionation. Methods and Materials: Electronic RT records from the nine provincial RT centers in Ontario were linked to the Ontario Cancer Registry to identify all courses of PRT for bone metastases. Results: Between 1984 and 2001, 44,884 patients received 74,432 courses of PRT for bone metastases in Ontario. The mean number of courses per patient was 1.7, and 65% of patients received only a single course of PRT for bone metastasis. The mean number of fractions per course was 3.9. The proportion of patients treated with a single fraction increased from 27.2% in 1984-1986 to 40.3% in 1987-1992 and decreased thereafter. Single fractions were used more frequently in patients with a shorter life expectancy, in older patients, and in patients who lived further from an RT center. Single fractions were used more frequently when the prevailing waiting time for RT was longer. There were wide variations in the use of single fractions among the different RT centers (intercenter range, 11.8-62.3%). Intercenter variations persisted throughout the study period and were not explained by differences in case mix. Conclusions: Despite increasing evidence of the effectiveness of single-fraction PRT for bone metastases, most patients continued to receive fractionated PRT throughout the two decades of this study. Single fractions were used more frequently when waiting times were longer. There was persistent, unexplained variation in the fractionation of PRT among different centers

  11. Pneumocystis carinii Pneumonia in Acute Lymphatic Leukaemia ...

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumocystis pneumonia while in remission from acute lymphatic leukaemia is presented. Clinical and aetiological aspects of this rare infection are discussed. Attention is drawn to diagnostic pitfalls encountered in leukaemia.

  12. Comparative and Developmental Anatomy of Cardiac Lymphatics

    Directory of Open Access Journals (Sweden)

    A. Ratajska

    2014-01-01

    Full Text Available The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

  13. What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs.

    Directory of Open Access Journals (Sweden)

    Randee J Kastner

    Full Text Available Lymphatic filariasis (LF is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up.We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration.Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050.Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.

  14. Esophageal Metastasis from Rectal Cancer Successfully Treated with Fluorouracil-Based Chemotherapy with Bevacizumab: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sho Watanabe

    2017-05-01

    Full Text Available Esophageal metastasis from colorectal carcinoma is uncommon, and diagnosis of esophageal metastasis is difficult. We report a case of a 54-year-old woman with postoperative recurrence of rectal cancer metastasizing to the esophagus. She underwent rectectomy and adjuvant chemotherapy with fluorouracil, leucovorin plus oxaliplatin for stage IIIB rectal cancer. Three years later, she presented with dysphagia and cough. Computed tomography showed thickening of the esophagus wall, enlargement of the lymph nodes in the mediastinum and abdomen, and ground-glass opacities in the right lung. Endoscopy revealed a submucosal tumor of the midthoracic esophagus. Histopathological analysis of the tumor biopsy showed infiltration of adenocarcinoma cells into the stroma of the esophagus; tumor cells were positive for caudal type homeobox 2 and negative for thyroid transcription factor 1. A transbronchial biopsy indicated pulmonary lymphangitic carcinomatosis of rectal adenocarcinoma. Based on those findings, she was diagnosed with recurrent rectal cancer. She received fluorouracil-based chemotherapy plus bevacizumab, which ameliorated her symptoms and induced a durable response without severe adverse events. Diagnosis of esophageal metastasis from rectal cancer can thus be made by repeated biopsy. Furthermore, aggressive systemic treatment with fluorouracil-containing chemotherapy and bevacizumab is a treatment option for colorectal cancer patients with esophageal metastasis.

  15. Whistle from Afar: A Case of Endotracheal Metastasis in Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Bitoti Chattopadhyay

    2012-01-01

    Full Text Available Endotracheal metastasis is a rare situation, usually associated with malignancies of breast and gastrointestinal tract, specially colon. Papillary carcinoma of thyroid commonly disseminates through lymphatic channels and tracheal involvement through vascular route is rarely reported. Here, we report a case of tracheal metastasis from papillary carcinoma of thyroid. The patient responded to external beam radiation therapy with cobalt 60 beams in a dose of 44 Gy followed by a 16 Gy boost. The patient is under followup and is presently asymptomatic. This paper adds to the repertoire of evidence in treatment of endotracheal metastasis.

  16. The lymphatics of the esophagus

    International Nuclear Information System (INIS)

    Okanobu, Koji

    1990-01-01

    For the studies of the esophageal lymphatics, endoscopic RI-lymphoscintigraphy was performed in 23 cases of esophageal cancer, 3 cases of lung cancer and 5 cases of gastric cancer. 99m Tc-Rhenium colloid was endoscopically injected into the submucosal layer of the esophagus near the tumor and the images of th lymph flow were obtained after about 3 hours. Single photon emission computerized tomography (SPECT) was used to acquire the three-dimensional images of the esophageal lymph flow on 19 patients. RI-uptake of all dissected lymph nodes was also counted after the operation. The results were shown as follows. Whole neck, thoracic and abdominal lymph nodes could be imaged in any case injected at any part of the thoracic esophagus. But the lymph flow in the upper third of the esophagus tended to move mainly upward, and the lymph flow in the lower third tended to move mainly downward. The block of intra-mural lymph vessels by the tumor had very important roles upon the esophageal lymph flow. The removal of upper mediastinal lymph nodes and intraabdominal lumph nodes as well as paraesophageal lymph nodes seemed to be very important for curative resection of carcinoma of the esophagus. (author)

  17. Giant pediatric cervicofacial lymphatic malformations.

    Science.gov (United States)

    Benazzou, Salma; Boulaadas, Malik; Essakalli, Leila

    2013-07-01

    Lymphatic malformations (LMs) are benign lesions. Most of them are found in head and neck regions as asymptomatic mass, but giant lymphangiomas may affect breathing or swallowing and constitute a major therapeutic challenge. A retrospective analysis of giant head and neck LMs with impairment of respiration or swallow for the past 11 years was performed in the Department of Maxillofacial Surgery and ENT of the Avicenne Medical University Center. Seven patients with large and extensive LMs of the head and neck were identified. There were 3 males and 4 females with a mean age of 6 years. The predominant reason for referral was airway compromise necessitating tracheostomy (57%) and dysphagia (43%). Three patients had macrocystic lesions; others were considered mixed or microcystic. All the patients underwent surgical excision as a primary treatment modality. Complete surgical resection was realized in 4 patients, and subtotal resection in 3 patients. Of 7 patients, 4 patients had complications including nerve damage and recurrence of the disease. The majority of the patients underwent only a single surgical procedure. Cervicofacial LMs in children should be managed in multidisciplinary setting. Surgery remains the first treatment for managing giant, life-threatening lesions.

  18. Unusual metastasis of left colon cancer: considerations on two cases.

    Science.gov (United States)

    Gubitosi, Adelmo; Moccia, Giancarlo; Malinconico, Francesca Antonella; Gilio, Francesco; Iside, Giovanni; Califano, Umberto G A; Foroni, Fabrizio; Ruggiero, Roberto; Docimo, Giovanni; Parmeggiani, Domenico; Agresti, Massimo

    2009-04-01

    Usually, left colon cancer metastasis concerns liver, abdominal lymph nodes and lungs. Other localizations are quite rare occurrences. In spite of this, some uncommon metastasis sites are reported in literature, such as: peritoneum, ovaries, uterus, kidney testis, bones, thyroid, oral cavity and central nervous system. We report two cases of unusual localizations of left colon cancer metastasis localization, one into the retroperitoneal space and the other at the left axillary lynphnodes and between liver and pancreas. In the first reported case the diffusion pathway may have been the lymphatic mesocolic vessels, partially left in place from the previous surgery. In the second case the alleged metastatic lane may have been through the periumbilical lymph nodes to the parasternal lymph nodes and then to the internal mammary ones, finally reaching the axillary limph nodes.

  19. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    Energy Technology Data Exchange (ETDEWEB)

    Gruber-Rouh, Tatjana, E-mail: tgruberrouh@googlemail.com [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Tsaur, Igor [Department of Urology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main (Germany); Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2014-12-15

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate.

  20. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    International Nuclear Information System (INIS)

    Gruber-Rouh, Tatjana; Naguib, Nagy N.N.; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar

    2014-01-01

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate

  1. SU-E-J-115: Using Markov Chain Modeling to Elucidate Patterns in Breast Cancer Metastasis Over Time and Space

    Energy Technology Data Exchange (ETDEWEB)

    Comen, E; Mason, J; Kuhn, P [The Scripps Research Institute, La Jolla, CA (United States); Nieva, J [Billings Clinic, Billings, Montana (United States); Newton, P [University of Southern California, Los Angeles, CA (United States); Norton, L; Venkatappa, N; Jochelson, M [Memorial Sloan-Kettering Cancer Center, NY, NY (United States)

    2014-06-01

    Purpose: Traditionally, breast cancer metastasis is described as a process wherein cancer cells spread from the breast to multiple organ systems via hematogenous and lymphatic routes. Mapping organ specific patterns of cancer spread over time is essential to understanding metastatic progression. In order to better predict sites of metastases, here we demonstrate modeling of the patterned migration of metastasis. Methods: We reviewed the clinical history of 453 breast cancer patients from Memorial Sloan Kettering Cancer Center who were non-metastatic at diagnosis but developed metastasis over time. We used the variables of organ site of metastases as well as time to create a Markov chain model of metastasis. We illustrate the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Results: Based on the clinical histories of 453 breast cancer patients who developed metastasis, we have learned (i) how to create the Markov transition matrix governing the probabilities of cancer progression from site to site; (ii) how to create a systemic network diagram governing disease progression modeled as a random walk on a directed graph; (iii) how to classify metastatic sites as ‘sponges’ that tend to only receive cancer cells or ‘spreaders’ that receive and release them; (iv) how to model the time-scales of disease progression as a Weibull probability distribution function; (v) how to perform Monte Carlo simulations of disease progression; and (vi) how to interpret disease progression as an entropy-increasing stochastic process. Conclusion: Based on our modeling, metastatic spread may follow predictable pathways. Mapping metastasis not simply by organ site, but by function as either a ‘spreader’ or ‘sponge’ fundamentally reframes our understanding of metastatic processes. This model serves as a novel platform from which we may integrate the evolving genomic landscape that drives cancer

  2. SU-E-J-115: Using Markov Chain Modeling to Elucidate Patterns in Breast Cancer Metastasis Over Time and Space

    International Nuclear Information System (INIS)

    Comen, E; Mason, J; Kuhn, P; Nieva, J; Newton, P; Norton, L; Venkatappa, N; Jochelson, M

    2014-01-01

    Purpose: Traditionally, breast cancer metastasis is described as a process wherein cancer cells spread from the breast to multiple organ systems via hematogenous and lymphatic routes. Mapping organ specific patterns of cancer spread over time is essential to understanding metastatic progression. In order to better predict sites of metastases, here we demonstrate modeling of the patterned migration of metastasis. Methods: We reviewed the clinical history of 453 breast cancer patients from Memorial Sloan Kettering Cancer Center who were non-metastatic at diagnosis but developed metastasis over time. We used the variables of organ site of metastases as well as time to create a Markov chain model of metastasis. We illustrate the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites. Results: Based on the clinical histories of 453 breast cancer patients who developed metastasis, we have learned (i) how to create the Markov transition matrix governing the probabilities of cancer progression from site to site; (ii) how to create a systemic network diagram governing disease progression modeled as a random walk on a directed graph; (iii) how to classify metastatic sites as ‘sponges’ that tend to only receive cancer cells or ‘spreaders’ that receive and release them; (iv) how to model the time-scales of disease progression as a Weibull probability distribution function; (v) how to perform Monte Carlo simulations of disease progression; and (vi) how to interpret disease progression as an entropy-increasing stochastic process. Conclusion: Based on our modeling, metastatic spread may follow predictable pathways. Mapping metastasis not simply by organ site, but by function as either a ‘spreader’ or ‘sponge’ fundamentally reframes our understanding of metastatic processes. This model serves as a novel platform from which we may integrate the evolving genomic landscape that drives cancer

  3. Cancer patients use hospital-based care until death: a further analysis of the Dutch Bone Metastasis Study.

    Science.gov (United States)

    Meeuse, Jan J; van der Linden, Yvette M; Post, Wendy J; Wanders, Rinus; Gans, Rijk O B; Leer, Jan Willem H; Reyners, Anna K L

    2011-10-01

    To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. The Dutch Bone Metastasis Study (DBMS) was a nationwide study proving equal effectiveness of single fraction palliative radiotherapy compared with multiple fractions for painful bone metastases in 1157 patients. The 860 (74%) patients who died during follow-up were included in the current analysis. The main outcome was the frequency of hospital-based (outpatient contact or admission) and/or general practitioner (GP) contact during the last 12 weeks of life. Changes in HCU towards death were related to data on quality of life and pain intensity using a multilevel regression model. Hospital-based HCU was reported in 1801 (63%) returned questionnaires, whereas GP contact was stated in 1246 (43%). In 573 (20%) questionnaires, both types of HCU were reported. In multilevel regression analyses, the frequency of outpatient contacts remained constant during the weeks towards death, whereas the frequency of GP contacts increased. Lower valuation of quality of life was related to both GP- and hospital-based HCU. There was a high consumption of hospital-based HCU in the last 12 weeks of life of cancer patients with bone metastases. Hospital-based HCU did not decrease during the weeks towards death, despite an increase in GP contacts. Future planning of palliative care and training programs should encompass close collaboration between medical specialists and GPs to optimize end-of-life care.

  4. Cholinergic innervation of human mesenteric lymphatic vessels.

    Science.gov (United States)

    D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

    2013-11-01

    The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

  5. Lamb congenital lymphatic malformation - a case report

    Directory of Open Access Journals (Sweden)

    Neria Santos

    2014-01-01

    Full Text Available Lymphatic malformations have been rarely reported in literature either in humans or in animals. However, in recent years, concern about these malformations in humans has increased. A five-month-old Rasa Aragonesa male lamb was received at the Ovine Clinical Service of the Veterinary Faculty of Zaragoza, Spain, with a history of cervical protuberances coming from birth. The lamb showed three round swollen lumps (5–12 cm in diameter parallel to the trachea on the left side of the neck. Clinical examination, haematology, ultrasonography, fluid examination and histopathology were performed. No abnormalities were found in blood samples and ultrasound confirmed a multicystic lesion with internal separations. Histological evaluation of the tissue revealed dilated lymphatic vessels and channels in the dermis and hypodermis; some lymphatic vessels were filled with amorphous proteinaceous material and occasional lymphocytes and macrophages. These protuberances were diagnosed as congenital lymphatic malformations. Most of the gross and microscopical lesions were very similar to those described in humans. To the authors’ knowledge, this is the first time that a congenital lymphatic malformation is described in sheep.

  6. Exercise training improves obesity-related lymphatic dysfunction.

    Science.gov (United States)

    Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

    2016-08-01

    Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic

  7. Exercise training improves obesity‐related lymphatic dysfunction

    Science.gov (United States)

    Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene

  8. Lymphatic Vascular Regeneration : The Next Step in Tissue Engineering

    NARCIS (Netherlands)

    Huethorst, Eline; Krebber, Merle M; Fledderus, Joost O; Gremmels, Hendrik; Xu, Yan Juan; Pei, Jiayi; Verhaar, Marianne C; Cheng, Caroline

    2016-01-01

    The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces

  9. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Nevine M.F. El Deeb

    2014-06-20

    Jun 20, 2014 ... migration of connective tissue cells, and re-epithelialization of the wound ... lymphatic vessels sprouting in experimental rabbit ear wounds.9The ..... of lymphatic flow within 14 days, regaining the ability to drain fluid and ...

  10. Temperature-dependent modulation of regional lymphatic contraction frequency and flow.

    Science.gov (United States)

    Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela; Moriondo, Andrea

    2017-11-01

    Lymph drainage and propulsion are sustained by an extrinsic mechanism, based on mechanical forces acting from the surrounding tissues against the wall of lymphatic vessels, and by an intrinsic mechanism attributable to active spontaneous contractions of the lymphatic vessel muscle. Despite being heterogeneous, the mechanisms underlying the generation of spontaneous contractions share a common biochemical nature and are thus modulated by temperature. In this study, we challenged excised tissues from rat diaphragm and hindpaw, endowed with spontaneously contracting lymphatic vessels, to temperatures from 24°C (hindpaw) or 33°C (diaphragmatic vessels) to 40°C while measuring lymphatic contraction frequency ( f c ) and amplitude. Both vessel populations displayed a sigmoidal relationship between f c and temperature, each centered around the average temperature of surrounding tissue (36.7 diaphragmatic and 32.1 hindpaw lymphatics). Although the slope factor of the sigmoidal fit to the f c change of hindpaw vessels was 2.3°C·cycles -1 ·min -1 , a value within the normal range displayed by simple biochemical reactions, the slope factor of the diaphragmatic lymphatics was 0.62°C·cycles -1 ·min -1 , suggesting the added involvement of temperature-sensing mechanisms. Lymph flow calculated as a function of temperature confirmed the relationship observed on f c data alone and showed that none of the two lymphatic vessel populations would be able to adapt to the optimal working temperature of the other tissue district. This poses a novel question whether lymphatic vessels might not adapt their function to accommodate the change if exposed to a surrounding temperature, which is different from their normal condition. NEW & NOTEWORTHY This study demonstrates to what extent lymphatic vessel intrinsic contractility and lymph flow are modulated by temperature and that this modulation is dependent on the body district that the vessels belong to, suggesting a possible

  11. The effectiveness of a clinical and home-based physical activity program and simple lymphatic drainage in the prevention of breast cancer-related lymphedema: A prospective randomized controlled study.

    Science.gov (United States)

    Dönmez, Ayşe Arıkan; Kapucu, Sevgisun

    2017-12-01

    To investigate the effectiveness of a clinical and home-based, nurse-led physical activity program (PAP) and simple lymphatic drainage (SLD) in the prevention of breast cancer-related lymphedema. A total of 52 breast cancer patients were randomized to either a PAP and SLD program (n = 25) or a control group (n = 27). Patients in both groups were also provided training for lymphedema. The PAP and SLD were administered through home visits by the investigators, twice a week for six weeks, in the intervention group. The control group did not undergo intervention. The circumference of the upper extremity, symptom severity, and physical function were measured in both groups. The upper extremity circumference increased by about two times from the baseline, in the control group, especially in the sixth week (p breast cancer surgery, starting from before surgery and continuing until after, to prevent breast cancer-related lymphedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Factor VIII-associated antigen in human lymphatic endothelium.

    Science.gov (United States)

    Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

    1987-03-01

    Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

  13. Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

    Directory of Open Access Journals (Sweden)

    Jerzy Laudański

    2011-04-01

    Full Text Available The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69. Positive LVI was significantly correlated with lymph node metastasis (p < 0.001, tumor size (p < 0.001, histological grading (p = 0.017, tumor depth (p = 0.001, and stage (p < 0.001. Multivariate logistic analysis identified LVI (p = 0.036 as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04 and overall survival (p = 0.032 in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97

  14. TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling

    DEFF Research Database (Denmark)

    Ji, Hong; Cao, Renhai; Yang, Yunlong

    2014-01-01

    of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-α-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages...

  15. A Web-based nomogram predicting para-aortic nodal metastasis in incompletely staged patients with endometrial cancer: a Korean Multicenter Study.

    Science.gov (United States)

    Kang, Sokbom; Lee, Jong-Min; Lee, Jae-Kwan; Kim, Jae-Weon; Cho, Chi-Heum; Kim, Seok-Mo; Park, Sang-Yoon; Park, Chan-Yong; Kim, Ki-Tae

    2014-03-01

    The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

  16. Cell Deformation in Cancer Metastasis: a BioMEMS Based Approach

    Energy Technology Data Exchange (ETDEWEB)

    Manimaran, M [Department of Medical Devices, Institute of Bioengineering and Nanotechnology (IBN) - A-STAR, 31 Biopolis Way, Nanos 04-01, Singapore 138669 (Singapore); Tay, Francis E H [Department of Medical Devices, Institute of Bioengineering and Nanotechnology (IBN) - A-STAR, 31 Biopolis Way, Nanos 04-01, Singapore 138669 (Singapore); NUS - Department of Mechanical Engineering, Singapore 117576., Department of Medical Devices, Institute of Bioengineering and Nanotechnology, 31 Biopolis way, 04-01 Nanos, Singapore 138669 (Singapore); Chaw, K C [Department of Medical Devices, Institute of Bioengineering and Nanotechnology (IBN) - A-STAR, 31 Biopolis Way, Nanos 04-01, Singapore 138669 (Singapore)

    2006-04-01

    Here we report a BioMEMS based microfluidic device as a deformation assay to study the deformability and growth capability of cells through microgaps. The micro-gaps are ranging from 3{mu}m to 30{mu}m with three microchannels parallel to each other to mimic the blood vessel bio-microenvironment. Flow conditions in the device can be controlled to have an environment as similar to that in vivo as possible. We used osteoblast cells with approximate size of 30 {mu}m as a model cell to study the deformation ability of this cell to migrate through the 3 {mu}m gap. Such a device enabled us, for the first time to measure the cell deformation with ease. More importantly, we are able to observe the cellular responses to gaps present in the device and understand the mechanics behind the morphological change of the cells.

  17. Spleen and Lymphatic System (For Parents)

    Science.gov (United States)

    ... System Print en español El bazo y el sistema linfático The lymphatic system is an extensive drainage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  18. Modelling Lymphatic Filariasis: Transmission and Control

    NARCIS (Netherlands)

    S. Swaminathan

    2004-01-01

    textabstractLymphatic filariasis (LF) is a mosquito borne parasitic disease of the tropics. Of the three species of parasites causing the disease, W. bancrofti transmitted by Culex quinquefasciatus is the most widely prevalent. Infection can lead to disabling chronic manifestations: lymphoedema,

  19. Lymphatic Filariasis: Transmission, Treatment and Elimination

    NARCIS (Netherlands)

    W.A. Stolk (Wilma)

    2005-01-01

    textabstractLymphatic filariasis (LF) is a mosquito-borne, tropical disease caused by filarial worms. Infection can lead to disabling chronic disease, characterized by swelling of extremities or external genitalia (lymphoedema, elephantiasis and hydrocele). Mass treatment with antifilarial drugs is

  20. The deep lymphatic anatomy of the hand.

    Science.gov (United States)

    Ma, Chuan-Xiang; Pan, Wei-Ren; Liu, Zhi-An; Zeng, Fan-Qiang; Qiu, Zhi-Qiang

    2018-04-03

    The deep lymphatic anatomy of the hand still remains the least described in medical literature. Eight hands were harvested from four nonembalmed human cadavers amputated above the wrist. A small amount of 6% hydrogen peroxide was employed to detect the lymphatic vessels around the superficial and deep palmar vascular arches, in webs from the index to little fingers, the thenar and hypothenar areas. A 30-gauge needle was inserted into the vessels and injected with a barium sulphate compound. Each specimen was dissected, photographed and radiographed to demonstrate deep lymphatic distribution of the hand. Five groups of deep collecting lymph vessels were found in the hand: superficial palmar arch lymph vessel (SPALV); deep palmar arch lymph vessel (DPALV); thenar lymph vessel (TLV); hypothenar lymph vessel (HTLV); deep finger web lymph vessel (DFWLV). Each group of vessels drained in different directions first, then all turned and ran towards the wrist in different layers. The deep lymphatic drainage of the hand has been presented. The results will provide an anatomical basis for clinical management, educational reference and scientific research. Copyright © 2018 Elsevier GmbH. All rights reserved.

  1. Laryngeal spaces and lymphatics: current anatomic concepts

    International Nuclear Information System (INIS)

    Welsh, L.W.; Welsh, J.J.; Rizzo, T.A. Jr.

    1983-01-01

    This investigation evaluates the anatomic concepts of individual spaces or compartments within the larynx by isotope and dye diffusion. The authors identified continuity of spaces particularly within the submucosal planes and a relative isolation within the fixed structures resulting from the longitudinal pattern of fibroelastic tissues, muscle bands, and perichondrium. The historical data of anatomic resistance are refuted by the radioisotope patterns of dispersion and the histologic evidence of tissue permeability to the carbon particles. There is little clinical application of the compartment concept to the perimeter of growth and the configuration of extensive endolaryngeal cancers. The internal and extralaryngeal lymphatic network is presented and the regional associations are identified. The normal ipsilateral relationship is distorted by dispersion within the endolarynx supervening the anatomic midline. The effects of lymphatic obstruction caused by regional lymphadenectomy, tumor fixation, and irradiation-infection sequelae are illustrated; these result in widespread bilateral lymphatic nodal terminals. Finally, the evidence suggests that the internal network is modified by external interruption to accommodate an outflow system in continuity with the residual patent lymphatic channels

  2. Lymphatic filariasis control in Tanga Region, Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Magesa, Stephen M.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds...

  3. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  4. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    Science.gov (United States)

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  5. Lymphatic filariasis among the Yakurr people of Cross River State, Nigeria

    Directory of Open Access Journals (Sweden)

    Iboh Cletus I

    2012-09-01

    Full Text Available Abstract Background In order to initiate a disease elimination programme for lymphatic filariasis based on mass drug administration, a proper understanding of the geographical distribution and degree of risk is essential. Methods An investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out among 785 people in four communities of Yakurr Local Government Area of Cross River State, Nigeria between March and August, 2009. Finger prick blood smear samples collected from the subjects were examined for W. bancrofti using standard parasitological protocol. The subjects were also screened for clinical manifestations of lymphatic filariasis. Results Of the 785 persons examined, 48 (6.1% were positive for microfilariae in their thick blood smear. There was a significant difference in the prevalence of lymphatic filariasis among the various age groups (P  0.05. The overall mean microfilarial density of the infected individuals was 5.6mf/50 μl. There was a significant variation (P  Conclusions The National Lymphatic Filariasis Elimination Programme should intervene by expanding the distribution of albendazole and ivermectin to all endemic areas including Yakurr Local Government Area of Cross River State, Nigeria.

  6. Mathematical models and lymphatic filariasis control: monitoring and evaluating interventions.

    Science.gov (United States)

    Michael, Edwin; Malecela-Lazaro, Mwele N; Maegga, Bertha T A; Fischer, Peter; Kazura, James W

    2006-11-01

    Monitoring and evaluation are crucially important to the scientific management of any mass parasite control programme. Monitoring enables the effectiveness of implemented actions to be assessed and necessary adaptations to be identified; it also determines when management objectives are achieved. Parasite transmission models can provide a scientific template for informing the optimal design of such monitoring programmes. Here, we illustrate the usefulness of using a model-based approach for monitoring and evaluating anti-parasite interventions and discuss issues that need addressing. We focus on the use of such an approach for the control and/or elimination of the vector-borne parasitic disease, lymphatic filariasis.

  7. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System,BONENAVI, on Bone Scintigraphy Images

    Directory of Open Access Journals (Sweden)

    TAKURO ISODA

    2017-01-01

    Full Text Available Objective(s: BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN and bone scan index (BSI values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. Methods: We analyzed 50 patients (36 males, 14 females; age range: 42–87 yrs, median age: 72.5 yrs with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer. Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic,osteolytic, and mixed components was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based among the three primary cancers and four types of bone metastasis.Results: There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer, 0.909; and lung cancer, 0.864. Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic, 0.939; mildly osteoblastic, 0.788; mixed type, 0.991; and osteolytic, 0.969. The possibility of a lesion-based ANN value below 0.5 was 10.9% for bone metastasis in prostate cancer, 12.9% for breast cancer, and 37

  8. Short time effects of radiotherapy on lymphatic vessels and restorative lymphatic pathways: experimental approaches ina mouse model.

    Science.gov (United States)

    Pastouret, F; Lievens, P; Leduc, O; Bourgeois, P; Tournel, K; Lamote, J; Zirak, C; Leduc, A

    2014-06-01

    Radiotherapy (RT) is an important component in the therapeutic approach to oncologic conditions. This study presents the investigative results on the impact of RT on lymphatic vessels and on the regenerative response of the lymphatic system in a mouse model. We first irradiated 3 groups of ten mice using brachytherapy in a single treatment of 20 Gy. We then performed morphological examination of the irradiated lymphatic vessels using an in vivo microscopic transillumination technique at 2, 4, and 6 weeks. Next we evaluated lymphatic flow using lymphoscintigraphy and in vivo microscopy at 6 to 11 weeks in: 10 additional mice following irradiation as above (IR), in 10 mice following incision of a lymphatic vessel (I), and in a non-treated control group of 10 mice (N). Intact lymphatic vessels were observed in all mice at 2, 4, and 8 weeks following the single dose of radiotherapy in the first group of mice and normal lymphatic flow was fully restored in the irradiated (IR) and incised (I) mice indicating that the reparative substitution lymphatic pathways are functioning normally. We found that following irradiation with one dose of 20 Gy, lymphatic vessels were not visibly damaged and also that lymphatic flow was consistently restored and substitutive lymphatic pathways formed.

  9. Classification of the lymphatic drainage status of a primary tumor: a proposal

    International Nuclear Information System (INIS)

    Munz, D.L.; Maza, S.; Ivancevic, V.; Geworski, L.

    2000-01-01

    Aim: Creation of a classification of the lymphatic drainage status of a primary tumour. It shall enable comparison of different approaches, standardisation and quality control. Methods: Identification and topographic localisation of the sentinel node(s) using lymphatic radionuclide gamma camera imaging and/or gamma probe detection and/or vital dye mapping. Results: A classification comprising four classes (D-Class I-IV) and distinct subclasses (A-E) proved to be simply to be learned and applicable as well as reliably reproducible. It is based on the number of sentinel lymph nodes and their locations and can be combined with the pathological and molecular biological lymph node status. D-classes/subclasses obtained in 420 patients with malignant melanoma of the skin are presented. Conclusions: The classification is applicable to different approaches. Its diagnostic, therapeutic and prognostic value should be studied prospectively in those primary tumours which preferably metastasise via their draining lymphatic vessels. (orig.) [de

  10. Application of trans-lymphatic interventional bio-chemotherapy in the treatment of malignant tumors

    International Nuclear Information System (INIS)

    Zhang Qingfan; Jiang Zhaohui; Miao Jianliang; Lu Xuehua; Yang Sheng

    1998-01-01

    Purpose: To investigate the effectiveness of intralymphatic infusion of anticancerous and biologic agents in the treatment of malignancy. Methods: Forty-one patients suffering from advanced metastatic cancers and 2 patients with primary lymphoma, resistant to standard therapies or intra-arterial chemotherapy, were treated with lymphatic injections of anticancerous drugs or combined with biochemotherapy. Results: Follow-up about one month after the therapy, comparison was made based on the findings of lymphatic radiography and CT, decrease in size of lymph-odes was demonstrated in all 40 cases. Conclusion: This therapeutic approach proved to be an effective and safe method for the palliative treatment of advanced lymphatic metastases and lymphomas. The procedure was feasible without serious complications

  11. Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance

    International Nuclear Information System (INIS)

    Bai, Bing; Ma, Wei; Wang, Kai; Ha, Sita; Wang, Jian-Bo; Tan, Bing-Xu; Wang, Na-Na; Yang, Sheng-Si; Jia, Yi-Bin; Cheng, Yu-Feng

    2013-01-01

    This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P<0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Although univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients

  12. Cavitary pulmonar metastasis

    International Nuclear Information System (INIS)

    Marchiori, E.; Matushita, J.P.K.; Azevedo, C.M. de

    1984-01-01

    Seven cases of cavitary lung metastasis, four from head and neck neoplasma, two from uterine carcinoma and one from hepatoma are reported. The physiopathology and the most common sites of this kind of lesion are discussed. The rarity of the solitary excavated metastasis from hepatoma, not reported previously in the literature reviewed, is emphasized. (Author) [pt

  13. Non-endemic cases of lymphatic filariasis.

    Science.gov (United States)

    Jones, Robert T

    2014-11-01

    Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history. © 2014 John Wiley & Sons Ltd.

  14. Development and plasticity of meningeal lymphatic vessels.

    Science.gov (United States)

    Antila, Salli; Karaman, Sinem; Nurmi, Harri; Airavaara, Mikko; Voutilainen, Merja H; Mathivet, Thomas; Chilov, Dmitri; Li, Zhilin; Koppinen, Tapani; Park, Jun-Hee; Fang, Shentong; Aspelund, Aleksanteri; Saarma, Mart; Eichmann, Anne; Thomas, Jean-Léon; Alitalo, Kari

    2017-12-04

    The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. © 2017 Antila et al.

  15. The lymphatics of the cardia of stomach

    International Nuclear Information System (INIS)

    Yonemura, Yutaka; Katayama, Kanji; Sawa, Toshiharu

    1985-01-01

    The lymphatics of the cardia of stomach was examined using lymphoscintigraphy with technetium 99m colloid in 98 patients with gastric cancer and 4 patients with esophageal cancer. The colloidal Tc-99m was injected into the submucosa of stomach 12 hr before operation with the aid of endoscopy. Each lymph node dissected from the specimens was measured by scintillation counter. Lymph nodes located along the left gastric, splenic and left inferior phrenic arteries were mainly involved in the lymphatics of the cardia of stomach. There was strong relationship between the cardia and the node of number 16. The lymphatics was also present in the mediastinum. These results suggest the necessities of the complete removal of the gastropancreatic mesenteriolum including the left inferior phrenic artery and the extirpation of the regional lymph nodes around the aorta above and below the left renal artery, in addition to the removal of both pancreas and spleen in cases of cardia tumors. Furthermore, in cases of squamous cell carcinoma or adenocarcinoma metastasizing to the intraperitoneal lymph nodes, it seems necessary to extirpate the complete mediastinal lymph nodes. (Namekawa, K.)

  16. The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens

    Directory of Open Access Journals (Sweden)

    Branden A. Smeester

    2013-01-01

    Full Text Available Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3 beginning at postimplantation day 3 (PID 3. Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7, starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA’s potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

  17. Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Masako, E-mail: n-masako@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Morita, Yoshihiro [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Department of Oral and Maxillofacial Surgery, Seichokai Hannan Municipal Hospital, Hannan, Osaka 599-0202 (Japan); Hata, Kenji [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Muragaki, Yasuteru, E-mail: ymuragak@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan)

    2016-07-15

    Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5′-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-κB was induced by acidic conditions, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis. - Highlights: • Acidity accelerates the growth, migration, and tube formation of LECs. • Acidic condition induces IL-8 expression in LECs. • IL-8 is critical for the changes of LECs. • IL-8 expression is induced via TRPV1 activation.

  18. Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry

    International Nuclear Information System (INIS)

    Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E

    2013-01-01

    We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for

  19. Lymphatic microangiopathy of the skin in systemic sclerosis.

    Science.gov (United States)

    Leu, A J; Gretener, S B; Enderlin, S; Brühlmann, P; Michel, B A; Kowal-Bielecka, O; Hoffmann, U; Franzeck, U K

    1999-03-01

    The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

  20. Lymphatic imaging: Lymphography, computed tomography and scintigraphy, 2nd ed

    International Nuclear Information System (INIS)

    Close, M.E.; Wallace, S.

    1985-01-01

    The latest addition to the Golden's Diagnostic Radiology series deals not only with imaging of the lymphatic system but also with lymphatic anatomy, its pathophysiology, and treatment of disorders. The first two chapters deal with the history of the discovery of the lymphatic system and its normal anatomy. The section on technique contains practical information and discussion of lymphatic physiology and the pathology of lymphomas. Half of the book's 16 chapters are devoted to problems encountered in clinical imaging. The approach is both by anatomy (thorax, neck, abdomen) and pathology (benign disease, lymphoma, solid tumors)

  1. Preoperative prediction of sentinel lymph node metastasis in breast cancer based on radiomics of T2-weighted fat-suppression and diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yuhao; Mo, Xiaokai [Guangdong General Hospital/Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); Shantou University Medical College, Graduate College, Shantou, Guangdong (China); Feng, Qianjin; Yang, Wei; Lu, Zixiao; Deng, Chunyan [Southern Medical University, The Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Guangzhou, Guangdong (China); Zhang, Lu; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Pei, Shufang; Huang, Wenhui; Liang, Changhong; Zhang, Bin; Zhang, Shuixing [Guangdong General Hospital/Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China)

    2018-02-15

    To predict sentinel lymph node (SLN) metastasis in breast cancer patients using radiomics based on T{sub 2}-weighted fat suppression (T{sub 2}-FS) and diffusion-weighted MRI (DWI). We enrolled 146 patients with histologically proven breast cancer. All underwent pretreatment T{sub 2}-FS and DWI MRI scan. In all, 10,962 texture and four non-texture features were extracted for each patient. The 0.623 + bootstrap method and the area under the curve (AUC) were used to select the features. We constructed ten logistic regression models (orders of 1-10) based on different combination of image features using stepwise forward method. For T{sub 2}-FS, model 10 with ten features yielded the highest AUC of 0.847 in the training set and 0.770 in the validation set. For DWI, model 8 with eight features reached the highest AUC of 0.847 in the training set and 0.787 in the validation set. For joint T{sub 2}-FS and DWI, model 10 with ten features yielded an AUC of 0.863 in the training set and 0.805 in the validation set. Full utilisation of breast cancer-specific textural features extracted from anatomical and functional MRI images improves the performance of radiomics in predicting SLN metastasis, providing a non-invasive approach in clinical practice. (orig.)

  2. Lymphatic Vascular-Based Therapy for IBD

    Science.gov (United States)

    2012-07-01

    significant preservation of crypts and epithelium. Adenoviral VEGF-C + DSS also significantly reduced histopathological injury produced DSS but to a... preserved than in VEGF-D. Adenoviral GFP + DSS did not provide significant protection against tissue injury (29 ± 2.3, not significant different vs. DSS...male or female C57BL/6 mice (Jackson Laboratories, Bar Harbor, ME) or kB- lacZ mice (provided by Dr. Sylvie Memet, Pasteur Institute, Paris, France

  3. VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations.

    Science.gov (United States)

    Hägerling, René; Drees, Dominik; Scherzinger, Aaron; Dierkes, Cathrin; Martin-Almedina, Silvia; Butz, Stefan; Gordon, Kristiana; Schäfers, Michael; Hinrichs, Klaus; Ostergaard, Pia; Vestweber, Dietmar; Goerge, Tobias; Mansour, Sahar; Jiang, Xiaoyi; Mortimer, Peter S; Kiefer, Friedemann

    2017-08-17

    Lack of investigatory and diagnostic tools has been a major contributing factor to the failure to mechanistically understand lymphedema and other lymphatic disorders in order to develop effective drug and surgical therapies. One difficulty has been understanding the true changes in lymph vessel pathology from standard 2D tissue sections. VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction), a light-sheet microscopy-based approach for the analysis of tissue biopsies, is based on digital reconstruction and visualization of microscopic image stacks. VIPAR allows semiautomated segmentation of the vasculature and subsequent nonbiased extraction of characteristic vessel shape and connectivity parameters. We applied VIPAR to analyze biopsies from healthy lymphedematous and lymphangiomatous skin. Digital 3D reconstruction provided a directly visually interpretable, comprehensive representation of the lymphatic and blood vessels in the analyzed tissue volumes. The most conspicuous features were disrupted lymphatic vessels in lymphedematous skin and a hyperplasia (4.36-fold lymphatic vessel volume increase) in the lymphangiomatous skin. Both abnormalities were detected by the connectivity analysis based on extracted vessel shape and structure data. The quantitative evaluation of extracted data revealed a significant reduction of lymphatic segment length (51.3% and 54.2%) and straightness (89.2% and 83.7%) for lymphedematous and lymphangiomatous skin, respectively. Blood vessel length was significantly increased in the lymphangiomatous sample (239.3%). VIPAR is a volume-based tissue reconstruction data extraction and analysis approach that successfully distinguished healthy from lymphedematous and lymphangiomatous skin. Its application is not limited to the vascular systems or skin. Max Planck Society, DFG (SFB 656), and Cells-in-Motion Cluster of Excellence EXC 1003.

  4. Hypoxia and metastasis in an orthotopic cervix cancer xenograft model

    International Nuclear Information System (INIS)

    Chaudary, Naz; Mujcic, Hilda; Wouters, Bradly G.; Hill, Richard P.

    2013-01-01

    Background: Hypoxia can promote tumor metastasis by mechanisms that are believed to result from changes in gene expression. The current study examined the role of putative metastatic genes regulated by cyclic hypoxia in relation to metastasis formation in orthotopic models of cervix cancer. Methods: Orthotopic tumors derived from ME180 human cervix cancer cells or from early generation human cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth in vivo and tumor growth and lymphnode metastases were monitored. Expression of the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth. Results: As reported previously, exposure of tumor bearing mice to cyclic hypoxia caused a reduction of tumor growth but a large increase in metastasis. Inhibition of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor size and reduced lymphatic metastasis to levels below those seen in control mice exposed to normoxic conditions. Conclusion: Blocking CXCR4 or Hh gene expression are potential therapeutic pathways for improving cervix cancer treatment

  5. PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

    Science.gov (United States)

    Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

    2013-11-28

    the lymphatic system would ultimately be 9796 times and 6.1 times greater after administration of dendrimer doxorubicin when compared to the solution and liposome formulations respectively. The recovery of doxorubicin in the sentinel lymph nodes draining the subcutaneous injection site was also quantified directly, and consistent with the lymph pharmacokinetic data, lymph node recovery was greatest for the dendrimer formulation (12% of dosed doxorubicin/g node) when compared to the liposome (1.4%/g node) and solution (dendrimer-based drug delivery systems have the potential to enhance drug exposure to lymph-based drug targets such as lymphatic metastases. © 2013.

  6. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and

  7. Real-time MRI-guided percutaneous sclerotherapy of low-flow head and neck lymphatic malformations in the pediatric population - a stepwise approach

    Energy Technology Data Exchange (ETDEWEB)

    Partovi, Sasan; Vidal, Lorenna; Lu, Ziang; Nakamoto, Dean A.; Buethe, Ji; Clampitt, Mark; Coffey, Michael; Patel, Indravadan J. [University Hospitals Cleveland Medical Center, Case Western Reserve University, Department of Radiology, Section of Vascular and Interventional Radiology, Cleveland, OH (United States)

    2017-05-15

    Real-time MRI-guided percutaneous sclerotherapy is a novel and evolving treatment for congenital lymphatic malformations in the head and neck. We elaborate on the specific steps necessary to perform an MRI-guided percutaneous sclerotherapy of lymphatic malformations including pre-procedure patient work-up and preparation, stepwise intraprocedural interventional techniques and post-procedure management. Based on our institutional experience, MRI-guided sclerotherapy with a doxycycline-gadolinium-based mixture as a sclerosant for lymphatic malformations of the head and neck region in children is well tolerated and effective. (orig.)

  8. Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Gregory M. Nelson

    2007-12-01

    Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

  9. Lymphatic vessel density in vocal cord carcinomas assessed with LYVE-1 receptor expression

    International Nuclear Information System (INIS)

    Koskinen, Walter J.; Bono, Petri; Leivo, Ilmo; Vaheri, Antti; Aaltonen, Leena-Maija; Joensuu, Heikki

    2005-01-01

    Background and purpose: Early stage vocal cord carcinomas are usually cured by radiation therapy despite the use of portals that exclude the cervical lymph nodes. We investigated whether the lymphatic vessel density (LVD) of vocal cord carcinomas differs from that of other head and neck carcinomas. Patients and methods: Deparaffinized tissue from tumors of 60 patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were immunostained for LYVE-1, a novel lymphatic vessel marker. Twenty-two had vocal cord carcinoma. Tumor blood vessel density (BVD) was assessed using immunostaining for CD31. Results: Tumor overall LVD, including both intra- and peritumoral lymph vessels, was 10-fold lower than the BVD (5 counts/mm 2 vs. 52 mm -2 , respectively). A high LVD was associated with a high BVD (P=.002), but neither was associated with the tumor size. Both tumor LVD and BVD were lower in vocal cord carcinomas than in HNSCCs arising at other sites (median, 0 vs. 7 mm -2 , P=.016; and median, 36 vs. 52 mm -2 , P=.006, respectively). Only one vocal cord carcinoma was associated with a regional metastasis at the time of the diagnosis. Among the rest of the cases tumor size was a better predictor for the presence of regional metastases than tumor BVD or LVD in a logistic regression model (odds ratio 2.2, 95% CI 1.1-4.5). Conclusion: Vocal cord carcinomas have a low lymph vessel density as compared with HNSCCs arising at other sites

  10. Lymphatic Leak Occurring After Surgical Lymph Node Dissection: A Preliminary Study Assessing the Feasibility and Outcome of Lymphatic Embolization

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    Baek, Yoolim; Won, Je Hwan [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of); Kong, Tae-Wook; Paek, Jiheum; Chang, Suk-Joon; Ryu, Hee-Sug [Ajou University School of Medicine, Department of Obstetrics and Gynecology, Gynecologic Cancer Center (Korea, Republic of); Kim, Jinoo, E-mail: jinoomail@gmail.com [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of)

    2016-12-15

    PurposeTo analyze imaging findings of lymphatic leakage associated with surgical lymph node dissection on lymphangiography and assess the outcome of lymphatic embolization.Materials and MethodsThis retrospective study comprised 21 consecutive patients who were referred for lymphatic intervention between March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography was performed through inguinal lymph nodes to identify the leak. When a leak was found, lymphatic embolization was performed by fine-needle injection of N-butyl cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into a pelvic lymph node located below the leakage. Electronic medical records and imaging studies were reviewed to assess the outcome.ResultLymphangiography revealed single or multiple leaks in all but one patient. Lymphatic embolization was performed in 20 patients with leaks. Including the patient who did not undergo embolization, 17 patients (81.0 %) showed initial response to treatment. Three patients underwent repeated embolization with successful results. The overall success rate was 95.2 %. The mean duration of hospitalization after lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months, two patients developed localized swelling in the groin following lipiodol injection. There were no complications related to lymphatic embolization. Three patients were found to have developed small, asymptomatic lymphoceles on CT or MRI that did not require further treatment.ConclusionLymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection. Furthermore, lymphatic embolization is feasible, effective, and safe for managing leaks demonstrated on lymphangiography.

  11. Lymphatic involvement in the histopathogenesis of mucous retention cyst.

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    Kundu, Sukalyan; Cheng, Jun; Maruyama, Satoshi; Suzuki, Makoto; Kawashima, Hiroyuki; Saku, Takashi

    2007-01-01

    Mucous retention cyst results from extravasation of saliva. Our intent was to study the role of lymphatics in its pathogenesis. Twenty-three surgical specimens of mucous retention cyst of the lip were examined for involvement of lymphatic vessels by a comparative immunohistochemical demonstration of lymphatic and blood vascular endothelial cells, as well as lymphatic and salivary contents. Mucous retention cysts were histopathologically classified into three stages: early, intermediate, and advanced. In the early stage, there was diffuse extravasation of mucous material in the interstitium of the lamina propria or the submucosal layer of the oral mucosa. In the intermediate stage, lymphatics, which were clearly revealed and immunohistochemically distinguished from blood vessels by monoclonal antibody D2-40, were dilated and finally ruptured, leaving fragments of lymphatic walls in the periphery of mucous pools. In the advanced stage, thick cyst walls of granulation tissue were formed around mucous retention. Lymphatics were no longer involved in the granulation tissue wall, which was actively driven by blood vessel formation. The results suggest that the lymphatic rupture seems to contribute to the enlargement in the pathogenesis of mucous retention cyst.

  12. Investigations of lymphatic drainage from the interstitial space

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    Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

    2017-11-01

    The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

  13. Effect of 3 years of biannual mass drug administration with albendazole on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in Republic of the Congo.

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    Pion, Sébastien D S; Chesnais, Cédric B; Weil, Gary J; Fischer, Peter U; Missamou, François; Boussinesq, Michel

    2017-07-01

    The standard treatment strategy of mass drug administration with ivermectin plus albendazole for lymphatic filariasis cannot be applied in central Africa, because of the risk of serious adverse events in people with high Loa loa microfilaraemia. Thus, alternative strategies are needed. We investigated one such alternative strategy for mass drug administration for elimination of lymphatic filariasis and soil-transmitted helminth infections in Republic of the Congo. In 2012, we started a 3 year community trial of biannual mass administration of albendazole in a village in Republic of the Congo. All volunteering inhabitants aged 2 years or older were offered albendazole (400 mg) every 6 months. Infection with Wuchereria bancrofti was diagnosed with a rapid card immunochromatographic test for antigenaemia. People with antigenaemia were tested for microfilaraemia by night blood smears. Individuals were also tested for soil-transmitted helminth infections (ie, hookworm, Ascaris lumbricoides, Trichuris trichiura) with the Kato-Katz method. Assessment surveys were done at 12, 24, and 36 months. The main outcome measure was change in infection rates from baseline to year 3. Therapeutic coverage was more than 80% in all six rounds of mass administration of albendazole. Between 2012 and 2015, W bancrofti antigenaemia and microfilaraemia rates in the community fell significantly, from 17·3% (95% CI 14·7-20·0) to 4·7% (3·3-6·6; palbendazole to eliminate lymphatic filariasis in areas where loiasis is co-endemic and ivermectin cannot be safely mass administered. Bill & Melinda Gates Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

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    Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

    2013-01-01

    distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. PMID:23220211

  15. Inflammatory manifestations of experimental lymphatic insufficiency.

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    Raymond Tabibiazar

    2006-07-01

    Full Text Available BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

  16. Lymphatic albumin clearance from psoriatic skin

    International Nuclear Information System (INIS)

    Staberg, B.; Klemp, P.; Aasted, M.; Worm, A.M.; Lund, P.

    1983-01-01

    In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with 125 I or 131 I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return

  17. Efficacy and feasibility of the immunomagnetic separation based diagnosis for detecting sentinel lymph node metastasis from breast cancer

    Directory of Open Access Journals (Sweden)

    Zhi XC

    2015-04-01

    Full Text Available Xiang-Cheng Zhi,1–3,* Min Zhang,1–3,* Ting-Ting Meng,1–3,* Xiao-Bei Zhang,1–3 Zhen-Dong Shi,1–3 Yan Liu,1–3 Jing-Jing Liu,1–3 Sheng Zhang,1–3 Jin Zhang1–3 1Third Department of Breast Cancer, People’s Republic of China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, People’s Republic of China; 2Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Tianjin, People’s Republic of China; 3Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: A purpose of this study was to establish a novel molecular diagnostic model and provide new insight into the intraoperative evaluation of the sentinel lymph node (SLN metastasis in breast cancer. A total of 124 breast cancer patients who met the criteria of sentinel lymph node biopsy (SLNB and underwent intraoperative biopsy were consecutively enrolled in this study. After the SLNs obtained from each patient were labeled, MOC-31 monoclonal antibody-mediated immunomagnetic separation (IMS and flow cytometry were used to determine the expressions of breast cancer metastasis-related markers, including Mucin 1 (MUC1, CD44v6, and HER2. Alternatively, conventional intraoperative hematoxylin and eosin (HE staining and cytokeratin immunohistochemistry (CK-IHC were performed to detect potential SLN metastasis. The sensitivity, specificity, and false-negative rate of the three intraoperative diagnostic methods were compared and analyzed. A total of 55 positive-SLNs were found in 38 breast cancer patients using IMS, yielding a sensitivity of 86.4% (38/44, specificity of 94.7% (36/38, accuracy of 93.5% (116/124, false-positive rate of 2.5% (2/80, false-negative rate of 13.6% (6/44, positive predictive value of 95.5% (42/44, and negative predictive value

  18. Anti-metastasis effect of fucoidan from Undaria pinnatifida sporophylls in mouse hepatocarcinoma Hca-F cells.

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    Peisheng Wang

    Full Text Available Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK 1/2, and nuclear transcription factor-κB (NF-κB, and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs. The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.

  19. Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

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    Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

    2017-04-01

    Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

  20. Scholars and scientists in the history of the lymphatic system.

    Science.gov (United States)

    Natale, Gianfranco; Bocci, Guido; Ribatti, Domenico

    2017-09-01

    The discovery of the lymphatic system has a long and fascinating history. The interest in anatomy and physiology of this system paralleled that of the blood cardiocirculatory system and has been maybe obscured by the latter. Paradoxically, if the closed blood system appeared open in Galen's anatomy and physiology, and took a very long time to be correctly described in terms of pulmonary and general circulation by ibn Al-Nafis/Michael Servetus/Realdo Colombo and William Harvey, respectively, the open lymphatic system was incorrectly described as a closed circuit connected with arteries and veins. In ancient times only macroscopic components of the lymphatic system have been described, although misinterpreted, including lymph nodes and lacteals, the latter being easily identified because of their milk-like content. For about 15 centuries the dogmatic acceptance of Galen's notions did not allow a significant progress in medicine. After Vesalius' revolution in anatomical studies, new knowledge was accumulated, and the 17th century was the golden age for the investigation of the lymphatic system with several discoveries: gut lacteals (Gaspare Aselli), cloacal bursa (Hieronimus Fabricius of Acquapendente), reservoir of the chyle (Jean Pecquet), extra-intestinal lymphatic vessels (Thomas Bartholin and Olaus Rudbeck dispute), hepatic lymph circulation (Francis Glisson). In the Enlightenment century Frederik Ruysch described the function of lymphatic valves, and Paolo Mascagni provided a magnificent iconography of the lymphatic network in humans. In recent times, Leonetto Comparini realized three-dimensional reconstructions of the liver lymphatic vessels, and Kari Alitalo discovered the lymphatic growth factor/receptor system. Far from a complete understanding of its anatomy and function, the lymphatic system still needs to be profoundly examined. © 2017 Anatomical Society.

  1. Magnetic Resonance Imaging of Liver Metastasis.

    Science.gov (United States)

    Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

    2016-12-01

    Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Comparison of three quality of life instruments in lymphatic filariasis: DLQI, WHODAS 2.0, and LFSQQ.

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    Cristina Thomas

    2014-02-01

    Full Text Available BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis aims to interrupt transmission of lymphatic filariasis and manage morbidity in people currently living with the disease. A component of morbidity management is improving health-related quality of life (HRQoL in patients. Measurement of HRQoL in current management programs is varied because of the lack of a standard HRQoL tool for use in the lymphatic filariasis population. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the psychometric properties of three health status measures were compared when used in a group of lymphatic filariasis patients and healthy controls. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0, the Dermatology Life Quality Index (DLQI, and the Lymphatic Filariasis Quality of Life Questionnaire (LFSQQ were administered to 36 stage II and stage III lymphatic filariasis subjects and 36 age and sex matched controls in Kerala, India. All three tools yielded missing value rates lower than 10%, suggesting high feasibility. Highest internal consistency was seen in the LFSQQ (α = 0.97. Discriminant validity analysis demonstrated that HRQoL was significantly lower in the LF group than in controls for the WHODAS 2.0, DLQI, and LFSQQ, but total HRQoL scores did not differ between stage II and stage III lymphedema subjects. The LFSQQ total score correlated most strongly with the WHODAS 2.0 (r = 0.91, p<0.001 and DLQI (r = 0.81, p<0.001. CONCLUSIONS/SIGNIFICANCE: The WHODAS 2.0, DLQI, and LFSQQ demonstrate acceptable feasibility, internal consistency, discriminate validity, and construct validity. Based on our psychometric analyses, the LFSQQ performs the best and is recommended for use in the lymphatic filariasis population.

  3. Correlation between Podoplanin-positive Lymphatic Microvessel Density 
and CT Characteristics of Non-small Cell Lung Cancer

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    Hui ZHOU

    2012-01-01

    Full Text Available Background and objective It has been proven that ymphatic microvessel density (LMVD was closely correlated with the lymphatic metastasis of non-small cell lung cancer (NSCLC. The aim of the present study is to explore the relationship between podoplanin-LMVD and multi-slice spiral computed tomography (MSCT characteristics of NSCLC. Methods MSCT scanning was performed on 34 cases of NSCLC (squamous carcinoma, 15 cases; adenocarcinoma, 15 cases; and adenosquamous carcinoma, 4 cases prior to operation. Clinical pathology results, including lymph node metastasis, were obtained. CT characteristics, such as shape of the edge, internal structure, and adjacent structures, were described. LMVD in the central and peripheral areas examined respectively using SP immunohistochemical technique were analyzed. Results Lymph node metastasis was found to be associated with LMVD in the peripheral areas. LMVD in the peripheral areas of the resected lesions, the MSCT findings of which included spinous process, pleural indentation, and carcinomatous lymphangitis, was higher than that of the lesions without these MSCT characteristics (P<0.05. Conclusion MSCT findings of spinous process, pleural indentation, or carcinomatous lymphangitis of NSCLC may suggest a higher level of tumor lymphangiogenesis with a higher risk of lymph node metastasis.

  4. Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

    International Nuclear Information System (INIS)

    Kelly, Paul J.; Lin Yijie Brittany; Yu, Alvin Y.; Alexander, Brian M.; Hacker, Fred; Marcus, Karen J.; Weiss, Stephanie E.

    2012-01-01

    Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women’s Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range, 1–3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15–18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41–1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective

  5. Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Paul J., E-mail: pkelly@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Lin Yijie Brittany; Yu, Alvin Y. [Harvard Medical School, Boston, MA (United States); Alexander, Brian M.; Hacker, Fred; Marcus, Karen J.; Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States)

    2012-01-01

    Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.

  6. Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway

    International Nuclear Information System (INIS)

    Yu, Shengjin; Lv, Huiming; Zhang, He; Jiang, Yu; Hong, Yu; Xia, Rongjun; Zhang, Qifang; Ju, Weiwei; Jiang, Lili; Ou, Geng; Zhang, Jinhui; Wang, Shujing; Zhang, Jianing

    2017-01-01

    Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERK) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis. - Highlights: • SDC-1 anchors VEGF-C via its HS chains. • Secreted HPA-1 from hepatocarcinoma cell cleaves HS chains of SDC-1. • The shedding of SDC-1 HS chains releases VEGF-C from SDC-1/VEGF-C complex. • LMWH inhibits VEGF-C secretion through stabilizing SDC-1/VEGF-C complex. • VEGF-C secretion from hepatocarcinoma cell facilitates LEC growth via ERK signaling.

  7. Retrocrural Lymph Node Metastasis Disclosed by (18)F-FDG PET/CT: A Predictor of Supra-diaphragmatic Spread in Ovarian Cancer.

    Science.gov (United States)

    Im, Hyung-Jun; Kim, Yong-Il; Paeng, Jin Chul; Chung, June-Key; Kang, Soon-Beom; Lee, Dong Soo

    2012-03-01

    Retrocrural lymph nodes (RCLNs) communicate with retroperitoneal and posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra-diaphragmatic extension will occur in abdomino-pelvic cancers. The authors investigated performance of (18)F-FDG PET/CT to diagnose RCLN metastasis and whether RCLN metastases were associated with supra-diaphragmatic lymphatic metastases of ovarian cancer. Sixty-seven patients with stage IV ovarian cancer who had undergone (18)F-FDG PET/CT were included in this retrospective study. Diagnostic performance of (18)F-FDG PET/CT for RCLN metastasis was evaluated. Patients were divided into two groups by presence or absence of supra-diaphragmatic LN metastasis. The prevalences of RCLN metastasis between the two groups were compared and the odds ratio was calculated. Sensitivity and specificity of (18)F-FDG PET/CT for RCLN metastasis were 96.3 and 100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases (40.3%). Fifty patients had supra-diaphragmatic LN metastases. (18)F-FDG PET/CT showed 26 RCLN metastases in patients with supra-diaphragmatic LN metastases (54.5%), and only 1 in patients without supra-diaphragmatic LN metastasis (5.9%), and the difference between two groups was statistically significant (P supra-diaphragmatic LN metastasis was 17.3 (95% confidence interval = 2.1 to 140.9, P = 0.008). Performance of (18)F-FDG PET/CT to diagnose RCLN metastasis was excellent. RCLN metastasis revealed by (18)F-FDG PET/CT was strongly associated with supra-diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could be used as a predictor of supra-diaphragmatic lymphatic metastasis of ovarian cancer.

  8. Extensive Tattoos Mimicking Lymphatic Metastasis on Positron Emission Tomography Scan in a Patient With Cervical Cancer.

    Science.gov (United States)

    Grove, Narine; Zheng, Ma; Bristow, Robert E; Eskander, Ramez N

    2015-07-01

    Positron emission tomography (PET) fused with computed tomography (CT) imaging is common in the clinical assessment of patients with locally advanced cervical cancer. Limitations to the utilization and interpretation of PET-CT scans in patients with cervical cancer have been described, including false-positive findings secondary to tattoo ink. A 32-year-old woman presented with clinical stage 1B1 cervical cancer and extensive tattoos of the lower extremities. Preoperative PET-CT scan identified two ileac lymph nodes with increased fluorine-18-deoxyglucose uptake suspicious for metastatic disease. At the time of surgical resection, bilateral pigmented lymph nodes were identified with histologic examination showing deposition of tattoo ink and no malignant cells. Physicians should be cognizant of the possible effects of tattoos on PET-CT findings while counseling patients and formulating a treatment program.

  9. Primary Intestinal Lymphangiectasia and its Association With Generalized Lymphatic Anomaly

    Directory of Open Access Journals (Sweden)

    Victoria María Díaz Marugán

    2016-01-01

    Full Text Available Background: Lymph is a fluid originating in the interstitial spaces of the body that contains cells, proteins, particles, chylomicrons, and sometimes bacteria. Objectives: The aim of the present study is to demonstrate that primary intestinal lymphangiectasia (PIL results from a disruption of lymphatic circulation, thus corresponding to a secondary rather than a primary event in the context of generalized lymphatic anomaly. Materials and Methods: In this case series and record review, an analysis of intestinal lymphatic involvement was performed on patients diagnosed with PIL between 1965 and 2013. Of the 21 patients included in the study, 10 had been diagnosed before 5 years of age (1 prenatal, 8 between 5 and 18 years of age, and 3 while older than 18 years of age. The follow-up period varied between 1 and 34 years. Clinical data, blood and fecal parameters, imaging studies, endoscopy results, biopsy analyses, treatment details, and outcome information were collected from medical records. Endoscopy, histological studies, magnetic resonance imaging, and lymphoscintigraphy were performed on all patients. Dynamic intranodal lymphangiography was performed on 8 patients. Results: Central lymphatic channel obstruction was identified in 12 patients (57%. Associated lymphatic malformation (LM was present in 16, diarrhea in 10, chylothorax in 11, chylous ascites in 10, pericardial effusion in 6, coagulopathy in 3, and osteolysis in 7. Conclusions: We consider intestinal lymphangiectasia not as an entity in itself, but as a consequence of lymphatic flow impairment in the thoracic duct, producing chylous reflux into the intestinal lymphatics.

  10. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

    Science.gov (United States)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

    2013-04-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

  11. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Ketao Jin

    Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

  12. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

    Science.gov (United States)

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

  13. Four-dimensional CT-based evaluation of volumetric modulated arc therapy for abdominal lymph node metastasis from hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhang Li; Xi Mian; Deng Xiaowu; Li Qiaoqiao; Huang Xiaoyan; Liu Mengzhong

    2012-01-01

    This study aimed to identify the potential benefits and limitations of a new volumetric modulated arc therapy (VMAT) planning system in Monaco, compared with conventional intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). Four-dimensional CT scans of 13 patients with abdominal lymph node metastasis from hepatocellular carcinoma were selected. Internal target volume was defined as the combined volume of clinical target volumes (CTVs) in the multiple four-dimensional computed tomography (4DCT) phases. Dose prescription was set to 45 Gy for the planning target volume (PTV) in daily 3.0-Gy fractions. The PTV dose coverage, organs at risk (OAR) doses, delivery parameters and treatment accuracy were assessed. Compared with 3DCRT, both VMAT and IMRT provided a systematic improvement in PTV coverage and homogeneity. Planning objectives were not fulfilled for the right kidney, in which the 3DCRT plans exceeded the dose constraints in two patients. Equivalent target coverage and sparing of OARs were achieved with VMAT compared with IMRT. The number of MU/fraction was 462±68 (3DCRT), 564±105 (IMRT) and 601±134 (VMAT), respectively. Effective treatment times were as follows: 1.8±0.2 min (3DCRT), 6.1±1.5 min (IMRT) and 4.8±1.0 min (VMAT). This study suggests that the VMAT plans generated in Monaco improved delivery efficiency for equivalent dosimetric quality to IMRT, and were superior to 3DCRT in target coverage and sparing of most OARs. However, the superiority of VMAT over IMRT in delivery efficiency is limited. (author)

  14. Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.

    2014-01-01

    BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interrupt......BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...

  15. Mapping lymphatic nodes: Role of thrombospondin

    International Nuclear Information System (INIS)

    Spana, G.S.; Liu, J.; Rao, P.S.; Thakur, M.L.

    2002-01-01

    Aim: Lymphatic (sentinel) node (SN) mapping determines the status of lymphatic basin draining a primary tumor, provides staging information of systemic spread of malignancy, and is vital in the management of breast cancer and melanoma. Thrombospondin (TSP), a matrix bound adhesive glycoprotein, promotes cell proliferation and angiogenesis. TSP receptors are expressed on lymphocytes, and on the cells of breast cancer and melanoma. We hypothesized that Tc-99m-CSVTCR, a small, soluble, and TSP specific peptide, can image SN. Method: CSVTCR was modified at the N terminus with Aba-G(D) AGG (TP1300) and labeled with Tc-99m. Female New Zealand rabbits were anesthetized and 125 μCi TP1300 was given into the plantar/palmer surface of each foot pad in the metacarpal/metatarsal region, followed by dynamic imaging for 2 hrs and quantification of Tc-99m in SN and injection site by ROI. Control rabbits received Tc-99m-O 4 - and TP1300>Tc-99mO- 4 . Tc-99m clearance from injection site was Tc-99m-O 4 >TP1300>>TSC. % ID/g in the axillary SN was greater in than the popliteal SN for all agents. For TP1300, SN to muscle Tc-99m ratios were 552 for axillary and 140 for popliteal nodes. With infiltrating tumor cells higher uptake in SN is expected. Summary: Due to high SN uptake, rapid clearance from injection site delivering low radiation dose at injection site and ease of handling, targeting TSP receptors with Tc-99m-TP1300, a soluble, receptor specific, small biomolecule for efficient imaging of SN is promising

  16. Lung Metastasis Mimicking Fingertip Infection

    Science.gov (United States)

    Soylemez, Salih; Demiroglu, Murat; Yayla, Mehmet Ali; Ozkan, Korhan; Alpan, Bugra; Ozger, Harzem

    2015-01-01

    Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient's pain during his terminal period, saves the functions of the limb, and increases life comfort. PMID:26236517

  17. Lung Metastasis Mimicking Fingertip Infection

    Directory of Open Access Journals (Sweden)

    Salih Soylemez

    2015-01-01

    Full Text Available Metastasis fingers (acral metastasis are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient’s pain during his terminal period, saves the functions of the limb, and increases life comfort.

  18. Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Chul; Kim, Jai Keun; Lee, Jei Hee [Ajou University School of Medicine, Department of Radiology, Suwon, Gyeonggi-do (Korea, Republic of); Kim, Myeong-Jin [Yonsei University Health system, Department of Diagnostic Radiology, Institute of Gastroenterology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Kim, Young Bae [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of); Shin, Sung Jae [Ajou University School of Medicine, Department of Gastroenterology, Suwon (Korea, Republic of)

    2016-02-15

    To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis. In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59 %, and 89.47 %, respectively) were significantly higher than those of LVI (64.86 %, and 61.76 %), but sensitivity and negative predictive value were not significantly different between MVI (60.71 %, and 76.09 %) and LVI (75.00 %, and 77.42 %). While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI. (orig.)

  19. Understanding the biology of urothelial cancer metastasis

    Directory of Open Access Journals (Sweden)

    Takashi Kobayashi

    2016-10-01

    Full Text Available Management of unresectable urothelial cancer (UC has been a clinical challenge for decades. While drug resistance is a key issue, precise understanding of biology of UC metastasis is another challenge for the improvement of treatment outcome of UC patients. Introduction of the cell biology concepts including epithelial-mesenchymal transition (EMT and cancer stemness seems to explain UC metastasis. Molecular genetics based on gene expression profiling, next generation sequencing, and explosion of non-coding RNA world has opened the door to intrinsic molecular subtyping of UC. Next steps include, based on the recently accumulated understanding, the establishment of novel disease models representing UC metastasis in various experimental platforms, particularly in vivo animal systems. Indeed, novel knowledge molecular genetics has not been fully linked to the modeling of UC metastasis. Further understanding of bladder carcinogenesis is needed particularly with regard to cell of origin related to tumor characteristics including driver gene alterations, pathological differentiations, and metastatic ability. Then we will be able to establish better disease models, which will consequently lead us to further understanding of biology and eventually the development of novel therapeutic strategies for UC metastasis.

  20. Experiences of a Community-Based Lymphedema Management Program for Lymphatic Filariasis in Odisha State, India: An Analysis of Focus Group Discussions with Patients, Families, Community Members and Program Volunteers.

    Directory of Open Access Journals (Sweden)

    Tali Cassidy

    2016-02-01

    Full Text Available Globally 68 million people are infected with lymphatic filariasis (LF, 17 million of whom have lymphedema. This study explores the effects of a lymphedema management program in Odisha State, India on morbidity and psychosocial effects associated with lymphedema.Focus groups were held with patients (eight groups, separated by gender, their family members (eight groups, community members (four groups and program volunteers (four groups who had participated in a lymphedema management program for the past three years. Significant social, physical, and economic difficulties were described by patients and family members, including marriageability, social stigma, and lost workdays. However, the positive impact of the lymphedema management program was also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the etiology of the disease. Program volunteers and community members stressed the role that the program had played in educating people, though interestingly, local explanations and treatments appear to coexist with knowledge of biomedical treatments and the mosquito vector.Local and biomedical understandings of disease can co-exist and do not preclude individuals from participating in biomedical interventions, specifically lymphedema management for those with lymphatic filariasis. There is a continued need for gender-specific psychosocial support groups to address issues particular to men and women as well as a continued need for improved economic opportunities for LF-affected patients. There is an urgent need to scale up LF-related morbidity management programs to reduce the suffering of people affected by LF.

  1. Optical coherent tomography and fluorescent microscopy for the study of meningeal lymphatic systems

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Namykin, A.; Fedosov, I.; Pavlov, A.; Karavaev, A.; Sindeeva, O.; Shirokov, A.; Ulanova, M.; Shushunova, N.; Khorovodov, A.; Agranovich, I.; Bodrova, A.; Sagatova, M.; Shareef, Ali Esmat; Saranceva, E.; Dvoryatkina, M.; Tuchin, V.

    2018-04-01

    The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.

  2. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    Saban, Marcia R; Wu, Xue-Ru; Saban, Ricardo; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie

    2007-01-01

    The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF

  3. Retrocrural Lymph Node Metastasis Disclosed by 18F-FDG PET/CT: A Predictor of Supra-diaphragmatic Spread in Ovarian Cancer

    International Nuclear Information System (INIS)

    Im, Hyung Jun; Kim, Yong il; Paeng, Jin Chul; Chung, June Key; Kang, Soon Beom; Lee, Dong Soo

    2012-01-01

    Retrocrual lymph nodes (RCLNs) communicate with retroperitoneal and posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra diaphragmatic extension will occur in abdomino pelvic cancers. The authors investigated performance of 18F FDG PET/CT to diagnose RCLN metastasis and whether RCLN metastases were associated with supra diaphragmatic lymphatic metastases of ovarian cancer. Sixty seven patients with stage IV ovarian cancer who had undergone 18F FDG PET/CT were included in this retrospective study. Diagnostic performance of 18F FDG PET/CT for RCLN metastasis was evaluated. Patients were divided into two groups by presence or absence of supra diaphragmatic LN metastasis. The prevalences of RCLN metastasis between the two groups were compared and the odds ratio was calculated. Sensitivity and specificity of 18F FDG PET/CT for RCLN metastasis were 96.3 and 100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases (40.3%). Fifty patients had supra diaphragmatic LN metastases. 18F FDG PET/CT showed 26 RCLN metastases in patients with supra diaphragmatic LN metastases (54.5%), and only 1 in patients without supra diaphragmatic LN metastasis (5.9%), and the difference between two groups was statistically significant (P 18F FDG PET/CT to diagnose RCLN metastasis was excellent. RCLN metastasis revealed by 18F FDG PET/CT was strongly associated with supra diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could be used as a predictor of supra diaphragmatic lymphatic metastasis of ovarian cancer

  4. Quantum dots trace lymphatic drainage from the mouse eye

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H, E-mail: yucely@smh.ca [Department of Ophthalmology and Vision Sciences, University of Toronto, M5T 2S8 (Canada)

    2011-10-21

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  5. The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

    Science.gov (United States)

    Escobedo, Noelia; Oliver, Guillermo

    2017-10-03

    Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Quantum dots trace lymphatic drainage from the mouse eye

    International Nuclear Information System (INIS)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H

    2011-01-01

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  7. Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

    Science.gov (United States)

    Mathur, Deepan; Somashekar, Santhosh; Navarrete, Cristina; Rodriguez, Maria M

    2014-08-01

    Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

  8. Staging Lung Cancer: Metastasis.

    Science.gov (United States)

    Shroff, Girish S; Viswanathan, Chitra; Carter, Brett W; Benveniste, Marcelo F; Truong, Mylene T; Sabloff, Bradley S

    2018-05-01

    The updated eighth edition of the tumor, node, metastasis (TNM) classification for lung cancer includes revisions to T and M descriptors. In terms of the M descriptor, the classification of intrathoracic metastatic disease as M1a is unchanged from TNM-7. Extrathoracic metastatic disease, which was classified as M1b in TNM-7, is now subdivided into M1b (single metastasis, single organ) and M1c (multiple metastases in one or multiple organs) descriptors. In this article, the rationale for changes in the M descriptors, the utility of preoperative staging with PET/computed tomography, and the treatment options available for patients with oligometastatic disease are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration

    International Nuclear Information System (INIS)

    Miyashita, Takenori; Burford, James L.; Hong, Young-Kwon; Gevorgyan, Haykanush; Lam, Lisa; Mori, Nozomu; Peti-Peterdi, Janos

    2013-01-01

    Highlights: •We newly developed the whole-mount imaging method of the tympanic membrane. •Lymphatic vessel loops were localized around the malleus handle and annulus tympanicus. •In regeneration, abundant lymphatic vessels were observed in the pars tensa. •Site-specific lymphatic vessels may play an important role in the tympanic membrane. -- Abstract: We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane

  10. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  11. The protein C pathway in cancer metastasis

    NARCIS (Netherlands)

    Spek, C. Arnold; Arruda, Valder R.

    2012-01-01

    Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that

  12. Profiling plasma extracellular vesicle by pluronic block-copolymer based enrichment method unveils features associated with breast cancer aggression, metastasis and invasion.

    Science.gov (United States)

    Zhong, Zhenyu; Rosenow, Matthew; Xiao, Nick; Spetzler, David

    2018-01-01

    Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects. However, the selectivity of the precipitation becomes critical. Here, we present a simple plasma EV enrichment protocol based on pluronic block copolymer. The enriched plasma EV was able to be verified by multiple platforms. Our results showed that the particles enriched from plasma by the copolymer were EV size vesicles with membrane structure; proteomic profiling showed that EV-related proteins were significantly enriched, while high-abundant plasma proteins were significantly reduced in comparison to other precipitation-based enrichment methods. Next-generation sequencing confirmed the existence of various RNA species that have been observed in EVs from previous studies. Small RNA sequencing showed enriched species compared to the corresponding plasma. Moreover, plasma EVs enriched from 20 advanced breast cancer patients and 20 age-matched non-cancer controls were profiled by semi-quantitative mass spectrometry. Protein features were further screened by EV proteomic profiles generated from four breast cancer cell lines, and then selected in cross-validation models. A total of 60 protein features that highly contributed in model prediction were identified. Interestingly, a large portion of these features were associated with breast cancer aggression, metastasis as well as invasion, consistent with the advanced clinical stage of the patients. In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity

  13. Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2015-02-01

    The mechanism through which the stresses developed in the diaphragmatic tissue during skeletal muscle contraction sustain local lymphatic function was studied in 10 deeply anesthetized, tracheotomized adult Wistar rats whose diaphragm was exposed after thoracotomy. To evaluate the direct effect of skeletal muscle contraction on the hydraulic intraluminal lymphatic pressures (Plymph) and lymphatic vessel geometry, the maximal contraction of diaphragmatic fibers adjacent to a lymphatic vessel was elicited by injection of 9.2 nl of 1 M KCl solution among diaphragmatic fibers while Plymph was recorded through micropuncture and vessel geometry via stereomicroscopy video recording. In lymphatics oriented perpendicularly to the longitudinal axis of muscle fibers and located at skeletal muscle contraction (Dmc) decreased to 61.3 ± 1.4% of the precontraction value [resting diameter (Drest)]; however, if injection was at >900 μm from the vessel, Dmc enlarged to 131.1 ± 2.3% of Drest. In vessels parallel to muscle fibers, Dmc increased to 122.8 ± 2.9% of Drest. During contraction, Plymph decreased as much as 22.5 ± 2.6 cmH2O in all submesothelial superficial vessels, whereas it increased by 10.7 ± 5.1 cmH2O in deeper vessels running perpendicular to contracting muscle fibers. Hence, the three-dimensional arrangement of the diaphragmatic lymphatic network seems to be finalized to efficiently exploit the stresses exerted by muscle fibers during the contracting inspiratory phase to promote lymph formation in superficial submesothelial lymphatics and its further propulsion in deeper intramuscular vessels. Copyright © 2015 the American Physiological Society.

  14. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

  15. Tongue metastasis mimicking an abscess.

    Science.gov (United States)

    Mavili, Ertuğrul; Oztürk, Mustafa; Yücel, Tuba; Yüce, Imdat; Cağli, Sedat

    2010-03-01

    Primary tumors metastasizing to the oral cavity are extremely rare. Lung is one of the most common primary sources of metastases to the tongue. Although the incidence of lung cancer is increasing, tongue metastasis as the initial presentation of the tumor remains uncommon. Due to the rarity of tongue metastasis, little is known about its imaging findings. Herein we report the magnetic resonance imaging and clinical findings of a lingual metastasis, mimicking an abscess, from a primary lung cancer.

  16. The clinical value of 99mTc-MIBI imaging for axillary lymph node metastasis of breast cancer

    International Nuclear Information System (INIS)

    Song Bangkun; Yang Jisheng; Shen Dawei; Zuo Lei; Jiang Ling; Zhou Ya

    2001-01-01

    Objective: To observe the clinical value of 99m Tc-MIBI imaging for axillary lymph node metastasis of breast cancer. Methods: 56 patients with breast cancer proven by pathology were imaged with 99m Tc-MIBI. Images were taken at 5, 30, 60 minutes. The axillary area of affected side was included in imaging field. Results: The primary foci in 55 cases were positive and one case was negative in uptake. Of the 56 cases, 35 had histologically proven axillary lymph node metastases. MIBI uptake was seen in 30 cases and negative in 5 cases. The sensitivity was 85.7% (30/35 cases). In 21 cases who had no metastasis, 3 cases showed false positive uptake and 18 cases were true negative, making the specificity 85.7%. In the case who had negative imaging for primary focus, which was non-palpable, had an enlarged axillary lymphatic node. Positive MIBI uptake of the node area was seen in this case. Conclusion: 99m Tc-MIBI imaging is valuable for the diagnosis of axillary nodal metastasis of breast cancer. Even though there is no palpable primary focus, if there is an enlarged axillary lymphatic node and positive MIBI uptake, metastasis should be considered

  17. A model to measure lymphatic drainage from the eye.

    Science.gov (United States)

    Kim, Minhui; Johnston, Miles G; Gupta, Neeru; Moore, Sara; Yücel, Yeni H

    2011-11-01

    Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics. The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. This study describes that model and presents our initial findings. Following intracameral injection of (125)I-bovine serum albumin (BSA), lymph was continuously collected via cannulated cervical lymphatic vessels and the thoracic lymphatic duct over either a 3-h or 5-h time period. In the same animals, blood samples were collected from the right jugular vein every 15 min. Lymphatic and TM drainage were quantitatively assessed by measuring (125)I-BSA in lymph and plasma, respectively. Radioactive tracer levels were also measured in UVS and "other" ocular tissue, as well as periocular tissue harvested 3 and 5 h post-injection. Tracer recovered from UVS tissue was used to estimate UVS drainage. The amount of (125)I-BSA recovered from different fluid and tissue compartments was expressed as a percentage of total recovered tracer. Three hours after tracer injection, percentage of tracer recovered in lymph and plasma was 1.64% ± 0.89% and 68.86% ± 9.27%, respectively (n = 8). The percentage of tracer in UVS, other ocular and periocular tissues was 19.87% ± 5.59%, 4.30% ± 3.31% and 5.32% ± 2.46%, respectively. At 5 h (n = 2), lymphatic drainage was increased (6.40% and 4.96% vs. 1.64%). On the other hand, the percentage of tracer recovered from UVS and other ocular tissue had decreased, and the percentage from periocular tissue showed no change. Lymphatic drainage increased steadily over the 3 h post-injection period, while TM

  18. Study on enhanced lymphatic tracing of isosulfan blue injection by influence of osmotic pressure on lymphatic exposure.

    Science.gov (United States)

    Ye, Tiantian; He, Rui; Wu, Yue; Shang, Lei; Wang, Shujun

    2018-04-01

    Isosulfan blue (IB) is being used as a lymphatic tracer has been approved by the FDA in 1981. This study aimed at improving lymphatic exposure of IB injection by osmotic pressure regulation to achieve step-by step lymphatic tracing. First, IB injection with appropriate osmotic pressure, stability, and suitable pH was prepared. Next, the lymphatic tracing ability of different osmotic pressure was studied to determine the blue-stained state of IB in three-level lymph nodes after subcutaneous administration. Furthermore, pharmacokinetics of lymphatic drainage, lymph node uptake, and plasma concentration was investigate to explore the improving law of the lymphatic tracing by osmotic pressure, and combined with tissue irritation to determine the optimal osmotic pressure. At last, the tissue distribution in mice of IB injection which had the property of optimal osmotic pressure was investigated. The results showed that increasing osmotic pressure could significantly reduce injection site retention and increase IB concentration of lymph node. The lymph nodes could be obviously blue-stained by IB injection which had 938 mmol/kg osmotic pressure and would not cause inflammatory reaction and blood exposure. The tissue distribution study suggested that IB injection which had 938 mmol/kg osmotic pressure was mainly distributed into gallbladder and duodenum that verified the reports that 90% IB was excreted through the feces through biliary excretion. In conclusion, this study provides the basic study to improve lymphatic exposure of IB injection by regulate the osmotic pressure and have the potential to be the helpful guidance for the elective lymph node dissection.

  19. Structural and functional features of central nervous system lymphatic vessels.

    Science.gov (United States)

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  20. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

    Science.gov (United States)

    McNellis, Emily M.; Mabry, Sherry M.; Taboada, Eugenio; Ekekezie, Ikechukwu I.

    2014-01-01

    Pulmonary lymphatic development in chronic lung disease (CLD) has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD. PMID:24527433

  1. Indirect measurement of lymphatic absorption in CAPD patients is not influenced by trapping

    NARCIS (Netherlands)

    Struijk, D. G.; Koomen, G. C.; Krediet, R. T.; Arisz, L.

    1992-01-01

    The disappearance rate of intraperitoneally administered macromolecules is often used to calculate lymphatic absorption during CAPD. The possible contribution of local accumulation (trapping) of such solutes in the tissues surrounding the peritoneal cavity, leading to overestimation of lymphatic

  2. The lymphatic mechanisms of brain cleaning: application of optical coherence tomography and fluorescence microscopy

    Science.gov (United States)

    Glushkovskaya-Semyachkina, O.; Abdurashitov, A.; Fedosov, I.; Namykin, A.; Pavlov, A.; Shirokov, A.; Shushunova, N.; Sindeeva, O.; Khorovodov, A.; Ulanova, M.; Sagatova, V.; Agranovich, I.; Bodrova, A.; Kurths, J.

    2018-04-01

    Here we studied the role of cerebral lymphatic system in the brain clearing using intraparenchymal injection of Evans Blue and gold nanorods assessed by optical coherent tomography and fluorescence microscopy. Our data clearly show that the cerebral lymphatic system plays an important role in the brain cleaning via meningeal lymphatic vessels but not cerebral veins. Meningeal lymphatic vessels transport fluid from the brain into the deep cervical node, which is the first anatomical "station" for lymph outflow from the brain. The lymphatic processes underlying brain clearing are more slowly vs. peripheral lymphatics. These results shed light on the lymphatic mechanisms responsible for brain clearing as well as interaction between the intra- and extracranial lymphatic compartment.

  3. MR imaging of edematous limbs in lymphatic and nonlymphatic edema

    International Nuclear Information System (INIS)

    Fujii, K.

    1994-01-01

    To evaluate the role of MR imaging in the diagnosis of edema, various types of edema were examined with MR imaging. MR imaging of edematous limbs was performed on 60 patients (lymphatic edema 48, nonlymphatic edema 12) using. T1-and T2-weighted spin-echo and shot inversion time inversion recovery sequences. Thickness and signal intensity of the cutis, subcutis and subfascia were evaluated in the images. In all 48 cases with lymphatic edema, trabecular structures suggesting dilated collateral lymphatic vessels were observed in the swollen subcutis. Two cases with nephrotic syndrome showed similar findings. In 6 cases with venous edema, fatty intensity was found in the subfascia. In the remaining 4 cases, the subcutis exhibited only water intensity. MR imaging is a potential contributor to the diagnosis of various edematous diseases. (orig./MG)

  4. Vulvar Metastasis from Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  5. Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis

    Directory of Open Access Journals (Sweden)

    Francesca Luisi

    2016-06-01

    Full Text Available Generalised lymphatic anomaly (GLA, also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.

  6. Iris metastasis of gastric adenocarcinoma.

    Science.gov (United States)

    Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, U Emrah; Cosar, C Banu; Ozkiris, Abdullah

    2016-03-08

    Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis. A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy. Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.

  7. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    Science.gov (United States)

    Ellsworth, Rachel E.; Field, Lori A.; Love, Brad; Kane, Jennifer L.; Hooke, Jeffrey A.; Shriver, Craig D.

    2011-01-01

    Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis. PMID:22295210

  8. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    International Nuclear Information System (INIS)

    Ellsworth, R.E.; Field, L.A.; Kane, J.L.; Love, B.; Hooke, J.A.; Shriver, C.D.

    2011-01-01

    Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n=41) and positive (n=35) lymph node status matched for possible confounding factors were subjected to laser micro dissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis

  9. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Rachel E. Ellsworth

    2011-01-01

    Full Text Available Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (=41 and positive (=35 lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (1.5 revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis.

  10. Validation of ALFIA: a platform for quantifying near-infrared fluorescent images of lymphatic propulsion in humans

    Science.gov (United States)

    Rasmussen, John C.; Bautista, Merrick; Tan, I.-Chih; Adams, Kristen E.; Aldrich, Melissa; Marshall, Milton V.; Fife, Caroline E.; Maus, Erik A.; Smith, Latisha A.; Zhang, Jingdan; Xiang, Xiaoyan; Zhou, Shaohua Kevin; Sevick-Muraca, Eva M.

    2011-02-01

    Recently, we demonstrated near-infrared (NIR) fluorescence imaging for quantifying real-time lymphatic propulsion in humans following intradermal injections of microdose amounts of indocyanine green. However computational methods for image analysis are underdeveloped, hindering the translation and clinical adaptation of NIR fluorescent lymphatic imaging. In our initial work we used ImageJ and custom MatLab programs to manually identify lymphatic vessels and individual propulsion events using the temporal transit of the fluorescent dye. In addition, we extracted the apparent velocities of contractile propagation and time periods between propulsion events. Extensive time and effort were required to analyze the 6-8 gigabytes of NIR fluorescent images obtained for each subject. To alleviate this bottleneck, we commenced development of ALFIA, an integrated software platform which will permit automated, near real-time analysis of lymphatic function using NIR fluorescent imaging. However, prior to automation, the base algorithms calculating the apparent velocity and period must be validated to verify that they produce results consistent with the proof-of-concept programs. To do this, both methods were used to analyze NIR fluorescent images of two subjects and the number of propulsive events identified, the average apparent velocities, and the average periods for each subject were compared. Paired Student's t-tests indicate that the differences between their average results are not significant. With the base algorithms validated, further development and automation of ALFIA can be realized, significantly reducing the amount of user interaction required, and potentially enabling the near real-time, clinical evaluation of NIR fluorescent lymphatic imaging.

  11. Lymphatic vessel assessment by podoplanin (D2-40 immunohistochemistry in breast cancer

    Directory of Open Access Journals (Sweden)

    Shailja Puri Wahal

    2015-01-01

    Conclusion: Taking into account our small sample size, we conclude that a further large-sized study should be carried out to further prove the role of lymphatics in tumor dissemination. New therapeutic options can be developed targeting the lymphatic channels to arrest the lymphatic spread of the breast cancer.

  12. Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

    Directory of Open Access Journals (Sweden)

    Masayuki Nagahashi

    2016-12-01

    Conclusions: In agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.

  13. Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation.

    Science.gov (United States)

    Bouvrée, Karine; Brunet, Isabelle; Del Toro, Raquel; Gordon, Emma; Prahst, Claudia; Cristofaro, Brunella; Mathivet, Thomas; Xu, Yunling; Soueid, Jihane; Fortuna, Vitor; Miura, Nayoki; Aigrot, Marie-Stéphane; Maden, Charlotte H; Ruhrberg, Christiana; Thomas, Jean Léon; Eichmann, Anne

    2012-08-03

    The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown. We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation. We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a(-/-) mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a(-/-) mice. Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.

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

    International Nuclear Information System (INIS)

    O'Mahony, Susan; Purushotham, Arnie D.; Rose, Sarah L.; Chilvers, Alison J.; Ballinger, James R.; Solanki, Chandra K.; Barber, Robert W.; Peters, A. Michael; Mortimer, Peter S.

    2004-01-01

    Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with 99m Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id 99m Tc-HIG was compared with sc 99m Tc-HIG, in three id 99m Tc-nanocolloid was compared with sc 99m Tc-nanocolloid, in three id 99m Tc-HIG was compared with id 99m Tc-nanocolloid and in three sc 99m Tc-HIG was compared with sc 99m Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance (k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, 99m Tc-HIG gave images that were

  15. MO-G-BRF-02: Enhancement of Texture-Based Metastasis Prediction Models Via the Optimization of PET/MRI Acquisition Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Vallieres, M; Laberge, S; Levesque I, R; El Naqa, I [McGill University, Montreal, QC (Canada)

    2014-06-15

    Purpose: We have previously identified a prediction model of lung metastases at diagnosis of soft-tissue sarcomas (STS) that is composed of two textural features extracted from FDG-PET and T1-weighted (T1w) MRI scans. The goal of this study is to evaluate whether the optimization in FDGPET and MRI acquisition parameters would enhance the prediction performance of texture-based models. Methods: Ten FDG-PET and T1w- MRI digitized tumor models were generated from imaging data of STS patients who underwent pre-treatment clinical scans between 2005 and 2011. Five of ten patients eventually developed lung metastases. Numerically simulated MR images were produced using echo times (TE) of 2 and 4 times the nominal clinical parameter (TEc), and repetition times (TR) of 0.5, 0.67, 1.5 and 2 times the nominal clinical parameter (TRc) found in the DICOM headers (TEc range: 9–13 ms, TRc range: 410-667 ms). PET 2D images were simulated using Monte-Carlo and were reconstructed using an ordered-subsets expectation maximization (OSEM) algorithm with 1 to 32 iterations and a post-reconstruction Gaussian filter of 0, 2, 4 or 6 mm width. For all possible combinations of PET and MRI acquisition parameters, the prediction model was constructed using logistic regression with new coefficients, and its associated prediction performance for lung metastases was evaluated using the area under the ROC curve (AUC). Results: The prediction performance over all simulations yielded AUCs ranging from 0.7 to 1. Notably, TR values below or equal to TRc and higher PET post-reconstruction filter widths yielded higher prediction performance. The best results were obtained with a combination of 4*TEc, TRc, 30 OSEM iterations and 2mm filter width. Conclusion: This work indicates that texture-based metastasis prediction models could be improved using optimized choices of FDG-PET and MRI acquisition protocols. This principle could be generalized to other texture-based models.

  16. Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature

    International Nuclear Information System (INIS)

    Tutt, Andrew; Shu, Henry; Springall, Robert; Cane, Paul; McCallie, Blair; Kam-Morgan, Lauren; Anderson, Steve; Buerger, Horst; Gray, Joe; Bennington, James; Esserman, Laura; Wang, Alice; Hastie, Trevor; Broder, Samuel; Sninsky, John; Brandt, Burkhard; Waldman, Fred; Rowland, Charles; Gillett, Cheryl; Lau, Kit; Chew, Karen; Dai, Hongyue; Kwok, Shirley; Ryder, Kenneth

    2008-01-01

    Given the large number of genes purported to be prognostic for breast cancer, it would be optimal if the genes identified are not confounded by the continuously changing systemic therapies. The aim of this study was to discover and validate a breast cancer prognostic expression signature for distant metastasis in untreated, early stage, lymph node-negative (N-) estrogen receptor-positive (ER+) patients with extensive follow-up times. 197 genes previously associated with metastasis and ER status were profiled from 142 untreated breast cancer subjects. A 'metastasis score' (MS) representing fourteen differentially expressed genes was developed and evaluated for its association with distant-metastasis-free survival (DMFS). Categorical risk classification was established from the continuous MS and further evaluated on an independent set of 279 untreated subjects. A third set of 45 subjects was tested to determine the prognostic performance of the MS in tamoxifen-treated women. A 14-gene signature was found to be significantly associated (p < 0.05) with distant metastasis in a training set and subsequently in an independent validation set. In the validation set, the hazard ratios (HR) of the high risk compared to low risk groups were 4.02 (95% CI 1.91–8.44) for the endpoint of DMFS and 1.97 (95% CI 1.28 to 3.04) for overall survival after adjustment for age, tumor size and grade. The low and high MS risk groups had 10-year estimates (95% CI) of 96% (90–99%) and 72% (64–78%) respectively, for DMFS and 91% (84–95%) and 68% (61–75%), respectively for overall survival. Performance characteristics of the signature in the two sets were similar. Ki-67 labeling index (LI) was predictive for recurrent disease in the training set, but lost significance after adjustment for the expression signature. In a study of tamoxifen-treated patients, the HR for DMFS in high compared to low risk groups was 3.61 (95% CI 0.86–15.14). The 14-gene signature is significantly

  17. Ampullary carcinoma with cutaneous metastasis

    Directory of Open Access Journals (Sweden)

    I-Ting Liu

    2016-06-01

    Full Text Available Carcinoma of the ampulla of Vater is a rare gastrointestinal tumor. Additionally, cutaneous metastasis from such an internal malignancy is also uncommon. We reported the case of a 55-year-old man afflicted with ampullary carcinoma with cutaneous metastasis. The patient did not undergo the standard Whipple procedure but received chemotherapy due to apparent left neck lymph node metastasis noted by initial PET/CT imaging. The skin metastasis presented as a left neck infiltrating purpuric lesion, which was confirmed by skin biopsy approximately one year after the patient's disease was first diagnosed. Thereafter, the patient received further chemotherapy pursuant to his course of medical management. Skin metastasis usually represents a poor patient prognosis. In these cases, treatment of cutaneous metastasis typically includes systemic chemotherapy and local management such as radiation therapy or tumor excision. And when choosing a chemotherapy regimen for the ampullary cancer, the histological subtypes (intestinal or pancreatobiliary should be comprehensively considered. In our review of the literature, the intestinal type seems to have less distant lymph node metastasis, advanced local invasion, as well as recurrence than pancreatobiliary type of ampullary cancer.

  18. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

    Energy Technology Data Exchange (ETDEWEB)

    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hofmann, Matthias [Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt (Germany); Kusachi, Shozo [Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama (Japan); Ninomiya, Yoshifumi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hirohata, Satoshi, E-mail: hirohas@cc.okayama-u.ac.jp [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); International Center, Okayama University, Okayama (Japan)

    2014-05-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC.

  19. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

    International Nuclear Information System (INIS)

    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi; Hofmann, Matthias; Kusachi, Shozo; Ninomiya, Yoshifumi; Hirohata, Satoshi

    2014-01-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC

  20. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

    NARCIS (Netherlands)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel; Swartz, Melody A.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J.

    2013-01-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic

  1. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, Nanna Bjørkbom; Simonsen, L; Holst, J J

    2013-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  2. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We detail...

  3. Nasopharyngeal carcinoma with pericardial metastasis

    Directory of Open Access Journals (Sweden)

    Shang-Wen Chen

    2011-07-01

    Full Text Available Nasopharyngeal carcinoma (NPC is prevalent in Taiwan and is characterized by a high frequency of nodal metastasis. The most common organs with distal metastases are the bones, lungs, and liver, with extremely rare cases to the pericardium. Herein, we report a rare case with NPC who presented with dyspnea and orthopnea. Serial studies, including pericardial biopsy, revealed NPC with pericardial metastasis and pericardial effusion. The tumor cells of both the original and metastatic tumors were positive for Epstein–Barr virus by in situ hybridization. This is the first histologically confirmed case of NPC with pericardial metastasis.

  4. [A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

    Science.gov (United States)

    Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

    2005-12-01

    A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

  5. The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and LymphangiogenesisSummary

    Directory of Open Access Journals (Sweden)

    Masatake Tanaka

    2016-11-01

    Full Text Available The lymphatic vascular system has been minimally explored in the liver despite its essential functions including maintenance of tissue fluid homeostasis. The discovery of specific markers for lymphatic endothelial cells has advanced the study of lymphatics by methods including imaging, cell isolation, and transgenic animal models and has resulted in rapid progress in lymphatic vascular research during the last decade. These studies have yielded concrete evidence that lymphatic vessel dysfunction plays an important role in the pathogenesis of many diseases. This article reviews the current knowledge of the structure, function, and markers of the hepatic lymphatic vascular system as well as factors associated with hepatic lymphangiogenesis and compares liver lymphatics with those in other tissues. Keywords: VEGF, Inflammation, Cirrhosis, Portal Hypertension

  6. Lymph node metastasis in maxillary sinus carcinoma

    International Nuclear Information System (INIS)

    Le, Q.-T.; Fu, Karen K.; Kaplan, Michael J.; Terris, David J.; Fee, Willard E.; Goffinet, Don R.

    2000-01-01

    Purpose: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. Methods and Materials: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. Results: The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the

  7. Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

    Science.gov (United States)

    Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

    2018-03-01

    Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; padvanced nasopharyngeal carcinoma and might be able to predict which patients benefit

  8. Cutaneous metastasis in anorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Krishnendra Varma

    2015-01-01

    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  9. Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Parodo Giuseppina

    2011-10-01

    Full Text Available Abstract This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.

  10. Adenocarcinoma arising at a colostomy site with inguinal lymph node metastasis: report of a case.

    Science.gov (United States)

    Iwamoto, Masayoshi; Kawada, Kenji; Hida, Koya; Hasegawa, Suguru; Sakai, Yoshiharu

    2015-02-01

    Inguinal lymph node metastasis from adenocarcinoma arising at a colostomy site is extremely rare, and the significance of surgical resection for metastatic inguinal lymph nodes has not been established. An 82-year-old woman who had undergone abdominoperineal resection 27 years earlier was admitted to our hospital complaining of bleeding from a colostomy. Physical examination revealed that a tumor at the colostomy site directly invaded into the peristomal skin, and that a left inguinal lymph node was firm and swollen. Positron emission tomography/computed tomography scan demonstrated accumulation of (18)F-fluorodeoxy glucose into both the colostomy tumor and the left swollen inguinal lymph node, while there was no evidence of metastasis to liver or lungs. She underwent open left hemicolectomy with wide local resection of the colostomy, and dissection of left inguinal lymph nodes. Histological diagnosis was a moderately differentiated adenocarcinoma that directly invaded into the surrounding skin and metastasized to the left inguinal lymph node. The patient has been followed up for >5 years without any sign of recurrence. In general, inguinal lymph node metastasis from colorectal cancers is regarded as a systemic disease with a poor prognosis, and so systemic chemotherapy and radiotherapy, but not surgical lymph node dissection, are recommended. Considering the lymphatic drainage route in the present case, inguinal lymph node metastasis does not represent a systemic disease but rather a sentinel nodal metastasis from adenocarcinoma at a colostomy site. Surgical dissection of metastatic inguinal lymph nodes should be considered to enable a favorable prognosis in the absence of distant metastasis to other organs. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sh. Hashemzadeh M. Safari

    2004-11-01

    Full Text Available Although splenic metastasis is fairly common in disseminated cancer, solitary splenic metastasis in the absence of diffuse dissemination is rare. We report a case of 44 year-old man who developed isolated splenic metastasis of colon cancer. The patient had undergone right sided hemicolectomy for colon cancer in 1988. In 2001, he underwent reoperation because of local recurrence of tumor in the anastomotic site. The patient was admitted to our hospital on Sep 2003 with abdominal pain. Chest X-ray was normal. Abdominal CT scan showed a large cystic lesion in the spleen. Splenectomy was performed for the patient. The spleen was enlarged, firm and irregular. Histological examination showed metastatic mucinous adenocarcinoma. Based on this case, we recommend that clinicians consider possibility of metastasis in cystic lesions of spleen, especially in patients with a history of a malignant disease.

  12. Development of Individualized Anti-Metastasis Strategies by Engineering Nanomedicines

    Science.gov (United States)

    He, Qianjun; Guo, Shengrong; Qian, Zhiyong; Chen, Xiaoyuan

    2015-01-01

    Metastasis is deadly and also tough to treat as it is much more complicated than the primary tumour. Anti-metastasis approaches available so far are far from being optimal. A variety of nanomedicine formulas provide a plethora of opportunities for developing new strategies and means for tackling metastasis. It should be noted that individualized anti-metastatic nanomedicines are different from common anti-cancer nanomedicines as they specifically target different populations of malignant cells. This review briefly introduces the features of the metastatic cascade, and proposes a series of nanomedicine-based anti-metastasis strategies aiming to block each metastatic step. Moreover, we also concisely introduce the advantages of several promising nanoparticle platforms and their potential for constructing state-of-the-art individualized anti-metastatic nanomedicines. PMID:26056688

  13. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes.

    Science.gov (United States)

    Bianchi, Roberta; Russo, Erica; Bachmann, Samia B; Proulx, Steven T; Sesartic, Marko; Smaadahl, Nora; Watson, Steve P; Buckley, Christopher D; Halin, Cornelia; Detmar, Michael

    2017-01-01

    The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn ΔLEC ) and induced gene deletion postnatally. Pdpn ΔLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn ΔLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn ΔLEC mice. These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes. © 2016 American Heart Association, Inc.

  14. DEGRO practical guidelines: radiotherapy of breast cancer III - radiotherapy of the lymphatic pathways

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Sedlmayer, F.; Fussl, C.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Piroth, M.D.; Souchon, R.; Wenz, F.; Haase, W.

    2014-01-01

    The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: ''breast cancer'', ''radiotherapy'', ''regional node irradiation''. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data suggest that the current restrictive use of RNI should be

  15. Lymphatic filarial species differentiation using evolutionarily modified tandem repeats: generation of new genetic markers.

    Science.gov (United States)

    Sakthidevi, Moorthy; Murugan, Vadivel; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

    2010-05-01

    Polymerase chain reaction based methods are promising tools for the monitoring and evaluation of the Global Program for the Elimination of Lymphatic Filariasis. The currently available PCR methods do not differentiate the DNA of Wuchereria bancrofti or Brugia malayi by a single PCR and hence are cumbersome. Therefore, we designed a single step PCR strategy for differentiating Bancroftian infection from Brugian infection based on a newly identified gene from the W. bancrofti genome, abundant larval transcript-2 (alt-2), which is abundantly expressed. The difference in PCR product sizes generated from the presence or absence of evolutionarily altered tandem repeats in alt-2 intron-3 differentiated W. bancrofti from B. malayi. The analysis was performed on the genomic DNA of microfilariae from a number of patient blood samples or microfilariae positive slides from different Indian geographical regions. The assay gave consistent results, differentiating the two filarial parasite species accurately. This alt-2 intron-3 based PCR assay can be a potential tool for the diagnosis and differentiation of co-infections by lymphatic filarial parasites. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  16. Effects of lymphatic drainage on cellulitis assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Meyer, Patricia Froes; Martins, Nara Mendes; Martins, Flavia Mendes; Monteiro, Rosimary Araujo; Mendonca, Karla Morganna Pereira Pinto de

    2008-01-01

    The aim of this study was to assess the use of magnetic resonance as a new method for evaluating the manual lymphatic drainage technique in treating cellulitis. Cellulitis is one of the main esthetic problems that lead women toward seeking guidance and specific treatments. There are various therapeutic approaches, owing to the multifactorial nature of its pathogen, although the effectiveness of most of these has not been definitively proven, given that the assessment methods used are mostly subjective or do not provide enough information on subcutaneous tissue. The introduction of magnetic resonance as a means of assessing a lymphatic drainage technique in cellulitis treatment makes the evaluation more accurate, since it enables a detailed study of subcutaneous architecture. (author)

  17. Effects of lymphatic drainage on cellulitis assessed by magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Patricia Froes; Martins, Nara Mendes; Martins, Flavia Mendes; Monteiro, Rosimary Araujo; Mendonca, Karla Morganna Pereira Pinto de [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude

    2008-12-15

    The aim of this study was to assess the use of magnetic resonance as a new method for evaluating the manual lymphatic drainage technique in treating cellulitis. Cellulitis is one of the main esthetic problems that lead women toward seeking guidance and specific treatments. There are various therapeutic approaches, owing to the multifactorial nature of its pathogen, although the effectiveness of most of these has not been definitively proven, given that the assessment methods used are mostly subjective or do not provide enough information on subcutaneous tissue. The introduction of magnetic resonance as a means of assessing a lymphatic drainage technique in cellulitis treatment makes the evaluation more accurate, since it enables a detailed study of subcutaneous architecture. (author)

  18. Core content for training in venous and lymphatic medicine.

    Science.gov (United States)

    Zimmet, Steven E; Min, Robert J; Comerota, Anthony J; Meissner, Mark H; Carman, Teresa L; Rathbun, Suman W; Jaff, Michael R; Wakefield, Thomas W; Feied, Craig F

    2014-10-01

    The major venous societies in the United States share a common mission to improve the standards of medical practitioners, the educational goals for teaching and training programs in venous disease, and the quality of patient care related to the treatment of venous disorders. With these important goals in mind, a task force made up of experts from the specialties of dermatology, interventional radiology, phlebology, vascular medicine, and vascular surgery was formed to develop a consensus document describing the Core Content for venous and lymphatic medicine and to develop a core educational content outline for training. This outline describes the areas of knowledge considered essential for practice in the field, which encompasses the study, diagnosis, and treatment of patients with acute and chronic venous and lymphatic disorders. The American Venous Forum and the American College of Phlebology have endorsed the Core Content. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Primary disorders of the lymphatic vessels--a unified concept.

    Science.gov (United States)

    Levine, C

    1989-03-01

    Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

  20. Lymphoscintigraphic studies of lymphatic drainage from the testes

    International Nuclear Information System (INIS)

    Yeh, S.D.; Morse, M.J.; Grando, R.; Kleinert, E.L.; Whitmore, W.F. Jr.

    1986-01-01

    Two colloidal radiopharmaceuticals, Au-198 and Tc-99m antimony, were used to evaluate the lymphatic drainage of the testis in experimental animals and humans. One to 24 hours after direct intratesticular injection of Au-198 colloid in dogs and 4-6 hours after injection of Tc-99m antimony colloid in men, distribution within retroperitoneal lymph nodes was demonstrated. Uptake within the para-aortic lymph nodes primarily draining the testis was decreased following proximal ligation of the spermatic vessels in dogs. Testicular lymphoscintigraphy successfully demonstrated an intact spermatic cord lymphatic communication to the para-aortic nodes in five of six patients with chronic lower-extremity lymphedema. When the intact testicle and spermatic cord were transposed to the thigh in a patient with chronic lymphedema of the lower extremity, percutaneous pedal lymphoscintigraphy successfully demonstrated uptake within the para-aortic lymph nodes draining the ipsilateral testis

  1. LCP nanoparticle for tumor and lymph node metastasis imaging

    Science.gov (United States)

    Tseng, Yu-Cheng

    A lipid/calcium/phosphate (LCP) nanoparticle formulation (particle diameter ˜25 nm) has previously been developed to delivery siRNA with superior efficiency. In this work, 111In was formulated into LCP nanoparticles to form 111In-LCP for SPECT/CT imaging. With necessary modifications and improvements of the LCP core-washing and surface-coating methods, 111In-LCP grafted with polyethylene glycol exhibited reduced uptake by the mononuclear phagocytic system. SPECT/CT imaging supported performed biodistribution studies, showing clear tumor images with accumulation of 8% or higher injected dose per gram tissue (ID/g) in subcutaneous, human-H460, lung-cancer xenograft and mouse-4T1, breast cancer metastasis models. Both the liver and the spleen accumulated ˜20% ID/g. Accumulation in the tumor was limited by the enhanced permeation and retention effect and was independent of the presence of a targeting ligand. A surprisingly high accumulation in the lymph nodes (˜70% ID/g) was observed. In the 4T1 lymph node metastasis model, the capability of intravenously injected 111In-LCP to visualize the size-enlarged and tumor-loaded sentinel lymph node was demonstrated. By analyzing the SPECT/CT images taken at different time points, the PK profiles of 111In-LCP in the blood and major organs were determined. The results indicated that the decrement of 111In-LCP blood concentration was not due to excretion, but to tissue penetration, leading to lymphatic accumulation. Larger LCP (diameter ˜65 nm) nanoparticles were also prepared for the purpose of comparison. Results indicated that larger LCP achieved slightly lower accumulation in the tumor and lymph nodes, but much higher accumulation in the liver and spleen; thus, larger nanoparticles might not be favorable for imaging purposes. We also demonstrated that LCP with a diameter of ˜25 nm were better able to penetrate into tissues, travel in the lymphatic system and preferentially accumulate in the lymph nodes due to 1) small

  2. PMab-48 Recognizes Dog Podoplanin of Lymphatic Endothelial Cells.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-02-01

    Podoplanin, a type I transmembrane glycoprotein, is a specific marker of lymphatic endothelial cells (LECs). Recently, we developed PMab-38, an anti-dog podoplanin monoclonal antibody that did not stain canine LECs. In this study, we newly developed PMab-48 against dog podoplanin. Immunohistochemical analysis revealed that PMab-48 reacts not only with canine squamous cell carcinoma cells but also with LECs of the normal colon. Therefore, PMab-48 may be useful in investigating the function of dog podoplanin in LECs.

  3. Studies of lymphatic drainage from testes by lymphoscintigraphy

    International Nuclear Information System (INIS)

    Yeh, S.D.J.; Morse, M.J.; Grando, R.; Kleinert, E.L.; Whitmore, W.F. Jr.

    1985-01-01

    Severe lymphedema of lower extremity may cause functional disability and foster recurrent lymphangitis. Surgical transportation of the testis to the thigh offers the possibility of enhancing lymphatic drainage from the leg via spermatic cord lymphatics. Testicular lymphoscintigraphy was employed to assess the quality of testicular lymphatic drainage prior to testis transposition. Images of abdomen and measurement of testis radioactivity were made serially after injection of Au 198 colloid into the testis of dogs before and after litigation of the spermatic cord. In the intact dogs, the residual radioactivities in the testis (5 dogs) were 53.5 +- 13.25, 41.6 +- 7.80 and 26.3 +- 5.66% at 2, 4 and 24 hours post injection. After ligation of spermatic cord, the residual activities in the testis were 95.0 +- 3.33, 86.4 +- 6.49 and 74.2 +- 6.28% at corresponding intervals post injection. Paraaortic nodes and liver were visualized in the abdominal images 1 hour after injection in the intact animals but only poorly seen in dogs following ligation. /sup 99m/Tc antimony colloid was used similarly in 5 patients who had severe lymphedema and abnormal pelvic lymphoscintigraphy following bipedal injection. With intratesticular injection, paraaortic lymph nodes and liver were visualized in 7 studies between 3 to 5 hours. Poor visualization was noted in two studies in patients who had previous radiation to the abdomen. The findings suggest that this simple technic can aid in the assessment of testicular lymphatic drainage and help to select patients for appropriate surgical intervention

  4. Follicular thyroid carcinoma invades venous rather than lymphatic vessels

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    Liu Yulin

    2010-01-01

    Full Text Available Abstract Follicular thyroid carcinoma (FTC tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker, can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02. The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003. Fourteen of 32 (44% FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations.

  5. Facial nerve mapping and monitoring in lymphatic malformation surgery.

    Science.gov (United States)

    Chiara, Jospeh; Kinney, Greg; Slimp, Jefferson; Lee, Gi Soo; Oliaei, Sepehr; Perkins, Jonathan A

    2009-10-01

    Establish the efficacy of preoperative facial nerve mapping and continuous intraoperative EMG monitoring in protecting the facial nerve during resection of cervicofacial lymphatic malformations. Retrospective study in which patients were clinically followed for at least 6 months postoperatively, and long-term outcome was evaluated. Patient demographics, lesion characteristics (i.e., size, stage, location) were recorded. Operative notes revealed surgical techniques, findings, and complications. Preoperative, short-/long-term postoperative facial nerve function was standardized using the House-Brackmann Classification. Mapping was done prior to incision by percutaneously stimulating the facial nerve and its branches and recording the motor responses. Intraoperative monitoring and mapping were accomplished using a four-channel, free-running EMG. Neurophysiologists continuously monitored EMG responses and blindly analyzed intraoperative findings and final EMG interpretations for abnormalities. Seven patients collectively underwent 8 lymphatic malformation surgeries. Median age was 30 months (2-105 months). Lymphatic malformation diagnosis was recorded in 6/8 surgeries. Facial nerve function was House-Brackmann grade I in 8/8 cases preoperatively. Facial nerve was abnormally elongated in 1/8 cases. EMG monitoring recorded abnormal activity in 4/8 cases--two suggesting facial nerve irritation, and two with possible facial nerve damage. Transient or long-term facial nerve paresis occurred in 1/8 cases (House-Brackmann grade II). Preoperative facial nerve mapping combined with continuous intraoperative EMG and mapping is a successful method of identifying the facial nerve course and protecting it from injury during resection of cervicofacial lymphatic malformations involving the facial nerve.

  6. Synchronization and Random Triggering of Lymphatic Vessel Contractions

    Science.gov (United States)

    Baish, James W.; Kunert, Christian; Padera, Timothy P.; Munn, Lance L.

    2016-01-01

    The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart–to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo. PMID:27935958

  7. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  8. Lymphatics of the cardia of stomach. Examination using RI lymphoscintigraphy

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    Yonemura, Yutaka; Katayama, Kanji; Sawa, Toshiharu

    1985-01-01

    The lymphatics of the cardia of stomach was examined using lymphoscintigraphy with technetium 99m colloid in 98 patients with gastric cancer and 4 patients with esophageal cancer. The colloidal Tc-99m was injected into the submucosa of stomach 12 hr before operation with the aid of endoscopy. Each lymph node dissected from the specimens was measured by scintillation counter. Lymph nodes located along the left gastric, splenic and left inferior phrenic arteries were mainly involved in the lymphatics of the cardia of stomach. There was strong relationship between the cardia and the node of number 16. The lymphatics was also present in the mediastinum. These results suggest the necessities of the complete removal of the gastropancreatic mesenteriolum including the left inferior phrenic artery and the extirpation of the regional lymph nodes around the aorta above and below the left renal artery, in addition to the removal of both pancreas and spleen in cases of cardia tumors. Furthermore, in cases of squamous cell carcinoma or adenocarcinoma metastasizing to the intraperitoneal lymph nodes, it seems necessary to extirpate the complete mediastinal lymph nodes. (Namekawa, K.).

  9. Microenvironment Determinants of Brain Metastasis

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    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  10. Reactive Astrocytes in Brain Metastasis

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    David Wasilewski

    2017-12-01

    Full Text Available Brain metastasis, the secondary growth of malignant cells within the central nervous system (CNS, exceeds the incidence of primary brain tumors (i.e., gliomas by tenfold and are seemingly on the rise owing to the emergence of novel targeted therapies that are more effective in controlling extracranial disease relatively to intracranial lesions. Despite the fact that metastasis to the brain poses a unmet clinical problem, with afflicted patients carrying significant morbidity and a fatal prognosis, our knowledge as to how metastatic cells manage to adapt to the tissue environment of the CNS remains limited. Answering this question could pave the way for novel and more specific therapeutic modalities in brain metastasis by targeting the specific makeup of the brain metastatic niche. In regard to this, astrocytes have emerged as the major host cell type that cancer cells encounter and interact with during brain metastasis formation. Similarly to other CNS disorders, astrocytes become reactive and respond to the presence of cancer cells by changing their phenotype and significantly influencing the outcome of disseminated cancer cells within the CNS. Here, we summarize the current knowledge on the contribution of reactive astrocytes in brain metastasis by focusing on the signaling pathways and types of interactions that play a crucial part in the communication with cancer cells and how these could be translated into innovative therapies.

  11. Nodal metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    The biological behavior and hence the prognosis of thyroid cancer (TC) depends among other factors on the extent of spread of the disease outside the thyroid bed. This effect is controversial, especially for nodal metastasis of well differentiated thyroid carcinoma (WDC). Nodal metastasis at the time of initial diagnosis behaves differently depending on the histology, age of the patient, presence of extrathyroidal extension, and the sex of the individual. The type of the surgery, administration of 131 I and thyroxin suppression also to some extent influence the rate of recurrence and mortality. Experience has shown that it is not as innocuous as a small intrathyroidal tumor without any invasion outside the thyroid bed and due consideration should be accorded to the management strategies for handling patients with nodal metastasis

  12. Intracardiac metastasis originated from chondrosarcoma.

    Science.gov (United States)

    Maurea, Nicola; Ragone, Gianluca; Coppola, Carmela; Caronna, Antonietta; Tocchetti, Carlo G; Agozzino, Lucio; Apice, Gaetano; Iaffaioli, Rosario V

    2017-05-01

    Primary cardiac tumors are extremely rare. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer. Cardiac metastasis of chondrosarcoma is absolutely not frequent. In the recent literature, a cardiac metastasis from chondrosarcoma has never been described. We report the case of an 18-year-old man with a diagnosis of cardiac metastasis that originated from a left scapular chondrosarcoma. Chondrosarcoma is a skeletal tumor with various grades of malignancy, rapidly evolving, and with a strong tendency to metastasize, with low responsiveness to chemotherapy. The onset of characteristic systemic symptoms in the late stage of the disease led to the diagnosis of a mass localized in the right atrium. Management and differential diagnosis of infective heart lesions were also very complex in a rapidly evolving life-threatening condition.

  13. Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

    Science.gov (United States)

    Srinivasan, Swetha; Vannberg, Fredrik O; Dixon, J Brandon

    2016-04-18

    It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

  14. The interaction between the meningeal lymphatics and blood-brain barrier

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Dubrovsky, A.; Pavlov, A.; Shushunova, N.; Maslyakova, G.; Navolokin, N.; Bucharskaya, A.; Tuchin, V.; Kurths, J.

    2018-02-01

    Here we show the interaction between the meningeal lymphatic system and the blood-brain barrier (BBB) function. In normal state, the meningeal lymphatic vessels are invisible on optical coherent tomography (OCT), while during the opening of the BBB, meningeal lymphatic vessels are clearly visualized by OCT in the area of cerebral venous sinuses. These results give a significant impulse in the new application of OCT for the study of physiology of meningeal lymphatic system as well as sheds light on novel strategies in the prognosis of the opening of the BBB related with many central nervous system diseases, such as stroke, brain trauma, Alzheimers disease, etc.

  15. The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

    Science.gov (United States)

    Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

    2017-08-01

    Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

  16. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

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    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  17. Oral bioavailability assessment and intestinal lymphatic transport of Org 45697 and Org 46035, two highly lipophilic novel immunomodulator analogues.

    Science.gov (United States)

    Caliph, Suzanne M; Faassen, W A Fried; Vogel, Gerard M; Porter, Christopher J H

    2009-08-01

    Org 45697 (MW 600.7, clogP 7.92, soybean oil solubility 50 mg/g) and Org 46035 (MW 601.6, clog P 8.46, soybean oil solubility 40 mg/g) are two poorly water soluble ( 5 fold) after oral administration in a long chain triglyceride lipid (olive oil) formulation. Subsequent studies have explored the potential for solubilising formulations, including lipid-based formulations, to enhance the oral bioavailability of Org 45697 and Org 46035 and secondly to explore the potential contribution of intestinal lymphatic transport to intestinal absorption. The experimental data show that solubilising formulations may provide for significant increases in oral bioavailability for Org 45697 and Org 46035 and that after co-administration with lipid, 35-50% of the absorbed dose may be transported to the systemic circulation via the intestinal lymph. Interestingly, the lymphatic transport of the less lipid soluble analogue, Org 46035 was approximately 40% lower than that of Org 45697 suggesting that relatively subtle differences in lipid solubility can have significant impact on the extent of lymphatic transport.

  18. Cutaneous metastasis of bilateral renal cell carcinoma.

    Science.gov (United States)

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  19. Metastasis genetics, epigenetics, and the tumor microenvironment

    Science.gov (United States)

    KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...

  20. Gut metastasis from breast carcinoma.

    Science.gov (United States)

    Al-Qahtani, Mohammed S

    2007-10-01

    Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone, and the brain. Metastases to the gastrointestinal tract are rare with patients presenting with small-bowel perforation, intestinal obstruction, and gastrointestinal bleeding. Here we report a case of a Saudi female presenting with invasive lobular carcinoma and ileo-cecal junction metastasis.

  1. Gut metastasis from breast carcinoma

    International Nuclear Information System (INIS)

    Al-Qahtani, Mohammad S.

    2007-01-01

    Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone and the brain. Metastases to the gastrointestinal tract are with patients presenting with small-bowel perforation, intestinal obstruction and gastrointestinal bleeding. Here we report a case of Saudi female presenting with invasive lobular carcinoma and i leo-junction metastasis. (author)

  2. Pulmonary Metastasis from Pseudomyxoma Peritonei

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    Toshiyuki Kitai

    2012-01-01

    Full Text Available Pseudomyxoma peritonei (PMP is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.

  3. Comparison of four staging systems of lymph node metastasis in gastric cancer.

    Science.gov (United States)

    Zhang, Ming; Zhu, Guanyu; Ma, Yan; Xue, Yingwei

    2009-11-01

    The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis. In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate). In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system. Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.

  4. Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol.

    Science.gov (United States)

    Hasegawa, Hideo; Suzuki, Ryuichi; Nagaoka, Takema; Tezuka, Yasuhiro; Kadota, Shigetoshi; Saiki, Ikuo

    2002-07-01

    Ginsenosides, the glycosides of Panax ginseng, are metabolized (deglycosylated) by intestinal bacteria after oral administration. 20(S)-Protopanaxatriol (M4) is the main bacterial metabolite of protopanaxatriol-type ginsenosides and mediates their antitumor effects. To clarify the mechanism of the M4-mediated antitumor effect, the antitumor activity and metabolism of M4 was examined, using the C57BL/6 mice implanted with B16-BL6 melanoma. The chronic oral administration of M4 inhibited the growth of B16-BL6 melanoma at the implanted site. Analyses using TLC, HPLC, MS and NMR suggest that orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its accumulation in the tissues including the liver and lung. The administration of M4 prior to the intravenous injection of B16-BL6 cells abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GM1. The esterified M4 (EM4) did not directly affect tumor growth in vitro, whereas it stimulated splenic NK cells to become cytotoxic to tumor cells. These results indicate that the antitumor activity of M4 is based on the NK cell-mediated tumor lysis enhanced by EM4.

  5. CT manifestation of peritoneal metastasis

    International Nuclear Information System (INIS)

    Cha, Soon Joo; Kang, Eun Young; Suh, Won Hyuck

    1989-01-01

    Peritoneal metastasis is frequent mode of dissemination of intraabdominal malignancies. Radiologic diagnosis of peritoneal metastasis has relied on indirect evidence on a barium UGI series and small bowel examination. With the advent of CT scanning, CT is capable of direct imaging of peritoneum. The sensitivity of CT in detecting peritoneal metastasis and CT manifestation of peritoneal metastatic lesions had reported occasionally, but rarely in Korea. So, authors illustrated the CT manifestation of peritoneal metastatic lesions in 32 cases of macroscopically proven cases in laparoscopy or laparotomy in Korea University Hae Wha Hospital during recent 4 years. The results are as follows. 1. Of total 32 cases, 18 cases were male and 14 cases were female. Age incidence was the most common in 6th decade. 2. The most common type of malignancy that cause peritoneal metastasis was the stomach cancer and next common type of malignancies were pancreas cancer in men and ovarian cancer in women. 3. Of total 32 cases of peritoneal metastasis which was confirmed by laparoscopy or laparotomy macroscopically, 23 cases (72%) were detected peritoneal thickening and/or omental pathology by CT, and the remaining 9 cases (28%) were not detected by CT. 4. Ascites was present in 19 cases (59%). 5. Parietal peritoneal thickening was present in 16 cases (50%) by CT and sheetlike pattern was the most common findings. The patterns of peritoneal thickening was relatively nonspecific and was not correlated with primary tumor type. 6. Tumor involvement of greater omentum by CT was present in 19 cases (59%). There were 7 cases of smudged appearance pattern, 6 cases of nodular pattern, 6 cases of omental cake pattern and no cystic mass pattern. The patterns of omental pathology was relatively nonspecific and was nor correlated with primary tumor type

  6. A microarray analysis of two distinct lymphatic endothelial cell populations

    Directory of Open Access Journals (Sweden)

    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  7. Survival of Lymphatic Cells after X-Irradiation in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Vos, O. [Medical Biological Laboratory, National Defense Research Organization TNO, Ruswuk, Z.H. (Netherlands)

    1967-07-15

    Lymphatic tissues are generally classified among the most radiosensitive tissues of the body. The main reason for this is that histologically extensive destruction is found within a few hours after irradiation. We tried to estimate the degree of cellular degeneration by making cell suspensions from lymph nodes and thymus of mice at different times after X-irradiation with 800 R or at 24 h after radiation with different doses. The numbers of normal viable cells we obtained were expressed as percentages of the cells recovered from unirradiated control mice.

  8. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  9. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimul...

  11. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    Science.gov (United States)

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity.

    Science.gov (United States)

    Wang, Yixin; Jin, Yi; Mäe, Maarja Andaloussi; Zhang, Yang; Ortsäter, Henrik; Betsholtz, Christer; Mäkinen, Taija; Jakobsson, Lars

    2017-10-01

    Tissue fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and its role in vessel maturation are unknown. Here, we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, Pdgfb overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  13. Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy

    NARCIS (Netherlands)

    Tanis, P. J.; Nieweg, O. E.; Valdés Olmos, R. A.; Kroon, B. B.

    2001-01-01

    Knowledge of the anatomy and physiology of the lymphatic system is helpful when considering a particular sentinel node biopsy technique. The delicate balance between internal and external pressures in a lymphatic channel can be influenced by the injection volume and by massage in a negative or

  14. Development and validation of a custom made indocyanine green fluorescence lymphatic vessel imager

    Science.gov (United States)

    Pallotta, Olivia J.; van Zanten, Malou; McEwen, Mark; Burrow, Lynne; Beesley, Jack; Piller, Neil

    2015-06-01

    Lymphoedema is a chronic progressive condition often producing significant morbidity. An in-depth understanding of an individual's lymphatic architecture is valuable both in the understanding of underlying pathology and for targeting and tailoring treatment. Severe lower limb injuries resulting in extensive loss of soft tissue require transposition of a flap consisting of muscle and/or soft tissue to close the defect. These patients are at risk of lymphoedema and little is known about lymphatic regeneration within the flap. Indocyanine green (ICG), a water-soluble dye, has proven useful for the imaging of lymphatic vessels. When injected into superficial tissues it binds to plasma proteins in lymph. By exposing the dye to specific wavelengths of light, ICG fluoresces with near-infrared light. Skin is relatively transparent to ICG fluorescence, enabling the visualization and characterization of superficial lymphatic vessels. An ICG fluorescence lymphatic vessel imager was manufactured to excite ICG and visualize real-time fluorescence as it travels through the lymphatic vessels. Animal studies showed successful ICG excitation and detection using this imager. Clinically, the imager has assisted researchers to visualize otherwise hidden superficial lymphatic pathways in patients postflap surgery. Preliminary results suggest superficial lymphatic vessels do not redevelop in muscle flaps.

  15. Flat-Panel Detector—Based Volume Computed Tomography: A Novel 3D Imaging Technique to Monitor Osteolytic Bone Lesions in a Mouse Tumor Metastasis Model

    Directory of Open Access Journals (Sweden)

    Jeannine Missbach-Guentner

    2007-09-01

    Full Text Available Skeletal metastasis is an important cause of mortality in patients with breast cancer. Hence, animal models, in combination with various imaging techniques, are in high demand for preclinical assessment of novel therapies. We evaluated the applicability of flat-panel volume computed tomography (fpVCT to noninvasive detection of osteolytic bone metastases that develop in severe immunodeficient mice after intracardial injection of MDA-MB-231 breast cancer cells. A single fpVCT scan at 200-wm isotropic resolution was employed to detect osteolysis within the entire skeleton. Osteolytic lesions identified by fpVCT correlated with Faxitron X-ray analysis and were subsequently confirmed by histopathological examination. Isotropic three-dimensional image data sets obtained by fpVCT were the basis for the precise visualization of the extent of the lesion within the cortical bone and for the measurement of bone loss. Furthermore, fpVCT imaging allows continuous monitoring of growth kinetics for each metastatic site and visualization of lesions in more complex regions of the skeleton, such as the skull. Our findings suggest that fpVCT is a powerful tool that can be used to monitor the occurrence and progression of osteolytic lesions in vivo and can be further developed to monitor responses to antimetastatic therapies over the course of the disease.

  16. Comparison of FDG PET and CT/MRI in the diagnosis of cervical lymph node metastasis of head and neck cancer: a level-by-level based study

    International Nuclear Information System (INIS)

    Yang, You Jung; Kim, J. S.; Kim, S. Y.; Nam, S. Y.; Lee, W. W.; Ryu, J. S.; Yeo, J. S.; Moon, D. H.

    2002-01-01

    We compared diagnostic accuracy of FDG PET and CT/MRI for regional lymph node metastasis of head and neck cancer according to the level of cervical lymph node. Thirty-two patients (M/F=27/5, 56±10yr) with head and neck cancer (glottic cancer; 16, tongue cancer; 9, others; 7) uncerwent FDG PET and CT/MRI (29/3) within 1 month before elective surgery with neck dissection (bilateral in 21, unilateral in 11). Whole body and additional regional neck images were acquired 1 hr after injection of FDG (555 MBq). PET images were visually interpreted according to the cervical lymph node level by 2 nuclear physicians independently without CT/MRI information. The findings of PET and CT/MRI were confirmed by the surgical pathology(153 levels of 43 neck dissections). There were 32 positive levels and 121 negative levels for metastatic lymph node lesions in pathology. The diagnostic sensitivity of PET [88%(28/32)] was significantly higher than that of CT/MRI [63%(20/32)] (p=0.021), whereas the specificity of PET [93%(113/121)] was similar to that of CT/MRI [92%(111/121)] (p>0.05). FDG PET was more sensitive than conventional CT/MRI in detecting metastatic lymph node of head and neck cancer

  17. [Study of Chinese herbal medicine in treating ascites and their mechanism in regulating lymphatic stomata].

    Science.gov (United States)

    Wu, Y; Li, J C; Mao, L G

    2001-09-01

    To study the therapeutic effect of Chinese herbal medicines (CHM) in treating ascites to elucidate its mechanism in regulating the lymphatic stomata and promoting the absorption of ascites from the peritoneal cavity. Using scanning electron microscope (SEM) and computerized image processing and quantitative analysis assays, the CHM extract consisting of Atractylodes macrocephala, Salvia miltiorrhiza, Codonopsis pilosula, Alismatis orientale and Leonurus heterophyllus were studied. Intraperitoneal injection of nitric oxide (NO) supplier or CHM administration could cause the average area of lymphatic stomata obviously enlarged (P inverted obviously, i.e. the average area and the density of lymphatic stomata were markedly reduced (P < 0.01). CHM might treat ascites through increasing the endogenous NO concentration to open the lymphatic stomata and in turn to conduct the peritoneal water through lymphatic path.

  18. Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion.

    Science.gov (United States)

    Pavlov, Vadim; Rosental, Benyamin; Hansen, Nathaniel F; Beers, Jody M; Parish, George; Rowbotham, Ian; Block, Barbara A

    2017-07-21

    The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. An Unusual Presentation of Lung Cancer Metastasis: Perianal Abscess

    Directory of Open Access Journals (Sweden)

    Murat Kilic

    2014-06-01

    Full Text Available Lung cancer is one of the most commonly diagnosed cancers in both men and women. Although the most frequent sites of distant metastasis of lung cancers are the pleura, liver, adrenal glands, skeletal system and brain, perianal region has been rarely reported as a metastasis site. A male patient was admitted to our emergency room with a long standing perianal abscess. During abscess drainage, a mass was noticed at the base of the abscess pouch, and thus a biopsy was taken. Pathologically, it was reported as a metastasis of squamous cell carcinoma, therefore some radiological  investigations and endoscopic procedures were performed to determine the primary focus of cancer. A pulmonary mass was revealed in PET/CT, and was considered as primary tumor. Both primary and metastatic perianal tumors can be rarely presented as an abscess formation. In this situation, a biopsy should be performed from the lesion to avoid misdiagnosis.

  20. Lymphatic drainage and sentinel node location in breast cancer

    International Nuclear Information System (INIS)

    Uren, R.F.; Howman-Giles, R.B.; Roberts, J.; Renwick, S.; Gillett, D.; Neische, F.; Ramsay-Stewart, G.

    1999-01-01

    Full text: Mammary lymphoscintigraphy using small volume (0.1-0.2 ml) peritumoral injections of 99 Tc m -antimony sulphide colloid provided a map of the lymph drainage of a breast cancer to its draining sentinel lymph nodes in 92 of 102 patients (over 90%). Non-migration of tracer is reduced by post-injection massage for 5 min but may occur especially if the lymphatics are blocked by metastases. Drainage included the axilla in 92%, internal mammary nodes in 43%, supraclavicular nodes in 12% and intramammary interval nodes in 10% of patients. One patient drained to an interpectoral node. Drainage across the centre-line of the breast occurred in 46% of patients but direct drainage to the contralateral side of the patient was not seen. Lymphatic drainage occurred to 1 node field in 52 patients, 2 node fields in 34 patients and 3 node fields in 6 patients, so that 43% of patients had multiple draining node fields. Drainage to non-axillary sites occurred in 51% of patients. In conclusion, mammary lymphoscintigraphy accurately maps sentinel node location in breast cancer. Approximately half of the patients will have sentinel nodes outside the axilla. To achieve complete lymph node staging in patients with breast cancer, it is logical to biopsy these non-axillary sentinel nodes as well as the sentinel nodes in the axilla. Failure to do so will potentially understage the node status in 50% of patients

  1. Histopathologic aspects of radiation effects on lymphatic tissues and malignancies

    International Nuclear Information System (INIS)

    Lushbaugh, C.C.; Swartzendruber, D.C.

    1976-01-01

    Morphologic study with the light microscope remains our most facile and rapid means of tissue identification, diagnosis and staging of diseases, and demonstration of radiation-induced and other toxic effects. The inadequacy of its use alone, however, for the solution of biologic problems is nowhere better illustrated than in such studies on lymphatic tissues as are reported in this symposium. Nearly every classical concept concerning lymphocyte biology and disease derived by morphologic methods has been challenged or disproved in recent years by applications of nonmorphologic technologies. Studies with light and electron microscopy in combination with cell-labeling techniques, histochemical methodology, virology, immunology, and radiation biology have corrected many of our misconceptions and provided unifying concepts of lymphatic-tissue structure and function which explain anew our observations of the past. For example, nearly everyone now accepts the biologic role of viruses in what once were considered radiation-caused neoplasms in rodents, although whether the role of radiation and other physical and chemical insults in human carcinogenesis is direct or indirect is still to be elucidated. Also, the exact relations that obtain between radiation and cancer induction via viruses even in well-studied rodent systems remain to be determined; and here morphologic studies continue to play an important integrating role for the multidisciplinary studies that are required

  2. [The mantle zone in lymphatic follicles and its stratification].

    Science.gov (United States)

    Bednár, B

    1993-04-01

    Ten inguinal lymph nodes and spleens from autopsies were chosen according to age decades in order to get an idea about usual appearance of follicular structures. The group was complemented by 4 palatine tonsils from routine biopsies. Phenotype was ascertained by using about 30 standard markers and results were compared with a basic histocytological picture. The appearance of lymphatic tissue was quite different according to location and age categories, nevertheless, there were common immunophenotypic and structural features of follicular mantle in younger persons. It mostly comprised four cellular layers, more conspicuous at the upper pole of the follicle. An innermost layer was small-celled blastic, MB 2 and IgD positive, the next B monocytoid layer had medium sized cells of a similar phenotype but more alc, phosphatase positive. An inconstant plasmacytoid layer and a clarocellular layer used to be incomplete. It was cytostructurally characteristic but immunohistologically non-standard (faint CD 19 et CD 20 positivity). T 4 lymphocytes and perhaps some other elements leaving germinal centres were admixed into the inner mantle layer. Various small lymphoid cells, especially T 8 lymphocytes and sometimes litoral cells, were admixed into mantle periphery. Mutual exchange of lymphatic cells between the germinal and mantle zones was very scant. The mantle zone is presumed therefore to be independent from the structural and functional point of view as well.

  3. A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

    Science.gov (United States)

    Haloob, Nora; Pepper, Christopher; Hartley, Benjamin

    2015-12-01

    Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Sclerotherapy for lymphatic malformations in children: a scoping review.

    Science.gov (United States)

    Churchill, Paige; Otal, Damanjot; Pemberton, Julia; Ali, Abdullah; Flageole, Helene; Walton, J Mark

    2011-05-01

    This scoping review assesses the literature and summarizes the current evidence on sclerotherapy for the treatment of lymphatic malformations in pediatric patients. A comprehensive search of published and unpublished literature was conducted using multiple databases. Title, abstract, and full-text screening was conducted by 2 independent clinicians. All discrepancies were resolved during consensus meetings. A total of 182 articles were retrieved. Forty-four articles were removed as duplicates, and 11 articles were added after reviewing prominent studies. After full-text abstraction, 44 articles and 2 conference proceedings (N = 882 patients) were included in the final results. Twelve articles were classified as level II and 34 articles as level IV evidence. Picibanil (OK-432) was the primary agent used in most included studies. Postinjection symptoms with OK-432 were primarily fever, swelling, and erythema at the site. Life-threatening complications were uncommon and involved postinjection swelling of cervical lesions causing airway compromise. The literature regarding sclerotherapy for lymphatic malformations is of a low level of evidence and suffers from a lack of standardization. Randomized clinical trials focused on OK-432, bleomycin, or alcoholic solution of zein; standardized dosing protocols; and consistent and reliable outcome reporting will be necessary for further development of treatment guidelines. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Predictive factors for lymph node metastasis in poorly differentiated early gastric cancer and their impact on the surgical strategy

    Science.gov (United States)

    Li, Hua; Lu, Ping; Lu, Yang; Liu, Cai-Gang; Xu, Hui-Mian; Wang, Shu-Bao; Chen, Jun-Qing

    2008-01-01

    AIM: To identify the predictive clinicopathological factors for lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to further expand the possibility of using endoscopic mucosal resection (EMR) for the treatment of poorly differentiated EGC. METHODS: Data were collected from 85 poorly-differentiated EGC patients who were surgically treated. Association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size (OR = 5.814, 95% CI = 1.050 - 32.172, P = 0.044), depth of invasion (OR = 10.763, 95% CI = 1.259 - 92.026, P = 0.030) and lymphatic vessel involvement (OR = 61.697, 95% CI = 2.144 - 175.485, P = 0.007) were the significant and independent risk factors for LNM. The LNM rate was 5.4%, 42.9% and 50%, respectively, in poorly differentiated EGC patients with one, two and three of the risk factors, respectively. No LNM was found in 25 patients without the three risk factors. Forty-four lymph nodes were found to have metastasis, 29 (65.9%) and 15 (34.1%) of the lymph nodes involved were within N1 and beyond N1, respectively, in 12 patients with LNM. CONCLUSION: Endoscopic mucosal resection alone may be sufficient to treat poorly differentiated intramucosal EGC (≤ 2.0 cm in diameter) with no histologically-confirmed lymphatic vessel involvement. When lymphatic vessels are involved, lymph node dissection beyond limited (D1) dissection or D1+ lymph node dissection should be performed depending on the tumor location. PMID:18636670

  6. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...

  7. An Unusual Presentation of Lung Cancer Metastasis: Perianal Abscess

    OpenAIRE

    Murat Kilic

    2014-01-01

    Lung cancer is one of the most commonly diagnosed cancers in both men and women. Although the most frequent sites of distant metastasis of lung cancers are the pleura, liver, adrenal glands, skeletal system and brain, perianal region has been rarely reported as a metastasis site. A male patient was admitted to our emergency room with a long standing perianal abscess. During abscess drainage, a mass was noticed at the base of the abscess pouch, and thus a biopsy was taken. Pathologically, it w...

  8. Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.

    Science.gov (United States)

    Hinson, Andrew M; Massoll, Nicole A; Jolly, Lee Ann; Stack, Brendan C; Bodenner, Donald L; Franco, Aime T

    2017-08-01

    The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic Braf V600E with and without Pten insufficiency. After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis. Although mice harboring Braf V600E mutations were smaller in body size compared with their wild-type (WT) littermates, the size of their thyroid glands and deep cervical lymph nodes were significantly larger. Additionally, the tumor-draining lymph nodes showed increased and enlarged lymphatic sinuses that were distributed throughout the cortex and medulla. Tumor-reactive lymphadenopathy and histiocytosis, but no frank metastases, were observed in all mice harboring Braf V600E mutations. The tumor-draining lymph nodes undergo significant structural alterations in immunocompetent mice, and this may represent a primer for papillary thyroid carcinoma (PTC) metastasis. © 2017 Wiley Periodicals, Inc.

  9. Correlation of NF-κB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Yan, Ming; Xu, Qin; Zhang, Ping; Zhou, Xiao-jian; Zhang, Zhi-yuan; Chen, Wan-tao

    2010-01-01

    Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets

  10. Effects of chronic exposure of hydroxychloroquine/chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases.

    Science.gov (United States)

    Fardet, L; Nazareth, I; Petersen, I

    2017-01-01

    Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases. The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database. Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6%) or chloroquine (1.4%) and 24,118 unexposed individuals were included in the study (median age: 56 [45-66] years, women: 76.8%). When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92-1.18], p =0.54), hematological malignancies (adjusted sHR: 1.00 [0.73-1.38], p =0.99), or skin cancers (adjusted sHR: 0.92 [0.78-1.07], p =0.26). The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44-0.95] for the overall population and 0.61 [0.38-1.00] for those diagnosed with incident cancers). The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81-1.00] in the overall population and 0.78 [0.64-0.96] in those diagnosed with incident cancer). Individuals on long-term exposure to hydroxychloroquine/chloroquine are not at lower risk of cancer. However, hydroxychloroquine/chloroquine may lower the risk of metastatic cancer and death.

  11. Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice.

    Science.gov (United States)

    Liang, Qianqian; Ju, Yawen; Chen, Yan; Wang, Wensheng; Li, Jinlong; Zhang, Li; Xu, Hao; Wood, Ronald W; Schwarz, Edward M; Boyce, Brendan F; Wang, Yongjun; Xing, Lianping

    2016-03-12

    In this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis. We used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice. LECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage. iNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory

  12. Percutaneous sclerotherapy of pediatric lymphatic malformations: experience and outcomes according to the agent used.

    Science.gov (United States)

    Gallego Herrero, C; Navarro Cutillas, V

    Analyze statistically the success, number of sessions required and complete duration of treatment of agents used in pediatric percutaneous sclerotherapy of lymphatic malformations, to determine the most suitable. Retrospective study based on outcomes from percutaneous sclerotherapy performed on lymphatic malformations of 56 patients conducted by pediatric interventional radiologist for 14 years. As first approach, the procedure consists of ultrasound-guided introduction of sclerosing agent. Sessions were repeated until clinical resolution. Success, number of sessions and the duration of treatment were recorded and statistical treatment of the data was performed to obtain further conclusions. Lost patients in follow up and other minority agents used were excluded from the data. Eventually, 52 patients treated with OK432 (n=29), Ethibloc (n=5) and combination therapy (n=18) were included. The average number of sessions and duration in months of treatment was respectively 2.38 and 8.6 for OK432, 1.4 and 5.6 for Ethibloc, and 1.83 and 2.30 for dual therapy. The results were statistically significant for the difference in duration between OK432 and dual therapy. Also, 60-80% of patients reached proper results related to success, but the difference was no significant among the agents. Other demographic and anatomical variables were analyzed, not showing any difference, which supports the homogeneity of the sample. Despite of no significant difference in success and number of sessions among agents, longer duration of treatment with OK432 than dual therapy could mean greater health costs and probably greater disturb for patient and family. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Brain drains: new insights into brain clearance pathways from lymphatic biology.

    Science.gov (United States)

    Bower, Neil I; Hogan, Benjamin M

    2018-05-01

    The lymphatic vasculature act as the drainage system for most of our tissues and organs, clearing interstitial fluid and waste and returning them to the blood circulation. This is not the case for the central nervous system (CNS), which is devoid of parenchymal lymphatic vessels. Nevertheless, the brain is responsible for 25% of the body's metabolism and only compromises 2% of the body's mass. This high metabolic load requires an efficient system to remove waste products and maintain homeostasis. Well-described mechanisms of waste clearance include phagocytic immune cell functions as well as perivascular fluid flow; however, the need for active drainage of waste from the brain is becoming increasingly appreciated. Recent developments in lymphatic vascular biology challenge the proposition that the brain lacks lymphatic drainage or an equivalent. In this review, we describe the roles of the glymphatic system (a key drainage mechanism in the absence of lymphatics), the recently characterized meningeal lymphatic vessels, and explore an enigmatic cell population found in zebrafish called mural lymphatic endothelial cells. These systems may play important individual and collective roles in draining and clearing wastes from the brain.

  14. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment.

    Directory of Open Access Journals (Sweden)

    Jarish N Cohen

    Full Text Available Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1. Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-β receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.

  15. Effects of chronic exposure of hydroxychloroquine/ chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Fardet L

    2017-11-01

    Full Text Available L Fardet,1–3 I Nazareth,1 I Petersen1 1Department of Primary Care and Population Health, University College London, UK; 2Department of Dermatology, Henri Mondor Hospital AP-HP, Créteil, France; 3Equipe d’Accueil 7379 EpiDermE, Université Paris Est Créteil, Créteil, France Background: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases.Methods: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database.Results: Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6% or chloroquine (1.4% and 24,118 unexposed individuals were included in the study (median age: 56 [45–66] years, women: 76.8%. When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92–1.18], p=0.54, hematological malignancies (adjusted sHR: 1.00 [0.73–1.38], p=0.99, or skin cancers (adjusted sHR: 0.92 [0.78–1.07], p=0.26. The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44–0.95] for the overall population and 0.61 [0.38–1.00] for those diagnosed with incident cancers. The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81–1.00] in the overall population and 0.78 [0.64–0.96] in those diagnosed with incident cancer.Conclusion: Individuals on long-term exposure

  16. Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.

    Directory of Open Access Journals (Sweden)

    Katrin Susanne Lips

    Full Text Available Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of

  17. Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

    Science.gov (United States)

    Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R.; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

    2013-01-01

    Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages

  18. Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Luukkainen, A; Seppälä, M; Renkonen, J; Renkonen, R; Hagstrő M, J; Huhtala, H; Rautiainen, M; Myller, J; Paavonen, T; Ranta, A; Torkkeli, T; Toppila-Salmi, S

    2017-06-01

    Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

  19. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  20. Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling.

    Science.gov (United States)

    Jing, Pengyu; Zhao, Nan; Ye, Mingxiang; Zhang, Yong; Zhang, Zhipei; Sun, Jianyong; Wang, Zhengxin; Zhang, Jian; Gu, Zhongping

    2018-07-28

    Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome. In this model, PRMT5 repressed the transcription of the miR-99 family by symmetrical dimethylation of histone H4R3, which increased FGFR3 expression and in turn activated Erk1/2 and Akt, leading to cell growth and metastasis in lung cancer. Furthermore, loss of PRMT5 exerted anti-metastasis effects on lung cancer progression by blocking histone-modification of miR-99 family. Overall, this study provides new insights into the PRMT5/miR-99 family/FGFR3 axis in regulating lung cancer progression and identifies PRMT5 as a promising prognostic biomarker and therapeutic target. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  1. Oral gingival metastasis: A diagnostic dilemma

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    Nalini Aswath

    2017-01-01

    Full Text Available Oral cavity is a rare target for metastasis with an incidence of 1% among all oral cancers. In 24% of such cases, oral metastasis is the first indication of an undiagnosed primary. Metastatic oral malignancies have been reported in the mandible, tongue, and gingiva. Although gingival metastasis has been reported from lung, prostate, rectal carcinoma in men and carcinoma of breast, adrenal glands, and genitalia in females, gingival metastasis from carcinoma of the penis has not been reported. Herein, a case of metastatic gingival carcinoma that developed after extraction of teeth from primary carcinoma of the penis is presented. An extensive literature search revealed no such similar case reports.

  2. CT diagnosis of peritoneal metastasis tumor

    International Nuclear Information System (INIS)

    Deng Xueying; Chen Xiaoqi; Qi Le; Huang Feng

    2005-01-01

    Objective: To study the CT findings and diagnosis of peritoneal metastasis. Methods: The CT findings of 17 cases with surgical- pathologically proved peritoneal metastasis were analyzed retrospectively. Results The CT findings of peritoneal metastasis included: (1)ascites (12 cases ); (2)the aternation of parietal peritoneum including broad band thickening (7 cases), nodular sign (2 cases), and massive thickening (1 cases); (3) the involved omentum and mesenterium: 'smut' appearances (7 cases), nodular sign (2 cases), 'omental cake' (5 cases); (4) the invlovement of mesenteric vessels; (5) single-or multi-cystic lesions within peritoneum (1 case) . Conclusion: CT scan is the first choice for metastasis of peritoneum. (authors)

  3. Fallopian tube cancer: incidence and role of lymphatic spread.

    Science.gov (United States)

    di Re, E; Grosso, G; Raspagliesi, F; Baiocchi, G

    1996-08-01

    Lymphatic spread pattern in 17 cases of adenocarcinoma of fallopian tube is reported. Median age of the patients was 48 years. All patients underwent surgical staging including total abdominal hysterectomy, bilateral salpingo-oopherectomy omentectomy, and appendectomy. Systematic pelvic and paraaortic lymphadenectomy was feasible in 15 cases. Majority of the patients (11 of 17 cases, 64%) had advanced disease and showed serous adenocarcinoma (83%). Lymph nodes were involved in 10 of 17 cases (59%). Node metastases rate increased significantly (P < 0.01) with intraperitoneal stage of disease and with grading. Interestingly, positive nodes were also found in 2 cases (33%) of 6 patients with disease still limited to fallopian tube. Overall, patients with negative nodes had a median survival of 76 months, compared with only 33 months if node metastases were found. In conclusion, combined pelvic and para-aortic lymphadenectomy seems to be necessary for staging and perhaps for prognosis of this disease.

  4. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  5. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

    Science.gov (United States)

    Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

    2009-01-01

    To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

  6. A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene.

    Science.gov (United States)

    Gobeil, Stephane; Zhu, Xiaochun; Doillon, Charles J; Green, Michael R

    2008-11-01

    Metastasis suppressor genes inhibit one or more steps required for metastasis without affecting primary tumor formation. Due to the complexity of the metastatic process, the development of experimental approaches for identifying genes involved in metastasis prevention has been challenging. Here we describe a genome-wide RNAi screening strategy to identify candidate metastasis suppressor genes. Following expression in weakly metastatic B16-F0 mouse melanoma cells, shRNAs were selected based upon enhanced satellite colony formation in a three-dimensional cell culture system and confirmed in a mouse experimental metastasis assay. Using this approach we discovered 22 genes whose knockdown increased metastasis without affecting primary tumor growth. We focused on one of these genes, Gas1 (Growth arrest-specific 1), because we found that it was substantially down-regulated in highly metastatic B16-F10 melanoma cells, which contributed to the high metastatic potential of this mouse cell line. We further demonstrated that Gas1 has all the expected properties of a melanoma tumor suppressor including: suppression of metastasis in a spontaneous metastasis assay, promotion of apoptosis following dissemination of cells to secondary sites, and frequent down-regulation in human melanoma metastasis-derived cell lines and metastatic tumor samples. Thus, we developed a genome-wide shRNA screening strategy that enables the discovery of new metastasis suppressor genes.

  7. Antenatal hemorrhage of a cervical lymphatic malformation presenting as a draining neck mass: An unusual presentation.

    Science.gov (United States)

    Haricharan, R N; Nawaz, M; Bettolli, M; Ferretti, E

    2014-01-01

    Lymphatic malformations in the neck can present as large fetal neck masses causing airway obstructions with potential perinatal demise and can pose a therapeutic challenge. We present a rare case of prenatally diagnosed large fetal neck mass with features of lymphatic malformation with intralesional hemorrhage of uncertain origin. Postnatal evaluation showed a complex cystic-solid lesion eroding through the skin with an open wound that made it clinically hard to differentiate from a teratoma. Given that malignancy could not be completely ruled out, surgery was favored. Final pathology showed a complex lymphatic malformation with intralesional hemorrhage, despite having no associated capillary, venous or arterial malformations.

  8. Normal anatomy of the lymphatic system in the CT-image

    International Nuclear Information System (INIS)

    Steinbrich, W.; Peters, P.E.

    1982-01-01

    To evaluate a pathologic process of a lymphatic node, detailed knowledge is required of the normal anatomy of the lumphatic system in an axial CT image. The anatomy is demonstrated in a comparative study before and after lymphography with CT-scans of patients with normal lymphadenographs. Hereby it appears that with the high-resolution scanning method and favourable imaging conditions even small lymphatic nodes can be differentiated without a lymphographic contrast technique. However, nerves and vessels cannot be differentiated. The extreme variability in the size of normal lymphatic nodes makes the differentiation of pathologic processes very difficult. (orig.) [de

  9. Short report: documentation of iodine deficiency in Haitian schoolchildren: implication for lymphatic filariasis elimination in Haiti.

    Science.gov (United States)

    Beach, M J; Streit, T G; Houston, R; May, W A; Addiss, D G; Lammie, P J

    2001-01-01

    In this study we documented unexpected moderate-to-severe iodine deficiency in Haitian schoolchildren although they live in a coastal community where presumably they have access to iodine-containing seafood. This fact combined with the lack of an iodized salt supply and endemic lymphatic filariasis makes community distribution of diethylcarbamazine-fortified, iodized salt an attractive strategy for elimination of lymphatic filariasis and iodine deficiency disorders in this area of Haiti. Combining lymphatic filariasis elimination with other public health interventions is one strategy to increase its public health benefit and maximize the impact of limited public health resources.

  10. Pulmonary metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.; Rajashekharrao, B.; Shah, D.H.

    1999-01-01

    Although thyroid cancer (TC) in its differentiated form is generally associated with a good prognosis and a near normal life expectancy, a subset of patients especially with distant metastatic disease may run an aggressive course leading to poor survival and early death. The clinical presentation and the manner in which the disease progresses differs with the site and type of the metastatic disease. The behaviour and course of skeletal metastasis has been described elsewhere. The biological behaviour and treatment of pulmonary metastatic disease is focussed on

  11. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  12. Dissecting and Targeting Latent Metastasis

    Science.gov (United States)

    2014-09-01

    Option in Brain Metastasis Manuel Valiente,1 Anna C. Obenauf,1 Xin Jin,1 Qing Chen,1 Xiang H.-F. Zhang,1,8 Derek J. Lee,1 Jamie E. Chaft,2 Mark G. Kris,2...of poor response to tamoxifen therapy in recurrent breast cancer. J. Natl. Cancer Inst. 87, 751–756. Francia, G., Cruz -Munoz, W., Man, S., Xu, P... Manuel Valiente1, Xin Jin1†, Ekrem Emrah Er1, Ruzeen Patwa1, Ke Xu3 and Joan Massagué1 1 Cancer Biology and Genetics Program, 2 Department of

  13. Endocannabinoids as Guardians of Metastasis

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    Irmgard Tegeder

    2016-02-01

    Full Text Available Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain. Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer. The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis.

  14. Metastasis

    Science.gov (United States)

    ... and Care Surgical Treatment Laparoscopic Surgery Vaccine Radiation Therapy Chemotherapy Clinical Trials Pain Management Nutrition and Exercise Holistic Care Pathology Intraductal Papillary Mucinous Neoplasms Islet Cell ...

  15. ADC Histogram Analysis of Cervical Cancer Aids Detecting Lymphatic Metastases-a Preliminary Study.

    Science.gov (United States)

    Schob, Stefan; Meyer, Hans Jonas; Pazaitis, Nikolaos; Schramm, Dominik; Bremicker, Kristina; Exner, Marc; Höhn, Anne Kathrin; Garnov, Nikita; Surov, Alexey

    2017-12-01

    Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities. Therefore, the principal aim of our study was to investigate the potential of 3T ADC histogram analysis to differentiate between CC with and without lymph node metastasis. The second aim was to elucidate possible differences in ADC histogram parameters between CC with limited vs. advanced tumor stages and well-differentiated vs. undifferentiated lesions. Finally, correlations of p53 expression and Ki-67 index with ADC parameters were analyzed. Eighteen female patients (mean age 55.4 years, range 32-79 years) with histopathologically confirmed cervical squamous cell carcinoma of the uterine cervix were prospectively enrolled. Tumor stages, tumor grading, status of metastatic dissemination, Ki67-index, and p53 expression were assessed in these patients. Diffusion weighted imaging (DWI) was obtained in a 3T scanner using the following b values: b0 and b1000 s/mm 2 . Group comparisons using Mann-Whitney U test revealed the following findings: nodal-positive CC had statistically significant lower ADC parameters (ADCmin, ADCmean, median ADC, Mode, p10, p25, p75, and p90) in comparison to nodal-negative CC (all p histogram analysis in 3T DWI. This information is crucial for the gynecological surgeon to identify the optimal treatment strategy for patients suffering from CC. Furthermore, ADCentropy was identified as a potential imaging biomarker for tumor heterogeneity and might be able to indicate further molecular changes like loss of p53 expression

  16. Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site.

    Science.gov (United States)

    Ryan, Gemma M; McLeod, Victoria M; Mehta, Dharmini; Kelly, Brian D; Stanislawski, Pauline C; Owen, David J; Kaminskas, Lisa M; Porter, Christopher J H

    2017-11-01

    Drug conjugation to dendrimer-based delivery systems has been shown to enhance delivery to the lymphatic system after subcutaneous administration. Dendrimer interaction with components of the interstitium at the injection site, however, may prevent drainage from the injection site. The current study sought to vary the length of a linker employed to conjugate methotrexate (MTX) to a PEGylated dendrimer, in an attempt to reduce MTX interaction with interstitial binding sites and enhance lymphatic drainage. Dendrimers with shorter linkers resulted in higher lymphatic drainage, presumably via shielding of interaction sites by the PEG mantle, but were not retained in lymph nodes. Improved drainage of dendrimers with longer linkers was achieved through coadministration with dextran to mask interactions at the injection site while maintaining retention within the node. Enhanced drug exposure to the lymph node has the potential to enhance the treatment of lymph-node resident cancer metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Oncoprotein metastasis and its suppression revisited

    Directory of Open Access Journals (Sweden)

    Radulescu Razvan T

    2010-04-01

    Full Text Available Abstract The past two decades have witnessed an increasing appreciation of the role of the tumor microenvironment, of genetic and epigenetic alterations in normal cells adjacent to tumors and of the migration of normal cells with aberrant intrinsic properties in cancer pathophysiology. Aside from these insights, a novel concept termed "oncoprotein metastasis" (OPM has recently been advanced and proposed to reflect protein-based neoplastic phenomena that might occur even before any modifications relating to the morphology, location or (epigenetic outfit of cells during the malignant process. Here, evidence is presented that supports the OPM perception and thus should contribute not only to further rethink the definition of a normal cell, but also the treatment of cancer disease in the years to come.

  18. Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

    Science.gov (United States)

    Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

    2015-01-01

    The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

  19. Treatment of Lymphatic Malformations With OK-432 (Picibanil) : Review of the Literature

    NARCIS (Netherlands)

    Poldervaart, Michelle T.; Breugem, Corstiaan C.; Speleman, Lucienne; Pasmans, Suzanne

    Introduction: Lymphatic malformations (LM) are benign structural defects that call cause serious complications because of their size and location. Traditionally surgical removal was the first treatment modality, but this Could be associated with many complications and risks. Since Ogita introduced

  20. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    the biophysical state of the primary tumor cell. To determine the cytoskeletal dynamics they chose magnetic twisting cytometry, where the spontaneous motion of surface bound marker beads was measured, which is a measure for the cytoskeletal remodeling dynamics. The group of Katarina Wolf measured the stiffness of the cell nucleus because it is the largest and stiffest organelle, which may hinder the migration of invasive tumor cells through dense connective tissue [2]. They combined atomic force confocal microscopy for measurement of bulk nuclear stiffness (the inverse of the compressibility) with simultaneous visualization of the cantilever-nucleus contact as well as monitoring of the cell's fate. The dynamics of tissue topology such as the mixing of compartments during cancer invasion and metastasis were theoretically analyzed by Lance L Munn [3]. In particular, he presented a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of tumor behaviors using correct tissue compartmentalization and connectivity. In the future, the topological analysis could be helpful for tumor diagnosis or monitoring tumor therapy. The group of Cynthia A Reinhart-King analyzed how the topological guidance of a 3D tumor cell migration at an interface of collagen densities affects cell motility [4]. In particular, they mimicked the heterogeneities in density of the tumor stroma by preparing gels with an interface of high and low density collagen gels and investigated how this affects cell motility. The author's review paper details the effect of focal adhesion proteins such as focal adhesion kinase (FAK) on cell motility and how this effect is driven by mechanical alterations of cells expressing FAK compared to cells with FAK knock-out [5]. In particular, it focused on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. This article highlights that both focal adhesion proteins

  1. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    International Nuclear Information System (INIS)

    Lee, Chul Min; Lee, Seung Hun; Bae, Ji Yoon

    2015-01-01

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis

  2. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  3. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    International Nuclear Information System (INIS)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

    2009-01-01

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  4. Flow rates in the head and neck lymphatics after food stimulation in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Thommesen, P.; Buhl, J.; Jansen, K.; Funch-Jensen, P.

    1981-02-01

    In 22 healthy subjects lymph transport flow rates was studied in the head lymphatics after food stimulation, mastication (chewing) and taste. After food stimulation there was a significantly higher transport rate (0.67 meter/hour) than after taste (0.57 meter/hour) and mastication (0.55 meter/hour). The calculation of transport flow rate was independent of quantitative distribution of radioactivity in the head and neck lymphatics, and it could therefore perhaps be of clinical value.

  5. Lymphatic drainage of lung segments in the visceral pleura: a cadaveric study.

    Science.gov (United States)

    Fourdrain, Alex; Lafitte, Sophie; Iquille, Jules; De Dominicis, Florence; Havet, Eric; Peltier, Johann; Bagan, Patrick; Berna, Pascal

    2018-01-01

    Although peribronchial lymphatic drainage of the lung has been well characterized, lymphatic drainage in the visceral pleura is less well understood. The objective of the present study was to evaluate the lymphatic drainage of lung segments in the visceral pleura. Adult, European cadavers were examined. Cadavers with a history of pleural or pulmonary disease were excluded. The cadavers had been refrigerated but not embalmed. The lungs were surgically removed and re-warmed. Blue dye was injected into the subpleural area and into the first draining visceral pleural lymphatic vessel of each lung segment. Twenty-one cadavers (7 males and 14 females; mean age 80.9 years) were dissected an average of 9.8 day postmortem. A total of 380 dye injections (in 95 lobes) were performed. Lymphatic drainage of the visceral pleura followed a segmental pathway in 44.2% of the injections (n = 168) and an intersegmental pathway in 55.8% (n = 212). Drainage was found to be both intersegmental and interlobar in 2.6% of the injections (n = 10). Lymphatic drainage in the visceral pleura followed an intersegmental pathway in 22.8% (n = 13) of right upper lobe injections, 57.9% (n = 22) of right middle lobe injections, 83.3% (n = 75) of right lower lobe injections, 21% (n = 21) of left upper lobe injections, and 85.3% (n = 81) of left lower lobe injections. In the lung, lymphatic drainage in the visceral pleura appears to be more intersegmental than the peribronchial pathway is-especially in the lower lobes. The involvement of intersegmental lymphatic drainage in the visceral pleura should now be evaluated during pulmonary resections (and especially sub-lobar resections) for lung cancer.

  6. Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization

    Science.gov (United States)

    Lee, Ji Yoon; Park, Changwon; Cho, Yong Pil; Lee, Eugine; Kim, Hyongbum; Kim, Pilhan; Yun, Seok H.; Yoon, Young-sup

    2010-01-01

    Background Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization. Methods and Results Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin+ cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin+ cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin+ cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin+ cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin+ cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role. Conclusions Our results provide compelling evidence that BM-derived podoplanin+ cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. PMID:20855662

  7. Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

    Science.gov (United States)

    Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.

    2017-01-01

    Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669

  8. Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging

    Directory of Open Access Journals (Sweden)

    Ann-Christin Niehoff

    2017-01-01

    Full Text Available Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA with inductively coupled plasma mass spectrometry imaging (ICP-MSI is presented. As a possible lymph marker, thulium(III(1R,4R,7R,10R-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III2,2′,2′′-(10-((2R,3S-1,3,4-trihydroxybutan-2-yl-1,4,7,10-tetraazacyclododecane-1,4,7-triyltriacetate (Gd-DO3A-butrol. Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors of the lymph nodes after application of contrast agents in different areas.

  9. Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

    Science.gov (United States)

    Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

    2015-09-01

    Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

  10. Comparison of the Blood and Lymphatic Microvessel Density of Pleomorphic Adenoma and Basal Cell Adenoma

    Directory of Open Access Journals (Sweden)

    Andresa Borges Soares

    2015-01-01

    Full Text Available Background Pleomorphic adenoma (PA is the most common tumor of the salivary gland, while basal cell adenoma (BCA is an uncommon neoplasm. Blood and lymphatic vessels are crucial for tumor metabolism. The aim of this study was to compare the blood and lymphatic vascular density and vascular and endothelial growth factor (VEGF expression in PA and BCA tumors. In addition, cell proliferation was evaluated in these tumors. Methods Blood and lymphatic vessel content, VEGF expression, and cell proliferation were analyzed in 30 cases of PA and 13 cases of BCA by immu-nohistochemistry using antibodies for CD34, CD105, D2-40, VEGF, and Mcm -2. Results Regarding CD34 and CD105 expression, PA demonstrated a high vascularity and a low number of positive vessels, respectively. D2-40-positive lymphatic vessels were mainly located in the tumor capsules, with small intratumoral lymphatic vessels observed occasionally. VEGF expression revealed a remarkably heterogeneous immunoreactivity, alternating from weak or negative to positive or intense. BCA presented significantly higher CD34, CD34, CD105, D2-40, and VEGF expression compared to PA. No significant difference was found in cell proliferation between the tumors. Conclusion Although PA and BCA are considered part of the same spectrum of differentiation, this study showed that the blood and lymphatic vascularization of these tumors is different.

  11. Lymphangiogenesis and lymphatic remodeling induced by filarial parasites: implications for pathogenesis.

    Directory of Open Access Journals (Sweden)

    Sasisekhar Bennuru

    2009-12-01

    Full Text Available Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases. Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.

  12. Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Jacob Ø; von Holstein, Sarah L; Prause, Jan U

    2014-01-01

    and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary...... hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma....

  13. Drug Development for Metastasis Prevention.

    Science.gov (United States)

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.

  14. Stereotactic radiotherapy for brain metastasis

    International Nuclear Information System (INIS)

    Noel, G.; Daisne, J.F.; Thillays, F.

    2012-01-01

    Stereotactic radiosurgery is now well implanted in the radiotherapy treatment tools of brain metastasis. The dose can be delivered in one or multiple sessions. Results seem equivalent. CT scan and MRI imaging are required to delineate and calculate dosimetry. Doses are variable according to the size of the metastases, localization, pathology or equipment. Stabilization or reduction of tumour size is the rules after stereotactic treatment. Impact in terms of overall survival is more difficult to apprehend because of the general context of the disease. Many questions remain unresolved, such as the usefulness of whole brain irradiation, adaptation of the treatment schedule to tumour pathophysiology, role of stereotactic treatment after surgery of metastases, etc. (authors)

  15. Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: A systematic review.

    Science.gov (United States)

    Berger-Richardson, David; Chesney, Tyler R; Englesakis, Marina; Govindarajan, Anand; Cleary, Sean P; Swallow, Carol J

    2017-03-01

    The risk of port-site metastasis after laparoscopic removal of incidental gallbladder cancer was previously estimated to be 14-30%. The present study was designed to determine the incidence of port-site metastasis in incidental gallbladder cancer in the modern era (2000-2014) versus the historic era (1991-1999). We also investigated the site of port-site metastasis. Using PRISMA, a systematic review was conducted to identify papers that addressed the development of port-site metastasis after laparoscopic resection of incidental gallbladder cancer. Studies that described cancer-specific outcomes in ≥5 patients were included. A validated quality appraisal tool was used, and a weighted estimate of the incidence of port-site metastasis was calculated. Based on data extracted from 27 papers that met inclusion criteria, the incidence of port-site metastasis in incidental gallbladder cancer has decreased from 18.6% prior to 2000 (95% confidence interval 15.3-21.9%, n = 7) to 10.3% since then (95% confidence interval 7.9-12.7%, n = 20) (P extraction site is at significantly higher risk than nonextraction sites. The incidence of port-site metastasis in incidental gallbladder cancer has decreased but remains high relative to other primary tumors. Any preoperative finding that raises the suspicion of gallbladder cancer should prompt further investigation and referral to a hepato-pancreato-biliary specialist. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Isolated metastasis of colon cancer to the scapula: is surgical resection warranted?

    Directory of Open Access Journals (Sweden)

    Onesti Jill K

    2011-10-01

    Full Text Available Abstract Background Distant metastases from colon cancer spread most frequently to the liver and the lung. Risk factors include positive lymph nodes and high grade tumors. Isolated metastases to the appendicular skeleton are very rare, particularly in the absence of identifiable risk factors. Case report The patient was a 55 year old male with no previous personal or family history of colon cancer. Routine screening revealed a sigmoid adenocarcinoma. He underwent resection with primary anastomosis and was found to have Stage IIA colon cancer. He declined chemotherapy as part of a clinical trial, and eight months later was found to have an isolated metastasis in his right scapula. This was treated medically, but grew to 12 × 15 cm. The patient underwent a curative forequarter amputation and is now more than four years from his original colon surgery. Discussion Stage IIA colon cancers are associated with a high five year survival rate, and chemotherapy is not automatically given. If metastases occur, they are likely to arise from local recurrence or follow lymphatic dissemination to the liver or lungs. Isolated skeletal metastases are quite rare and are usually confined to the axial skeleton. To our knowledge, this is the first reported case of an isolated scapular metastasis in a patient with node negative disease. The decision to treat the recurrence with radiation and chemotherapy did not reduce the tumor, and a forequarter amputation was eventually required. Conclusion This case highlights the importance of adequately analyzing the stage of colon cancer and offering appropriate treatment. Equally important is the early involvement of a surgeon in discussing the timing of the treatment for recurrence. Perhaps if the patient had received chemotherapy or earlier resection, he could have been spared the forequarter amputation. The physician must also be aware of the remote possibility of an unusual presentation of metastasis in order to pursue

  17. The CT diagnose of pleural metastasis tumour

    International Nuclear Information System (INIS)

    Chen Liqun; Han Kaibin; Pan Heng; Huang Xiaoru; Zhou Bingcao; Huang Yuehua

    2007-01-01

    Objective: To discuss the CT characteristic of pleural metastasis tumour,enhance the diagnostic level of pleural metastasis tumour. Methods: Review 30 cases which have been performed CT scan in our hospital during March 2002 to June 2003, which have been approved to pleural metastasis tumour by pathology and clinic. Make use of GE Hispeed.zx/i spiral CT,10mm thickness,10mm increment, l.5 pitch, some of them use 10mm or high resolution mode. All cases have been performed normal scan, 25 cases with contrast scan. Results: The CT representation of pleural metastasis tumour are encapsulated pleural effusion with irregular pleural thickening(56.6%), nodular pleural thickening(46.6%), pleural masses (13.3%), pneumothorax (3.3%), etc. Encapsulated pleural effusion and nodular pleural thickening are 76.6%, use contrast mode to scan pleural pathological changes enhance upon middle level, CT value increment > 20HU, there are 66.6% cases with other chest metastasis symptom, 73.3% primary lesion are pulmonary cancer, and 20% no primary lesion are found. Conclusion: Combine primary lesion history and other chest metastasis symptom, Spiral CT examination can differentiate most of pleural metastasis tumour, but it is difficult to differentiate the cases between with a little pleural effusion or light band pleural thickening and reactive alteration. (authors)

  18. Mortality from lymphatic and haematopoietic cancer in Scottish coastal towns

    International Nuclear Information System (INIS)

    Lloyd, O.Ll.; Macdonald, J.; Lloyd, M.M.

    1984-01-01

    Using annual Scottish registration data, the authors have been examining mortality from cancers including all leukaemias, classified within malignant neoplasm of lymphatic and haematopoietic tissue, from 1969/73. The results showed: (1) Coastal burghs had a higher standardised mortality than did inland burghs; (2) the SMRs in communities of the east coast as a whole were consistently higher than those in west-coast communities, whether small burghs, large burghs, or cities were considered; (3) all segments of the eastern coastline, other than the open coastline stretching from Aberdeenshire to Angus, showed relatively high SMRs; (4) on the west coast, the highest SMRs (of only 100) were in Ayrshire and Glasgow; (5) in terms of statistical significance at the level p<=0.5, mortality in inland burghs was significantly low, while in east-coast burghs, in Edinburgh, and in Aberdeen it was significantly high. The geographical distribution cannot be explained in terms of nuclear power stations, and differs importantly from that given by registration data for leukaemia alone (Heasman et al, May 26, p.1188). (U.K.)

  19. Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage

    Directory of Open Access Journals (Sweden)

    Maria Filomena Rabaça Roque Botelho

    2009-03-01

    Full Text Available Lung deep lymphatic drainage (LDLD plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry.Lung deep lymphatic chains (LDLC constitute one of the first sites of lung tumours’ dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies.Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC.Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes. Conclusion: the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes. Resumo: A drenagem linfática pulmonar profunda (DLPP desempenha um papel importante na remoção de materiais estranhos, constituindo os macrófagos alveolares a primeira linha de defesa fagocitária, dada a grande afinidade para

  20. [Cytostructure of the mantle zone in lymphatic tissue].

    Science.gov (United States)

    Bednár, B

    1993-04-01

    Four cellular layers of the follicular mantle zone in palatine tonsil lymphatic tissue were studied by electron microscopy after simultaneous immunophenotypical investigation. The first layer of the mantle zone consisting of small blastic cells was analogous to the small (centrocytoid) blastic layer of germinal centres. The second B monocytoid layer was lacking analogy in basic series of lymphocytes and seemed to be an independent morphological and probably functional unit. Plasmacytoid and clarocellular elements in outer layers of follicular mantle zone were in a way similar to T plasmacytoid and clarocellular components of Sézary syndrome infiltrates but considering transitional forms they had a local origin from incompletely transformed elements of B monocytoid layer. Inner follicular mantle zone was discussed as a source of incompletely transformed B lymphocytes for further mantle layers where their immunophenotypical modulation is taking place according to actual need. Outer mantle layers are aggressive against damaged epithelial and litoral structures and may be instrumental in a common reaction of B and T components.

  1. Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

  2. Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

    Science.gov (United States)

    Hooper, Pamela J.; Chu, Brian K.; Mikhailov, Alexei; Ottesen, Eric A.; Bradley, Mark

    2014-01-01

    Background In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF. Methodology/Principal Findings To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012. Conclusions/Significance Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal. PMID:25411843

  3. Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role of the lymphatic system.

    Science.gov (United States)

    Bellini, C; Ergaz, Z; Boccardo, F; Bellini, T; Campisi, C C; Bonioli, E; Ramenghi, L A

    2013-06-01

    Pleural fluid effusion particularly chylothorax is a relatively rare occurrence in the newborn, but when it occurs it is often life-threatening. In this article, we describe and illustrate the morphologic features of the visceral and parietal pleura including pleural lymphatics and the physiology and pathophysiology of pleural fluid balance. The role and function of the lymphatic system in controlling the volume and composition of pleural liquid are detailed and a conceptual scheme presented. Finally, the crucial role of inadequate lymphatic drainage (either functional overload from an imbalance in Starling forces or mechanical insufficiency from lymphatic dysplasia) is emphasized.

  4. Immunohistochemical Examination on the Distribution of Cells Expressed Lymphatic Endothelial Marker Podoplanin and LYVE-1 in the Mouse Tongue Tissue

    Science.gov (United States)

    Noda, Yuya; Amano, Ikuko; Hata, Minoru; Kojima, Hiroshi; Sawa, Yoshihiko

    2010-01-01

    The clinical study for lingual disease requires the detailed investigation of the lingual lymphatic network and lymphatic marker-positive cells. Recently, it has been reported that several tissue cells and leukocytes express lymphatic markers, LYVE-1 and podoplanin. This study was aimed to clarify the lingual distribution of cells expressing LYVE-1 and podoplanin. In the mouse tongue, podoplanin is expressed in nerve sheaths, lingual gland myoepithelial cells, and lymphatic vessels. LYVE-1 is expressed in the macrophage marker Mac-1-positive cells as well as lymphatic vessels, while factor-VIII was detected in only blood endothelial cells. α-SMA was detected in vascular smooth muscle and myoepithelial cells. Therefore, identification of lymphatic vessels in lingual glands, the combination of LYVE-1 and factor-VIII, or LYVE-1 and Mac-1 is useful because myoepithelial cells express podoplanin and α-SMA. The immunostaining of factor-VIII on lymphatic vessels was masked by the immunostaining to LYVE-1 or podoplanin because lymphatic vessels express factor-VIII to a far lesser extent than blood vessels. Therefore, except for the salivary glands, the combination of podoplanin and α-SMA, or factor-VIII is useful to identify lymphatic vessels and blood vessels with smooth muscle, or blood capillaries. PMID:20514293

  5. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

    Science.gov (United States)

    D'Andrea, Vito; Panarese, Alessandra; Taurone, Samanta; Coppola, Luigi; Cavallotti, Carlo; Artico, Marco

    2015-09-01

    The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

  6. Delphian node metastasis in head and neck cancers--oracle or myth?

    Science.gov (United States)

    Iyer, N Gopalakrishna; Shaha, Ashok R; Ferlito, Alfio; Thomas Robbins, K; Medina, Jesus E; Silver, Carl E; Rinaldo, Alessandra; Takes, Robert P; Suárez, Carlos; Rodrigo, Juan P; Bradley, Patrick J; Werner, Jochen A

    2010-09-15

    Delphian node (DN) refers to the pre-laryngeal or pre-cricoid nodal tissue often identified during laryngeal or thyroid surgery. The original nomenclature is based on the assumption that metastasis to this node was predictive of aggressive disease and poor outcome for patients. In this article, we review the existing literature on the topic to determine the significance of DN metastasis in laryngeal, hypopharyngeal and thyroid cancers. (c) 2010 Wiley-Liss, Inc.

  7. 99mTc MDP SPECT-CT-Based Modified Mirels Classification for Evaluation of Risk of Fracture in Skeletal Metastasis: A Pilot Study.

    Science.gov (United States)

    Riaz, Saima; Bashir, Humayun; Niazi, Imran Khalid; Butt, Sumera; Qamar, Faisal

    2018-06-01

    Mirels' scoring system quantifies the risk of sustaining a pathologic fracture in osseous metastases of weight bearing long bones. Conventional Mirels' scoring is based on radiographs. Our pilot study proposes Tc MDP bone SPECT-CT based modified Mirels' scoring system and its comparison with conventional Mirels' scoring. Cortical lysis was noted in 8(24%) by SPECT-CT versus 2 (6.3%) on X-rays. Additional SPECT-CT parameters were; circumferential involvement [1/4 (31%), 1/2 (3%), 3/4 (37.5%), 4/4 (28%)] and extra-osseous soft tissue [3%]. Our pilot study suggests the potential role of SPECT-CT in predicting risk of fracture in osseous metastases.

  8. DEGRO practical guidelines: radiotherapy of breast cancer III - radiotherapy of the lymphatic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Sautter-Bihl, M.L. [Staedtisches Klinikum Karlsruhe, Klinik fuer Radioonkologie und Strahlentherapie, Karlsruhe (Germany); Sedlmayer, F.; Fussl, C. [LKH Salzburg, Paracelsus Medical University Hospital, Department of Radiotherapy and Radiation Oncology, Salzburg (Austria); Budach, W. [University Hospital Duesseldorf, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, P. [Klinikum Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Harms, W. [St. Clara Hospital, Basel, Basel (Switzerland); Piroth, M.D. [Helios-Klinikum Wuppertal, Klinik fuer Strahlentherapie und Radioonkologie, Wuppertal (Germany); Souchon, R. [University Hospital Tuebingen, Tuebingen (Germany); Wenz, F. [University Hospital Mannheim, Mannheim (Germany); Haase, W.

    2014-04-15

    The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: ''breast cancer'', ''radiotherapy'', ''regional node irradiation''. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data

  9. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  10. Leptomeningeal metastasis mimicking Chronic Subdural Hematoma

    Directory of Open Access Journals (Sweden)

    Jain Saurabh

    2017-12-01

    Full Text Available The presentation of Leptomeningeal Metastasis varies widely. It can also present a condition very similar to Chronic Subdural Hematoma. One should have a low threshold for suspicion while diagnosing such conditions to avoid catastrophic events.

  11. Leptomeningeal metastasis mimicking Chronic Subdural Hematoma

    OpenAIRE

    Jain Saurabh

    2017-01-01

    The presentation of Leptomeningeal Metastasis varies widely. It can also present a condition very similar to Chronic Subdural Hematoma. One should have a low threshold for suspicion while diagnosing such conditions to avoid catastrophic events.

  12. Colorectal cancer presenting as bone metastasis

    Directory of Open Access Journals (Sweden)

    M C Suresh Babu

    2017-01-01

    Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

  13. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  14. Osthole inhibits bone metastasis of breast cancer

    OpenAIRE

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-01-01

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potent...

  15. Tumour metastasis-associated gene profiling using one-dimensional microfluidic beads array

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Great efforts have been made on the early diagnosis and molecular mechanism research of tumour metastasis in recent years. In this paper, based on the one-dimensional microfluidic beads array, a novel platform for tumour metastasis-associated genes profiling has been developed by depositing nucleic acids functional beads in the microchannel. This platform is sensitive (limit of detection: 0.02 nmol/L) and can perform mRNAs analysis without PCR. Two human colon cancer cell lines (primary and metastatic) from the same patient were used as a model, and transcriptional expression profiling of multiple tumour metastasis-associated genes in these two cell lines was successfully achieved. Furthermore, the results obtained on the beads array were validated by RT-PCR. This novel beads array has advantages of high sensitivity, little sample consumption, short assay time, low cost and high throughput capability. It holds the potential in early diagnosis and mechanism research of tumour metastasis.

  16. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

    Directory of Open Access Journals (Sweden)

    Fang Li

    2017-05-01

    Full Text Available Huperzine A (Hup-A is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01. The absorption rate constant (Ka and the apparent permeability coefficient (Papp for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax of the blocking model were significantly lower than those of the control model (P<0.05. The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

  17. The effect of cisterna chyli ablation combined with thoracic duct ligation on abdominal lymphatic drainage.

    Science.gov (United States)

    Sicard, Gretchen K; Waller, Ken R; McAnulty, Jonathan F

    2005-01-01

    To evaluate the effect of cisterna chyli ablation (CCA) and thoracic duct ligation (TDL) on abdominal lymphatic drainage in normal dogs. Experimental study. Nine female beagle dogs. TDL was performed in 3 dogs and was combined with CCA (CCA-TDL) and local omentalization in 6 dogs. Contrast lymphangiography was attempted in all dogs immediately before and after TDL. Dogs were reanesthetized at 31-37 days for lymphatic studies by new methylene blue (NMB) injection into a mesenteric lymph node and by contrast lymphangiography. In 6 CCA-TDL dogs, 2 had direct shunting of contrast from the lymphatic system into major abdominal veins, 3 had contrast material that dissipated into abdominal vessels within the mesenteric root, and 1 had shunting into the azygous vein. NMB was not observed within the omental pedicle after CCA-TDL. Chylous drainage was by the azygous vein in all 3 TDL dogs. CCA-TDL disrupted chylous drainage to the thoracic duct and resulted in direct intraabdominal lymphaticovenous anastomoses identified by shunting of lymphatic flow directly into the abdominal vasculature in 5 of 6 CCA-TDL dogs. Omentalization of the cisternal ablation site was not beneficial in augmenting extrathoracic lymphatic drainage and is not recommended with CCA-TDL. CCA-TDL represents a novel approach to surgical redirection of chylous drainage to the venous circulation outside of the thorax and may be useful in the treatment of spontaneous chylothorax in the dog.

  18. PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats.

    Science.gov (United States)

    Kaminskas, Lisa M; Kota, Jagannath; McLeod, Victoria M; Kelly, Brian D; Karellas, Peter; Porter, Christopher Jh

    2009-12-03

    Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.

  19. Orofacial lymphatic malformation: management with a three steps diode laser protocol

    Science.gov (United States)

    Miccoli, Simona; Tempesta, Angela; Limongelli, Luisa; Caporusso, Concetta; Di Venere, Daniela; Petruzzi, Massimo; Lacaita, Mariagrazia; Maiorano, Eugenio; Favia, Gianfranco

    2014-01-01

    Lymphatic Malformation (LM) according to ISSVA Classification, is a rare benign disorder with unknown aetiology. LM may grow slowly over years or develop rapidly over the course of days becoming a bulky lump, infected or bleeding. We propose our three steps Diode Laser protocol for LM management, based on its persistent vascular blood component. 1. Histological and cytological examination, to evaluate the vascular blood component (10-40%), shows mature lymphocytes with red blood cells and endothelial cells. 2. Diode Laser Photocoagulation (DLP) in pulsed mode (on 100ms / off 400ms) at 10W and 800nm with a 300μm fibre kept 2-3mm from the tissues, to reduce the lesion. 3. Diode Laser surgical excision in pulsed mode (on 50ms / off 200ms) at 8W and 800nm with a 300 μm fibre in close contact with tissues, and histological intraoperative margins control on frozen sections. Even if it has inconstant results (lesions decreasing rate is 10% to 40% proportionally to vascular blood component), DLP simplifies the last and the most important step. Use of Diode Laser also in surgical excision reduces intra and postoperatory complications.

  20. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

    DEFF Research Database (Denmark)

    Louveau, Antoine; Plog, Benjamin A.; Antila, Salli

    2017-01-01

    Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss...... the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges...... and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems....

  1. Lymphatic mapping to tailor selective lymphadenectomy in squamous cell carcinoma of oral cavity

    International Nuclear Information System (INIS)

    Haq, M.E.U.; Warraich, R.A.; Abid, H.

    2010-01-01

    Objective: The purpose of this study was to determine the distribution of cervical lymph node metastases in the Squamous cell carcinoma of oral tongue and or floor of mouth; hence to improve the pretreatment evaluation of these patients. Study design: Descriptive study. Setting: Department of Oral and Maxillofacial Surgery, King Edward Medical University/ Mayo Hospital Lahore. From July 1, 2008 to December 31, 2009. Methods: This study was carried out on 50 consecutive patients who were having Squamous cell carcinoma of oral tongue and or floor of the mouth with T1 - T4 lesions. Results: Neck lymph node levels I and II were the most common sites of cervical lymph node metastases that was, 30%. Levels IV and V were involved very rarely. The overall metastases to cervical lymph node levels I - III combined was seen in 90% cases of oral tongue or floor of the mouth. Conclusion: The most common region for cervical lymph node metastases in Squamous Cell Carcinoma of oral tongue and floor of mouth is levels I - III in the ipsilateral neck, so based on pattern of metastases, supraomohyoid neck dissection for cN+ and functional neck dissection for cN+ necks are suggested. Key Words: Oral Squamous cell carcinoma (OSCC), cervical lymph node metastasis, cN+ (clinically lymph node negative), cN+ (clinically lymph node positive) (N1 - N/sub 3/), pN+ (pathologically lymph node metastases found), elective neck dissection, occult metastasis, radical neck dissection (RND). (author)

  2. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Science.gov (United States)

    2010-01-01

    Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs). This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A-LC and Child C-LC). Immunohistochemical (IHC), Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver. PMID:21059220

  3. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  4. Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

    International Nuclear Information System (INIS)

    Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An; Olivera, Gustavo; Somlo, George

    2007-01-01

    Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk

  5. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2018-04-01

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

  6. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  7. Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

    Energy Technology Data Exchange (ETDEWEB)

    Short, Robert F.; Shiels, William E. [Ohio State University College of Medicine and Public Health, Department of Radiology, The Children' s Radiological Institute, Children' s Hospital, Columbus, OH (United States); Sferra, Thomas J. [Ohio State University College of Medicine and Public Health, Department of Gastroenterology, The Columbus Children' s Research Institute, Children' s Hospital, Columbus, OH (United States); Nicol, Kathleen K. [Ohio State University College of Medicine and Public Health, Department of Pathology, Children' s Hospital, Columbus, OH (United States); Schofield, Minka; Wiet, Gregory J. [Ohio State University College of Medicine and Public Health, Department of Otolaryngology, Children' s Hospital, Columbus, OH (United States)

    2007-06-15

    Lymphatic malformation is a common benign mass in children and adults and is representative of a derangement in lymphangiogenesis. These lesions have high recurrence rates and significant morbidity associated with surgery. Several sclerotherapy regimens have been developed clinically to treat lymphatic malformations; however, an animal model has not been developed that is adequate to test the efficacy of image-guided therapeutic interventions. To develop an animal model suitable for evaluation of percutaneous treatments of lymphatic malformations. Male Harlan Sprague-Dawley rats (n = 9) received two US-guided injections of Incomplete Freund's Adjuvant (IFA) over a 2-week period. All nine rats were injected twice into the peritoneum (IP); a subgroup (n = 3) received additional injections into the neck. Three animals that received IP injections of saline were used as controls. The injection sites were monitored for the development of lesions by high-resolution ultrasonography at 2-week intervals for 100 days. High-resolution (4.7 Tesla) magnetic resonance imaging was then performed on two animals noted to have developed masses. The rats were sacrificed and histologic examination of the identified lesions was performed, including immunohistochemical staining for vascular (CD31) and lymphatic (Flt-4 and Prox-1) endothelium. All animals injected with IFA developed cystic lesions. The three animals injected at dual sites were noted to have both microcystic and macrocystic malformations in the neck and microcystic plaque-like lesions in the peritoneum. The macrocystic malformations ({>=}5 mm) in the neck were detected by ultrasonography and grossly later during necropsy. Histopathologic analysis revealed the cystic spaces to be lined by lymphatic endothelium supported by a connective tissue stroma. Control animals did not exhibit detectable lesions with either ultrasonography or necropsy. This model represents a promising tool for translational development of image

  8. Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

    International Nuclear Information System (INIS)

    Short, Robert F.; Shiels, William E.; Sferra, Thomas J.; Nicol, Kathleen K.; Schofield, Minka; Wiet, Gregory J.

    2007-01-01

    Lymphatic malformation is a common benign mass in children and adults and is representative of a derangement in lymphangiogenesis. These lesions have high recurrence rates and significant morbidity associated with surgery. Several sclerotherapy regimens have been developed clinically to treat lymphatic malformations; however, an animal model has not been developed that is adequate to test the efficacy of image-guided therapeutic interventions. To develop an animal model suitable for evaluation of percutaneous treatments of lymphatic malformations. Male Harlan Sprague-Dawley rats (n = 9) received two US-guided injections of Incomplete Freund's Adjuvant (IFA) over a 2-week period. All nine rats were injected twice into the peritoneum (IP); a subgroup (n = 3) received additional injections into the neck. Three animals that received IP injections of saline were used as controls. The injection sites were monitored for the development of lesions by high-resolution ultrasonography at 2-week intervals for 100 days. High-resolution (4.7 Tesla) magnetic resonance imaging was then performed on two animals noted to have developed masses. The rats were sacrificed and histologic examination of the identified lesions was performed, including immunohistochemical staining for vascular (CD31) and lymphatic (Flt-4 and Prox-1) endothelium. All animals injected with IFA developed cystic lesions. The three animals injected at dual sites were noted to have both microcystic and macrocystic malformations in the neck and microcystic plaque-like lesions in the peritoneum. The macrocystic malformations (≥5 mm) in the neck were detected by ultrasonography and grossly later during necropsy. Histopathologic analysis revealed the cystic spaces to be lined by lymphatic endothelium supported by a connective tissue stroma. Control animals did not exhibit detectable lesions with either ultrasonography or necropsy. This model represents a promising tool for translational development of image

  9. Lymphatic drainage pathways from the cervix uteri: implications for radical hysterectomy?

    Science.gov (United States)

    Kraima, A C; Derks, M; Smit, N N; Van Munsteren, J C; Van der Velden, J; Kenter, G G; DeRuiter, M C

    2014-01-01

    Radical hysterectomy with pelvic lymphadenectomy is the treatment of choice for early-stage cervical cancer. Wertheim's original technique has been often modified, mainly in the extent of parametrectomy. Okabayashi's technique is considered as the most radical variant regarding removal of the ventral parametrium and paracolpal tissues. Surgical outcome concerning recurrence and survival is good, but morbidity is high due to autonomic nerve damage. While the autonomic network has been studied extensively, the lymphatic system is less understood. This study describes the lymphatic drainage pathways of the cervix uteri and specifically the presence of lymphatics in the vesico-uterine ligament (VUL). A developmental series of 10 human female fetal pelves was studied. Paraffin embedded blocks were sliced in transverse sections of 8 or 10 μm. Analysis was performed by staining with antibodies against LYVE-1 (lymphatic endothelium), S100 (Schwann cells), alpha-Smooth Muscle Actin (smooth muscle cells) and CD68 (macrophages). The results were three-dimensionally represented. Two major pathways drained the cervix uteri: a supra-ureteral pathway, running in the cardinal ligament superior to the ureter, and a dorsal pathway, running in the utero-sacral ligament towards the rectal pillars. No lymph vessels draining the cervix uteri were detected in the VUL. In the paracolpal parametrium lymph vessels draining the upper vagina fused with those from the bladder. The VUL does not contain lymphatics from the cervix uteri. Hence, the favorable survival outcomes of the Okabayashi technique cannot be explained by radical removal of lymphatic pathways in the ventrocaudal parametrium. © 2013.

  10. Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

    Science.gov (United States)

    Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

    2015-11-06

    Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

  11. Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report

    International Nuclear Information System (INIS)

    Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

    2015-01-01

    Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism

  12. Prolonged lymphatic leak after retroperitoneal lymph node dissection: a case report

    Directory of Open Access Journals (Sweden)

    Browne Katherine M

    2009-08-01

    Full Text Available Abstract Introduction Persistent lymphatic drainage following retroperitoneal lymph node dissection for testicular tumor is an uncommon complication. Case presentation We describe a 21-year old man of Caucasian origin who had metastatic non-seminomatous germ cell tumor of the testis, and underwent retroperitoneal lymph node dissection, nephrectomy and partial inferior vena cava excision for a residual mass. The patient subsequently developed persistent lymphatic drainage causing foot drop that eventually responded to conservative medical and surgical measures. Conclusion This postoperative condition usually responds well to conservative measures but has the potential for serious morbidity if it is not managed appropriately.

  13. Flow rates in the head and neck lymphatics after food stimulation in healthy subjects

    International Nuclear Information System (INIS)

    Thommesen, P.; Buhl, J.; Jansen, K.; Funch-Jensen, P.; Central Hospital Randers; Municipal Hospital Aarhus

    1981-01-01

    In 22 healthy subjects lymph transport flow rates was studied in the head lymphatics after food stimulation, mastication (chewing) and taste. After food stimulation there was a significantly higher transport rate (0.67 meter/hour) than after taste (0.57 meter/hour) and mastication (0.55 meter/hour). The calculation of transport flow rate was independent of quantitative distribution of radioactivity in the head and neck lymphatics, and it could therefore perhaps be of clinical value. (orig.) [de

  14. Lymphatic endothelial cell line (CH3) from a recurrent retroperitoneal lymphangioma.

    Science.gov (United States)

    Way, D; Hendrix, M; Witte, M; Witte, C; Nagle, R; Davis, J

    1987-09-01

    An endothelial cell line derived from a massive recurrent chyle-containing retroperitoneal lymphangioma was isolated in monolayer culture. Scanning and transmission electron microscopy and immunohistochemistry confirmed a close resemblance to blood vascular endothelium with typical cobblestone morphology, positive immunofluorescence staining for endothelial marker Factor VIII-associated antigen and fibronectin, and prominent Weibel-Palade bodies. The endothelial cells also exhibited other ultrastructural features characteristic of lymphatic endothelium, including sparse microvillous surface projections, overlapping intercellular junctions, and abundant intermediate filaments. This endothelial cell line represents a new source of proliferating lymphatic endothelium for future study, including structural and functional comparison to blood vascular endothelium.

  15. Laparoscopic management of abdominal lymphatic cyst in children.

    Science.gov (United States)

    Tran, Ngoc Son; Nguyen, Thanh Liem

    2012-06-01

    The aim of this study is to investigate the feasibility and effectiveness of laparoscopic surgery (LS) in management of abdominal lymphatic cyst (ALC) in children. Medical records of all patients undergoing LS for ALC at the National Hospital of Pediatrics, Hanoi, Vietnam, from May 2007 to June 2011 were reviewed. For LS, one umbilical port of 10 mm and up to three other 3-5-mm ports were used. Cystic fluid was aspirated prior to removal of the cyst. When intestinal resection was indicated, the mesenteric cyst with the bowel loop was delivered out of the abdomen through a minimally enlarged umbilical incision; resection of the intestinal segment together with the cyst and the bowel anastomosis were both performed extracorporally. Forty-seven patients were identified, with a mean age of 4.3 ± 3.7 years. The most common symptoms were abdominal pain (72.3%) and abdominal distention (34.0%). Four patients presented with acute abdomen due to infection or hemorrhage of the cyst. Mean size of the ALC was 9.5 ± 5.5 cm (range, 3.4-30 cm). In 12 cases the ALC was omental, and in 35 cases it was mesenteric. Laparoscopic cyst excision was performed in 36 cases (76.6%) versus laparoscopy-assisted bowel resection en bloc with the cyst in 8 cases (17.0%); in 3 patients (6.4%), conversion to open surgery was required. Mean operative time was 79 ± 39 minutes. There were no intra- or postoperative complications. Mean length of hospital stay after laparoscopic management was 3.8 ± 1.6 days. The results of pathologic investigation showed benign cystic lymphangioma in all cases. During follow-up ranging from 1 month to 4 years, recurrence was seen in 1 patient (2.1%) with complex mesenteric cyst. All other patients remained in good health. Laparoscopic management is safe, feasible, and effective and should be the treatment of choice for most cases of ALC in children.

  16. Expression of YY1 correlates with progression and metastasis in esophageal squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Luo J

    2014-09-01

    difference in YY1 expression in patients with or without lymphatic invasion. The Transwell assay revealed that the overexpression of YY1 promoted the invasion ability of TE-1 cells and the inhibition of YY1 could reverse this promotion. Conclusion: YY1 expression was associated with TNM stage and lymph node metastasis, suggesting that YY1 can influence human esophageal cancer progression and metastasis. Keywords: immunohistochemistry, transwell assay, clinicopathological features, invasion

  17. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  18. Repopulation of the Stem-Cell Compartment in Haemopoietic and Lymphatic Tissues of Mice after X-Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Vos, O. [Medical Biological Laboratory of the National Defense Organization TNO, Rijswijk Z.H. (Netherlands)

    1968-08-15

    Repopulation in haemopoietic tissues of mice was studied at various times after irradiation with a sub-lethal X-ray dose of 460 R and after exposure to a lethal X-ray dose of 800 R followed by transplantation of 4 x 10{sup 6} syngeneic bone-marrow cells. The number of stem cells was determined with the exogenous and endogenous spleen colony technique in the bone-marrow of the femur and in the spleen. Repopulation in lymphatic tissues was investigated at various times after sub-lethal irradiation with 460 R, sub-lethal irradiation with 460 R followed by allogeneic skin transplantation, lethal irradiation with 800 R followed by transplantation of 2 x 10{sup 6} syngeneic bone-marrow cells, and irradiation with 800 R followed by transplantation of 2 x 10{sup 6} and 5 x 10{sup 6} syngeneic bone-marrow and lymph node cells, respectively. The number of stem cells was estimated in the spleen and in lymph nodes with a technique based on a graft-versus- host reaction. The results showed that a rapid repopulation occurred in haemopoietic tissues under all circumstances. In the spleen an overshoot was found during a period beginning shortly after the 7th day and lasting for some weeks. In lymphatic tissues repopulation by stem cells was slow. During the first one or two weeks some decrease was even observed. This was followed by a slow repopulation that around 100 days after irradiation reached a level slightly below that found in control animals. Small differences of repopulation in the various organs and under different circumstances are discussed. It was postulated that immuno-competent lymphatic stem cells (antigen-sensitive cells or PC{sub 1} cells) do not proliferate or do so only to a limited extent. This compartment must be replenished by repopulation of differentiating stem cells from the bone marrow. It seems probable that stem-cell depletion or antigeneic stimulation has only a marginal effect upon repopulation. (author)

  19. Evaluation of Lymphatic Filariasis and Onchocerciasis in Three Senegalese Districts Treated for Onchocerciasis with Ivermectin.

    Directory of Open Access Journals (Sweden)

    Nana O Wilson

    2016-12-01

    Full Text Available In Africa, onchocerciasis and lymphatic filariasis (LF are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA. Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF and Ov16 (onchocerciasis antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5-9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas.

  20. Surgical management of morbidity due to lymphatic filariasis: the usefulness of a standardized international clinical classification of hydroceles.

    Science.gov (United States)

    Capuano, G P; Capuano, C

    2012-03-01

    The objective of this work is to evaluate the usefulness of a standardized clinical classification of hydroceles in lymphatic filariasis endemic countries to guide their surgical management. 64 patients with hydroceles were operated in 2009-2010, in Level II hospitals (WHO classification), during two visits to Fiji, by the same mobile surgical team. The number of hydroceles treated was 83. We developed and evaluated a much needed clinical classification of hydroceles based on four criteria: Type (uni/bilateral); Side (left/right); Stage of enlargement of the scrotum rated from I to VI; Grade of burial of the penis rated from 0 to 4. It lead to the conclusion that 1) A Stage I or II hydrocele, associated with Grade 0 or 1 penis burial could be considered a "Simple Hydrocele". The surgical treatment is simple with no anticipated early complication. WHO Level II of health care structure seems adapted. 2) A Stage III or IV hydrocele associated with Grade 2, 3 or 4 penis burial could be considered a "Complicated Hydrocele". The operation is longer, more complicated and the possibility of occurrence of complications seems greater. A level III health care facility would be more adapted under the normal functioning of the health system. We conclude that a standardized clinical classification of hydroceles based on the Stage of enlargement of the scrotum and the Grade of burial of the penis appears to be a useful tool to guide the decision about the level of care and the surgical technique required. We use the same classification for penoscrotal lymphoedema. A decision tree is presented for the management of hydroceles in lymphatic filariasis endemic countries which could usefully complement the "Algorithm for management of scrotal swelling" proposed by WHO in 2002. An international classification system of hydroceles would also allow standardization and facilitate study design and comparisons of their results.

  1. Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

    Science.gov (United States)

    Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

    2018-01-25

    The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

  2. [Surgical managment of colorectal liver metastasis].

    Science.gov (United States)

    Prot, Thomas; Halkic, Nermin; Demartines, Nicolas

    2007-06-27

    Surgery offer the only curative treatment for colorectal hepatic metastasis. Nowadays, five-year survival increases up to 58% in selected cases, due to the improvement and combination of chemotherapy, surgery and ablative treatment like embolisation, radio-frequency or cryoablation. Surgery should be integrated in a multi disciplinary approach and initial work-up must take in account patient general conditions, tumor location, and possible extra hepatic extension. Thus, a surgical resection may be performed immediately or after preparation with chemotherapy or selective portal embolization. Management of liver metastasis should be carried out in oncological hepato-biliary centre.

  3. The role of exosomes in cancer metastasis.

    Science.gov (United States)

    Steinbichler, Teresa Bernadette; Dudás, József; Riechelmann, Herbert; Skvortsova, Ira-Ida

    2017-06-01

    Exosomes are small membrane vesicles with a size ranging from 40 to 100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis. Metastasis is a complex multistep process of cancer cell invasion, survival in blood vessels, attachment to and colonization of the host organ. Exosomes influence every step of this cascade and can be targeted by oncological treatment. This review highlights the role of exosomes in the various steps of the metastatic cascade and how exosome dependent pathways can be targeted as therapeutic approach or used for liquid biopsies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The Multiple Roles of Exosomes in Metastasis

    Science.gov (United States)

    WEIDLE, H. ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWEN; RÜGER, RÜDIGER

    2016-01-01

    Exosomes are important contributors to cell−cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes. PMID:28031234

  5. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  6. Duodenal Metastasis of Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Huang-Chi Chen

    2008-12-01

    Full Text Available Metastatic malignant mesothelioma of the pleura is uncommon at the time of initial diagnosis. The gastrointestinal lumen is rarely found at autopsy in patients with widespread disease. Here, we describe an extremely rare case of isolated duodenal metastasis of sarcomatoid mesothelioma of the pleura in a 73-year-old man, without memory of any direct exposure to asbestos. The possibility of gastrointestinal tract metastasis should be considered in the presence of anemia or positive occult blood test in patients with malignant pleural mesothelioma.

  7. Prognostic Significance of Pre-operative FDG-PET in Colorectal Cancer Patients with Hepatic Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyo Sang; Lee, Won Woo; Kim, Duck Woo; Kang, Sung Bum; Lee, Kyoung Ho; Lee, Keun Wook; Kim, Jee Hyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul (Korea, Republic of)

    2009-10-15

    The purpose of this study was to assess the prognostic value of preoperative FDG-PET in colorectal cancer (CRC) patients with hepatic metastasis (HM). 24 CRC patients (M:F=14:10; age, 63{+-}10 yrs) with HM who had undergone preoperative FDG PET were included. Cure-intent surgery was performed in all the patients and HMs were controlled using resection (n=13), radio-frequency ablation (RFA) (n=7), and resection plus RFA (n=4). Potential prognostic markers tested were maxSUV of primary tumor, maxSUV of HM, maxSUV ratio of HM over primary tumor (M/P ratio), histologic grade, CEA level, venous/lymphatic/nerve invasion, T stage, N stage, no. of HM, no. of lymph node metastasis, and treatment modality of HM. 14 CRC patients developed a recurrence with a median follow-up duration of 244 days, whereas 10 patients did not develop recurrence with a median follow-up duration of 504 days. M/P ratios but other potential prognostic markers were significantly higher in the recurrent patients (0.72{+-}0.14) than recurrence-free patients (0.54{+-}0.23) (p=0.038). M/P ratio only was found to predict recurrence by Cox multivariate analysis (hazard ratio 37.7, 95% confidence interval 2.01-706.1, p=0.016). The 11 patients with lower M/P ratio of <0.61 had significantly better disease-free survival rate than the 13 patients with higher M/P ratio ({>=}0.61) (p=0.026). maxSUV ratio of HM over primary tumor (M/P ratio) may be useful for prognosis prediction of CRC patients with HM. Higher FDG uptake of HM than that of primary tumor may indicate a more advanced status in stage IV CRC.

  8. Occurrence of lymph node metastasis in early-stage parotid gland cancer.

    Science.gov (United States)

    Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

    2012-02-01

    Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

  9. Effect of Physical Methods of Lymphatic Drainage on Postexercise Recovery of Mixed Martial Arts Athletes.

    Science.gov (United States)

    Zebrowska, Aleksandra; Trybulski, Robert; Roczniok, Robert; Marcol, Wieslaw

    2017-08-16

    Physical methods are reported to be important for accelerating skeletal muscle regeneration, decreasing muscle soreness, and shortening of the recovery time. The aim of the study was to assess the effect of the physical methods of lymphatic drainage (PMLD) such as manual lymphatic drainage (MLD), the Bodyflow (BF) therapy, and lymphatic drainage by deep oscillation (DO) on postexercise regeneration of the forearm muscles of mixed martial arts (MMA) athletes. Eighty MMA athletes aged 27.5 ± 6.4 years were allocated to 4 groups: MLD, the BF device, DO therapy, and the control group. Blood flow velocity in the cephalic vein was measured with the ultrasound Doppler velocity meter. Maximal strength of the forearm muscles (Fmax), muscle tissue tension, pain threshold, blood lactate concentration (LA), and activity of creatine kinase were measured in all groups at rest, after the muscle fatigue test (post-ex) and then 20 minutes, 24, and 48 hours after the application of PMLD. The muscle fatigue test reduced Fmax in all subjects, but in the groups receiving MLD, DO, and BF significantly higher Fmax was observed at recovery compared with post-ex values. The application of MDL reduced the postexercise blood LA and postexercise muscle tension. The lymphatic drainage methods, whether manual or using electro-stimulation and DO, improve postexercise regeneration of the forearm muscles of MMA athletes. The methods can be an important element of therapeutic management focused on optimizing training effects and reducing the risk of injuries of the combat sports athletes.

  10. Hobnail hemangioma reclassified as superficial lymphatic malformation: a study of 52 cases.

    Science.gov (United States)

    Trindade, Felicidade; Kutzner, Heinz; Tellechea, Óscar; Requena, Luis; Colmenero, Isabel

    2012-01-01

    Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. There are no limitations. Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. Indirect measurement of lymphatic absorption with inulin in continuous ambulatory peritoneal dialysis (CAPD) patients

    NARCIS (Netherlands)

    Struijk, D. G.; Krediet, R. T.; Koomen, G. C.; Boeschoten, E. W.; vd Reijden, H. J.; Arisz, L.

    1990-01-01

    To elucidate the importance of possible trapping of macromolecules in peritoneal tissue on the calculation of peritoneal lymphatic drainage, we compared the transport of inulin administered i.v. and i.p. in nine continuous ambulatory peritoneal dialysis (CAPD) patients on two separate days. In the

  12. IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

    DEFF Research Database (Denmark)

    Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine

    2013-01-01

    OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the ...

  13. Lymphangiography: Forgotten Tool or Rising Star in the Diagnosis and Therapy of Postoperative Lymphatic Vessel Leakage

    International Nuclear Information System (INIS)

    Kos, Sebastian; Haueisen, Harald; Lachmund, Ulrich; Roeren, Thomas

    2007-01-01

    Since the advent of computed tomography, numbers and expertise in Lymphangiography (LAG) have markedly dropped. The intention of our study was to demonstrate the persisting diagnostic and therapeutic impact of LAG on the postoperative patient with known or suspected lymphatic vessel leakage. Between May 1, 1999, and April 30, 2006, we investigated pedal lipiodol-LAGs (18 monopedal, 2 bipedal) on 22 patients (16 male, 6 female) with known or suspected postoperative chylothorax, chylaskos, lymphocele, or lymphatic fistula. Ages varied from 26 to 81 years. The spectrum of operative procedures was broad: 6 thoracic, 5 abdominal, and 11 peripheral operations were performed. In 20 patients who underwent mono- or bipedal LAG for lymphatic vessel injury, we were able to demonstrate the specific site of leakage in 15 cases (75%) and found signs of extravasation in 5 patients (25%). Furthermore, in 11 patients (55%) we were able to avoid surgery because of closure of the leak after LAG. As the conservative therapeutic approach usually takes 2-3 weeks to reveal its therapeutic effects, 73.3% (11/15) of the patients who were not reoperated before this hallmark was passed did not need any further operation. Our study clearly demonstrates that even in the decades of modern cross-sectional imaging, classic LAG is a powerful and highly reliable tool to visualize and even assist occlusion of the postoperatively damaged lymphatic vessel and may thereby avoid the need for reoperation

  14. Composition of the Extracellular Matrix of Lymphatic Novel Threadlike Structures: Is It Keratin?

    Directory of Open Access Journals (Sweden)

    Hyub Huh

    2013-01-01

    Full Text Available Background. The lumen of novel threadlike structures (NTSs is enclosed by a single layer of endothelial cells surrounded by extracellular matrix (ECM. We hypothesized that collagen may be a component of the ECM associated with lymphatic NTSs. Methods. Six female New Zealand white rabbits were anesthetized, and the NTS structures within lymphatic vessels were identified by contrast-enhanced stereomicroscopy or alcian blue staining. Isolated NTS specimens were stained with acridine orange, YOYO-1, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI. The structural and molecular composition of the ECM was investigated using transmission electron microscopy (TEM, electrospray ionization-mass spectrometry, and proteomic analysis. Results. The lymph vessel wall was stained red by DiI, and rod-shaped nuclei were stained green by YOYO-1. The area surrounding the NTS was also stained red and contained green rod-shaped nuclei. TEM images showed that the NTS consisted of many ECM fibers and the ECM fibers appeared to be ~100 nm in diameter and had narrowly spaced striated bands. Proteomic analysis of the lymphatic NTS-associated ECM identified 4 proteins: keratin 10, cytokeratin 3, cytokeratin 12, and soluble adenylyl cyclase. Conclusion. The TEM study suggested that the lymphatic NTS-associated ECM did not contain collagen. This was confirmed by proteomic analysis, which showed that keratin was the major component of the ECM.

  15. Impact of Surgical Route in Influencing the Risk of Lymphatic Complications After Ovarian Cancer Staging.

    Science.gov (United States)

    Bogani, Giorgio; Borghi, Chiara; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Scaffa, Cono; Perotto, Stefania; Leone Roberti Maggiore, Umberto; Montanelli, Luca; Di Donato, Violante; Infantino, Carmelo; Lorusso, Domenica; Raspagliesi, Francesco

    Lymphatic complications are a common occurrence after staging surgery for early-stage ovarian cancer (eEOC). We investigated whether the introduction of minimally invasive surgery influences the risk of developing lymphoceles and lymphorrhea in patients undergoing staging for eEOC. For this purpose, data of consecutive patients affected by eEOC undergoing staging surgery between January 1980 and January 2016 were retrospectively reviewed, and a systematic review and meta-analysis was performed. This systematic review was registered in the International Prospective Register of Systematic Review. Among 341 patients included in the present study, 47 severe postoperative complications occurred (13.7%), including 40 lymphatic complications: 31 symptomatic lymphoceles (9%) and 9 cases of lymphorrhea (2.6%), respectively. Laparoscopic staging correlated with a lower risk of developing any severe lymphatic complications in comparison with open surgery (p = .02). In particular, the laparoscopic approach and para-aortic node involvement were associated with a trend toward lower lymphoceles (odds ratio, .13; 95% confidence interval, .07-2.20; p = .05) and a trend toward higher risk of lymphorrhea developing (odds ratio, 4.02; 95% confidence interval, .93-17.3; p = .06), respectively. In conclusion, the implementation of a minimally invasive approach might result in a slight reduction of lymphatic complications after eEOC staging. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

  16. A novel podoplanin-GFPCre mouse strain for gene deletion in lymphatic endothelial cells.

    Science.gov (United States)

    Gil, Hyea Jin; Ma, Wanshu; Oliver, Guillermo

    2018-04-01

    The lymphatic vascular system is a one-direction network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice. Unfortunately, only few mouse Cre strains relatively specific for lymphatic endothelial cells (LECs) are currently available. In this article, we report the generation of a novel Podoplanin (Pdpn) GFPCre transgenic mouse strain using its 5' regulatory region. Pdpn encodes a transmembrane mucin-type O-glycoprotein that is expressed on the surface of embryonic and postnatal LECs, in addition to few other cell types. Our detailed characterization of this novel strain indicates that it will be a valuable additional genetic tool for the analysis of gene function in LECs. © 2018 Wiley Periodicals, Inc.

  17. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

  18. [Value of CT lymphangiography in the detection of lymphatic leakage: a report of nine cases].

    Science.gov (United States)

    Safar, K; Aouaifia, A; Oudjit, A; Le Pimpec-Barthes, F; Riquet, M; Legmann, P

    2011-01-01

    To demonstrate the value of CT lymphangiography to detect lymphatic leakage, especially at the thoracic level, prior to therapeutic intervention. Between 2004 and 2008, nine patients underwent lymphangiography, followed by CT for the evaluation of intractable lymphatic leakage in spite of optimal medical management. Patients included seven females and two males, with age ranging between 25 and 58 years. Lymphangiography was performed after unilateral or bilateral foot injection(s) of Lipiodol ultrafluid followed by standard radiographs of the chest and abdomen and CT of the chest, abdomen and pelvis. The images were reviewed by two experienced radiologists. Lipiodol leakage was observed in six patients, while three patients showed evidence of lymphangiectasia of the abdominal and/or thoracic lymphatics. Spontaneous resolution of leakage after lymphangiography occurred in three cases. CT lymphangiography allows direct evaluation of lymphatics, from pelvis to chest, in order to detect the site of leakage at the origin of a chylous effusion and assist in its management. Copyright © 2010 Elsevier Masson SAS and Éditions françaises de radiologie. All rights reserved.

  19. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

  20. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  1. A Lymphatic dwelling filarioid nematode, Rumenfilaria andersoni (Filarioidea; Splendidofilariinae), is an emerging parasite in Finnish cervids

    Science.gov (United States)

    Background-Recent studies revealed expansion of filarioid nematodes into the northern Finland. In addition to Setaria tundra, unidentified and very abundant filarioids, representing Rumenfilaria andersoni, were found inhabiting the lymphatic vessels of reindeer. Our study explores the biology and d...

  2. Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage

    DEFF Research Database (Denmark)

    Parving, H H; Hansen, J M; Nielsen, S L

    1979-01-01

    of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain...

  3. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.

    Directory of Open Access Journals (Sweden)

    Joseph Andrews

    2010-01-01

    Full Text Available We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis.We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model using Affymetrix gene expression (U133, promoter (1.0R, and SNP/CNV (SNP 6.0 microarray platforms to correlate data from gene expression, epigenetic (DNA methylation, and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo methylation with the loss (or gain of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis.Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer progression and metastasis.

  4. Inhibition of Breast Cancer Metastasis by Heregulin-Beta 1

    National Research Council Canada - National Science Library

    Yu, Dihua

    1999-01-01

    The major goal of this Idea proposal is to determine whether and how HRG-Beta1 inhibits breast cancer metastasis and to identify the functional domains that are sufficient for inhibition of breast cancer metastasis...

  5. Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

    2007-03-15

    Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

  6. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

    Science.gov (United States)

    Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

    2017-05-22

    Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to

  7. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Adam Silumbwe

    2017-05-01

    Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation

  8. Evaluation of the recombinant antigens Wb14 and WbT for the capture antibody diagnosis of lymphatic filariasis

    Directory of Open Access Journals (Sweden)

    André Filipe Pastor

    2018-03-01

    Full Text Available BACKGROUND Lymphatic filariasis (LF is a parasitic disease caused mainly by the Wuchereria bancrofti worm and that affects up to 120 million people worldwide. LF is the second cause of chronic global deformity, responsible for 15 million people with lymphedema (elephantiasis and 25 million men with scrotal hydrocele. Its diagnosis is still associated with numerous difficulties, such as the sample collection periods (microfilaria nocturnal periodicity and limited diagnostic kits. OBJECTIVES The aim of this work was to evaluate two recombinant antigens (Wb14 and WbT as part of an enzyme-linked immunosorbent assay (ELISA based antibody capture tests for LF. METHODS The recombinant antigens rWb14 and rWbT were expressed in Escherichia coli BL21 and an antibody capture ELISA was performed. For this, sera were used from microfilaremic individuals with W. bancrofti (MF, chronic pathology (CP, individuals infected with Strongyloides (SP and healthy controls from endemic (EN and non-endemic (NE areas. FINDINGS Both tests showed similar results, with 90% sensitivity and 96.6% specificity. In comparison with the BM14 ELISA commercial test, the Wb14 and WbT antigens performed with identical sensitivity but greater specificity. Reduced positivity with the CP suggested a potential to monitor cure. This was not confirmed, however, when sera from individuals up to seven years after treatment were assayed. MAIN CONCLUSIONS The Wb14 and WbT ELISAs were considered efficient and promising diagnostic tests. Due to the importance of antibody capture analysis to evaluate the Global Program to Eliminate Lymphatic Filariasis (GPELF, the tests proposed here appear as great alternatives to the available commercial system.

  9. Modelling strategies to break transmission of lymphatic filariasis--aggregation, adherence and vector competence greatly alter elimination.

    Science.gov (United States)

    Irvine, M A; Reimer, L J; Njenga, S M; Gunawardena, S; Kelly-Hope, L; Bockarie, M; Hollingsworth, T D

    2015-10-22

    With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be

  10. Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report.

    Science.gov (United States)

    Luginbuehl, Miriam; Imhof, Alexander; Klarer, Alexander

    2017-11-23

    Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

  11. Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into lymph.

    Science.gov (United States)

    Hodge, Lisa M; Bearden, Melissa K; Schander, Artur; Huff, Jamie B; Williams, Arthur; King, Hollis H; Downey, H Fred

    2010-06-01

    Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.

  12. Octreotide in Intestinal Lymphangiectasia: Lack of a Clinical Response and Failure to Alter Lymphatic Function in a Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    S Makhija

    2004-01-01

    Full Text Available Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing

  13. Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

    Science.gov (United States)

    2011-01-01

    affect breast cancer metastasis with a subcutaneous mouse tumor implantation model of breast cancer metastasis. HMLE -Twist1 cells expressing shRNAs...13 4 Introduction Distant metastases are responsible for the vast majority of breast cancer deaths. This process...to migrate and invade is therefore essential to the metastatic process. The initial steps of breast cancer metastasis, local invasion and

  14. Computed tomography demonstration of a hypothalamic metastasis

    International Nuclear Information System (INIS)

    Chakeres, D.W.

    1983-01-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal. (orig.)

  15. Computed tomography demonstration of a hypothalamic metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Chakeres, D.W.

    1983-05-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal.

  16. Diagnosis and treatment of brain metastasis

    International Nuclear Information System (INIS)

    Sajama, Carlos; Lorenzoni, Jose; Tagle, Patricio

    2008-01-01

    Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated

  17. A new protein Girdin in tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; FU Li; GU Feng; MA Yong-jie

    2010-01-01

    @@ The phosphatidylinositol 3-kinase/Akt serine/threonine kinase system regulates multiple cellular processes through the phosphorylation of a great number of downstream substrates and has been recognized as an important pathway for signal transduction, and in cancer invasion and metastasis.

  18. Detection of cancer before distant metastasis

    NARCIS (Netherlands)

    Coumans, F.A.W.; Siesling, Sabine; Terstappen, Leonardus Wendelinus Mathias Marie

    2013-01-01

    Background To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the

  19. Detection of cancer before distant metastasis

    NARCIS (Netherlands)

    Coumans, Frank A. W.; Siesling, Sabine; Terstappen, Leon W. M. M.

    2013-01-01

    Background: To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the

  20. Diagnosis of bone metastasis from thyroid carcinoma

    DEFF Research Database (Denmark)

    Bechsgaard, Thor; Lelkaitis, Giedrius; Jensen, Karl E

    2015-01-01

    (MRI), but histology revealed a metastasis from thyroid carcinoma, although the patient had no previous history of thyroid malignancy and resection of the thyroid gland was without malignancy. Ultrasound-guided biopsy was possible due to cortical destruction and the multidisciplinary approach with re...

  1. Presumed choroidal metastasis of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J.

    1990-01-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma

  2. Effect of water resource development and management on lymphatic filariasis, and estimates of populations at risk.

    Science.gov (United States)

    Erlanger, Tobias E; Keiser, Jennifer; Caldas De Castro, Marcia; Bos, Robert; Singer, Burton H; Tanner, Marcel; Utzinger, Jürg

    2005-09-01

    Lymphatic filariasis (LF) is a debilitating disease overwhelmingly caused by Wuchereria bancrofti, which is transmitted by various mosquito species. Here, we present a systematic literature review with the following objectives: (i) to establish global and regional estimates of populations at risk of LF with particular consideration of water resource development projects, and (ii) to assess the effects of water resource development and management on the frequency and transmission dynamics of the disease. We estimate that globally, 2 billion people are at risk of LF. Among them, there are 394.5 million urban dwellers without access to improved sanitation and 213 million rural dwellers living in close proximity to irrigation. Environmental changes due to water resource development and management consistently led to a shift in vector species composition and generally to a strong proliferation of vector populations. For example, in World Health Organization (WHO) subregions 1 and 2, mosquito densities of the Anopheles gambiae complex and Anopheles funestus were up to 25-fold higher in irrigated areas when compared with irrigation-free sites. Although the infection prevalence of LF often increased after the implementation of a water project, there was no clear association with clinical symptoms. Concluding, there is a need to assess and quantify changes of LF transmission parameters and clinical manifestations over the entire course of water resource developments. Where resources allow, integrated vector management should complement mass drug administration, and broad-based monitoring and surveillance of the disease should become an integral part of large-scale waste management and sanitation programs, whose basic rationale lies in a systemic approach to city, district, and regional level health services and disease prevention.

  3. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

    Science.gov (United States)

    Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

    2008-12-01

    The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

  4. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  5. A prognostic gene signature for metastasis-free survival of triple negative breast cancer patients.

    Science.gov (United States)

    Lee, Unjin; Frankenberger, Casey; Yun, Jieun; Bevilacqua, Elena; Caldas, Carlos; Chin, Suet-Feung; Rueda, Oscar M; Reinitz, John; Rosner, Marsha Rich

    2013-01-01

    Although triple negative breast cancers (TNBC) are the most aggressive subtype of breast cancer, they currently lack targeted therapies. Because this classification still includes a heterogeneous collection of tumors, new tools to classify TNBCs are urgently required in order to improve our prognostic capability for high risk patients and predict response to therapy. We previously defined a gene expression signature, RKIP Pathway Metastasis Signature (RPMS), based upon a metastasis-suppressive signaling pathway initiated by Raf Kinase Inhibitory Protein (RKIP). We have now generated a new BACH1 Pathway Metastasis gene signature (BPMS) that utilizes targets of the metastasis regulator BACH1. Specifically, we substituted experimentally validated target genes to generate a new BACH1 metagene, developed an approach to optimize patient tumor stratification, and reduced the number of signature genes to 30. The BPMS significantly and selectively stratified metastasis-free survival in basal-like and, in particular, TNBC patients. In addition, the BPMS further stratified patients identified as having a good or poor prognosis by other signatures including the Mammaprint® and Oncotype® clinical tests. The BPMS is thus complementary to existing signatures and is a prognostic tool for high risk ER-HER2- patients. We also demonstrate the potential clinical applicability of the BPMS as a single sample predictor. Together, these results reveal the potential of this pathway-based BPMS gene signature to identify high risk TNBC patients that can respond effectively to targeted therapy, and highlight BPMS genes as novel drug targets for therapeutic development.

  6. Correlation between tumor size and surveillance of lymph node metastasis for IB and IIA cervical cancer by magnetic resonance images

    International Nuclear Information System (INIS)

    Kim, See Hyung; Lee, Hee Jung; Kim, Young Whan

    2012-01-01

    Purpose: To assess the feasibility of preoperative MRI based measurement of tumor size with regard to lymph node (LN) metastasis in early uterine cervical cancer. Material and Methods: A retrospective review of patients with FIGO stage IB–IIA cervical cancer who underwent lymphadenectomy was performed. Diagnostic accuracy of MRI in detecting LN metastasis and rate of LN recurrence in terms of tumor size (≤4 cm versus >4 cm) were analyzed. ROC curve analysis was used to determine LN size for differentiating LN metastasis in terms of tumor size. P 4 cm revealed higher diagnostic accuracy of MRI in detecting LN metastasis (85.4% versus 50.6%, P = 0.023) and rate of LN recurrence (20.0% versus 6.4%, P = 0.031) in than those with size with ≤4 cm, the differences were statistically significant. Discriminant analysis of LN size for the differentiation of metastasis from non-metastasis resulted in cut-off values (11.8 mm; size with >4 cm versus 8.3 mm; size with ≤4 cm) and diagnostic accuracy (84.0% of size with >4 cm versus 72.0% of size with ≤4 cm). Conclusion: MRI has limited sensitivity, but high specificity in predicting surveillance of LN metastasis in the preoperative early cervical cancer, especially useful tool for patients with tumor size with >4 cm.

  7. Renal Metastasis from Primary Cervical Cancer: A Case Report

    International Nuclear Information System (INIS)

    Jeon, Seong Woo; Kim, See Hyung; Kwon, Sun Young

    2013-01-01

    Metastasis of malignant tumors to the kidney is clinically rare and often discovered by autopsy. Primary lymphoma and lung cancer are known that can metastasize to the kidney. Other malignant tumor metastasis to the kidney is very unusual. Primary cervical cancer metastasis to adjacent pelvic organs and lymph nodes are well known followed by abdominal solid organs such as the liver and adrenal glands. However, reported primary cervical cancer metastasis to the kidney is extremely rare and mostly appeared as bilateral multiple renal masses. We report here on a rare case of unilateral single renal metastasis from primary cervical cancer after concur- rent chemoradiotherapy.

  8. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jiangdong Xiang

    2017-02-01

    dehydrogenase were found between the low-MLR group (MLR ≤ 0.23 and the high-MLR group (MLR > 0.23. Correspondingly, dramatic differences were observed between the two groups in OS. CONCLUSION: Our results show that the peripheral blood MLR before surgery could be a significant predictor of advanced stages, advanced pathologic grades, and positive lymphatic metastasis in ovarian cancer patients.

  9. Prevalence of depression and associated clinical and socio-demographic factors in people living with lymphatic filariasis in Plateau State, Nigeria.

    Science.gov (United States)

    Obindo, James; Abdulmalik, Jibril; Nwefoh, Emeka; Agbir, Michael; Nwoga, Charles; Armiya'u, Aishatu; Davou, Francis; Maigida, Kurkat; Otache, Emmanuel; Ebiloma, Ajuma; Dakwak, Samuel; Umaru, John; Samuel, Elisha; Ogoshi, Christopher; Eaton, Julian

    2017-06-01

    Lymphatic filariasis is a chronic, disabling and often disfiguring condition that principally impacts the world's poorest people. In addition to the well-recognised physical disability associated with lymphedema and hydrocele, affected people often experience rejection, stigma and discrimination. The resulting emotional consequences are known to impact on the quality of life and the functioning of the affected individuals. However, the management of this condition has focused on prevention and treatment through mass drug administration, with scant attention paid to the emotional impact of the condition on affected individuals. This study aimed to determine the prevalence and severity of depression among individuals with physical disfigurement from lymphatic filariasis in Plateau State, Nigeria. A cross-sectional 2-stage convenience study was conducted at 5 designated treatment centers across Plateau State, Nigeria. All available and consenting clients with clearly visible physical disfigurement were recruited. A semi-structured socio-demographic questionnaire, Rosenberg Self-esteem and a 9-item Patient Health Questionnaire (PHQ-9) were administered at the first stage. Those who screened positive (with a PHQ-9 score of five and above) were further interviewed using the Depression module of the Composite International Diagnostic Interview (CIDI). Ninety-eight individuals met the criteria and provided consent. Twenty percent of the respondents met criteria for depression, with the following proportions based on severity: Mild (42.1%), Moderate (31.6%) and Severe (26.3%). History of mental illness (OR 40.83, p = 0.008); Median duration of the illness was 17 years (IQR 7.0-30 years) and being unemployed (OR 12.71, p = 0.003) were predictive of depression. High self-esteem was negatively correlated (OR 0.09, pdepression is high among individuals with lymphatic filariasis and depression in sufferers is associated with low self-esteem and low levels of life satisfaction.

  10. Prevalence of depression and associated clinical and socio-demographic factors in people living with lymphatic filariasis in Plateau State, Nigeria.

    Directory of Open Access Journals (Sweden)

    James Obindo

    2017-06-01

    Full Text Available Lymphatic filariasis is a chronic, disabling and often disfiguring condition that principally impacts the world's poorest people. In addition to the well-recognised physical disability associated with lymphedema and hydrocele, affected people often experience rejection, stigma and discrimination. The resulting emotional consequences are known to impact on the quality of life and the functioning of the affected individuals. However, the management of this condition has focused on prevention and treatment through mass drug administration, with scant attention paid to the emotional impact of the condition on affected individuals. This study aimed to determine the prevalence and severity of depression among individuals with physical disfigurement from lymphatic filariasis in Plateau State, Nigeria.A cross-sectional 2-stage convenience study was conducted at 5 designated treatment centers across Plateau State, Nigeria. All available and consenting clients with clearly visible physical disfigurement were recruited. A semi-structured socio-demographic questionnaire, Rosenberg Self-esteem and a 9-item Patient Health Questionnaire (PHQ-9 were administered at the first stage. Those who screened positive (with a PHQ-9 score of five and above were further interviewed using the Depression module of the Composite International Diagnostic Interview (CIDI.Ninety-eight individuals met the criteria and provided consent. Twenty percent of the respondents met criteria for depression, with the following proportions based on severity: Mild (42.1%, Moderate (31.6% and Severe (26.3%. History of mental illness (OR 40.83, p = 0.008; Median duration of the illness was 17 years (IQR 7.0-30 years and being unemployed (OR 12.71, p = 0.003 were predictive of depression. High self-esteem was negatively correlated (OR 0.09, p<0.004.Prevalence of depression is high among individuals with lymphatic filariasis and depression in sufferers is associated with low self-esteem and low

  11. Prognostic outcomes in advanced breast cancer: the metastasis-free interval is important.

    Science.gov (United States)

    Shen, Tiansheng; Gao, Cheng; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-12-01

    Metastatic breast cancer is a heterogeneous disease with a diverse clinical course. There have been limited studies regarding prognostic outcomes in patients with de novo metastatic breast cancer versus those with metastatic recurrence, with controversial observations. In this study, we sought to examine the difference in survival outcomes among patients with advanced breast cancer stratified based on metastasis-free interval (MFI) and to further explore the role of systemic therapy in these patient groups. Of 569 consecutive patients with stage IV breast cancer between 1998 and 2013, 201 had de novo metastatic disease (metastasis at diagnosis) and 368 developed metastatic recurrence, including 168 with an MFI≤24 months and 200 with an MFI>24 months. In the 492 patients who received systemic therapy, de novo metastasis was an independent favorable prognostic factor for overall survival after metastasis when compared with metastatic recurrence irrespective of MFI. Compared with the patients with metastatic recurrence with an MFI≤24 months, those with an MFI>24 months had a superior survival outcome, although it did not reach statistical significance by multivariate analysis. In contrast, de novo metastatic breast cancer was associated with a worse prognosis when compared with recurring metastasis in the patients who did not receive systemic treatment. These findings provide more insight into the natural history of advanced breast cancer, thus necessitating further investigation into the molecular mechanism of drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Diet Modulation is an Effective Complementary Agent in Preventing and Treating Breast Cancer Lung Metastasis

    Science.gov (United States)

    Zhao, Xiangmin; Rezonzew, Gabriel; Wang, Dezhi; Siegal, Gene P.; Hardy, Robert W.

    2014-01-01

    A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary stearate with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets (corn oil control diet/CO, low fat /LF or stearate/ST) the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50% compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings. PMID:24832758

  13. Lymphangiogenesis and Lymphatic Absorption Are Related and Increased in Chronic Kidney Failure, Independent of Exposure to Dialysis Solutions

    NARCIS (Netherlands)

    Vlahu, Carmen A.; de Graaff, Marijke; Aten, Jan; Struijk, Dirk G.; Krediet, Raymond T.

    2015-01-01

    Increased lymphatic absorption might contribute to ultrafiltration failure in peritoneal dialysis (PD). Lymphangiogenesis develops during PD, but little is known about the relationship between its morphologic and functional parameters. The relationships between lymph vessel density, the effective

  14. Predictors of survival in surgically treated patients of spinal metastasis

    Directory of Open Access Journals (Sweden)

    Pravin Padalkar

    2011-01-01

    Full Text Available Background: The spinal metastasis occurs in up to 40% of cancer patient. We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases. We also assessed the different variables separately with respect to their value in predicting postsurgical life expectancy. Finally, we suggest criteria for selecting patients for surgery based on the postoperative survival pattern. Materials and Methods: We retrospectively analyzed 102 patients who had been operated for metastatic disease of the spine. Predictive scoring was done according to the scoring systems proposed by Tokuhashi and Tomita. Overall survival was assessed using Kaplan-Meier survival analysis. Using the log rank test and Cox regression model we assessed the value of the individual components of each scoring system for predicting survival in these patients. Result: The factors that were most significantly associated with survival were the general condition score (Karnofsky Performance Scale (P=.000, log rank test, metastasis to internal organs (P=.0002 log rank test, and number of extraspinal bone metastases (P=.0058. Type of primary tumor was not found to be significantly associated with survival according to the revised Tokuhashi scoring system (P=.9131, log rank test. Stepwise logistic regression revealed that the Tomita score correlated more closely with survival than the Tokuhashi score. Conclusion: The patient′s performance status, extent of visceral metastasis, and extent of bone metastases are significant predictors of survival in patients with metastatic disease. Both revised Tokuhashi and Tomita scores were significantly correlated with survival. A revised Tokuhashi score of 7 or more and a Tomita score of 6 or less indicated >50% chance of surviving 6 months postoperatively. We recommend that the Tomita score be used for prognostication in patients who are contemplating surgery, as it is simpler to score and has a higher

  15. Development of a Tissue-Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema.

    Science.gov (United States)

    Kanapathy, Muholan; Kalaskar, Deepak; Mosahebi, Afshin; Seifalian, Alexander M

    2016-03-01

    Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. Study Regarding the Effectiveness of Manual Lymphatic Drainage in the Case of Patients with Breast Cancer that Present Lymphedema

    OpenAIRE

    Alexandru MIOC; Corina PANTEA

    2013-01-01

    Lymphedema is defined as a persistent increase of tissue volume caused by the blocked or absent lymphatic drainage. The purpose of this study is to analyse the effectiveness of lymphatic drainage in the treatment of lymphedema after a mastectomy, with the aim of reducing the volume of the lymphedema and improving overall symptomatology, as well as providing information regarding the impact of this treatment on quality-of-life and the physical limitations of these patients. With these objectiv...

  17. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

    Science.gov (United States)

    Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

    2009-12-01

    Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

  18. Cancer metabolism and the dynamics of metastasis.

    Science.gov (United States)

    Dattoli, G; Guiot, C; Delsanto, P P; Ottaviani, P L; Pagnutti, S; Deisboeck, T S

    2009-02-07

    Cancer growth dynamics, commonly simulated with a Gompertzian model, is analyzed in the framework of a more recent and realistic model. In particular, we consider the setting of a tumor embedded in a host organ and investigate their interaction. We assume that, at least in some cases, tumor metastasis may be triggered by an 'energetic crisis', when the tumor exceeds the 'carrying capacity' of the host organ. As a consequence, dissemination of clusters of cancer cells is set in motion, with a statistical probability given by a Poisson distribution. The model, although still at a preclinical level, is fully quantitative and is applied, as an example, to the case of prostate cancer. The results confirm that, at least for the more aggressive cancers, metastasis starts very early during tumorigenesis and a quantitative link is found between the tumor's doubling time, its 'aggressiveness' and the metastatic potential.

  19. Lymphatic compensation during the postoperative period after breast cancer treatment with axillary dissection

    Directory of Open Access Journals (Sweden)

    Mariana Maia Freire de Oliveira

    2015-06-01

    Full Text Available Lymphedema secondary to breast cancer causes physical and psychological morbidity and compromises quality of life. The objective of this literature review was to study lymphatic compensation after surgery for breast cancer and the factors that influence this process, with a view to understanding the etiopathogenesis of lymphedema. Articles indexed on Pubmed published from 1985 to 2012 were reviewed. According to the literature, lymphangiogenesis reduces damage to lymph vessels; there is little evidence that Vascular Endothelial Growth Factor is elevated in women with lymphedema; lymphovenous communications can be observed 60 days after surgery; women without lymphedema have acquired alternative mechanisms for removal of proteins from the interstitial space; and active exercise stimulates lymphatic and venous pumping. Health professionals should teach these patients about the risk factors for lymphedema. The effects of lymphangiogenesis, proteolysis and lymphovenous communications on development of lymphedema should be studied, since these events are intimately related.

  20. Effects of lymphatic drainage and cryotherapy on indirect markers of muscle damage.

    Science.gov (United States)

    Behringer, Michael; Jedlicka, Diana; Mester, Joachim

    2018-06-01

    Muscle enzymes are cleared from the extracellular space by the lymphatic system, while smaller proteins enter the bloodstream directly. We investigated if manual lymphatic drainage (MLD), local cryotherapy (CRY), and rest (RST) differently affect the time course of creatine kinase (CK, 84 kDa) and heart-type fatty acid binding protein (h-FABP, 15 kDa) in the blood. Randomized controlled trial. After 4x20 unilateral, eccentric accentuated knee extensions (with one-third of the maximal isometric force) 30 sports students randomly received either a 30 min MLD, CRY or they rested (RST) for the same amount of time. CK, h-FABP, neutrophil granulocytes, and the perceived muscle soreness were assessed before, immediately after, and 1 hour, 4 hours, and 24 hours after the exercise. All measures increased significantly (Psports physicians and conditioning specialists who use biochemical muscle damage markers to adjust the training load and volume of athletes.

  1. Role of the paraventricular nucleus in the reflex diuresis to pulmonary lymphatic obstruction in rabbits.

    Science.gov (United States)

    Choudhary, Rishabh Charan; Sharma, Ravindra Kumar; Gulati, Kavita; Ravi, Krishnan

    2016-01-01

    The changes in urine flow and renal sympathetic nerve activity (RSNA) due to pulmonary lymphatic obstruction (PLO) were examined in anesthetized, artificially ventilated New Zealand white rabbits. PLO was produced by pressurizing an isolated pouch created in the right external jugular vein at the points of entry of the right lymphatic ducts. During this maneuver, urine flow increased from 8.5 ± 0.3 mL/10 min to 12 ± 0.5 mL/10 min (P acid microinjections into the PVN. The results show that (i) neurons in the PVN are an important relay site in the reflex arc, which is activated by PLO; and (ii) this activation is regulated by glutamatergic and partly by GABAergic input to the PVN.

  2. Use of Magnetic Nanoparticles to Visualize Threadlike Structures inside Lymphatic Vessels of Rats

    Directory of Open Access Journals (Sweden)

    Hyeon-Min Johng

    2007-01-01

    Full Text Available A novel application of fluorescent magnetic nanoparticles was made to visualize a new tissue which had not been detectable by using simple stereomicroscopes. This unfamiliar threadlike structure inside the lymphatic vessels of rats was demonstrated in vivo by injecting nanoparticles into lymph nodes and applying magnetic fields on the collecting lymph vessels so that the nanoparticles were taken up by the threadlike structures. Confocal laser scanning microscope images of cryosectioned specimens exhibited that the nanoparticles were absorbed more strongly by the threadlike structure than by the lymphatic vessels. Further examination using a transmission electron microscope revealed that the nanoparticles had been captured between the reticular fibers in the extracellular matrix of the threadlike structures. The emerging technology of nanoparticles not only allows the extremely elusive threadlike structures to be visualized but also is expected to provide a magnetically controllable means to investigate their physiological functions.

  3. Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1.

    Science.gov (United States)

    Liu, Xinyi; Uemura, Akiyoshi; Fukushima, Yoko; Yoshida, Yutaka; Hirashima, Masanori

    2016-11-22

    The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching. Conditional ablation in mice demonstrates that PlexinD1 is primarily required in lymphatic endothelial cells (LECs). In vitro analyses show that Sema3G binds to neuropilin-2 (Nrp2), which forms a receptor complex with PlexinD1. Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent manner. Our findings shed light on a molecular mechanism by which LECs are distributed away from arteries and form a branching network during lymphatic vascular development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Autoradiographic investigations on the prednisolone-induced atrophy and on interdependent reactions in different lymphatic tissues of rabbit

    International Nuclear Information System (INIS)

    Steigueber, F.

    1980-01-01

    Under the application of 3 H-thymidine the method of organ extirpation (thymectomy and appendectomy) was combined with the cell labeling technique. By autoradiographic evaluation of histologic specimens the content of labelled lymphocytes in the examined tissues was determined. Thymus, appendix, subcutaneous lymphatic nodes and spleen were examined. In the thymus the application of prednisolone induced organ atrophy. Appendectomy leads in the thymic marrow to an increase of the mitotic activity. In the appendix the application of prednisolone causes the emptying of basal lymphatic follicles. Thymectomy induces a large increase of the mitotic activity of the lymphatic tissue. Not all lymphatic nodes show identical changes after organ extirpation and after prednisolone application, but considerable differences. Only a decreased proliferation of labled lymphocytes, occuring under prednisolone application, can be detected in the marrow of the mesenteric lymphatic nodes and of the red splenic pulp in the animal with thymectomy. This result is also valid for the marrow of the remaining deep lymphatic nodes, after thymectomy and appendectomy. The lymphocyte counting in the peripheral blood done during prednisolone treatment, does not indicate that the lymphocyte values depend to a notable extent on the previous surgical treatment of the animals. (orig./MG) [de

  5. Intramuscular metastasis from malignant melanoma: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Hirohi; Itai, Yuji; Niitsu, Mamoru [Dept. of Radiology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Fujiwara, Masachika; Watanabe, Teruo [Department of Pathology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan); Satomi, Hisae; Otsuka, Fujio [Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan)

    1999-12-01

    We present a rare case of intramuscular metastasis from malignant melanoma. The lesion showed intermediate to high signal intensity on T1-weighted magnetic resonance (MR) images and mixed signal intensities containing high and low signals on T2-weighted images. The signal intensity on T1-weighted images, which is due to the paramagnetic effect of melanin, is a characteristic MR finding of this entity. (orig.)

  6. Mandibular metastasis of cholangiocarcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Tae Min [Dept. of Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of); Kim, Kee Dong; Jeong, Ho Gui; Park, Won Se [Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of)

    2015-12-15

    Tumors metastasizing from distant regions to the oral and maxillofacial region are uncommon, comprising only 1%-2% of all malignancies. Cholangiocarcinoma is a malignancy that arises from cholangiocytes, which are epithelial cells that line the bile ducts. These cancers are difficult to diagnose and have a poor prognosis. In this paper, we report a rare case of mandibular metastasis of cholangiocarcinoma diagnosed at the primary site and discuss the radiographic findings observed in this case.

  7. Isolated penile metastasis from bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Demuren, O.A. [Department of Radiology and Imaging, Armed Forces Hospital, Riyadh (Saudi Arabia); Koriech, O. [Department of Oncology, Armed Forces Hospital, Riyadh (Saudi Arabia)

    1999-10-01

    Metastases of the penis are uncommon, with only approximately 300 cases reported since 1870. In up to 70 % of patients, the primary tumour is located in the urogenital tract. Furthermore, isolated metastases of the penis are exceptionally rare. We report a case of solitary squamous cell metastasis of the penis presenting with painful swelling initially thought to be inflammatory in origin. The CT and MR imaging findings are presented with a short review of the literature. (orig.) With 2 figs., 9 refs.

  8. The Role of Extracellular Vesicles in Metastasis

    Science.gov (United States)

    2017-10-01

    transferred via ESVs to osteoblasts. These bone cells represent the most common tissue target for breast cancer metastasis, and we will mimic ESV...separation of beads will result in good separation of bead-complexed exosomes and microvesicles. Furthermore, we show that we can use the same device to...proteins for 3 common exosome tetraspanin markers (CD9, CD63, and CD81) [Andreu & Yanez-Mo 2014] in tandem (pLLNL-exo-GFP) in order to both increase

  9. Prediction of Metastasis Using Second Harmonic Generation

    Science.gov (United States)

    2016-07-01

    small but statistically significant difference in average F/B of treated US patients versus untreated Dutch patients. Fig. 1. Display of all...predictive ability of models incorporating F/B using a multivariate linear model, but this time applying the analysis to the entire ER+ and ER- cohort. As...AWARD NUMBER: W81XWH-15-1-0040 TITLE: Prediction of Metastasis Using Second Harmonic Generation PRINCIPAL INVESTIGATOR: Edward Brown

  10. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

    DEFF Research Database (Denmark)

    Louveau, Antoine; Plog, Benjamin A; Antila, Salli

    2017-01-01

    to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege...... and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems....

  11. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

  12. Ethanol inhibits B16-BL6 melanoma metastasis and cell phenotypes associated with metastasis.

    Science.gov (United States)

    Kushiro, Kyoko; Núñez, Nomelí P

    2012-01-01

    Every year, approximately 68,000 new cases of malignant melanoma are diagnosed in the US. Ethanol consumption inhibits metastasis of melanoma in mice, but the mechanism is not well understood. C57BL/6J ob/+ mice, given either water or 20% ethanol, were injected intravenously with B16-BL6 melanoma cells to determine pulmonary metastasis. The effects of ethanol on cell phenotypes and markers of the epithelial-to-mesenchymal transition were determined in cell culture. In mice, ethanol consumption inhibited experimental pulmonary metastasis. This inhibition was associated with decreased body weight, and levels of systemic leptin, and insulin. In cell culture, ethanol inhibited B16-BL6 cell motility, invasion, and anchorage-independent growth. Additionally, ethanol reduced Snai1 expression and increased E-cadherin expression. Lastly, ethanol increased the expression of Kiss1 metastasis-suppressor and the metastasis suppressor Nm23/nucleoside diphosphate kinase. In both animal and in cell culture conditions, ethanol inhibited the metastatic ability of B16-BL6 melanoma cells.

  13. Chemokines: novel targets for breast cancer metastasis

    Science.gov (United States)

    Ali, Simi; Lazennec, Gwendal

    2007-01-01

    Recent studies have highlighted the possible involvement of chemokines and their receptors in breast cancer progression and metastasis. Chemokines and their receptors constitute a superfamily of signalling factors whose prognosis value in breast cancer progression remains unclear. We will examine here the expression pattern of chemokines and their receptors in mammary gland physiology and carcinogenesis. The nature of the cells producing chemokines or harboring chemokine receptors appears to be crucial in certain conditions for example, the infiltration of the primary tumor by leukocytes and angiogenesis. In addition, chemokines, their receptors and the interaction with glycosaminoglycan (GAGs) are key players in the homing of cancer cells to distant metastasis sites. Several lines of evidence, including in vitro and in vivo models, suggest that the mechanism of action of chemokines in cancer development involves the modulation of proliferation, apoptosis, invasion, leukocyte recruitment or angiogenesis. Furthermore, we will discuss the regulation of chemokine network in tumor neovascularity by decoy receptors. The reasons accounting for the deregulation of chemokines and chemokine receptors expression in breast cancer are certainly crucial for the comprehension of chemokine role in breast cancer and are in several cases linked to estrogen receptor status. The targeting of chemokines and chemokine receptors by antibodies, small molecule antagonists, viral chemokine binding proteins and heparins appears as promising tracks to develop therapeutic strategies. Thus there is significant interest in developing strategies to antagonize the chemokine function, and an opportunity to interfere with metastasis, the leading cause of death in most patients. PMID:17717637

  14. Lymphatic dwelling filarioid nematodes in reindeer Rangifer tarandus tarandus, (cervidae) in Finland, identified as Rumenfilaria andersoni Lankester & Snider, 1982 (nematoda: Onchocercidae: Splendidofilariinae).

    Science.gov (United States)

    Laaksonen, S; Saari, S; Nikander, S; Oksanen, A; Bain, O

    2010-03-01

    A filarioid nematode inhabiting the lymphatic vessels of the subserosal rumen and mesenteries associated with a high prevalence of its microfilariae in peripheral blood was observed in Finnish reindeer (Rangifer tarandus tarandus) in 2004 and 2006. Adult specimens were collected by dissecting lymphatic vessels from slaughtered animals, where some of the nematodes were seen through the wall of the dilated vessels as thin white winding threads obscuring the vessel. The morphology of adult worms and microfilaria is described based on light and scanning electron microscopy. These filariae belong to the subfamily Splendidofilariinae of the Onchocercidae and resemble Rumenfilaria andersoni, recovered from different host and localization, the ruminal veins of Alces alces in Canada. Comparison of paratypes of this species revealed only minor differences which were not sufficient to separate the filarioid parasitic in R. tarandus in Finland and we identify the nematode as R. andersoni. However, the findings suggest two different parasite populations. The finalizing of this taxonomic question in the future requires an integrated approach, in which the DNA-based and morphological identifications are consistent.

  15. Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis

    Directory of Open Access Journals (Sweden)

    de Souza Dziedzom K

    2012-11-01

    Full Text Available Abstract Lymphatic Filariasis (LF is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF. The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomal forms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies.

  16. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Irene Vergara

    2016-03-01

    Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

  17. Lymphatic recovery of exogenous oleic acid in rats on long chain or specific structured triacylglycerol diets

    DEFF Research Database (Denmark)

    Vistisen, Bodil; Mu, Huiling; Høy, Carl-Erik

    2006-01-01

    Specific structured triacylglycerols, MLM (M = medium-chain fatty acid, L = long-chain fatty acid), rapidly deliver energy and long-chain fatty acids to the body and are used for longer periods in human enteral feeding. In the present study rats were fed diets of 10 wt% MLM or LLL (L = oleic acid......% and 45%, respectively). However, the recovery of exogenous 18:1 n-9 was higher after a single bolus of MLM compared with a bolus of LLL in rats on the MLM diet (40% and 24%, respectively, P = 0.009). The recovery of lymphatic 18:1 n-9 of the LLL bolus tended to depend on the diet triacylglycerol...... structure and composition (P = 0.07). This study demonstrated that with a diet containing specific structured triacylglycerol, the lymphatic recovery of 18:1 n-9 after a single bolus of fat was dependent on the triacylglycerol structure of the bolus. This indicates that the lymphatic recovery of long...

  18. Refinements of the radiographic cadaver injection technique for investigating minute lymphatic vessels.

    Science.gov (United States)

    Suami, Hiroo; Taylor, G Ian; O'Neill, Jennifer; Pan, Wei-Ren

    2007-07-01

    The authors previously reported a new technique with which to delineate the lymphatic vessels, using hydrogen peroxide to identify them and a lead oxide suspension to demonstrate them on radiographs. This technique provided excellent studies of the lymph vessels in human cadavers, but there was still room for improvement. Lymph collecting vessels run superficially in some regions, where they may be damaged while the surgeon is attempting to find them. Vessels smaller than 0.3 mm in diameter could not be cannulated with a 30-gauge needle, which was the smallest the authors had available, and the lead oxide suspension often blocked this cannula. The authors also encountered problems holding the cannula steady. The authors solved these problems by using a mixture of hydrogen peroxide and ink to better identify the lymphatics, an extruded glass tube instead of a metal needle to cannulate them, an agate pestle and mortar to grind the lead oxide into finer particles, powdered milk to suspend the lead oxide, and a micromanipulator to facilitate accurate and steady cannulation of the vessels. This study developed these modifications to focus on tributaries of the collecting lymphatic channels that are smaller than 0.3 mm in diameter.

  19. Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

    Directory of Open Access Journals (Sweden)

    Martínez Helena

    2011-03-01

    Full Text Available Abstract Background Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. Methods A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments. The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment. The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image. Discussion The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. Trial registration ClinicalTrials (NCT: NCT01152099

  20. Understanding the three-dimensional anatomy of the superficial lymphatics of the limbs.

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2014-11-01

    There are minimal data in the current literature regarding the depth of the superficial lymphatic collectors of the limbs in relation to the various subcutaneous tissue layers. Injection, microdissection, radiographic, and histologic studies of the superficial lymphatics and the subcutaneous tissues of 32 limbs from 15 human cadavers were performed. Five layers were consistently identified in the integument of all the upper and lower limb specimens: (1) skin, (2) subcutaneous fat, (3) superficial fascia, (4) loose areolar tissue, and (5) deep fascia. Layer 2 was further divided into superficial (2a) and deep (2c) compartments by a thin, transparent, horizontal septum (layer 2b). The main superficial veins and the superficial nerves coursed in layer 4. The lymphatic collectors were found at layer 2c and layer 4. The use of consistent nomenclature to describe the subcutaneous tissue layers facilitates a greater understanding and discussion of the anatomy. In lymphovenous anastomosis for the treatment of lymphedema, indocyanine green lymphography is an unreliable method for identification of the superficial collectors of the thigh. The medial proximal leg, the dorsum of the wrist over the anatomical snuffbox, and the volar proximal forearm provide suitable areas for locating superficial collectors with nearby matching size veins. In vertical medial thigh lift, choosing a dissection plane superficial to the great saphenous vein is unlikely to preserve the collectors of the ventromedial bundle.

  1. Endoscopically observable white nodule caused by distal intramural lymphatic spread of rectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Tsumura Ayako

    2012-10-01

    Full Text Available Abstract This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.

  2. Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on systematic noncompliance with mass drug administration

    Directory of Open Access Journals (Sweden)

    Silvia Cabral

    Full Text Available ABSTRACT The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment. A rapid immunochromatographic test (ICT was performed during the survey to screen for filariasis. It was found that the survey subjects knew about filariasis and MDA. Filariasis was identified as a disease (86.2% and 74.4% associated it with the presence of swelling in the legs. About 80% knew about MDA, and the main source of information was healthcare workers (68.3%. For men the main reasons for systematic noncompliance with MDA were that “the individual had not received the medication” (p=0.03 and for women “the individual either feared experiencing adverse reactions”. According to the ICT, the prevalence of lymphatic filariasis was 2%. The most important causes of systematic noncompliance were not receiving the drug and fear of side-effects. For successful implementation of MDA programs, good planning, educational campaigns promoting the benefits of MDA, adoption of measures to minimize the impact of adverse effects and improvement of drug distribution logistics are needed.

  3. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics.

    Science.gov (United States)

    Louveau, Antoine; Plog, Benjamin A; Antila, Salli; Alitalo, Kari; Nedergaard, Maiken; Kipnis, Jonathan

    2017-09-01

    Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.

  4. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro.

    Science.gov (United States)

    Kornuta, Jeffrey A; Nipper, Matthew E; Dixon, J Brandon

    2013-01-04

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these shortcomings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. MicroRNA classifier and nomogram for metastasis prediction in colon cancer

    NARCIS (Netherlands)

    Goossens-Beumer, I.J.; Derr, R.S.; Buermans, H.P.; Goeman, J.J.; Bohringer, S.; Morreau, H.; Nitsche, U.; Janssen, K.P.; Velde, C.J. van de; Kuppen, P.J.

    2015-01-01

    BACKGROUND: Colon cancer prognosis and treatment are currently based on a classification system still showing large heterogeneity in clinical outcome, especially in TNM stages II and III. Prognostic biomarkers for metastasis risk are warranted as development of distant recurrent disease mainly

  6. Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain.

    Science.gov (United States)

    Lee, Se Jeong; Kang, Won Young; Yoon, Yeup; Jin, Ju Youn; Song, Hye Jin; Her, Jung Hyun; Kang, Sang Mi; Hwang, Yu Kyeong; Kang, Kyeong Jin; Joo, Kyeung Min; Nam, Do-Hyun

    2015-12-24

    Glioblastoma multiforme (GBM) is characterized by extensive local invasion, which is in contrast with extremely rare systemic metastasis of GBM. Molecular mechanisms inhibiting systemic metastasis of GBM would be a novel therapeutic candidate for GBM in the brain. Patient-derived GBM cells were primarily cultured from surgical samples of GBM patients and were inoculated into the brains of immune deficient BALB/c-nude or NOD-SCID IL2Rgamma(null) (NSG) mice. Human NK cells were isolated from peripheral blood mononucleated cells and expanded in vitro. Patient-derived GBM cells in the brains of NSG mice unexpectedly induced spontaneous lung metastasis although no metastasis was detected in BALB/c-nude mice. Based on the difference of the innate immunity between two mouse strains, NK cell activities of orthotopic GBM xenograft models based on BALB/c-nude mice were inhibited. NK cell inactivation induced spontaneous lung metastasis of GBM cells, which indicated that NK cells inhibit the systemic metastasis. In vitro cytotoxic activities of human NK cells against GBM cells indicated that cytotoxic activity of NK cells against GBM cells prevents systemic metastasis of GBM and that NK cells could be effective cel