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Sample records for melanoma sentinel lymph

  1. Popliteal lymphadenectomy on sentinel lymph node melanoma metastasis.

    PubMed

    Barrasa Shaw, Antonio; Sancho Merle, Francisca; Fuster Diana, Carlos; Campos Máñez, Jorge; Vázquez Albadalejo, Carlos

    2006-03-01

    Popliteal lymph node dissection is a procedure that surgeons rarely perform and, therefore, scarcely represented in bibliography. In this paper we present the case of a patient with melanoma metastasis to popliteal sentinel lymph nodes showing the surgical procedure and discussing some epidemiological and technical issues.

  2. Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical techniques

    PubMed Central

    Wainstein, Alberto JA; Drummond-Lage, Ana P; Kansaon, Milhem JM; Bretas, Gustavo O; Almeida, Rodrigo F; Gloria, Ana LF; Figueiredo, Ana RP

    2015-01-01

    Background The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN) biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure. Methods Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens). Results Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility. Conclusion Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. PMID:25565762

  3. Rapid immunohistochemistry of sentinel lymph nodes for metastatic melanoma.

    PubMed

    Eudy, Grant E; Carlson, Grant W; Murray, Douglas R; Waldrop, Sandra M; Lawson, Dianne; Cohen, Cynthia

    2003-08-01

    Sentinel lymph node (SLN) biopsy is performed on patients with malignant melanoma (MM) to assess the need for selective complete lymphadenectomy. Melanoma metastasis to regional lymph nodes is an important prognostic indicator in patients with MM. This study assesses the sensitivity and specificity of rapid immunohistochemistry (RIHC) in intraoperative delineation of melanoma metastasis to SLN. RIHC for S-100 protein, HMB45, and a melanoma marker cocktail (melan A, HMB45, and tyrosinase) was performed on 71 SLNs obtained from 28 patients with MM. Frozen sections (6 micro thick) on plus slides were fixed for 2 to 3 minutes in cold acetone and then stored at -70 degrees C. The EnVision kit (Dako, Carpinteria, CA) for rapid immunohistochemistry (RIHC) on frozen tissue sections was used, and the staining technique took 19 minutes. Together with preparation of the frozen sections and fixation in acetone, immunostained slides were available in approximately 25 minutes. Of the 71 SNLs examined, 7 showed melanoma metastasis in permanent sections. RIHC of frozen sections detected metastatic melanoma in 6 SLNs, with a sensitivity of 86% for HMB45 and 71% for S-100 protein and the melanoma cocktail and a specificity of 97% for HMB45 and 100% for S-100 and the melanoma cocktail. We conclude that RIHC for HMB45, S-100 protein, and the melanoma cocktail may help detect melanoma metastasis in SLN intraoperatively, leading to total lymph node dissection and obviating the need for 2 surgical procedures. Section folds and background stain can make interpretation difficult. Intraoperative time constraints require a more rapid technique. A recent consensus group has discouraged frozen-section examination of SLN.

  4. [Sentinel lymph node in malignant melanoma].

    PubMed

    Salas, Carmen; Pérez, Natividad

    2004-06-01

    The authors describe the technique called sentry ganglion, the ganglion which has the highest risk of receiving neoplastic cells and towards which a primary tumor directs its metastasis. The authors explain the procedure for carrying out a biopsy on this ganglion and its warnings regarding different neoplasias and specifically regarding melanoma.

  5. 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies.

    PubMed

    Lee, Jonathan J; Granter, Scott R; Laga, Alvaro C; Saavedra, Arturo P; Zhan, Qian; Guo, Weimin; Xu, Shuyun; Murphy, George F; Lian, Christine G

    2015-02-01

    Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N=18) or nodal nevi (N=10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.

  6. Comparison between 18F-Fluorodeoxyglucose Positron Emission Tomography and Sentinel Lymph Node Biopsy for Regional Lymph Nodal Staging in Patients with Melanoma: A Review of the Literature

    PubMed Central

    Mirk, Paoletta; Treglia, Giorgio; Salsano, Marco; Basile, Pietro; Giordano, Alessandro; Bonomo, Lorenzo

    2011-01-01

    Aim. to compare 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) to sentinel lymph node biopsy (SLNB) for regional lymph nodal staging in patients with melanoma. Methods. We performed a literature review discussing original articles which compared FDG-PET to SLNB for regional lymph nodal staging in patients with melanoma. Results and Conclusions. There is consensus in the literature that FDG-PET cannot replace SLNB for regional lymph nodal staging in patients with melanoma. PMID:22242204

  7. Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis.

    PubMed

    Harrell, Maria I; Iritani, Brian M; Ruddell, Alanna

    2007-02-01

    Lymphangiogenesis is associated with human and murine cancer metastasis, suggesting that lymphatic vessels are important for tumor dissemination. Lymphatic vessel alterations were examined using B16-F10 melanoma cells implanted in syngeneic C57Bl/6 mice, which form tumors metastasizing to draining lymph nodes and subsequently to the lungs. Footpad tumors showed no lymphatic or blood vessel growth; however, the tumor-draining popliteal lymph node featured greatly increased lymphatic sinuses. Lymph node lymphangiogenesis began before melanoma cells reached draining lymph nodes, indicating that primary tumors induce these alterations at a distance. Lymph flow imaging revealed that nanoparticle transit was greatly increased through tumor-draining relative to nondraining lymph nodes. Lymph node lymphatic sinuses and lymph flow were increased in mice implanted with unmarked or with foreign antigen-expressing melanomas, indicating that these effects are not due to foreign antigen expression. However, tumor-derived immune signaling could promote lymph node alterations, as macrophages infiltrated footpad tumors, whereas lymphocytes accumulated in tumor-draining lymph nodes. B lymphocytes are required for lymphangiogenesis and increased lymph flow through tumor-draining lymph nodes, as these alterations were not observed in mice deficient for B cells. Lymph node lymphangiogenesis and increased lymph flow through tumor-draining lymph nodes may actively promote metastasis via the lymphatics.

  8. Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

    PubMed Central

    Ulmer, Anja; Dietz, Klaus; Hodak, Isabelle; Polzer, Bernhard; Scheitler, Sebastian; Yildiz, Murat; Czyz, Zbigniew; Lehnert, Petra; Fehm, Tanja; Hafner, Christian; Schanz, Stefan; Röcken, Martin; Garbe, Claus; Breuninger, Helmut; Fierlbeck, Gerhard; Klein, Christoph A.

    2014-01-01

    Background Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. Methods and Findings We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3–123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61–2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02–2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories. Conclusions Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and

  9. Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases.

    PubMed

    Kakavand, Hojabr; Vilain, Ricardo E; Wilmott, James S; Burke, Hazel; Yearley, Jennifer H; Thompson, John F; Hersey, Peter; Long, Georgina V; Scolyer, Richard A

    2015-12-01

    Melanoma patients with sentinel lymph node metastases have variable 5-year survival rates (39-70%). The prognostic significance of tumor-infiltrating lymphocytes in sentinel lymph node metastases from such patients is currently unknown. Anti-PD-1/PD-L1 inhibitors have significantly improved clinical outcome in unresectable AJCC stage IIIC/IV metastatic melanoma patients, and are being trialed in the adjuvant setting in advanced stage disease, however, their role in early stage (sentinel lymph node positive) metastatic disease remains unclear. The aims of this study were to characterize, in sentinel lymph nodes, the subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumor PD-L1 expression as this may provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in sentinel lymph node positive metastatic melanoma patients. Sentinel lymph nodes containing metastatic melanoma from 60 treatment-naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 using immunohistochemistry on serial sections. The results were correlated with clinicopathologic features and outcome. Positive correlations between recurrence-free/overall survival with the number of CD3+ tumor-infiltrating lymphocytes (hazard ratio=0.36 (0.17-0.76), P=0.005; hazard ratio=0.29 (0.14-0.61), P=0.0005, respectively), the number of CD4+ tumor-infiltrating lymphocytes (hazard ratio=0.34 (0.15-0.77), P=0.007; hazard ratio=0.32 (0.14-0.74), P=0.005, respectively), and the number of CD8+ tumor-infiltrating lymphocytes (hazard ratio =0.42 (0.21-0.85), P=0.013; hazard ratio =0.32 (0.19-0.78), P=0.006, respectively) were observed. There was also a negative correlation with the number of peritumoral PD-1+ lymphocytes (hazard ratio=2.67 (1.17-6.13), P=0.016; hazard ratio=2.74 (1.14-6.76), P=0.019, respectively). Tumoral PD-L1 expression was present in 26 cases (43%) but did not

  10. Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

    PubMed Central

    Meves, Alexander; Nikolova, Ekaterina; Heim, Joel B.; Squirewell, Edwin J.; Cappel, Mark A.; Pittelkow, Mark R.; Otley, Clark C.; Behrendt, Nille; Saunte, Ditte M.; Lock-Andersen, Jorgen; Schenck, Louis A.; Weaver, Amy L.; Suman, Vera J.

    2015-01-01

    Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. PMID:26150443

  11. Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients.

    PubMed

    Messaoudene, Meriem; Périer, Aurélie; Fregni, Giulia; Neves, Emmanuelle; Zitvogel, Laurence; Cremer, Isabelle; Chanal, Johan; Sastre-Garau, Xavier; Deschamps, Lydia; Marinho, Eduardo; Larousserie, Frederique; Maubec, Eve; Avril, Marie-Françoise; Caignard, Anne

    2015-01-01

    Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells.

  12. Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density.

    PubMed

    Marinaccio, Christian; Giudice, Giuseppe; Nacchiero, Eleonora; Robusto, Fabio; Opinto, Giuseppina; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico

    2016-08-01

    The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest

  13. A critical reappraisal of false negative sentinel lymph node biopsy in melanoma.

    PubMed

    Manca, G; Romanini, A; Rubello, D; Mazzarri, S; Boni, G; Chiacchio, S; Tredici, M; Duce, V; Tardelli, E; Volterrani, D; Mariani, G

    2014-06-01

    Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis

  14. Accuracy of sentinel lymph node dissection for melanoma staging in the presence of a collision tumour with a lymphoproliferative disease.

    PubMed

    Gero, Daniel; Queiros da Mota, Vanessa; Boubaker, Ariane; Berthod, Gregoire; de Leval, Laurence; Demartines, Nicolas; Matter, Maurice

    2014-08-01

    Sentinel lymph node dissection (SLND) identifies melanoma patients with metastatic disease who would benefit from radical lymph node dissection (RLND). Rarely, patients with melanoma have an underlying lymphoproliferative disease, and melanoma metastases might develop as collision tumours in the sentinel lymph node (SLN). The aim of this study was to measure the incidence and examine the effect of collision tumours on the accuracy of SLND and on the validity of staging in this setting. Between 1998 and 2012, 750 consecutive SLNDs were performed in melanoma patients using the triple technique (lymphoscintigraphy, gamma probe and blue dye). The validity of SLND in collision tumours was analysed. False negativity was reflected by the disease-free survival. The literature was reviewed on collision tumours in melanoma. Collision tumours of melanoma and chronic lymphocytic leukaemia (CLL) were found in two SLN and in one RLND (0.4%). Subsequent RLNDs of SLND-positive cases were negative for melanoma. The patient with negative SLND developed relapse after 28 months with an inguinal lymph node metastasis of melanoma; RLND showed collision tumours. The literature review identified 12 cases of collision tumours. CLL was associated with increased melanoma incidence and reduced overall survival. This is, to our knowledge, the first assessment of the clinical value of SLND when collision tumours of melanoma and CLL are found. In this small series of three patients with both malignancies present in the same lymph node basin, lymphocytic infiltration of the CLL did not alter radioisotope uptake into the SLN. No false-negative result was observed. Our data suggest the validity of SLND in collision tumours, but given the rarity of the problem, further studies are necessary to confirm this reliability.

  15. Dermal Melanoma: A Report on Prognosis, Outcomes, and the Utility of Sentinel Lymph Node Biopsy

    PubMed Central

    DOEPKER, MATTHEW P.; THOMPSON, ZACHARY J.; HARB, JENNIFER N.; MESSINA, JANE L.; PULEO, CHRISTOPHER A.; EGAN, KATHLEEN M.; SARNAIK, AMOD A.; GONZALEZ, RICARDO J.; SONDAK, VERNON K.; ZAGER, JONATHAN S.

    2016-01-01

    Introduction Historically dermal melanoma (DM) has been labeled as either stage IIIB (in-transit) or stage IV (M1a) disease. We sought to investigate the natural history of DM and the utility and prognostic significance of sentinel lymph node biopsy (SLNB). Methods Patients with DM undergoing SLNB at a single center from 1998 to 2009 were identified. Results Eighty-three patients met criteria, 10 (12%) patients had a positive SLNB. Of those, 5 (50%) recurred (all with distant disease). Twenty-one (29%) of the 73 SLNB negative patients recurred and of those, 15 (71%) developed distant metastases, whereas 6 (29%) developed local or regional recurrence, including two false-negative regional nodal recurrences. No in-transit recurrences were recorded. Five-year recurrence-free and disease-specific survival was significantly better for patients with a negative SLNB versus positive SLNB (56.8% vs. 22.2% P =0.02, 81.1% vs. 61.0%, P =0.05, respectively). Conclusion SLNB has prognostic significance for RFS and DSS, and should be utilized in the management of DM based on a >10% yield and low false-negative rate. Our data demonstrate patients with DM do not recur in an in-transit fashion, which along with the survival outcomes suggest the behavior of DM is consistent with primary cutaneous melanoma of similar thickness rather than an isolated in-transit or distant dermal metastasis from a regressed cutaneous primary. PMID:26661407

  16. Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)

    PubMed Central

    2012-01-01

    Background Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. Methods A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. Results The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. Conclusion Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated. PMID:23228015

  17. Sentinel lymph node scintigraphy in cutaneous melanoma using a planar calibration phantom filled with Tc-99m pertechnetate solution for body contouring

    PubMed Central

    PEŞTEAN, CLAUDIU; BĂRBUŞ, ELENA; PICIU, ANDRA; LARG, MARIA IULIA; SABO, ALEXANDRINA; MOISESCU-GOIA, CRISTINA; PICIU, DOINA

    2016-01-01

    Background and aims Melanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used. Methods The study was conducted in the Department of Nuclear Medicine of Oncology Institute “Prof. Dr. Ion Chiricuţă” Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2–3 hours and when necessary, additional images at 6–7 hours. The acquisition matrix used was 128×128 pixels for an acquisition time of 5 – 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements

  18. Sentinel lymph node dissection in stage I/II melanoma patients: surgical management and clinical follow-up study.

    PubMed

    Macripò, Giuseppe; Quaglino, Pietro; Caliendo, Virginia; Ronco, Anna Maria; Soltani, Shoreh; Giacone, Elena; Pau, Stefano; Fierro, Maria Teresa; Bernengo, Maria Grazia

    2004-04-01

    Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followed up and eventually treated, is reported in this prospective study. The aim was to analyse the parameters associated with a higher risk of occult nodal metastases, to evaluate the clinical outcome of melanoma patients who underwent SLN procedure, and to identify by means of multivariate analysis the prognostic parameters with independent predictive value on disease-free survival (DFS) in node-positive and negative patients. The SLN was tumour-negative in 228 patients (83.2%). A disease progression occurred in 25 (10.9%); among them, 10 patients in whom the initially identified SLN had been negative, developed a clinically and histologically evident positive lymph node in the same basin during follow-up. Five-year DFS and overall survival were 75% and 82%, respectively. In 46 patients (16.8%), the SLN proved to be tumour positive. The percentage of SLN-positive patients varied according to the primary thickness, from 11.8% in patients with Breslow of 2 mm or lower, to 34.7% in patients with Breslow from 2 to 4 mm, up to 55.9% in patients with Breslow greater than 4 mm (P<0.001). Only two patients with Breslow thickness lower than 1 mm had positive SLN biopsy. Five-year DFS and overall survival (OS) were 42 and 69%, respectively, significantly lower than those of negative SLN-patients (P<0.001). Multivariate analyses showed that the parameters with prognostic independent value on DFS were SLN status (micrometastases or macrometastases; P=0.0001), and to a lesser extent, Breslow thickness (P=0.04). In conclusion, our data support the clinical usefulness of SLN dissection as a reliable and accurate staging method in patients with cutaneous melanoma. SLN

  19. Clinico-pathological features of patients with melanoma and positive sentinel lymph node biopsy: a single institution experience.

    PubMed

    Homolak, Damir; Šitum, Mirna; Čupić, Hrvoje

    2015-01-01

    Sentinel lymph node biopsy (SLNB) is an established method for the assessment of tumor aggressiveness in patients with primary cutaneous melanoma (PCM). To improve the criteria for the selection of SLNB candidates, the aim of our study was to determine clinico-pathohistological parameters that can serve as predictors of metastatic progression. We retrospectively evaluated all available clinico-pathohistological parameters in 844 patients with PCM diagnosed between January 1, 2005 and December 31, 2010. SLNB was conducted in 484 (57.3%) patients, 122 (14.5%) of whom had a positive node. The association between predictors and SLNB outcomes (positive SLNB and metastatic development) was tested using logistic regression analysis. The main predictors of positive SLNB were Breslow thickness (adjusted odds ratio (AOR)=1.22; 95% confidence interval (CI)=1.11-1.33), Clark levels (AOR=1.78; 95% CI=1.31-2.40), ulceration (AOR=3.1; 95% CI=1.65-5.81), microsatellitosis, gender, and tumor localization. The predictors of metastatic spread were Breslow thickness (AOR=1,69; 95% CI=1.51-1.89), Clark level (AOR=3.59; 95% CI=2.79-4.62), nodular type of melanoma (AOR=8.21; 95% CI=1.70-39.53), ulceration, mitotic rate, microsatellitosis, gender, and tumor localization. It seems that these parameters should be taken into consideration when selecting patients for SLNB since tumor thickness is not a sufficient predictor of SLNB outcome, particularly in case of very thin lesions.

  20. Surgery and sentinel lymph node biopsy.

    PubMed

    Faries, Mark B; Morton, Donald L

    2007-12-01

    In patients with melanoma, surgery is pivotal not only for the primary tumor but also for regional and often distant metastases. The minimally invasive technique of sentinel node (SN) biopsy has become standard for detection of occult regional node metastasis in patients with intermediate-thickness primary melanoma; in these patients it has a central role in determining prognosis and a significant impact on survival when biopsy results are positive. Its role in thin melanoma remains under evaluation. The regional tumor-draining SN also is a useful model for studies of melanoma-induced immunosuppression. Although completion lymphadenectomy remains the standard of care for patients with SN metastasis, results of ongoing phase III trials will indicate whether SN biopsy without further lymph node surgery is adequate therapy for certain patients with minimal regional node disease.

  1. Sentinel Lymph Node Biopsy

    MedlinePlus

    ... center of the chest (near the breastbone), cancer cells may spread first to lymph nodes inside the chest (under the breastbone) before they can be detected in the axilla. The number of lymph nodes in the axilla varies from person to person but usually ranges from 20 to ...

  2. Local delivery of CpG-B and GM-CSF induces concerted activation of effector and regulatory T cells in the human melanoma sentinel lymph node.

    PubMed

    van den Hout, Mari F C M; Sluijter, Berbel J R; Santegoets, Saskia J A M; van Leeuwen, Paul A M; van den Tol, M Petrousjka; van den Eertwegh, Alfons J M; Scheper, Rik J; de Gruijl, Tanja D

    2016-04-01

    Impaired immune effector functions in the melanoma sentinel lymph node (SLN) may allow for early metastatic events. In an effort to determine the optimal way to strengthen immune defenses, 28 clinical stage I-II melanoma patients were randomized in a 3-arm Phase II study to receive, prior to excision and sampling of the SLN, i.d. injections of saline or low-dose CpG-B (CpG), alone or combined with GM-CSF (GM), around the melanoma excision site. We previously described the combined administration of these DC-targeting agents to result in activation and recruitment of potentially cross-presenting BDCA3(+) DCs to the SLN. In this report we describe the effects on effector and regulatory T and NK cell subsets. Local low-dose CpG administration resulted in lower CD4/CD8 ratios, Th1 skewing, increased frequencies of melanoma-specific CD8(+) T cells and possible recruitment of effector NK cells, irrespective of GM co-administration. These immune-potentiating effects were counterbalanced by increased IL-10 production by T cells and significantly higher levels of FoxP3 and CTLA4 in regulatory T cells (Tregs) with correspondingly higher suppressive activity in the SLN. Notably, CpG ± GM-administered patients showed significantly lower numbers of SLN metastases (saline: 4/9, CpG + GM: 1/9, CpG: 0/10, p = 0.04). These findings indicate that i.d. delivery of low-dose CpG ± GM potentially arms the SLN of early-stage melanoma patients against metastatic spread, but that antitumor efficacy may be further boosted by counteracting the collateral activation of Tregs.

  3. Sentinel node biopsy in the management of malignant melanoma.

    PubMed

    Russell-Jones, R; Acland, K

    2001-09-01

    The technique of sentinel lymph node (SLN) biopsy has been in use for almost a decade, but its effect on survival has not yet been established. It is however the most accurate method for staging patients with primary cutaneous melanoma who lack clinical evidence of metastatic disease. This article discusses the rationale and logistics of SLN biopsy, and the management strategies that can be employed in those patients who are SLN positive. Future therapeutic trial in patients with primary cutaneous melanoma will only be meaningful if the SLN status of the subjects is established.

  4. Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Jose, Jithin; Grootendorst, Diederik J.; Vijn, Thomas W.; Wouters, Michel W.; van Boven, Hester; van Leeuwen, Ton G.; Steenbergen, Wiendelt; Ruers, Theo J. M.; Manohar, Srirang

    2011-09-01

    The pathological status of the sentinel lymph node is important for accurate melanoma staging, ascertaining prognosis and planning treatment. The standard procedure involves biopsy of the node and histopathological assessment of its status. Drawbacks of this examination include a finite sampling of the node with the likelihood of missing metastases, and a significant time-lag before histopathological results are available to the surgeon. We studied the applicability of photoacoustic computed tomographic imaging as an intraoperative modality for examining the status of resected human sentinel lymph nodes. We first applied the technique to image ex vivo pig lymph nodes carrying metastases-simulating melanoma cells using multiple wavelengths. The experience gained was applied to image a suspect human lymph node. We validated the photoacoustic imaging results by comparing a reconstructed slice with a histopathological section through the node. Our results suggest that photoacoustics has the potential to develop into an intraoperative imaging method to detect melanoma metastases in sentinel lymph nodes.

  5. Sentinel lymph node biopsy reveals a positive popliteal node in clear cell sarcoma.

    PubMed

    Nishida, Yoshihiro; Yamada, Yoshihisa; Tsukushi, Satoshi; Shibata, Shinichi; Ishiguro, Naoki

    2005-01-01

    Clear cell sarcoma of the tendons and aponeuroses is an aggressive, rare soft tissue tumor with frequent metastases to regional lymph nodes. Sentinel lymph node biopsy, which has dramatically changed the management of melanoma, was used for clear cell sarcoma for an evaluation of popliteal and groin lymph node status. Although all isosulfan blue-stained groin lymph nodes were negative for malignancy, a popliteal lymph node was positive. Adjuvant 50 Gy of radiotherapy to the popliteal node might have been effective for local control for one year.

  6. Sentinel Lymph Nodes for Breast Carcinoma A Paradigm Shift

    PubMed Central

    Maguire, Aoife; Brogi, Edi

    2016-01-01

    Context Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. Objective To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. Data Sources Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Conclusions The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin–stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non–sentinel lymph node involvement. This information is important to decide on further axillary treatment. PMID:27472237

  7. Epidermal growth factor facilitates melanoma lymph node metastasis by influencing tumor lymphangiogenesis.

    PubMed

    Bracher, Andreas; Cardona, Ana Soler; Tauber, Stefanie; Fink, Astrid M; Steiner, Andreas; Pehamberger, Hubert; Niederleithner, Heide; Petzelbauer, Peter; Gröger, Marion; Loewe, Robert

    2013-01-01

    Alterations in epidermal growth factor (EGF) expression are known to be of prognostic relevance in human melanoma, but EGF-mediated effects on melanoma have not been extensively studied. As lymph node metastasis usually represents the first major step in melanoma progression, we were trying to identify a potential role of primary tumor-derived EGF in the mediation of melanoma lymph node metastases. Stable EGF knockdown (EGFkd) in EGF-high (M24met) and EGF-low (A375) expressing melanoma cells was generated. Only in EGF-high melanoma cells, EGFkd led to a significant reduction of lymph node metastasis and primary tumor lymphangiogenesis in vivo, as well as impairment of tumor cell migration in vitro. Moreover, EGF-induced sprouting of lymphatic but not of blood endothelial cells was abolished using supernatants of M24met EGFkd cells. In addition, M24met EGFkd tumors showed reduced vascular endothelial growth factor-C (VEGF-C) expression levels. Similarly, in human primary melanomas, a direct correlation between EGF/VEGF-C and EGF/Prox-1 expression levels was found. Finally, melanoma patients with lymph node micrometastases undergoing sentinel node biopsy were found to have significantly elevated EGF serum levels as compared with sentinel lymph node-negative patients. Our data indicate that tumor-derived EGF is important in mediating melanoma lymph node metastasis.

  8. Sentinel Lymph Node Mapping of Liver

    PubMed Central

    Wada, Hideyuki; Hyun, Hoon; Vargas, Christina; Genega, Elizabeth M.; Gravier, Julien; Gioux, Sylvain; Frangioni, John V.; Choi, Hak Soo

    2015-01-01

    Background Although the sentinel lymph nodes (SLN) hypothesis has been applied to many tissues and organs, liver has remained unstudied. At present, it is unclear whether hepatic SLNs even exist. If so, they could alter management in intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the extent of surgery while still providing precise nodal staging. We investigated whether invisible yet tissue-penetrating near-infrared (NIR) fluorescent light can provide simultaneous identification of both the sentinel lymph node (SLN) and all other regional lymph nodes (RLN) in the liver. Method In twenty five Yorkshire pigs, we determined whether SLNs exist in liver, and compared the effectiveness of two clinically available NIR fluorophores, methylene blue (MB) and indocyanine green (ICG), and two novel NIR fluorophores previously described by our group, ESNF14 and ZW800-3C, for SLN and RLN mapping. Results ESNF14 showed the highest signal-to-background ratio (SBR) and longest retention time in SLNs, without leakage to second-tier lymph nodes. ICG had apparent leakage to second-tier nodes, while ZW800-3C suffered from poor migration after intraparenchymal injection. However, when injected intravenously, ZW800-3C was able to highlight all RLNs in liver over a 4–6 h period. Simultaneous dual channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous identification and image-guided resection of SLNs and RLNs in liver. Conclusion The NIR imaging technology enables real-time intraoperative identification of SLNs and RLNs in the liver of swine. If these results are confirmed in patients, new strategies for the surgical management of intrahepatic malignancies should be possible. PMID:25968620

  9. Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy

    PubMed Central

    Egger, Michael E.; Edwards, Michael J.; Ross, Merrick I.; Reintgen, Douglas S.; Noyes, R. Dirk; Martin, Robert C.G.; Goydos, James S.; Beitsch, Peter D.; Urist, Marshall M.; Ariyan, Stephan; Sussman, Jeffrey J.; Davidson, B. Scott; Gershenwald, Jeffrey E.; Hagendoorn, Lee J.; Stromberg, Arnold J.; Scoggins, Charles R.

    2016-01-01

    Purpose The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients and Methods Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). Results In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. Conclusion No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI. PMID:26858331

  10. Sentinel Lymph Nodes Mapping in Cervical Cancer a Comprehensive Review

    PubMed Central

    Diab, Yasser

    2017-01-01

    Objective A comprehensive literature search for more recent studies pertaining to sentinel lymph node mapping in the surveillance of cervical cancer to assess if sentinel lymph node mapping has sensitivity and specificity for evaluation of the disease; assessment of posttreatment response and disease recurrence in cervical cancer. Materials and Methods The literature review has been constructed on a step wise study design that includes 5 major steps. This includes search for relevant publications in various available databases, application of inclusion and exclusion criteria for the selection of relevant publications, assessment of quality of the studies included, extraction of the relevant data and coherent synthesis of the data. Results The search yielded numerous studies pertaining to sentinel lymph node mapping, especially on the recent trends, comparison between various modalities and evaluation of the technique. Evaluation studies have appraised high sensitivity, high negative predictive values and low false-negative rate for metastasis detection using sentinel lymph node mapping. Comparative studies have established that of all the modalities for sentinel lymph node mapping, indocyanine green sentinel lymph node mapping has higher overall and bilateral detection rates. Corroboration of the deductions of these studies further establishes that the sentinel node detection rate and sensitivity are strongly correlated to the method or technique of mapping and the history of preoperative neoadjuvant chemotherapy. Conclusions The review takes us to the strong conclusion that sentinel lymph node mapping is an ideal technique for detection of sentinel lymph nodes in cervical cancer patients with excellent detection rates and high sensitivity. The review also takes us to the supposition that a routine clinical evaluation of sentinel lymph nodes is feasible and a real-time florescence mapping with indocyanine green dye gives better statistically significant overall and

  11. Metastasis to the popliteal lymph nodes in lower extremity melanoma and their management.

    PubMed

    Morcos, Basem; Al-Ahmad, Firas

    2011-06-01

    Melanomas located anywhere below the knee can drain to the popliteal fossa. Sentinel nodes in the popliteal fossa are found in 1-9.6% of cases. The positivity rate in these nodes is 12.5-30%, which is comparable to rates in conventional nodal basins. Formal dissection of the popliteal fossa for a positive sentinel node is indicated. Inguinal dissection based only on the presence of involved popliteal lymph nodes is not warranted.

  12. Successful live cell harvest from bisected sentinel lymph nodes research report.

    PubMed

    Elliott, Bruce; Cook, Martin G; John, R Justin; Powell, Barry W E M; Pandha, Hardev; Dalgleish, Angus G

    2004-08-01

    Sentinel lymph nodes provide an excellent opportunity to study early immune responses to cancer. However, harvesting live cells has not previously been possible, because it conflicts with the need to preserve tissue for histological interpretation. This study used scrape cytology on 26 sentinel and 8 non-sentinel nodes, harvested from 17 stage I/II melanoma patients undergoing sentinel node biopsy. Numbers of viable cells harvested before and after cryopreservation were measured and the effect on subsequent histology assessed. The mean number of cells harvested from 26 sentinel nodes was 7.06 x 10(6) (range 0.1-32.2), with a mean viability of 99.5% (range 87-100, lower 95% CI 98.5%). Furthermore, counts and viabilities were well maintained after cryopreservation. Flow cytometry confirmed CD3+, CD20+ and lineage-1-/HLA-DR+ subpopulations, consistent with T-lymphocytes, B-lymphocytes and dendritic cells, respectively. Importantly, there was no discernible change in histological detail and the proportion of positive sentinel nodes remained unchanged. This technique will allow more functional and quantitative approaches to sentinel lymph node research.

  13. [Sentinel node in melanoma and breast cancer. Current considerations].

    PubMed

    Vidal-Sicart, S; Vilalta Solsona, A; Alonso Vargas, M I

    2015-01-01

    The main objectives of sentinel node (SN) biopsy is to avoid unnecessary lymphadenectomies and to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the or those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies reports the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.

  14. Lymphoscintigraphy in cutaneous melanoma: an updated total body atlas of sentinel node mapping.

    PubMed

    Intenzo, Charles M; Truluck, Christina A; Kushen, Medina C; Kim, Sung M; Berger, Adam; Kairys, John C

    2009-01-01

    Lymphoscintigraphy has become part of the standard of care for patients with a new or recurrent diagnosis of melanoma, in helping determine the status of regional lymph nodes. Correct identification of sentinel lymph nodes enables the surgeon to further delineate the extent of malignancy by allowing sampling of the appropriate nodal group. Performing the lymphoscintigraphy prior to the planned operation allows limited surgery with less extensive postoperative morbidity. For this reason, a thorough knowledge of the lymph node drainage patterns from the different primary tumor locations, as well as of proper lymphoscintigraphic techniques and radiopharmaceuticals, constitutes an important armamentarium in the hands of surgeons, radiologists, and nuclear medicine physicians.

  15. Popliteal lymph node dissection for metastases of cutaneous malignant melanoma.

    PubMed

    Teixeira, Frederico; Moutinho, Vitor; Akaishi, Eduardo; Mendes, Gabriella; Perina, Andre; Lima, Tiberio; Lallee, Margareth; Couto, Sergio; Utiyama, Edivaldo; Rasslan, Samir

    2014-05-01

    Popliteal lymph node dissection is performed when grossly metastatic nodal disease is encountered in the popliteal fossa or after microscopic metastasis is found in interval sentinel nodes during clinical staging of cutaneous malignant melanoma. Initially, an S-shaped incision is made to gain access to the popliteal fossa. A careful en bloc removal of fat tissue and lymph nodes is made to preserve and avoid the injury of peroneal and tibial nerves as well as popliteal vessels, following the previous recommendations. This rare surgical procedure was successfully employed in a patient with cutaneous malignant melanoma and nodal metastases at the popliteal fossa. The technique described by Karakousis was reproduced in a step-by-step fashion to allow anatomical identification of the neurovascular structures and radical resection with no post-operative morbidity and prompt recovery. Popliteal lymph node dissection is a rarely performed operative procedure. Following a lymphoscintigraphic examination of the popliteal nodal station, surgeons can be asked to explore the popliteal fossa. Detailed familiarity of the operative procedure is necessary, however, to avoid complications.

  16. Detection of melanoma metastases in resected human lymph nodes by noninvasive multispectral photoacoustic imaging.

    PubMed

    Langhout, Gerrit Cornelis; Grootendorst, Diederik Johannes; Nieweg, Omgo Edo; Wouters, Michel Wilhelmus Jacobus Maria; van der Hage, Jos Alexander; Jose, Jithin; van Boven, Hester; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theodoor Jacques Marie

    2014-01-01

    Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR(©) multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes.

  17. Application of novel iron core/iron oxide shell nanoparticles to sentinel lymph node identification

    NASA Astrophysics Data System (ADS)

    Cousins, Aidan; Howard, Douglas; Henning, Anna M.; Nelson, Melanie R. M.; Tilley, Richard D.; Thierry, Benjamin

    2015-12-01

    Current `gold standard' staging of breast cancer and melanoma relies on accurate in vivo identification of the sentinel lymph node. By replacing conventional tracers (dyes and radiocolloids) with magnetic nanoparticles and using a handheld magnetometer probe for in vivo identification, it is believed the accuracy of sentinel node identification in nonsuperficial cancers can be improved due to increased spatial resolution of magnetometer probes and additional anatomical information afforded by MRI road-mapping. By using novel iron core/iron oxide shell nanoparticles, the sensitivity of sentinel node mapping via MRI can be increased due to an increased magnetic saturation compared to traditional iron oxide nanoparticles. A series of in vitro magnetic phantoms (iron core vs. iron oxide nanoparticles) were prepared to simulate magnetic particle accumulation in the sentinel lymph node. A novel handheld magnetometer probe was used to measure the relative signals of each phantom, and determine if clinical application of iron core particles can improve in vivo detection of the sentinel node compared to traditional iron oxide nanoparticles. The findings indicate that novel iron core nanoparticles above a certain size possess high magnetic saturation, but can also be produced with low coercivity and high susceptibility. While some modification to the design of handheld magnetometer probes may be required for particles with large coercivity, use of iron core particles could improve MRI and magnetometer probe detection sensitivity by up to 330 %.

  18. EANM-EORTC general recommendations for sentinel node diagnostics in melanoma.

    PubMed

    Chakera, Annette H; Hesse, Birger; Burak, Zeynep; Ballinger, James R; Britten, Allan; Caracò, Corrado; Cochran, Alistair J; Cook, Martin G; Drzewiecki, Krzysztof T; Essner, Richard; Even-Sapir, Einat; Eggermont, Alexander M M; Stopar, Tanja Gmeiner; Ingvar, Christian; Mihm, Martin C; McCarthy, Stanley W; Mozzillo, Nicola; Nieweg, Omgo E; Scolyer, Richard A; Starz, Hans; Thompson, John F; Trifirò, Giuseppe; Viale, Giuseppe; Vidal-Sicart, Sergi; Uren, Roger; Waddington, Wendy; Chiti, Arturo; Spatz, Alain; Testori, Alessandro

    2009-10-01

    The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

  19. Sentinel lymph node biopsy indications and controversies in breast cancer.

    PubMed

    Wiatrek, Rebecca; Kruper, Laura

    2011-05-01

    Sentinel lymph node biopsy (SLNB) has become the standard of care for early breast cancer. Its use in breast cancer has been evaluated in several randomized controlled trials and validated in multiple prospective studies. Additionally, it has been verified that SLNB has decreased morbidity when compared to axillary lymph node dissection (ALND). The technique used to perform sentinel lymph node mapping was also evaluated in multiple studies and the accuracy rate increases when radiocolloid and blue dye are used in combination. As SLNB became more accepted, contraindications were delineated and are still debated. Patients who have clinically positive lymph nodes or core biopsy-proven positive lymph nodes should not have SLNB, but should have an ALND as their staging procedure. The safety of SLNB in pregnant patients is not fully established. However, patients with multifocal or multicentric breast cancer and patients having neoadjuvant chemotherapy are considered candidates for SLNB. However, the details of which specific neoadjuvant patients should have SLNB are currently being evaluated in a randomized controlled trial. Patients with ductal carcinoma in situ (DCIS) benefit from SLNB when mastectomy is planned and when there is a high clinical suspicion of invasion. With the advent of SLNB, pathologic review of breast cancer lymph nodes has evolved. The significance of occult metastasis in SLNB patients is currently being debated. Additionally, the most controversial subject with regards to SLNB is determining which patients with positive SLNs benefit from further axillary dissection.

  20. Efficacy of Methylene Blue in Sentinel Lymph Node Biopsy for Early Breast Cancer

    PubMed Central

    Özdemir, Altan; Mayir, Burhan; Demirbakan, Kenan; Oygür, Nezihi

    2014-01-01

    Objective Sentinel lymph node biopsy is the recommended approach in the evaluation of axilla during breast cancer surgery. In this study, results of patients who underwent methylene blue sentinel lymph node biopsy were evaluated. Materials and Methods The study included 32 female patients with T1 and T2 tumors. 5 ml of 1% methylene blue was injected into the peritumoral area or around the cavity. The axillary sentinel lymph node was found and removed, and then axillary dissection was performed. The sentinel lymph node and axillary dissection specimen were histopathologically examined and the results were compared. Results The sentinel lymph node was found in 30 (94%) patients. Lymph node metastasis was not observed in 17 patients in both the sentinel lymph node and axilla. Two patients had metastasis in the axilla although this was not detected in sentinel lymph node. Eleven patients had metastasis both in the sentinel lymph node and in the axilla. The accuracy rate was 93%, and the false negativity rate was identified as 15%. Conclusion Sentinel lymph node biopsy by methylene blue is a method that can be applied with high accuracy. Methylene blue can be considered as an alternative to isosulphane blue in sentinel lymph node biopsy.

  1. Pigmentation in the sentinel node correlates with increased sentinel node tumor burden in melanoma patients.

    PubMed

    van Lanschot, Cornelia G F; Koljenović, Senada; Grunhagen, Dirk-Jan; Verhoef, Cornelis; van Akkooi, Alexander C J

    2014-06-01

    The prognosis of sentinel node (SN)-positive melanoma patients is predicted by a number of characteristics such as size and site of the metastases in the SN. The pathway and prognosis of strong pigmentation of melanoma metastases in the SN is unclear. The aim of this study is to evaluate the role of pigmentation and growth pattern of metastases in the SN with respect to survival. A total of 389 patients underwent an SN procedure (1997-2011). Ninety-five patients had a positive SN and material from 75 patients was available for review. The median follow-up time was 75 months (range 6-164). Pigmentation was scored from 0 to 2 using the following scale: 0=absent, 1=slight, and 2=strong. Growth pattern was scored as either eccentric (1) or infiltrative (2). SN tumor burden was measured according to the Rotterdam criteria. The primary melanoma had a median Breslow thickness of 2.90 mm (0.8-12.00 mm). Ulceration was present in 34 patients (45.3%). There was a median SN tumor burden of 0.5 mm (0.05-7.00 mm). In a total of 75 patients, 59 patients (79%) had no pigmentation, 13 patients (17%) had slight pigmentation, and three patients (4%) had strong pigmentation in the SN. Because of the small numbers, the classification was modified to either absent 59 (79%) or present 16 (21%) pigmentation, respectively. The SN tumor burden was significantly higher (P=0.031) for patients with pigmentation. Patients with pigmentation had a 5-year melanoma-specific survival (MSS) of 47% and a 10-year MSS of 33%. Patients without pigmentation had a 5-year MSS of 70% and a 10-year MSS of 59% (P=0.06). There was no difference in MSS for patients with an eccentric or an infiltrative growth pattern, nor did it correlate with other prognostic factors. Multivariate analysis for MSS showed five significant factors associated with worse prognosis: male sex (P=0.036), nodular melanoma (P=0.001), truncal site (P=0.0001), SN tumor burden more than 1.0 mm (P=0.022), and positive completion lymph node

  2. Sentinel lymph node biopsy is a prognostic measure in pediatric melanoma☆

    PubMed Central

    Kim, Jina; Sun, Zhifei; Gulack, Brian C.; Adam, Mohamed A.; Mosca, Paul J.; Rice, Henry E.; Tracy, Elisabeth T.

    2016-01-01

    Background/Purpose Sentinel lymph node biopsy (SLNB)-based management has been shown to improve disease-free survival in adult melanoma, but there is scant evidence regarding the utility of SLNB in pediatric melanoma. Methods The 2004–2011 Surveillance, Epidemiology, and End Results database was queried for patients with primary cutaneous melanoma of Breslow depth > 0.75 mm and clinically negative nodes. Pediatric patients, defined as less than 20 years of age, were grouped by whether they underwent SLNB or not. Kaplan–Meier analysis was performed to compare melanoma-specific survival (MSS) in propensity-matched groups. Results 310 pediatric patients met study criteria: 261 (84%) underwent SLNB, while 49 (16%) did not. There was no difference in MSS between matched children who received SLNB and those who did not (p = 0.36). Among children who received SLNB, a positive SLNB was associated with worse MSS compared to a negative SLNB (89% vs. 100% at 84 months, p = 0.04). However, children with a positive SLNB had more favorable survival compared to patients > 20 years of age (88% vs. 66% at 84 months, p = 0.02). Conclusions SLNB does not confer a survival benefit to children with melanoma, but it provides valuable prognostic information regarding MSS. PMID:27041229

  3. Sentinel lymph node biopsy for cutaneous head and neck malignancies.

    PubMed

    Dwojak, Sunshine; Emerick, Kevin S

    2015-03-01

    Sentinel lymph node biopsy (SLNB) is a procedure that can provide critical information regarding pathologic lymph node status and accurate regional staging. This is very important for developing treatment plans and providing prognostic guidance for cutaneous malignancies. The head and neck (HN) region is unique from other body sites due to its complex lymphatic drainage pathways, multiple lymph node basins, proximity of important cranial nerves and potential for contralateral or bilateral drainage. These unique aspects of the HN previously created some uncertainty about the use of SLNB in the HN. This review will discuss the current reliable status of HN SLNB and provide a guide for its current application in cutaneous malignancy of the HN.

  4. Sentinel lymph node imaging by a fluorescently labeled DNA tetrahedron.

    PubMed

    Kim, Kyoung-Ran; Lee, Yong-Deok; Lee, Taemin; Kim, Byeong-Su; Kim, Sehoon; Ahn, Dae-Ro

    2013-07-01

    Sentinel lymph nodes (SLNs) are the first lymph nodes which cancer cells reach after traveling through lymphatic vessels from the primary tumor. Evaluating the nodal status is crucial in accurate staging of human cancers and accordingly determines prognosis and the most appropriate treatment. The commonly used methods for SLN identification in clinics are based on employment of a colloid of radionuclide or injection of a small dye. Although these methods have certainly contributed to improve surgical practice, new imaging materials are still required to overcome drawbacks of the techniques such as inconvenience of handling radioactive materials and short retention time of small dyes in SLNs. Here, we prepare a fluorescence-labeled DNA tetrahedron and perform SLN imaging by using the DNA nanoconstruct. With a successful identification of SLNs by the DNA nanoconstruct, we suggest that DNA tetrahedron hold great promises for clinical applications.

  5. Arm lymphoscintigraphy after axillary lymph node dissection or sentinel lymph node biopsy in breast cancer

    PubMed Central

    Sarri, Almir José; Dias, Rogério; Laurienzo, Carla Elaine; Gonçalves, Mônica Carboni Pereira; Dias, Daniel Spadoto; Moriguchi, Sonia Marta

    2017-01-01

    Purpose Compare the lymphatic flow in the arm after breast cancer surgery and axillary lymph node dissection (ALND) versus sentinel lymph node biopsy (SLNB) using lymphos-cintigraphy (LS). Patients and methods A cross-sectional study with 39 women >18 years who underwent surgical treatment for unilateral breast cancer and manipulation of the axillary lymph node chain through either ALND or SLNB, with subsequent comparison of the lymphatic flow of the arm by LS. The variables analyzed were the area reached by the lymphatic flow in the upper limb and the sites and number of lymph nodes identified in the ALND or SLNB groups visualized in the three phases of LS acquisition (immediate dynamic and static images, delayed scan images). For all analyses, the level of significance was set at 5%. Results There was a significant difference between the ALND and SLNB groups, with predominant visualization of lymphatic flow and/or lymph nodes in the arm and axilla (P=0.01) and extra-axillary lymph nodes (P<0.01) in the ALND group. There was no significant difference in the total number of lymph nodes identified between the two groups. However, there was a significant difference in the distribution of lymph nodes in these groups. The cubital lymph node was more often visualized in the immediate dynamic images in the ALND group (P=0.004), while the axillary lymph nodes were more often identified in the delayed scan images of the SLNB group (P<0.01). The deltopectoral lymph node was only identified in the ALND group, but with no significant difference. Conclusion The lymphatic flow from the axilla was redirected to alternative extra-axillary routes in the ALND group. PMID:28331338

  6. Decreased identification rate of sentinel lymph node after neoadjuvant chemotherapy.

    PubMed

    Kang, Seok Hyung; Kim, Seok-Ki; Kwon, Youngmee; Kang, Han-Sung; Kang, Jae Hee; Ro, Jungsil; Lee, Eun Sook

    2004-10-01

    We prospectively studied the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy by comparing the identification rate and the false-negative rate (FNR) with the results obtained from the patients without chemotherapy. From October 2001 to March 2003, a total of 284 consecutive patients who underwent SLNB and axillary lymph node dissection (ALND) at the Center for Breast Cancer, National Cancer Center were enrolled. Of the 284 patients, 54 underwent neoadjuvant chemotherapy prior to operation. The sentinel lymph node (SLN) was mapped by radioactive colloid alone or in combination with blue dye. All SLNs were evaluated by 2 mm serial sections after hematoxylin-eosin staining. The overall SLN identification rate was 91.9% (261/284): 72.2% (39/54) of the patients after chemotherapy and 96.5% (222/230) of the patients without chemotherapy. These results suggest that preoperative chemotherapy significantly affects lymphatic mapping ( p< 0.001). Among the patients with chemotherapy, there were 3 false negatives in 39 successfully mapped tumors, yielding an FNR of 11.1% (3/27), a negative prediction value (NPV) of 80.0% (12/15), and an accuracy of 92.3% (36/39). There were 10 false negatives among 222 successfully detected patients without chemotherapy, yielding an FNR of 9.9% (10/101), an NPV of 92.4% (121/131), and an accuracy of 95.5% (212/222). These results were not statistically different when compared ( p > 0.05). Although the SLN identification rate significantly decreased after neoadjuvant chemotherapy, SLNB could accurately predict axillary status. Thus SLNB can be an alternative to ALND even after neoadjuvant chemotherapy in cases of successful identification of the SLN.

  7. Sentinel Lymph Node Biopsy in Early Breast Cancer.

    PubMed

    Kühn, Thorsten

    2011-01-01

    The role of axillary surgery for the treatment of primary breast cancer is in a process of constant change. During the last decade, axillary dissection with removal of at least 10 lymph nodes (ALD) was replaced by sentinel lymph node biopsy (SLNB) as a staging procedure. Since then, the indication for SLNB rapidly expanded. Today's surgical strategies aim to minimize the rate of patients with a negative axillary status who undergo ALD. For some subgroups of patients, the indication for SLNB (e.g. multicentric disease, large tumors) or its implication for treatment planning (micrometastatic involvement, neoadjuvant chemotherapy) is being discussed. Although the indication for ALD is almost entirely restricted to patients with positive axillary lymph nodes today, the therapeutic effect of completion ALD is more and more questioned. On the other hand, the diagnostic value of ALD in node-positive patients is discussed. This article reflects today's standards in axillary surgery and discusses open issues on the diagnostic and therapeutic role of SLNB and ALD in the treatment of early breast cancer.

  8. Nanoparticles in Sentinel Lymph Node Assessment in Breast Cancer

    PubMed Central

    Johnson, Laura; Charles-Edwards, Geoff; Douek, Michael

    2010-01-01

    The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still involves a surgical procedure with associated morbidity in many patients with no axillary involvement. Nanotechnology encompasses a broad spectrum of scientific specialities, of which nanomedicine is one. The potential use of dual-purpose nanoprobes could enable imaging the axilla simultaneous identification and treatment of metastatic disease. Whilst most applications of nanomedicine are still largely in the laboratory phase, some potential applications are currently undergoing clinical evaluation for translation from the bench to the bedside. This is an exciting new area of research where scientific research may become a reality. PMID:24281206

  9. Compact intraoperative imaging device for sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Bauer, Adam Q.; Akers, Walter; Sudlow, Gail; Liang, Kexian; Shen, Duanwen; Berezin, Mikhail; Culver, Joseph P.; Achilefu, Samuel

    2011-03-01

    We have developed a novel real-time intraoperative fluorescence imaging device that can detect near-infrared (NIR) fluorescence and map sentinel lymph nodes (SLNs). In contrast to conventional imaging systems, this device is compact, portable, and battery-operated. It is also wearable and thus allows hands-free operation of clinicians. The system directly displays the fluorescence in its goggle eyepiece, eliminating the need for a remote monitor. Using this device in murine lymphatic mapping, the SLNs stained with indocyanine green (ICG) can be readily detected. Fluorescence-guided SLN resection under the new device was performed with ease. Ex vivo examination of resected tissues also revealed high fluorescence level in the SLNs. Histology further confirmed the lymphatic nature of the resected SLNs.

  10. Intraoperative Imaging Guidance for Sentinel Node Biopsy in Melanoma Using a Mobile Gamma Camera

    SciTech Connect

    Dengel, Lynn T; Judy, Patricia G; Petroni, Gina R; Smolkin, Mark E; Rehm, Patrice K; Majewski, Stan; Williams, Mark B; Slingluff Jr., Craig L

    2011-04-01

    The objective is to evaluate the sensitivity and clinical utility of intraoperative mobile gamma camera (MGC) imaging in sentinel lymph node biopsy (SLNB) in melanoma. The false-negative rate for SLNB for melanoma is approximately 17%, for which failure to identify the sentinel lymph node (SLN) is a major cause. Intraoperative imaging may aid in detection of SLN near the primary site, in ambiguous locations, and after excision of each SLN. The present pilot study reports outcomes with a prototype MGC designed for rapid intraoperative image acquisition. We hypothesized that intraoperative use of the MGC would be feasible and that sensitivity would be at least 90%. From April to September 2008, 20 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and SLNB was performed with use of a conventional fixed gamma camera (FGC), and gamma probe followed by intraoperative MGC imaging. Sensitivity was calculated for each detection method. Intraoperative logistical challenges were scored. Cases in which MGC provided clinical benefit were recorded. Sensitivity for detecting SLN basins was 97% for the FGC and 90% for the MGC. A total of 46 SLN were identified: 32 (70%) were identified as distinct hot spots by preoperative FGC imaging, 31 (67%) by preoperative MGC imaging, and 43 (93%) by MGC imaging pre- or intraoperatively. The gamma probe identified 44 (96%) independent of MGC imaging. The MGC provided defined clinical benefit as an addition to standard practice in 5 (25%) of 20 patients. Mean score for MGC logistic feasibility was 2 on a scale of 1-9 (1 = best). Intraoperative MGC imaging provides additional information when standard techniques fail or are ambiguous. Sensitivity is 90% and can be increased. This pilot study has identified ways to improve the usefulness of an MGC for intraoperative imaging, which holds promise for reducing false negatives of SLNB for melanoma.

  11. Mastoscopic sentinel lymph node biopsy in breast cancer

    PubMed Central

    Ding, Boni; Zhang, Hongyan; Li, Xiaorong; Qian, Liyuan; Chen, Xuedong; Wu, Wei; Wen, Yanguang; Zhao, Yujun

    2015-01-01

    Background Previous studies have demonstrated that mastoscopic sentinel lymph node biopsy (MSLNB) has good identification rate (IR) and low false negative rate (FNR). However, few studies have directly compared the surgical performance and peri- and post-operative factors of MSLNB with conventional sentinel lymph node biopsy (SLNB). Methodology Sixty patients diagnosed with breast cancer were recruited and randomly assigned to one of the three groups: MSLNB, SLNB and SLNB with lipolysis injection. Peri- and post-operative parameters were compared using general linear models. To examine the effect of age on these parameters, we performed separate analysis stratified by age (≤50 years old vs. >50 years old). Results Patients in the MSLNB group experienced longer surgery and suffered higher surgical cost than patients who underwent conventional SLNB or SLNB with lipolysis injection (p<0.0001). Despite this, they had significantly less blood loss than those who underwent conventional SLNB (22.0±7.0 ml vs.73.5±39.6 ml; p<0.0001). Analysis by age group indicates a similar pattern of difference among the three groups. MSLNB and conventional SLNB have similar IR and FNR. Conclusion As a minimally invasive technique, MSLNB can significantly reduce blood loss while providing similar IR and FNR, indicating that it can be a promising alternative to conventional SLNB. Conclusion Variations in popliteal artery terminal branching pattern occurred in 7.4% to 17.6% of patients. Pre-surgical detection of these variations with MD CTA may help to reduce the risk of iatrogenic arterial injury by enabling a better surgical treatment plan. PMID:28352718

  12. Features Predicting Sentinel Lymph Node Positivity in Merkel Cell Carcinoma

    PubMed Central

    Schwartz, Jennifer L.; Griffith, Kent A.; Lowe, Lori; Wong, Sandra L.; McLean, Scott A.; Fullen, Douglas R.; Lao, Christopher D.; Hayman, James A.; Bradford, Carol R.; Rees, Riley S.; Johnson, Timothy M.; Bichakjian, Christopher K.

    2011-01-01

    Purpose Merkel cell carcinoma (MCC) is a relatively rare, potentially aggressive cutaneous malignancy. We examined the clinical and histologic features of primary MCC that may correlate with the probability of a positive sentinel lymph node (SLN). Methods Ninety-five patients with MCC who underwent SLN biopsy at the University of Michigan were identified. SLN biopsy was performed on 97 primary tumors, and an SLN was identified in 93 instances. These were reviewed for clinical and histologic features and associated SLN positivity. Univariate associations between these characteristics and a positive SLN were tested for by using either the χ2 or the Fisher's exact test. A backward elimination algorithm was used to help create a best multiple variable model to explain a positive SLN. Results SLN positivity was significantly associated with the clinical size of the lesion, greatest horizontal histologic dimension, tumor thickness, mitotic rate, and histologic growth pattern. Two competing multivariate models were generated to predict a positive SLN. The histologic growth pattern was present in both models and combined with either tumor thickness or mitotic rate. Conclusion Increasing clinical size, increasing tumor thickness, increasing mitotic rate, and infiltrative tumor growth pattern were significantly associated with a greater likelihood of a positive SLN. By using the growth pattern and tumor thickness model, no subgroup of patients was predicted to have a lower than 15% to 20% likelihood of a positive SLN. This suggests that all patients presenting with MCC without clinical evidence of regional lymph node disease should be considered for SLN biopsy. PMID:21300936

  13. Combination of dacarbazine and dimethylfumarate efficiently reduces melanoma lymph node metastasis.

    PubMed

    Valero, Teresa; Steele, Silvia; Neumüller, Karin; Bracher, Andreas; Niederleithner, Heide; Pehamberger, Hubert; Petzelbauer, Peter; Loewe, Robert

    2010-04-01

    Dimethylfumarate (DMF) has been shown to reduce melanoma growth and metastasis in animal models. We addressed the question of whether DMF is as effective in its antitumor activity as the US Food and Drug Administration-approved alkylating agent dacarbazine (DTIC). We also tested the possibility of an improved antitumoral effect when both therapeutics were used together. Using our severe combined immunodeficiency (SCID) mouse model, in which xenografted human melanoma cells metastasize from primary skin sites to sentinel nodes, we show that these treatments, alone or in combination, reduce tumor growth at primary sites. Our main finding was that metastasis to sentinel nodes is significantly delayed only in mice treated with a combination of DTIC and DMF. Subsequent experiments were able to show that a combination of DTIC/DMF significantly reduced lymph vessel density in primary tumors as examined by real-time PCR and immunohistochemistry. In addition, DTIC/DMF treatment significantly impaired melanoma cell migration in vitro. In vivo, DTIC/DMF therapy significantly reduced mRNA expression and protein concentration of the promigratory chemokines CXCL2 and CXCL11. In addition, our data suggest that this xenotransplantation model is suitable for preclinical testing of various combinations of antimelanoma agents.

  14. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Cancer.gov

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  15. microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response

    PubMed Central

    Vallacchi, Viviana; Camisaschi, Chiara; Dugo, Matteo; Vergani, Elisabetta; Deho, Paola; Gualeni, Ambra; Huber, Veronica; Gloghini, Annunziata; Maurichi, Andrea; Santinami, Mario; Sensi, Marialuisa; Castelli, Chiara; Rivoltini, Licia; Rodolfo, Monica

    2016-01-01

    Sentinel node biopsy (SNB) is a main staging biomarker in melanoma and is the first lymph node to drain the tumor, thus representing the immunological site where anti-tumor immune dysfunction is established and where potential prognostic immune markers can be identified. Here we analyzed microRNA (miR) profiles in archival tumor-positive SNBs derived from melanoma patients with different outcomes and performed an integrated analysis of transcriptional data to identify deregulated immune signaling networks. Twenty-six miRs were differentially expressed in melanoma-positive SNB samples between patients with disease progression and non-progressing patients, the majority being previously reported in the regulation of immune responses. A significant variation in miR expression levels was confirmed in an independent set of SNB samples. Integrated information from genome-wide transcriptional profiles and in vitro assessment in immune cells led to the identification of miRs associated with the regulation of the TNF receptor superfamily member 8 (TNFRSF8) gene encoding the CD30 receptor, a marker increased in lymphocytes of melanoma patients with progressive disease. These findings indicate that miRs are involved in the regulation of pathways leading to immune dysfunction in the sentinel node and may provide valuable markers for developing prognostic molecular signatures for the identification of stage III melanoma patients at risk of recurrence. PMID:27983661

  16. Sentinel lymph node metastases in cancer: causes, detection and their role in disease progression.

    PubMed

    Nathanson, S D; Shah, R; Rosso, K

    2015-02-01

    Malignant tumors of ectodermal or endodermal origin may metastasize to the sentinel lymph node, the first lymph node encountered by tumor cells that enter lymphatics in the organ of origin. This pathway is enabled by the anatomy of the disease and the causes of metastasis are the result of complex interactions that include mechanical forces within the tumor and host tissues, and molecular factors initiated by tumor cell proliferation, elaboration of cytokines and changes in the tumor microenvironment. Mechanical stresses may influence complex biochemical, genetic and other molecular events and enhance the likelihood of metastasis. This paper summarizes our understanding of interacting molecular, anatomical and mechanical processes which facilitate metastasis to SLNs. Our understanding of these interacting events is based on a combination of clinical and basic science research, in vitro and in vivo, including studies in lymphatic embryology, anatomy, micro-anatomy, pathology, physiology, molecular biology and mechanobiology. The presence of metastatic tumor in the SLN is now more accurately identifiable and, based upon prospective clinical trials, paradigm-changing SLN biopsy has become the standard of clinical practice in breast cancer and melanoma.

  17. Importance of sentinel lymph nodes in colorectal cancer: a pilot study.

    PubMed

    Köksal, Hande; Bostanci, Hasan; Mentes, B Bülent

    2007-01-01

    Accurate identification of lymph nodes involved in metastases is vitally important for predicting survival, and it facilitates decision making with regard to adjuvant therapy. The study described here, which was undertaken to evaluate the role of sentinel lymph node mapping in refining the staging of colorectal cancer, was performed prospectively in 19 patients with colorectal cancer who underwent surgery from January to July 2005. Sentinel lymph node sampling was performed during each operation with isosulfan blue dye. Additional immunohistochemical staining was performed only if the sentinel nodes were negative for metastasis. In 18 of 19 patients, at least 1 sentinel node was identified. In 5 of 18 patients, sentinel nodes were positive for metastasis, and in 3 of 5, the sentinel node was the only node containing metastasis that was detected by immunohistochemical staining. In 3 patients, metastases in nonsentinel lymph nodes were detected by hematoxylin and eosin staining; these were determined to be false-negative results. Upstaging associated with sentinel lymph node mapping may reveal disease that might otherwise remain undetected by conventional methods. Patients who are upstaged may benefit from adjuvant therapies that have been shown to improve survival.

  18. Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis

    PubMed Central

    Proulx, Steven T.; Luciani, Paola; Christiansen, Ailsa; Karaman, Sinem; Blum, Katrin S.; Rinderknecht, Matthias; Leroux, Jean-Christophe; Detmar, Michael

    2013-01-01

    Tumor lymphangiogenesis promotes metastatic cancer spread to lymph nodes and beyond. However, the potential remodeling and functionality of tumor-draining lymphatic vessels has remained unclear. Thus, we aimed to develop non-invasive imaging methods for repeated quantitative imaging of lymphatic drainage and of contractile collecting lymphatic vessel function in mice, with colloidal near-infrared (NIR) tracers and a custom fluorescence stereomicroscope specially adapted for NIR sensitive imaging. Using these tools, we quantitatively determined pulse rates and valvular function of collecting lymphatic vessels with high resolution. Unexpectedly, we found that tumor-draining lymphatic vessels in a melanoma footpad model initially were dilated but remained functional, despite lower pulse rates. In two independent tumor models, impaired lymphatic function was detected once metastases were present in draining lymph nodes. Importantly, we found that lymphatic dysfunction, induced by metastatic tumor spread to sentinel lymph nodes, can lead to a rerouting of lymphatic flow away from the metastatic lymph node, via collateral lymphatic vessels, to alternate lymph nodes. These findings might have important clinical implications for the procedure of sentinel lymph node mapping that represents the standard of care for determining prognosis and treatment of melanoma and breast cancer patients. PMID:23566803

  19. Lymphoscintigraphic SPECT/CT-Contralateral Axillary Sentinel Lymph Node Drainage in Breast Cancer.

    PubMed

    Koyyalamudi, Ratna T; Rossleigh, Monica Anne

    2017-02-01

    A 58-year-old woman with previous right breast carcinoma treated with lumpectomy, right axillary clearance, chemo-radiotherapy, and adjuvant hormonal therapy underwent a lymphoscintigraphy for a new right breast lesion. On planar images, an alternate route of lymphatic drainage was observed to the right internal mammary chain and the left axilla. A chest SPECT/CT was performed to confirm the location of the sentinel nodes. The patient underwent a right mastectomy and left axillary sentinel lymph node biopsy, which showed no evidence of lymphovascular invasion. Combining planar imaging and SPECT/CT techniques can accurately identify sentinel lymph nodes at their new unpredicted location.

  20. Liposome-coated quantum dots targeting the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Chu, Maoquan; Zhuo, Shu; Xu, Jiang; Sheng, Qiunan; Hou, Shengke; Wang, Ruifei

    2010-01-01

    Sentinel lymph node (SLN) mapping with near-infrared (NIR) quantum dot (QDs) have many advantages over traditional methods. However, as an inorganic nanomaterial, QDs have low biocompatibility and low affinity to the lymphatic system. Here, we encapsulated QDs into nanoscale liposomes and then used these liposome-coated QDs for SLN mapping. The results showed that the liposome-coated QDs exhibited core-shell characterization, and their fluorescence emission did not decrease but slightly increased after being continuously excited by a xenon lamp source (150 W) at 488 nm at 37 °C for 1 h. After storing at 4 °C for more than one and half years, the liposome-coated QDs were found to have retained their spherical structure containing a large amount of QDs. When liposome-coated QDs with average size of 55.43 nm were injected intradermally into the paw of a mouse, the SLN was strongly fluorescent within only a few seconds and visualized easily in real time. Moreover, the fluorescence of the QDs trapped in the SLN could be observed for at least 24 h. Compared with the SLN mapping of QDs absent of liposomes and liposome-coated QDs with a larger average size (100.3 and 153.6 nm), more QDs migrated into the SLN when the liposome-coated QDs with smaller average size (55.43 nm) were injected. This technique may make a great contribution to the improvement of the biocompatibility of QDs and the targeting delivery capacity of QDs into the SLN.

  1. Melanoma.

    PubMed

    Gershenwald, J E

    2001-01-01

    The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).

  2. Results of optical Monte Carlo simulations of a compact γ camera for the detection of sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Lowe, Dean; Truman, Andrew; Kwok, Harry; Bergman, Alanah

    2001-07-01

    Breast cancer is most often treatable when detected in the early stages, before the primary disease spreads to sentinel lymph nodes in the axilla and supraclavicular region. A sentinel lymph node is the closest adjacent lymph node to receive lymphatic drainage from a primary breast tumour. It is from these nodes that cancer cells metastasise throughout the lymphatic system, spreading the disease. This work details the optical Monte Carlo modelling of an ultra compact, nuclear medicine γ camera that will be used intra-operatively to detect malignant sentinel lymph nodes. This development will improve the identification and localisation of these sentinel nodes, thereby facilitating improved techniques for axillary lymph node dissection, and sentinel lymph node biopsy.

  3. Sentinel lymph node in oesophageal cancer—a systematic review and meta-analysis

    PubMed Central

    Nagaraja, Vinayak; Cox, Michael R.

    2014-01-01

    Background Sentinel lymph nodes (SLNs) have been used to predict regional lymph node metastasis in patients with melanoma and breast cancer. However, the validity of the SLN hypothesis is still controversial for oesophageal cancer. We performed this meta-analysis to evaluate the feasibility and accuracy of radio-guided SLN mapping for oesophageal cancer. Methods A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rates and 95% confidence interval (95% CI). Results The search identified 23 relevant articles. The overall detection rate was 0.93 (95% CI: 0.894-0.950), sensitivity 0.87 (95% CI: 0.811-0.908), negative predictive value 0.77 (95% CI: 0.568-0.890) and the accuracy was 0.88 (95% CI: 0.817-0.921). In the adenocarcinoma cohort, detection rate was 0.98 (95% CI: 0.923-0.992), sensitivity 0.84 (95% CI: 0.743-0.911) and the accuracy was 0.87(95% CI: 0.796-0.913). In the squamous cell carcinoma group, detection rate was 0.89 (95% CI: 00.792-0.943), sensitivity 0.91 (95% CI: 0.754-0.972) and the accuracy was 0.84 (95% CI: 0.732-0.914). Conclusions It is possible to identify and obtain a SLN before neoadjuvant therapy in oesophageal cancer. However, further work is needed to optimize radiocolloid type, refine the technique and develop a quick and accurate way to determine SLN status intraoperatively. This technique has to be further evaluated before it can be applied widely. PMID:24772341

  4. Long-term treatment outcome after only popliteal lymph node dissection for nodal metastasis in malignant melanoma of the heel: the only "interval node" dissection can be an adequate surgical treatment.

    PubMed

    Tanaka, Kentaro; Mori, Hiroki; Okazaki, Mutsumi; Nishizawa, Aya; Yokozeki, Hiroo

    2013-01-01

    We present a patient with malignant melanoma on his heel. Wide local excision was performed, along with sentinel lymph node biopsy of the inguinal and popliteal lesions. The primary site was clear of tumor at all margins; the inguinal nodes were negative, but the popliteal node was positive for metastatic melanoma. Only radical popliteal lymph node dissection was performed. The patient went on to receive adjuvant chemoimmunotherapy. There was no recurrence or complication until the long-term followup. Popliteal drainage from below the knee is uncommon, and the rate of popliteal-positive and inguinal-negative cases is estimated to be less than 1% of all melanomas. There is no established evidence about how to treat lymph nodes in these cases. Because we considered popliteal nodes as a regional, not interval, lymph node basin, only popliteal lymph node dissection was performed, and good postoperative course was achieved. The first site of drainage is the sentinel node, and the popliteal node can be a sentinel node. The inguinal node is not a sentinel node in all lower extremity melanomas. This case illustrates the importance of individual detailed investigation of lymphatic drainage patterns from foot to inguinal and popliteal nodes.

  5. EFFECT OF TIME TO SENTINEL-NODE BIOPSY ON THE PROGNOSIS OF CUTANEOUS MELANOMA

    PubMed Central

    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Puig, Susana; Robert, Caroline; Saiag, Philippe; Martín-Cuevas, Paula; Gallego, Elena; Herrera-Acosta, Enrique; Aguilera, José; Malvehy, Josep; Carrera, Cristina; Cavalcanti, Andrea; Rull, Ramón; Vilalta-Solsona, Antonio; Lannoy, Emilie; Boutros, Celine; Benannoune, Naima; Tomasic, Gorana; Aegerte, Philippe; Vidal-Sicart, Sergi; Palou, Josep; Alos, LLúcia; Requena, Celia; Traves, Víctor; Pla, Ángel; Bolumar, Isidro; Soriano, Virtudes; Guillén, Carlos; Herrera-Ceballos, Enrique

    2016-01-01

    Instroduction In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumor and sentinel-node biopsy. The objective of this study is to analyze the prognostic implications of this delay. Patients and method This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. Results A delay time of 40 days or less (HR, 1.7; CI, 1.2 to 2.5) increased Breslow thickness (Breslow ≥2 mm, HR >3.7; CI 1.4 to 10.7), ulceration (HR 1.6; CI, 1.1 to 2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9 to 4.2), and primary melanoma localized in the head or neck were independently associated with worse melanoma-specific survival (all P<0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Conclusion Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma. PMID:26072362

  6. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage.

    PubMed

    Rohner, Nathan Andrew; McClain, Jacob; Tuell, Sara Lydia; Warner, Alex; Smith, Blair; Yun, Youngho; Mohan, Abhinav; Sushnitha, Manuela; Thomas, Susan Napier

    2015-11-01

    Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (-1 cmH2O) and LNs from naive animals (-1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.

  7. Sentinel Lymph Node Biopsy: Quantification of Lymphedema Risk Reduction

    DTIC Science & Technology

    2006-10-01

    dosimetry to lymph node critical for arm drainage . (Months 1-36) a. Subject enrollment Thirty seven subjects have enrolled in the study. This is 13...lymphatic system compensates for extensive lymph node loss has remained obscure. Our results suggest that collateral drainage pathways involving...planning. Gamma camera-based lymphoscintigraphy images lymph vessels and nodes, and provides information about their drainage territories. However

  8. Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?

    PubMed

    Weaver, Donald L

    2003-06-01

    Sentinel lymph node biopsy is changing surgical management of breast cancer and pathologic evaluation of lymph nodes. Although it has long been known that lymph nodes contain occult metastases, pathologists have not generally pursued their identification. Compared with level I-II axillary dissection, the reduced number of sentinel lymph nodes has made additional evaluation more attractive; however, the consequences of increased detection of micrometastases has not been fully explored or appreciated. National data suggest that the composition of traditional TNM stage groupings is changing, with a recent increase in node-positive, stage II breast cancer, most likely the result of increased pathologic scrutiny. Clinical management of this new group of stage II patients is complicated by the lack of a historic prognostic comparison group because many of these patients would have been classified as stage I, node-negative in the past. Early outcome data in sentinel lymph node biopsy suggest no adverse outcome for patients with metastases no larger than 2.0 mm, a finding aligned with the current definition of micrometastasis. When sentinel lymph nodes are sliced at 2.0-mm intervals and totally embedded, the probability of identifying all metastases >2.0 mm is high. Using reasonable sampling strategies, minute metastases have a nearly equal chance of being missed or detected. New staging guidelines have established a lower limit for micrometastases and defined metastases no larger than 0.2 mm as isolated tumor cells or tumor cell clusters; nodes with isolated tumor cells will be classified as node negative (pN0) for stage grouping. Rigorous strategies designed to reliably detect single cells or small cell clusters in sentinel nodes remain time-intensive and cost prohibitive.

  9. Sentinel lymph node biopsy in breast cancer: a comprehensive literature review.

    PubMed

    Salem, Ahmed

    2009-01-01

    Sentinel lymph node biopsy has emerged as the new standard of care for nodal staging in early-stage breast disease. In the this review, the procedure of SLNB in breast cancer will be examined in greater detail with the aim of understanding techniques that may improve results and of identifying future research questions in this field.

  10. Sentinel lymph nodes detection with an imaging system using Patent Blue V dye as fluorescent tracer

    NASA Astrophysics Data System (ADS)

    Tellier, F.; Steibel, J.; Chabrier, R.; Rodier, J. F.; Pourroy, G.; Poulet, P.

    2013-03-01

    Sentinel lymph node biopsy is the gold standard to detect metastatic invasion from primary breast cancer. This method can help patients avoid full axillary chain dissection, thereby decreasing the risk of morbidity. We propose an alternative to the traditional isotopic method, to detect and map the sentinel lymph nodes. Indeed, Patent Blue V is the most widely used dye in clinical routine for the visual detection of sentinel lymph nodes. A Recent study has shown the possibility of increasing the fluorescence quantum yield of Patent Blue V, when it is bound to human serum albumin. In this study we present a preclinical fluorescence imaging system to detect sentinel lymph nodes labeled with this fluorescent tracer. The setup is composed of a black and white CCD camera and two laser sources. One excitation source with a laser emitting at 635 nm and a second laser at 785 nm to illuminate the region of interest. The prototype is operated via a laptop. Preliminary experiments permitted to determine the device sensitivity in the μmol.L-1 range as regards the detection of PBV fluorescence signals. We also present a preclinical evaluation performed on Lewis rats, during which the fluorescence imaging setup detected the accumulation and fixation of the fluorescent dye on different nodes through the skin.

  11. Axillary and internal mammary sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy

    PubMed Central

    Cao, Xiao-Shan; Li, Hui-Juan; Cong, Bin-Bin; Sun, Xiao; Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Chun-Jian; Wang, Yong-Sheng

    2016-01-01

    With the improvement of neoadjuvant chemotherapy (NAC), the proportion of pathological complete response (pCR) in the breast and axillary lymph node (ALN) is increasing. The evaluation of pCR does not include the status of internal mammary lymph node (IMLN). This study is to evaluate the roles of both axillary sentinel lymph node biopsy (ASLNB) and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC. There were 74 patients enrolled into this study. IM-SLNB was performed on patients with radioactive internal mammary sentinel lymph node (IM-SLN). Patients (n = 8) with cN0 and ycN0 received ASLNB, and axillary lymph node dissection (ALND) in cases of positive axillary sentinel lymph node (ASLN). Patients (n = 48) with cN+ but ycN0 received ASLNB and ALND. Patients (n = 18) with ycN+ received ALND without ASLNB. The visualization rate of IM-SLN was 56.8% (42/74). The success rate of IM-SLNB was 97.6% (41/42) and the metastasis rate of IM-SLN was 7.3% (3/41). The success rate of ASLNB was 100% (56/56). The false negative rate (FNR) of ASLNB was 17.2% (5/29). The FNR in patients with 1, 2 and ≥ 3ASLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/8) respectively. ASLNB could be performed on ycN0 after NAC, and ALND should be performed on initially ALN-positive patients. IM-SLNB should be considered after NAC, especially for patients with clinically positive axillary nodes before NAC, which might help make clear of the pathological nodal staging of both ALN and IMLN, improve the definition of nodal pCR, and guide the individual adjuvant regional and systemic therapy. PMID:27738336

  12. Axillary and internal mammary sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy.

    PubMed

    Cao, Xiao-Shan; Li, Hui-Juan; Cong, Bin-Bin; Sun, Xiao; Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Chun-Jian; Wang, Yong-Sheng

    2016-11-08

    With the improvement of neoadjuvant chemotherapy (NAC), the proportion of pathological complete response (pCR) in the breast and axillary lymph node (ALN) is increasing. The evaluation of pCR does not include the status of internal mammary lymph node (IMLN). This study is to evaluate the roles of both axillary sentinel lymph node biopsy (ASLNB) and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC. There were 74 patients enrolled into this study. IM-SLNB was performed on patients with radioactive internal mammary sentinel lymph node (IM-SLN). Patients (n = 8) with cN0 and ycN0 received ASLNB, and axillary lymph node dissection (ALND) in cases of positive axillary sentinel lymph node (ASLN). Patients (n = 48) with cN+ but ycN0 received ASLNB and ALND. Patients (n = 18) with ycN+ received ALND without ASLNB. The visualization rate of IM-SLN was 56.8% (42/74). The success rate of IM-SLNB was 97.6% (41/42) and the metastasis rate of IM-SLN was 7.3% (3/41). The success rate of ASLNB was 100% (56/56). The false negative rate (FNR) of ASLNB was 17.2% (5/29). The FNR in patients with 1, 2 and ≥ 3ASLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/8) respectively. ASLNB could be performed on ycN0 after NAC, and ALND should be performed on initially ALN-positive patients. IM-SLNB should be considered after NAC, especially for patients with clinically positive axillary nodes before NAC, which might help make clear of the pathological nodal staging of both ALN and IMLN, improve the definition of nodal pCR, and guide the individual adjuvant regional and systemic therapy.

  13. Development of a handheld fluorescence imaging camera for intraoperative sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    Szyc, Łukasz; Bonifer, Stefanie; Walter, Alfred; Jagemann, Uwe; Grosenick, Dirk; Macdonald, Rainer

    2015-05-01

    We present a compact fluorescence imaging system developed for real-time sentinel lymph node mapping. The device uses two near-infrared wavelengths to record fluorescence and anatomical images with a single charge-coupled device camera. Experiments on lymph node and tissue phantoms confirmed that the amount of dye in superficial lymph nodes can be better estimated due to the absorption correction procedure integrated in our device. Because of the camera head's small size and low weight, all accessible regions of tissue can be reached without the need for any adjustments.

  14. Label-free 3D optical imaging of microcirculation within sentinel lymph node in vivo

    NASA Astrophysics Data System (ADS)

    Jung, Yeongri; Zhi, Zhongwei; Wang, Ruikang K.

    2011-03-01

    Sentinel lymph node (SLN) is the first lymph node to drain wastes originated from cancerous tissue. There is a need for an in vivo imaging method that can image the intact SLN in order to further our understanding of its normal as well as abnormal functions. We report the use of ultrahigh sensitive optical microangiography (UHS-OMAG) to image functional microvascular and lymphatic vessel networks that innervate the intact lymph node in mice in vivo. The promising results show a potential role of UHS-OMAG in the future understanding and diagnosis of the SLN involvement in cancer development.

  15. Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

    PubMed Central

    Mihic-Probst, Daniela; Seifert, Burkhardt; Soldini, Davide; Dummer, Reinhard; Knuth, Alexander; van den Broek, Maries; Moch, Holger

    2011-01-01

    MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis. PMID:21738656

  16. Lymph Node Melanosis in a Patient With Metastatic Melanoma of Unknown Primary

    DTIC Science & Technology

    2009-08-01

    1332 Arch Pathol Lab Med—Vol 133, August 2009 Lymph Node Melanosis With Metastatic Melanoma—Malafronte & Sorrells Case Report Lymph Node Melanosis in...lignant melanoma, exhibiting a spectrum of clinico - pathologic features. Partially regressed melanomas most often present clinically as either...tumoral or nodular melanosis, is considered and treated as a variant of com- pletely regressed melanoma.4 Only a small number of cases of tumoral melanosis

  17. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

    PubMed Central

    B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

    2015-01-01

    The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging. PMID:26179014

  18. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

    2015-07-01

    The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging.

  19. Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection.

    PubMed

    Kadkhodayan, Sima; Farahabadi, Elham Hosseini; Yousefi, Zohreh; Hasanzadeh, Malihe; Sadeghi, Ramin

    2014-01-01

    Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged.

  20. Dendronized iron oxide colloids for imaging the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Jouhannaud, J.; Garofalo, A.; Felder-Flesch, D.; Pourroy, G.

    2015-03-01

    Various methods have been used in medicine for more than one century to explore the lymphatic system. Radioactive colloids (RuS labelled with 99mTc) or/and Vital Blue dye are injected around the primary tumour and detected by means of nuclear probe or visual colour inspection respectively. The simultaneous clinical use of both markers (dye and radionuclide) improves the sensitivity of detection close to 100%. Superparamagnetic iron oxides (SPIOs) are currently receiving much attention as strong T2 weighted magnetic resonance imaging contrast agents that can be potentially used for preoperative localization of sentinel nodes, but also for peroperative detection of sentinel node using hand-held probes. In that context, we present the elaboration of dendronized iron oxide nanoparticles elaborated at the Institute of Physics and Chemistry of Materials of Strasbourg.

  1. Multispectral real-time fluorescence imaging for intraoperative detection of the sentinel lymph node in gynecologic oncology.

    PubMed

    Crane, Lucia M A; Themelis, George; Buddingh, K Tim; Buddingh, Tim; Harlaar, Niels J; Pleijhuis, Rick G; Sarantopoulos, Athanasios; van der Zee, Ate G J; Ntziachristos, Vasilis; van Dam, Gooitzen M

    2010-10-20

    The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases. Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema. As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor. In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix. The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid. Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion. It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used. The aim of this video article is to demonstrate the detection of

  2. A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging.

    PubMed

    Zhou, Zhengyang; Chen, Hongwei; Lipowska, Malgorzata; Wang, Liya; Yu, Qiqi; Yang, Xiaofeng; Tiwari, Diana; Yang, Lily; Mao, Hui

    2013-07-01

    The ability to reliably detect sentinel lymph nodes for sentinel lymph node biopsy and lymphadenectomy is important in clinical management of patients with metastatic cancers. However, the traditional sentinel lymph node mapping with visible dyes is limited by the penetration depth of light and fast clearance of the dyes. On the other hand, sentinel lymph node mapping with radionucleotide technique has intrinsically low spatial resolution and does not provide anatomic details in the sentinel lymph node mapping procedure. This work reports the development of a dual modality imaging probe with magnetic resonance and near infrared imaging capabilities for sentinel lymph node mapping using magnetic iron oxide nanoparticles (10 nm core size) conjugated with a near infrared molecule with emission at 830 nm. Accumulation of magnetic iron oxide nanoparticles in sentinel lymph nodes leads to strong T2 weighted magnetic resonance imaging contrast that can be potentially used for preoperative localization of sentinel lymph nodes, while conjugated near infrared molecules provide optical imaging tracking of lymph nodes with a high signal to background ratio. The new magnetic nanoparticle based dual imaging probe exhibits a significant longer lymph node retention time. Near infrared signals from nanoparticle conjugated near infrared dyes last up to 60 min in sentinel lymph node compared to that of 25 min for the free near infrared dyes in a mouse model. Furthermore, axillary lymph nodes, in addition to sentinel lymph nodes, can be also visualized with this probe, given its slow clearance and sufficient sensitivity. Therefore, this new dual modality imaging probe with the tissue penetration and sensitive detection of sentinel lymph nodes can be applied for preoperative survey of lymph nodes with magnetic resonance imaging and allows intraoperative sentinel lymph node mapping using near infrared optical devices.

  3. Popliteal lymph node dissection.

    PubMed

    Sholar, Alina; Martin, Robert C G; McMasters, Kelly M

    2005-02-01

    Most sentinel nodes are located in the cervical, axillary, and inguinal nodal basins. Sometimes, however, sentinel nodes exist outside these traditional nodal basins. Popliteal nodal metastasis is relatively uncommon, and popliteal lymph node dissection is infrequently necessary. However, with lymphoscintigraphic identification of popliteal sentinel nodes, surgeons are more frequently called on to address the popliteal nodal basin. Therefore, knowledge of the anatomy and surgical technique for popliteal lymphadenectomy is essential. This case study illustrates the importance of considering the approach to the popliteal lymph node basin for patients with melanoma.

  4. Novel handheld magnetometer probe based on magnetic tunnelling junction sensors for intraoperative sentinel lymph node identification.

    PubMed

    Cousins, A; Balalis, G L; Thompson, S K; Forero Morales, D; Mohtar, A; Wedding, A B; Thierry, B

    2015-06-03

    Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required.

  5. Novel Handheld Magnetometer Probe Based on Magnetic Tunnelling Junction Sensors for Intraoperative Sentinel Lymph Node Identification

    PubMed Central

    Cousins, A.; Balalis, G. L.; Thompson, S. K.; Forero Morales, D.; Mohtar, A.; Wedding, A. B.; Thierry, B.

    2015-01-01

    Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required. PMID:26038833

  6. Secretory breast carcinoma in a 6-year-old girl: mastectomy with sentinel lymph node dissection.

    PubMed

    Soyer, Tutku; Yaman Bajin, İnci; Orhan, Diclehan; Yalçin, Bilgehan; Özgen Kiratli, Pinar; Oğuz, Berna; Karnak, İbrahim

    2015-07-01

    Secretory breast carcinoma (SBC) is a rare type of breast neoplasia that was originally described in children. SBC is an indolent breast tumor with good clinical outcome and rare systemic involvement. Since, majority of studies concerning pediatric SBC have been case reports, it has been difficult to clearly elucidate the characteristics and optimal treatment strategies for SBC in children. Although treatment recommendations vary, surgical excision is the primary mode of treatment. Also, necessity of axillary and/or sentinel lymph node dissection is another matter of discussion in children. We report a 6-year-old girl who was diagnosed as SBC was reported to discuss the use of mastectomy with sentinel lymph node dissection in the treatment of this rare tumor in children.

  7. Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique: High Visualization Rate and Accurate Staging.

    PubMed

    Qiu, Peng-Fei; Cong, Bin-Bin; Zhao, Rong-Rong; Yang, Guo-Ren; Liu, Yan-Bing; Chen, Peng; Wang, Yong-Sheng

    2015-10-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns because of the low visualization rate of internal mammary sentinel lymph nodes (IMSLN) with the traditional radiotracer injection technique. In this study, various injection techniques were evaluated in term of the IMSLN visualization rate, and the impact of IM-SLNB on the diagnostic and prognostic value were analyzed.Clinically, axillary lymph nodes (ALN) negative patients (n = 407) were divided into group A (traditional peritumoral intraparenchymal injection) and group B (modified periareolar intraparenchymal injection). Group B was then separated into group B1 (low volume) and group B2 (high volume) according to the injection volume. Clinically, ALN-positive patients (n = 63) were managed as group B2. Internal mammary sentinel lymph node biopsy was performed for patients with IMSLN visualized.The IMSLN visualization rate was significantly higher in group B than that in group A (71.1% versus 15.5%, P < 0.001), whereas the axillary sentinel lymph nodes were reliably identified in both groups (98.9% versus 98.3%, P = 0.712). With high injection volume, group B2 was found to have higher IMSLN visualization rate than group B1 (75.1% versus 45.8%, P < 0.001). The IMSLN metastasis rate was only 8.1% (12/149) in clinically ALN-negative patients with successful IM-SLNB, and adjuvant treatment was altered in a small proportion. The IMSLN visualization rate was 69.8% (44/63) in clinically ALN-positive patients with the IMSLN metastasis rate up to 20.5% (9/44), and individual radiotherapy strategy could be guided with the IM-SLNB results.The modified injection technique (periareolar intraparenchymal, high volume, and ultrasound guidance) significantly improved the IMSLN visualization rate, making the routine IM-SLNB possible in daily practice. Internal mammary

  8. Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

    PubMed

    Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

    2015-03-01

    Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.

  9. Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

    2006-02-01

    Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

  10. Routine positron emission tomography and positron emission tomography/computed tomography in melanoma staging with positive sentinel node biopsy is of limited benefit.

    PubMed

    Constantinidou, Anastasia; Hofman, Michael; O'Doherty, Michael; Acland, Katharine M; Healy, Ciaran; Harries, Mark

    2008-02-01

    Positron emission tomography (PET) is increasingly used for the staging and management of melanoma. The aim of this study was to evaluate the role of PET or PET/ computed tomography (CT) as a routine procedure in patients with positive sentinel node biopsy (SNB). Thirty patients with melanoma of Breslow thickness greater than 1 mm who had PET or PET/CT scans performed within 100 days after a positive SNB were reviewed retrospectively. Two patients (6%) had a positive PET scan, none of which were melanoma related. The first patient had a synchronous neuroendocrine thyroid tumour and the second patient had increased uptake in the chest wall, which proved to be old trauma. Lymph node dissection was positive in five cases (16%). With a median follow-up of 24 months, 21 patients remained disease free. In none of the 30 cases did the early PET scan after a positive SNB alter subsequent melanoma management. The role of PET scanning soon after a positive sentinel node biopsy seems to be of limited benefit. It is questionable whether any imaging is beneficial at this stage. The results of this review suggest that PET scanning might not be indicated for this group of patients.

  11. Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging

    SciTech Connect

    Russo, Paolo; Curion, Assunta S.; Mettivier, Giovanni; Esposito, Michela; Aurilio, Michela; Caraco, Corradina; Aloj, Luigi; Lastoria, Secondo

    2011-03-15

    Purpose: The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. Methods: The room-temperature CdTe pixel detector (1 mm thick) has 256x256 square pixels arranged with a 55 {mu}m pitch (sensitive area 14.08x14.08 mm{sup 2}), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. Results: For {sup 99m}Tc, at 50 mm distance, a background-subtracted sensitivity of 6.5x10{sup -3} cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3x10{sup -2} cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq {sup 99m}Tc and prior localization with standard gamma camera lymphoscintigraphy. Conclusions: The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter

  12. Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging

    PubMed Central

    Yang, Xiangyu; Wang, Zhe; Zhang, Fuwu; Zhu, Guizhi; Song, Jibin; Teng, Gao-Jun; Niu, Gang; Chen, Xiaoyuan

    2017-01-01

    Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging

  13. Portable widefield imaging device for ICG-detection of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Govone, Angelo Biasi; Gómez-García, Pablo Aurelio; Carvalho, André Lopes; Capuzzo, Renato de Castro; Magalhães, Daniel Varela; Kurachi, Cristina

    2015-06-01

    Metastasis is one of the major cancer complications, since the malignant cells detach from the primary tumor and reaches other organs or tissues. The sentinel lymph node (SLN) is the first lymphatic structure to be affected by the malignant cells, but its location is still a great challenge for the medical team. This occurs due to the fact that the lymph nodes are located between the muscle fibers, making it visualization difficult. Seeking to aid the surgeon in the detection of the SLN, the present study aims to develop a widefield fluorescence imaging device using the indocyanine green as fluorescence marker. The system is basically composed of a 780nm illumination unit, optical components for 810nm fluorescence detection, two CCD cameras, a laptop, and dedicated software. The illumination unit has 16 diode lasers. A dichroic mirror and bandpass filters select and deliver the excitation light to the interrogated tissue, and select and deliver the fluorescence light to the camera. One camera is responsible for the acquisition of visible light and the other one for the acquisition of the ICG fluorescence. The software developed at the LabVIEW® platform generates a real time merged image where it is possible to observe the fluorescence spots, related to the lymph nodes, superimposed at the image under white light. The system was tested in a mice model, and a first patient with tongue cancer was imaged. Both results showed the potential use of the presented fluorescence imaging system assembled for sentinel lymph node detection.

  14. Update on detection of sentinel lymph nodes in patients with breast cancer.

    PubMed

    Aarsvold, John N; Alazraki, Naomi P

    2005-04-01

    Sentinel lymph node biopsy is now the practice of choice for the management of many patients with breast cancer. This was not true in the early 1990s, when the first such procedures were performed and protocols for such were refined often. This was also not true in the first years of the 21st century, when a decade of collective experience and information acquired from numerous clinical investigations dictated additional subtle and not-so-subtle refinements of the procedures. However, it is true today; reports of the latest round of clinical investigations indicate that there are several breast cancer sentinel node procedures that result in successful identification of potential sentinel nodes in nearly all patients who are eligible for such procedures. A significant component of many of these successful sentinel node procedures is a detection and localization protocol that involves radiotracer methodologies, including radiopharmaceutical administration, preoperative nuclear medicine imaging, and intraoperative gamma counting. The present state and roles of nuclear medicine protocols used in breast cancer sentinel lymph node biopsy procedures is reviewed with emphasis on discussion of recent results, unresolved issues, and future considerations. Included are brief reviews of present radiotracer and blue-dye techniques for node localization, including remarks about injection strategies, counting probe technology, and radiation safety. Included also are discussions of on-going investigations of the implications of the presence of micrometastases; of the management value of detection, localization, and excision of extra-axillary nodes such as internal mammary nodes; and of the broad range of recurrence rates presently being reported. Remarks on the present and possible near- and long-term roles for nuclear medicine in the staging of breast cancer patients including comments on positron emission tomography and intraoperative imaging conclude the article.

  15. Computed tomography and radiographic indirect lymphography for visualization of mammary lymphatic vessels and the sentinel lymph node in normal cats.

    PubMed

    Patsikas, Michail N; Papadopoulou, Paraskevi L; Charitanti, Afroditi; Kazakos, George M; Soultani, Christina B; Tziris, Nikolaos E; Tzegas, Sotirios I; Jakovljevic, Samuel; Savas, Ioannis; Stamoulas, Konstantinos G

    2010-01-01

    The potential of computed tomography indirect lymphography (CT-indirect lymphography) and radiographic indirect lymphography to demonstrate the draining lymphatic vessels and sentinel lymph node of normal mammary glands was tested in 31 healthy female cats. The lymphatic drainage of each mammary gland was studied initially by CT-indirect lymphography after intramammary injection of 0.5 ml of iopamidol, followed by images acquired at 1, 5, 15, and 30 min after injection. One day after CT-indirect lymphography, the lymph drainage of the mammary gland was assessed using radiographic in direct lymphography af terintramammary injection of 0.5 ml of ethiodized oil followed by radiographs made at 1, 5, 15, 30, 45, and 60 min after injection. The time between intramammary injection and opacification of the draining mammary lymphatic vessels and the sentinel lymph node, the duration of adequate opacification of the draining mammary lymphatic vessels and of the sentinel lymph node and also the number and course of draining mammary lymphatic vessels and location of sentinel lymph node were compared for CT-indirect lymphography vs. radiographic indirect lymphography in each examined gland. This results suggest that radiographic indirect lymphography is easy to perform and can be used for accurate demonstration of the draining lymphatic pathways of mammary glands in radiographs made at 5-30 min after injection. However, CT-indirect lymphography was able to better demonstrate small lymphatic vessels and accurately define the exact topography of the sentinel lymph node in images acquired at 1 min after injection.

  16. Pathologic examination of the sentinel lymph node: what is the best method?

    PubMed

    Treseler, Patrick

    2006-01-01

    Sentinel lymph node biopsy (SLNB) has become an acceptable alternative to complete axillary dissection to determine whether breast cancer has spread to axillary lymph nodes. Yet the best method for pathologic examination of the sentinel lymph node (SLN) remains controversial. For years there has been speculation that micrometastases in axillary lymph nodes were clinically insignificant and thus lymph nodes did not require sectioning at close intervals. Yet essentially all studies, including a recent large prospective study, have found a significantly poorer prognosis associated even with metastases less than 2 mm in size-the most common definition of micrometastasis-suggesting that such small metastases cannot be safely overlooked. The use of immunohistochemistry (IHC) to detect keratin proteins will reveal metastatic breast carcinoma in about 18% of axillary lymph nodes that appear negative on routine stains. The preponderance of evidence to date suggests a significantly poorer prognosis in patients with such occult metastases, although data from large prospective studies are lacking. Molecular techniques such as polymerase chain reaction (PCR) offer even more sensitive methods for detecting occult metastasis in SLNs, although false positives are a particular problem in techniques that do not permit morphologic correlation, and for now they remain a research tool. Intraoperative examination of the SLN permits a completion axillary dissection to be performed during the same procedure if metastatic tumor is found; however, intraoperative techniques such as cytologic examination and frozen section lack sensitivity, and can result in loss of up to 50% of the SLN tissue. A proposal for optimal pathologic examination of the SLN is offered based on the above data.

  17. Technique of sentinel lymph node biopsy and lymphatic mapping during laparoscopic colon resection for cancer

    PubMed Central

    Bianchi, PP; Andreoni, B; Rottoli, M; Celotti, S; Chiappa, A; Montorsi, M

    2007-01-01

    Background: The utility of lymph node mapping to improve staging in colon cancer is still under evaluation. Laparoscopic colectomy for colon cancer has been validated in multi-centric trials. This study assessed the feasibility and technical aspects of lymph node mapping in laparoscopic colectomy for colon cancer. Methods: A total of 42 patients with histologically proven colon cancer were studied from January 2006 to September 2007. Exclusion criteria were: advanced disease (clinical stage III), rectal cancer, previous colon resection and contraindication to laparoscopy. Lymph-nodal status was assessed preoperatively by computed tomography (CT) scan and intra-operatively with the aid of laparoscopic ultrasound. Before resection, 2–3 ml of Patent Blue V dye was injected sub-serosally around the tumour. Coloured lymph nodes were marked as sentinel (SN) with metal clips or suture and laparoscopic colectomy with lymphadenectomy completed as normal. In case of failure of the intra-operative procedure, an ex vivo SN biopsy was performed on the colectomy specimen after resection. Results: A total number of 904 lymph nodes were examined, with a median number of 22 lymph nodes harvested per patient. The SN detection rate was 100%, an ex vivo lymph node mapping was necessary in four patients. Eleven (26.2%) patients had lymph-nodal metastases and in five (45.5%) of these patients, SN was the only positive lymph node. There were two (18.2%) false-negative SN. In three cases (7.1%) with aberrant lymphatic drainage, lymphadenectomy was extended. The accuracy of SN mapping was 95.2% and negative predictive value was 93.9%. Conclusions: Laparoscopic lymphatic mapping and SN removal is feasible in laparoscopic colectomy for colon cancer. The ex vivo technique is useful as a salvage technique in case of failure of the intra-operative procedure. Prospective studies are justified to determine the real accuracy and false-negative rate of the technique. PMID:22275957

  18. Validation study for the hypothesis of internal mammary sentinel lymph node lymphatic drainage in breast cancer.

    PubMed

    Cong, Bin-Bin; Qiu, Peng-Fei; Liu, Yan-Bing; Zhao, Tong; Chen, Peng; Cao, Xiao-Shan; Wang, Chun-Jian; Zhang, Zhao-Peng; Sun, Xiao; Yu, Jin-Ming; Wang, Yong-Sheng

    2016-07-05

    According to axilla sentinel lymph node lymphatic drainage pattern, we hypothesized that internal mammary sentinel lymph node (IM-SLN) receives lymphatic drainage from not only the primary tumor area, but also the entire breast parenchyma. Based on the hypothesis a modified radiotracer injection technique was established and could increase the visualization rate of the IM-SLN significantly. To verify the hypothesis, two kinds of tracers were injected at different sites of breast. The radiotracer was injected with the modified technique, and the fluorescence tracer was injected in the peritumoral intra-parenchyma. The location of IM-SLN was identified by preoperative lymphoscintigraphy and intraoperative gamma probe. Then, internal mammary sentinel lymph node biopsy (IM-SLNB) was performed. The fluorescence status of IM-SLN was identified by the fluorescence imaging system. A total of 216 patients were enrolled from September 2013 to July 2015. The overall visualization rate of IM-SLN was 71.8% (155/216). The success rate of IM-SLNB was 97.3% (145/149). The radiotracer and the fluorescence tracer were identified in the same IM-SLN in 127 cases, the correlation and the agreement is significant (Case-base, rs=0.836, P<0.001; Kappa=0.823, P<0.001). Different tracers injected into the different sites of the intra-parenchyma reached the same IM-SLN, which demonstrates the hypothesis that IM-SLN receives the lymphatic drainage from not only the primary tumor area but also the entire breast parenchyma.

  19. Evaluation of the Probability of Non-sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Metastasis using Two Different Methods

    PubMed Central

    Başoğlu, İrfan; Çelik, Muhammet Ferhat; Dural, Ahmet Cem; Ünsal, Mustafa Gökhan; Akarsu, Cevher; Baytekin, Halil Fırat; Kapan, Selin; Alış, Halil

    2015-01-01

    Objective The aim of this retrospective clinical study was to evaluate the accuracy and feasibility of two different clinical scales, namely the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Tenon’s axillary scoring system, which were developed for predicting the non-sentinel lymph node (NSLN) status in our breast cancer patients. Material and Methods The medical records of patients who were diagnosed with breast cancer between January 2010 and November 2013 were reviewed. Those who underwent sentinel lymph node biopsy (SLNB) for axillary staging were recruited for the study, and patients who were found to have positive SLNB and thus were subsequently subjected to axillary lymph node dissection (ALND) were also included. Patients who had neoadjuvant therapy, who had clinically positive axilla, and who had stage 4 disease were excluded. Patients were divided into two groups. Group 1 included those who had negative NSLNs, whereas Group 2 included those who had positive NSLNs. The following data were collected: age, tumor size, histopathological characteristics of the tumor, presence of lymphovascular invasion, presence of multifocality, number of negative and positive NSLNs, size of metastases, histopathological method used to define metastases, and receptor status of the tumor. The score of each patient was calculated according to the MSKCC nomogram and Tenon’s axillary scoring system. Statistical analysis was conducted to investigate the correlation between the scores and the involvement of NSLNs. Results The medical records of patients who were diagnosed with breast cancer and found to have SLNB for axillary staging was reviewed. Finally, 50 patients who had positive SLNB and thus were subsequently subjected to ALND were included in the study. There were 17 and 33 patients in Groups 1 and 2, respectively. Both the MSKCC nomogram and Tenon’s axillary scoring system were demonstrated to be significantly accurate in the prediction of the

  20. Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging

    NASA Astrophysics Data System (ADS)

    Luke, Geoffrey P.; Bashyam, Ashvin; Homan, Kimberly A.; Makhija, Suraj; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-11-01

    A biopsy of the first lymph node to which a tumor drains—the sentinel lymph node (SLN)—is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN, gradually spreading throughout a large portion of the node.

  1. Transaxillary breast augmentation: two breast cancer patients with successful sentinel lymph node diagnosis.

    PubMed

    Mottura, A Aldo; Del Castillo, René

    2007-01-01

    In recent years, some surgeons have been warned of possible problems with sentinel lymph node diagnosis (SLND) for patients who have undergone transaxillary breast augmentation (TBA), although no scientific studies support this warning. The authors report two additional cases of breast cancer in which the SLND was successfully performed for patients with previous TBA. The surgical anatomy of the axilla, the groups of lymph nodes, and a personal way of performing TBA are described. Five other reports concerning the same issue are thoroughly discussed. Four of these are clinical in vivo reports, and one is a cadaver study. The four in vivo studies and what we are reporting now clearly demonstrate that what was said regarding possible problems in the SLND after TBA was not founded on clinical research and contradicts these five clinical findings.

  2. Regional Disease Control in Selected Patients with Sentinel Lymph Node Involvement and Omission of Axillary Lymph Node Dissection.

    PubMed

    Cserni, Gábor; Maráz, Róbert

    2015-09-01

    Whether an axillary lymph node dissection (ALND) is needed for breast cancer patients with minimal sentinel lymph node (SLN) involvement is arguable despite recent data supporting the omission of axillary clearance in these patients. Data on disease recurrence of 111 patients with SLN involvement and no ALND were analysed. Patients with minimal SLN involvement were assessed for their risk of non-SLN metastasis by means of several nomograms. The series included patients with isolated tumour cells (n = 76), micrmetastasis (n = 33) and macrometastasis (n = 2) who were followed for a median of 37 months (range 12-148 months). Six patients died, 3 of disease and 3 of unrelated causes. Eight further patients had breast cancer related events: 1 local breast recurrence and seven distant metastases. No axillary regional recurrence was detected. Disease related events were not associated with the risk of non-SLN metastasis. The presented data suggest that omitting ALND in patients with low volume SLN metastasis may be a safe procedure, and support the observation that systemic disease recurrence may not be associated with axillary recurrence or the risk of NSLN involvement predicted by nomograms.

  3. Lessons Learned from the Initial 100 Patient Experience with Sentinel Lymph Node Mapping in the Evaluation of Breast Cancer

    PubMed Central

    Fuhrman, George M.; Burch, Ernest G.; Farr, Gist H.; King, Tari A.; Farkas, Emily; Bolton, John S.

    2000-01-01

    The initial reports of sentinel lymph node mapping for breast cancer currently appearing in the surgical literature are demonstrating the practicality and accuracy of the technique to evaluate patients for axillary nodal disease. We reviewed our initial 100 patient experience with sentinel node mapping to evaluate our ability to employ this technique in breast cancer patients. We combined a peritumoral injection of a radioactive substance and blue dye. Each sentinel node was evaluated with frozen section analysis, hematoxylin and eosin staining, and, if still negative, five re-cuts were taken from deeper levels of the node and evaluated for immunohistochemical evidence of cytokeratin staining. Sentinel node(s) were identified in all but two patients with 51% demonstrating metastasis. We have demonstrated the ability to accurately perform sentinel node mapping in the evaluation of our breast cancer patients. This exciting advance should become a standard part of breast cancer surgery. PMID:21765657

  4. Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma.

    PubMed

    Ishii, Hiroki; Chikamatsu, Kazuaki; Sakakura, Koichi; Miyata, Masanori; Furuya, Nobuhiko; Masuyama, Keisuke

    2010-05-01

    The main factor that affects the prognosis of patients with oral squamous cell carcinoma (OSCC) is regional lymph node metastases, which usually spreads first to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells in several malignancies can induce lymphangiogenesis in SLNs before metastasizing. To elucidate the mechanisms of tumor dissemination of OSCC, we investigated whether primary tumors induce lymphangiogenesis within SLNs in patients with OSCC. The mRNA expression of lymphatic-specific markers, including VEGFR-3, Prox-1, and LYVE-1 in 23 metastasis-negative SLNs obtained from 10 patients with OSCC, was investigated using a quantitative real-time RT-PCR assay, and compared with control lymph nodes from patients with non-cancerous diseases. In addition, VEGF-C and VEGF-D expressions of the primary tumor were examined by immunohistochemistry. In SLNs, there were highly significant correlations between the three lymphatic markers examined. Interestingly, the level of LYVE-1 expression in SLNs, despite the absence of metastasis, was significantly higher than in control lymph nodes. Moreover, SLNs from patients with VEGF-C-positive tumor showed a significantly higher expression of VEGFR-3 than those from patients with VEGF-C-negative tumor. Our findings suggest that in OSCC, the primary tumor actively induces lymphangiogenesis in SLNs prior to the onset of metastases, and where tumor-derived VEGF-C plays an important role.

  5. A handheld SPIO-based sentinel lymph node mapping device using differential magnetometry

    NASA Astrophysics Data System (ADS)

    Waanders, S.; Visscher, M.; Wildeboer, R. R.; Oderkerk, T. O. B.; Krooshoop, H. J. G.; ten Haken, B.

    2016-11-01

    Sentinel lymph node biopsy has become a staple tool in the diagnosis of breast cancer. By replacing the morbidity-plagued axillary node clearance with removing only those nodes most likely to contain metastases, it has greatly improved the quality of life of many breast cancer patients. However, due to the use of ionizing radiation emitted by the technetium-based tracer material, the current sentinel lymph node biopsy has serious drawbacks. Most urgently, the reliance on radioisotopes limits the application of this procedure to small parts of the developed world, and it imposes restrictions on patient planning and hospital logistics. Magnetic alternatives have been tested in recent years, but all have their own drawbacks, mostly related to interference from metallic instruments and electromagnetic noise coming from the human body. In this paper, we demonstrate an alternative approach that utilizes the unique nonlinear magnetic properties of superparamagnetic iron oxide nanoparticles to eliminate the drawbacks of both the traditional gamma-radiation centered approach and the novel magnetic techniques pioneered by others. Contrary to many other nonlinear magnetic approaches however, field amplitudes are limited to 5 mT, which enables handheld operation without additional cooling. We show that excellent mass sensitivity can be obtained without the need for external re-balancing of the probe to negate any influences from the human body. Additionally, we show how this approach can be used to suppress artefacts resulting from the presence of metallic instruments, which are a significant dealbreaker when using conventional magnetometry-based approaches.

  6. Optimization of a gamma imaging probe for axillary sentinel lymph mapping

    NASA Astrophysics Data System (ADS)

    Georgiou, M.; Loudos, G.; Stratos, D.; Papadimitroulas, P.; Liakou, P.; Georgoulias, P.

    2012-09-01

    Sentinel lymph node (SLN) mapping is a technique for assessing whether early-stage invasive breast cancer has metastasized, thus determining prognosis and treatment options. SLN identification is achieved using the blue-dye and radioactive colloids techniques, which are sometimes combined with lymphoscintigraphy. Furthermore, intra-operative gamma acoustic probes, as well as gamma imaging probes are used during surgery. The purpose of this study is the construction of a gamma probe for sentinel lymph node imaging and its optimization in terms of sensitivity with respect to spatial resolution. The reference probe has small field of view (2.5 × 2.5 cm2) and is based on a position sensitive photomultiplier tube (PSPMT) coupled to a pixellated CsI(Tl) scintillator. Following experimental validation, we simulated the system using the GATE Monte Carlo toolkit (GATE v6.1) and modeled various collimator geometries, in order to evaluate their performance and propose the optimal configuration. The constraints of the proposed gamma imaging probe are i) sensitivity close to 2 cps/kBq and ii) spatial resolution equal to 6 mm at 2 cm source-to-collimator distance and ~ 10 mm at 5 cm. An integrated structure that achieves those requirements is a tungsten collimator with 2 × 2 mm2square holes, 16 mm thickness, 0.15 mm septa, where each CsI(Tl) 2 × 2 × 5 mm3 crystal pixel is placed inside the collimator.

  7. Improvement of the sentinel lymph node detection rate of cervical sentinel lymph node biopsy using real-time fluorescence navigation with indocyanine green in head and neck skin cancer.

    PubMed

    Nakamura, Yasuhiro; Fujisawa, Yasuhiro; Nakamura, Yoshiyuki; Maruyama, Hiroshi; Furuta, Jun-ichi; Kawachi, Yasuhiro; Otsuka, Fujio

    2013-06-01

    The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the "shine-through" phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary.

  8. Sentinel Lymph Node Detection Using Carbon Nanoparticles in Patients with Early Breast Cancer

    PubMed Central

    Lu, Jianping; Zeng, Yi; Chen, Xia; Yan, Jun

    2015-01-01

    Purpose Carbon nanoparticles have a strong affinity for the lymphatic system. The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy using carbon nanoparticles in early breast cancer and to optimize the application procedure. Methods Firstly, we performed a pilot study to demonstrate the optimized condition using carbon nanoparticles for sentinel lymph nodes (SLNs) detection by investigating 36 clinically node negative breast cancer patients. In subsequent prospective study, 83 patients with clinically node negative breast cancer were included to evaluate SLNs using carbon nanoparticles. Another 83 SLNs were detected by using blue dye. SLNs detection parameters were compared between the methods. All patients irrespective of the SLNs status underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. Results In pilot study, a 1 ml carbon nanoparticles suspension used 10–15min before surgery was associated with the best detection rate. In subsequent prospective study, with carbon nanoparticles, the identification rate, accuracy, false negative rate was 100%, 96.4%, 11.1%, respectively. The identification rate and accuracy were 88% and 95.5% with 15.8% of false negative rate using blue dye technique. The use of carbon nanoparticles suspension showed significantly superior results in identification rate (p = 0.001) and reduced false-negative results compared with blue dye technique. Conclusion Our study demonstrated feasibility and accuracy of using carbon nanoparticles for SLNs mapping in breast cancer patients. Carbon nanoparticles are useful in SLNs detection in institutions without access to radioisotope. PMID:26296136

  9. Experimental study of 99mTc-aluminum oxide use for sentinel lymph nodes detection

    NASA Astrophysics Data System (ADS)

    Chernov, V. I.; Sinilkin, I. G.; Zelchan, R. V.; Medvedeva, A. A.; Lyapunov, A. Yu.; Bragina, O. D.; Varlamova, N. V.; Skuridin, V. S.

    2016-08-01

    The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals 99mTc-Al2O3 and 99mTc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of 99mTc-Al2O3 and 99mTc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of 99mTc-Al2O3 and 99mTc-Nanocis was researched on 50 white male rats. The possibility of the use of 99mTc-Al2O3 and 99mTc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particle was 52-77 nm for 99mTc-Al2O3 and 16.7-24.5 nm for 99mTc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of 99mTc-Al2O3 was 8.6% in it, and the accumulation of 99mTc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of 99mTc-Al2O3 in the lymph node was significantly higher than 99mTc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that 99mTc-Al2O3 and 99mTc-Nanocis actively accumulated into the lymphatic system. By using 99mTc-Al2O3 inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the 99mTc-Al2O3 accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of 99mTc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of 99mTc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic

  10. Radioguided sentinel lymph node biopsy in patients with papillary thyroid carcinoma

    PubMed Central

    Carcoforo, Paolo

    2016-01-01

    Background The ATA guidelines do not recommend prophylactic central compartment neck dissection in patients with T1–T2 papillary thyroid carcinoma (PTC) with no clinical evidence of lymph node metastasis, however patients’ staging is recommended. Lymph node metastasis may be present also in small PTC, but preoperative ultrasound identifies suspicious cervical lymphadenopathy in 20–30% of patients. The role of sentinel lymph node biopsy (SLNB) remain open to debate. It has been shown that the identification rate of SLN in PTC patients is improved using a radiotracer compared to a dye technique. The aim of this systematic review was to evaluate the role of radioguided SLNB (rSLNB) in the treatment of PTC patients. Methods A systematic search was performed in the PubMed and Embase database to identify all original articles regarding the application of rSLNB in PTC patients. The primary outcome was false negative rate (FNR) of the rSLNB; the secondary outcomes were SLN intraoperative identification rate (IIR), site of lymph node metastasis, and persistent disease during follow up. Results Twelve studies were included. Most of PTC patients were T1–T2. The overall SLN IIR, SLN metastatic rate, and FNR were 92.1%, 33.6%, and 25.4%, respectively. Overall, lymph node metastasis were found in the central compartment (23.0%) and in the lateral compartments (10.6%). The persistent disease in patients who underwent SLNB associated to lymph node dissection (LND) in the same compartment of the SLN regardless of the SLN status was 0.6%. Conclusions In all PTC patients, also in T1–T2 stage, due to the high FNR the SLNB performed alone should be abandoned and converted into a technique to guide the lymphadenectomy in a specific neck compartment (i.e., central or lateral) based on the radioactivity, regardless of the SLN status, for better lymph node staging and selection of patients for postoperative radioiodine ablation. PMID:28149805

  11. [Colorectal melanoma: review of two distinct forms of presentation].

    PubMed

    Díaz-Sánchez, Antonio; Lara, Miguel Ángel; Ortega, Patricia; Aramendi, Teresa; González, Carmen; Alberdi, José M; Del Valle, Emilio; Casado, Isabel; Campos, Rocío; Aldeguer, Mercedes

    2011-02-01

    Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45.

  12. In vivo photoacoustic and ultrasonic mapping of rat sentinel lymph nodes with a modified commercial ultrasound imaging system

    NASA Astrophysics Data System (ADS)

    Erpelding, Todd N.; Kim, Chulhong; Pramanik, Manojit; Guo, Zijian; Dean, John; Jankovic, Ladislav; Maslov, Konstantin; Wang, Lihong V.

    2010-02-01

    Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients, relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers. While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive detection method for accurate SLN mapping is needed. In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used clinically for accurate, noninvasive SLN mapping.

  13. Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin

    PubMed Central

    Tellier, Franklin; Steibel, Jérôme; Chabrier, Renée; Blé, François Xavier; Tubaldo, Hervé; Rasata, Ravelo; Chambron, Jacques; Duportail, Guy; Simon, Hervé; Rodier, Jean-François; Poulet, Patrick

    2012-01-01

    Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10−4 to 1.7 × 10−2, which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L−1 was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L−1 range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals. PMID:23024922

  14. Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin.

    PubMed

    Tellier, Franklin; Steibel, Jérôme; Chabrier, Renée; Blé, François Xavier; Tubaldo, Hervé; Rasata, Ravelo; Chambron, Jacques; Duportail, Guy; Simon, Hervé; Rodier, Jean-François; Poulet, Patrick

    2012-09-01

    Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10(-4) to 1.7 × 10(-2), which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L(-1) was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L(-1) range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals.

  15. Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping

    PubMed Central

    Schiavone, Maria B.; Zivanovic, Oliver; Zhou, Qin; Leitao, Mario M.; Levine, Douglas A.; Soslow, Robert A.; Alektiar, Kaled M.; Makker, Vicky; Iasonos, Alexia; Abu-Rustum, Nadeem R.

    2016-01-01

    Purpose To evaluate the outcome of patients with uterine carcinosarcoma undergoing sentinel lymph node (SLN) mapping. Methods A prospectively maintained database was reviewed for all women with uterine cancer treated at our institution from 1/1/98–8/31/14. Patients were grouped based on whether they had undergone SLN mapping or routine lymphadenectomy at the time of staging. SLN evaluation was performed according to a standard institutional protocol that incorporates a surgical algorithm and pathologic ultrastaging. Results We identified 136 patients with uterine carcinosarcoma who had undergone lymph node evaluation; 48 had surgical staging with SLN mapping and 88 had routine lymphadenectomy consisting of pelvic and/or paraaortic lymph node dissection. Stage distribution for the SLN group included: stage I, 31(65%); stage II, 1(2%); stage III, 11(23%); stage IV, 5(10%). Stage distribution for the non-SLN group included: stage I, 48(55%); stage II, 4(4%); stage III, 19(22%); stage IV, 17(19%) (p=0.4). Median number of lymph nodes removed was 8 and 20, respectively (p≤0.001). Median number of positive nodes was similar between the groups(p=0.2). Of the 67 patients who had a documented recurrence, 14/20(70%) in the SLN and 34/47(74%) in the non-SLN group demonstrated a distant/multifocal pattern of recurrence. There was no difference in median progression-free survival between the groups (23 vs 23.2 months, respectively; p=0.7). Conclusions Progression-free survival in women with uterine carcinosarcoma undergoing SLN mapping with adjuvant therapy appears similar to that of patients treated prior to the incorporation of the SLN protocol. Additional prospective studies with longer follow-up are necessary to validate these early results. PMID:25994210

  16. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma.

    PubMed Central

    Wang, X; Heller, R; VanVoorhis, N; Cruse, C W; Glass, F; Fenske, N; Berman, C; Leo-Messina, J; Rappaport, D; Wells, K

    1994-01-01

    BACKGROUND. The presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. METHODS. The assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. RESULTS. Eleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene

  17. Evaluation of Breast Sentinel Lymph Node Coverage by Standard Radiation Therapy Fields

    SciTech Connect

    Rabinovitch, Rachel Ballonoff, Ari; Newman, Francis M.S.; Finlayson, Christina

    2008-04-01

    Background: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. Methods and Materials: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria. Results: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. Conclusions: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.

  18. Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer.

    PubMed

    Cserni, G; Boross, G; Maráz, R; Leidenius, M H K; Meretoja, T J; Heikkila, P S; Regitnig, P; Luschin-Ebengreuth, G; Zgajnar, J; Perhavec, A; Gazic, B; Lázár, G; Takács, T; Vörös, A; Audisio, R A

    2012-06-01

    Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.

  19. A dual-modality photoacoustic and ultrasound imaging system for noninvasive sentinel lymph node detection: preliminary clinical results

    NASA Astrophysics Data System (ADS)

    Erpelding, Todd N.; Garcia-Uribe, Alejandro; Krumholz, Arie; Ke, Haixin; Maslov, Konstantin; Appleton, Catherine; Margenthaler, Julie; Wang, Lihong V.

    2014-03-01

    Sentinel lymph node biopsy (SLNB) has emerged as an accurate, less invasive alternative to axillary lymph node dissection, and it has rapidly become the standard of care for patients with clinically node-negative breast cancer. The sentinel lymph node (SLN) hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first (i.e., sentinel) lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasound imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real-time. Our clinical results demonstrate that real-time photoacoustic imaging can provide sensitive and specific detection of methylene blue dye in vivo. While preliminary studies have shown that in vivo detection of SLNs by using co-registered photoacoustic and ultrasound imaging is feasible, further investigation is needed to demonstrate robust SLN detection.

  20. Development of a Macromolecular Dual-Modality MR-Optical Imaging for Sentinel Lymph Node Mapping

    PubMed Central

    Melancon, Marites P.; Wang, Yuetang; Wen, Xiaoxia; Bankson, James A.; Stephens, L. Clifton; Jasser, Samar; Gelovani, Juri G.; Myers, Jeffrey N.; Li, Chun

    2009-01-01

    Objective To evaluate the effectiveness of a dual magnetic resonance-near infrared fluorescence optical imaging agent, poly(L-glutamic acid)-DTPA-Gd-NIR813, for both preoperative and intraoperative visualization and characterization of sentinel lymph nodes (SLN) in mice. Materials and Methods Poly(L-glutamic acid) was conjugated with DTPA-Gd and NIR813 dye to obtain PG-DTPA-Gd-NIR813. To confirm drainage into the SLNs, this agent was injected subcutaneously into the front paw of nude mice followed by isosulfan blue (n = 6). Furthermore, PG-DTPA-Gd-NIR813 was injected subcutaneously at doses of 0.002 mmol Gd/kg (4.8 nmol eq. NIR813) and 0.02 mmol Gd/kg (48 nmol eq. NIR813) (n = 3/dose). To differentiate metastatic from non-metastatic lymph nodes, nude mice bearing human oral squamous cell carcinoma (DM14) were injected intralingually with 0.02 mmol Gd/kg PG-DTPA-Gd-NIR813 (n=3). Pre- and post-contrast images were taken using 4.7T Bruker MRI scanner and Xenogen optical imaging system. The status of lymph nodes resected under the guidance of optical imaging was confirmed by histologic examinations. Results PG-DTPA-Gd-NIR813 co-localized with isosulfan blue, indicating drainage to the SLN. After subcutaneous injection, axiliary and branchial lymph nodes were clearly visualized with both T1-weighted MR and optical imaging within 3 min of contrast injection, even at the lowest dose tested (0.002 mmol Gd/kg). After intralingual injection in tumor-bearing mice, MR imaging identified 4 of the 6 superficial cervical lymph nodes, whereas NIRF optical imaging identified all 6 cervical nodes. The pattern of contrast enhancement of SLN visualized in MR images showed a characteristic ring-shaped appearance with a central filling defect, possibly resulting from nodal infiltration of metastatic lesions. Histopathologic examination of the SLNs resected under NIRF imaging guidance revealed micrometastases in all 6 SLNs identified by NIRF imaging. Conclusion The dual modality imaging

  1. [Analysis of predictive tools for further axillary involvement in patients with sentinel-lymph-node-positive, small (< or =15 mm) invasive breast cancer].

    PubMed

    Cserni, Gábor; Bori, Rita; Sejben, István; Boross, Gábor; Maráz, Róbert; Svébis, Mihály; Rajtár, Mária; Tekle Wolde, Eliza; Ambrózay, Eva

    2009-11-29

    Small breast cancers often require different treatment than larger ones. The frequency and predictability of further nodal involvement was evaluated in patients with positive sentinel lymph nodes and breast cancers < or =15 mm by means of 8 different predictive tools. Of 506 patients with such small tumors 138 with positive sentinel nodes underwent axillary dissection and 39 of these had non-sentinel node involvement too. The Stanford nomogram and the micrometastatic nomogram were the predictive tools identifying a small group of patients with low probability of further axillary involvement that might not require completion axillary lymph node dissection. Our data also suggest that the Tenon score can separate subsets of patients with a low and a higher risk of non-sentinel node metastasis. Predictive tools based on multivariate models can help in omitting completion axillary dissection in patients with low risk of non-sentinel lymph node metastasis based on their small tumor size.

  2. Sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with breast cancer: Are the current false negative rates acceptable?

    PubMed

    Patten, D K; Zacharioudakis, K E; Chauhan, H; Cleator, S J; Hadjiminas, D J

    2015-08-01

    The advent of sentinel lymph node biopsy has revolutionised surgical management of axillary nodal disease in patients with breast cancer. Patients undergoing neo-adjuvant chemotherapy for large breast primary tumours may experience complete pathological response on a previously positive sentinel node whilst not eliminating the tumour from the other lymph nodes. Results from 2 large prospective cohort studies investigating sentinel lymph node biopsy after neo-adjuvant chemotherapy demonstrate a combined false negative rate of 12.6-14.2% and identification rate of 80-89% with the minimal acceptable false negative rate and identification rate being set at 10% and 90%, respectively. A false negative rate of 14% would have been classified as unacceptable when compared to the figures obtained by the pioneers of sentinel lymph node biopsy which was 5% or less.

  3. Is blue dye still required during sentinel lymph node biopsy for breast cancer?

    PubMed Central

    Peek, Mirjam CL; Kovacs, Tibor; Baker, Rose; Hamed, Hisham; Kothari, Ash; Douek, Michael

    2016-01-01

    Background In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. Methods Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. Results A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. Conclusion The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation. PMID:27729939

  4. Local recurrence and assessment of sentinel lymph node biopsy in deep soft tissue leiomyosarcoma of the extremities

    PubMed Central

    2011-01-01

    Background Leiomyosarcoma of deep soft tissues of the extremities is a rare malignant tumour treated primarily by surgery. The incidence of local recurrence and lymph node metastasis is uncertain and it is not known whether a sentinel lymph node biopsy is indicated in these tumours. Methods A retrospective review of patients treated for extremity deep soft tissue leiomyosarcoma at our institution over a 10-year period was conducted. Patients developing local recurrence or lymph node metastasis were identified. The presence or absence of lymphatics in the primary tumours was assessed by immunohistochemical expression of LYVE-1 and podoplanin. Results 27 patients (mean age 62 years) were included in the study. 15 were female and 12 male. Lymph node metastasis was seen in only two cases (7%); intratumoural lymphatics were identified in the primary tumours of both these cases. Local recurrence occurred in 25.9% of cases despite complete excision and post-operative radiotherapy; the mean time to recurrence was 10.1 months. Conclusion On the basis of this study, we do not advocate sentinel lymph node biopsy in this group of patients except in those cases in which intratumoural lymphatics can be demonstrated. Close follow up is important especially for high grade leiomyosarcomas, particularly in the first year, as these tumours have a high incidence of local recurrence. PMID:22612847

  5. The added value of a portable gamma camera for intraoperative detection of sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report.

    PubMed

    Mayoral, M; Paredes, P; Sieira, R; Vidal-Sicart, S; Marti, C; Pons, F

    2014-01-01

    The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity is still subject to debate although some studies have reported its feasibility. The main reason for this debate is probably due to the high false-negative rate for floor-of-mouth tumors per se. We report the case of a 54-year-old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph nodes were identified at right Ib, left IIa and Ia levels. However, these sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe owing to the activity originating from the injection site. The use of a portable gamma camera made it possible to localize and excise all the sentinel lymph nodes. This case demonstrates the usefulness of this tool to improve sentinel lymph node detecting in floor-of-mouth tumors, especially those close to the injection area.

  6. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

    PubMed Central

    Pouw, Joost J; Ahmed, Muneer; Anninga, Bauke; Schuurman, Kimberley; Pinder, Sarah E; Van Hemelrijck, Mieke; Pankhurst, Quentin A; Douek, Michael; ten Haken, Bennie

    2015-01-01

    Introduction Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model. Materials and methods Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter dH =32 nm; Sienna+®, dH =59 nm; and ferumoxide, dH =111 nm), and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo), iron quantification (vibrating sample magnetometry), and histopathological assessments were performed on all ex vivo nodes. Results Transcutaneous “hotspots” were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for the 111 nm tracer, at the same time point. Ex vivo magnetometer counts were significantly greater for the 59 nm tracer than for the other tracers. Significantly more nodes per basin were excised for the 32 nm tracer compared to other tracers, indicating poor retention of the 32 nm tracer. Using the 59 nm tracer resulted in a significantly higher iron accumulation compared to the 32 nm tracer. Conclusion The 59 nm tracer demonstrated rapid lymphatic uptake, retention in the first nodes reached, and accumulation in high concentration, making it the most suitable tracer for intraoperative sentinel lymph node localization. PMID:25709445

  7. Near-Infrared Fluorescence Sentinel Lymph Node Mapping of the Oral Cavity in Head and Neck Cancer Patients

    PubMed Central

    van der Vorst, Joost R.; Schaafsma, Boudewijn E.; Verbeek, Floris P.R.; Keereweer, Stijn; Jansen, Jeroen C.; van der Velden, Lilly-Ann; Langeveld, Antonius; Hutteman, Merlijn; Löwik, Clemens; van de Velde, Cornelis J.H.; Frangioni, John V.; Vahrmeijer, Alexander L.

    2013-01-01

    Objectives Elective neck dissection is frequently performed during surgery in head and neck cancer patients. The sentinel lymph node (SLN) procedure can prevent the morbidity of a neck dissection and improve lymph node staging by fine pathology. Near-infrared (NIR) fluorescence imaging is a promising technique to identify the sentinel lymph node (SLN) intraoperatively. This feasibility study explored the use of indocyanine green adsorbed to human serum albumin (ICG:HSA) for SLN mapping in head and neck cancer patients. Materials and Methods A total of 10 consecutive patients with oral cavity or oropharyngeal cancer and a clinical N0 neck were included. After exposure of the neck, 1.6 mL of ICG:HSA (500 μM) was injected at 4 quadrants around the tumor. During the neck dissection, levels I, II, III and IV were measured for fluorescence using the Mini-FLARE imaging system. Results In all 10 patients, NIR fluorescence imaging enabled visualization of one or more SLNs. A total of 17 SLNs were identified. The mean contrast between the fluorescent signal of the lymph nodes and of the surrounding tissue was 8.7 ± 6.4. In 3 patients, of which 1 was false-negative, lymph node metastases were found. After administration of ICG:HSA, the average number of fluorescent lymph nodes significantly increased over time (P < 0.001). Conclusion This study demonstrated feasibility to detect draining lymph nodes in head and neck cancer patients using NIR fluorescence imaging. However, the fluorescent tracer quickly migrated beyond the SLN to higher tier nodes. PMID:22939692

  8. Impact of immunohistochemistry in sentinel lymph node biopsy in head and neck cancer.

    PubMed

    Chone, Carlos Takahiro; Aniteli, Marcello B; Magalhães, Rodrigo S; Freitas, Leandro L; Altemani, Albina; Ramos, Celso D; Etchebehere, Elba; Crespo, Agricio N

    2013-01-01

    To determine the sensitivity, specificity, negative predictive value (NPV) and accuracy of hematoxylin-eosin (HE) staining compared to immunohistochemistry (IHC) in sentinel lymph node (SLN) histological analyses of head and neck squamous cell carcinoma. The Clinical prospective study was carried out at Tertiary referral university hospital. Patients with oral, lip and oropharyngeal squamous cell carcinoma undergoing elective neck dissection with clinically and radiologically negative necks were included. All patients were submitted to computer tomography scan for the evaluation of lymphatic metastases. The surgical procedure consisted of tumor resection, SLN sampling and elective neck dissection. Negative SLNs via HE were then submitted for IHC analysis of cytokeratin AE1/AE3 and step serial section (SSS). The main outcome measures were the negative predictive value of conventional HE staining techniques in the diagnosis of lymphatic metastases with the SSS/IHC analysis. Of 46 patients undergoing 63 neck procedures, 53 were SLN negative and 10 were positive on HE analysis. Using SSS/IHC analysis of these 53 negative SLNs on HE, two (3.8 %) were found to be positive. For HE, the sensitivity, specificity, NPV and accuracy were 77, 100, 94, and 95 %, respectively. With subsequent analysis with SSS/IHC, these values increased to 92, 100, 98 and 98 %, respectively. SSS/IHC is important in SLN analysis as the false negative rate decreased significantly while increasing the inherent sensitivity of the analyses.

  9. Scanning elastic scattering spectroscopy detects metastatic breast cancer in sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Austwick, Martin R.; Clark, Benjamin; Mosse, Charles A.; Johnson, Kristie; Chicken, D. Wayne; Somasundaram, Santosh K.; Calabro, Katherine W.; Zhu, Ying; Falzon, Mary; Kocjan, Gabrijela; Fearn, Tom; Bown, Stephen G.; Bigio, Irving J.; Keshtgar, Mohammed R. S.

    2010-07-01

    A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20×20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.

  10. Sentinel lymph node biopsy and neoadjuvant chemotherapy in breast cancer patients.

    PubMed

    Benson, John R; Jatoi, Ismail

    2014-03-01

    Patient selection and timing of sentinel lymph node (SLN) in the context of primary chemotherapy continues to evolve; there is some evidence that primary chemotherapy may modify lymphatic drainage patterns and cause differential downstaging between SLNs and non-SLNs. SLN biopsy undertaken prior to chemotherapy will minimize the risk of a false-negative result, may allow more accurate initial staging and provides important information on prognostication which can guide decisions about adjuvant radiotherapy. However, quantification of regional metastatic load is incomplete and some advocate SLN biopsy after primary chemotherapy to take advantage of nodal downstaging and avoidance of axillary dissection in up to 40% of patients. Initial reports on false-negative rates for SLN biopsy after primary chemotherapy in patients who had proven axillary node metastases at presentation based on needle core biopsy were relatively high and a cause for clinical concern. However, more recent data suggest that SLN biopsy is as accurate when performed post- as pre-neochemotherapy and current practice incorporates both approaches.

  11. Cutaneous melanomas of the eyelid.

    PubMed

    Boulos, Patrick R; Rubin, Peter A D

    2006-01-01

    Cutaneous eyelid melanomas are very rare lesions. The lentiginous subtypes are the most frequent melanocytic lesions of the eyelid and can be likened to conjunctival melanocytic lesions like PAM, PAM with atypia and conjunctival melanoma. Compared to melanomas elsewhere on the body, eyelid melanomas have special considerations. Eyelid skin is very thin, the mucocutaneous junction at the lid margin can affect prognosis, the lymphatic drainage pattern is very variable and there is an inherent difficulty to excise wide margins without sacrificing important structures. A customized excision approach, using tissue-sparing "Slow-Mohs" technique, is suggested. Sentinel lymph node dissection has an evolving therapeutic role but remains controversial.

  12. Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience

    PubMed Central

    Verbeek, Floris P.R.; Troyan, Susan L.; Mieog, J. Sven D.; Liefers, Gerrit-Jan; Moffitt, Lorissa A.; Rosenberg, Mireille; Hirshfield-Bartek, Judith; Gioux, Sylvain; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.; Frangioni, John V.

    2014-01-01

    NIR fluorescence imaging using indocyanine green (ICG) has the potential to improve the SLN procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 ml of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of near-infrared (NIR) fluorescence for sentinel lymph node (SLN) mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using 99Technetium-colloid in all subjects and patent blue in 27 (28%) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99%) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean = 1.9, range = 1–5) were resected: 100% NIR fluorescent, 88% radioactive, and 78% (of 40 nodes) blue. In 2 of 95 subjects (2.1%), SLNs containing macrometastases were found only by NIR fluorescence, and in 1 patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies. PMID:24337507

  13. Surgical sentinel lymph node biopsy in early breast cancer. Could it be avoided by performing a preoperative staging procedure? A pilot study

    PubMed Central

    Testori, Alberto; Meroni, Stefano; Moscovici, Oana Codrina; Magnoni, Paola; Malerba, Paolo; Chiti, Arturo; Rahal, Daoud; Travaglini, Roberto; Cariboni, Umberto; Alloisio, Marco; Orefice, Sergio

    2012-01-01

    Summary Background The aim of this pilot trial was to study the feasibility of sentinel node percutaneous preoperative gamma probe-guided biopsy as a valid preoperative method of assessment of nodal status compared to surgical sentinel lymph node biopsy. Material/Methods This prospective study enrolled 10 consecutive patients without evidence of axillary lymph node metastases at preoperative imaging. All patients underwent sentinel node occult lesion localization (SNOLL) using radiotracer intradermic injection that detected a “hot spot” corresponding to the sentinel node in all cases. Gamma probe over the skin detection with subsequent ultrasonographically guided needle biopsy of the sentinel node were performed. The percutaneous needle core histopathological diagnosis was compared to the results of the surgical biopsy. Results Preoperative sentinel node identification was successful in all patients. Conclusions The combination of preoperative gamma probe sentinel node detection and ultrasound-guided biopsy could represent a valid alternative to intraoperative sentinel node biopsy in clinically and ultrasonographically negative axillary nodes, resulting in shorter duration of surgery and lower intraoperative risks. PMID:22936189

  14. A dual-reporter fluorescent imaging approach can be used to estimate sentinel lymph node tumor burden

    NASA Astrophysics Data System (ADS)

    Tichauer, Kenneth M.; Samkoe, Kimberley S.; Gunn, Jason R.; Govindan, Ramesh; Viswanathan, Aravind; Hoopes, P. Jack; Hasan, Tayyaba; Kaufman, Peter A.; Pogue, Brian W.

    2013-03-01

    The presence of metastatic tumor cells in tumor-draining lymph nodes is an important indicator for cancer staging and therapy. Current clinical approaches of assessing lymph node tumor burden require invasive surgery that can be associated with nerve damage and other complications. In this study, a dual-reporter fluorescence molecular imaging approach, previously validated for quantifying targeted reporter binding in various human tumor xenographs, was assessed as a means of quantifying tumor burden in metastatic disease in mice. The utility of the dual-reporter imaging approach to measure tumor burden in sentinel lymph nodes was investigated in a bioluminescent human breast cancer xenograph model in 18 female nude mice. Once the presence of tumor in the lymph node was confirmed by bioluminescent imaging, fluorescently labeled anti-EGFR antibody and an untargeted antibody (labeled with a different fluorophore) were injected intradermally, proximal to the lymph node, and the uptake of the two reporters was imaged simultaneously with a with a flat-panel fluorescent scanner. Preliminary results demonstrated a statistically significant correlation between the dual-reporter measured tumor burden and the bioluminescent measure of tumor burden.

  15. Showcase of Intraoperative 3D Imaging of the Sentinel Lymph Node in a Breast Cancer Patient using the New Freehand SPECT Technology.

    PubMed

    Schnelzer, Andreas; Ehlerding, Alexandra; Blümel, Christina; Okur, Asli; Scheidhauer, Klemens; Paepke, Stefan; Kiechle, Marion

    2012-12-01

    After the development of a hand-held intraoperative device for 3D real-time imaging of radioactively labeled sentinel lymph nodes in the human body, we present our first experience with the newest version of the freehand single-photon emission computed tomography (SPECT) technology in the operating room. The freehand SPECT system combines a gamma probe and an optical infrared positioning system, and provides surgeons with 3D imaging including exact depth information of the radioactive target. This technology was used intraoperatively in a female breast cancer patient to localize the axillary sentinel lymph nodes. The data obtained with freehand SPECT correlate well with conventional lymphoscintigraphy and with data collected using a conventional hand-held probe. By offering fast real-time intraoperative imaging, the new freehand SPECT system might facilitate the detection and removal of the sentinel lymph node(s) in certain situations and can be used for documentation and quality assurance purposes.

  16. TOPICAL REVIEW (Non-targeted) radioactive/fluorescent nanoparticles and their potential in combined pre- and intraoperative imaging during sentinel lymph node resection

    NASA Astrophysics Data System (ADS)

    Buckle, Tessa; Chin, Patrick T. K.; van Leeuwen, Fijs W. B.

    2010-12-01

    One clinical precedent for the use of nanosized imaging agents is the localization of the tumor draining sentinel lymph nodes. In this application, radiocolloids such as 99mTc-NanoColl are currently used to plan the surgical procedure and to provide acoustic guidance during the intervention. Additional injections of dyes are common to provide optical surgical guidance. Bimodal imaging agents, which are both radioactive and fluorescent, have the potential to be used for both surgical planning and intraoperative fluorescence guidance towards the sentinel lymph nodes. This review provides an overview of the radioactive, fluorescent, and size properties of (non-targeted) bimodal nanoparticles, and their (potential) value in sentinel lymph node detection.

  17. Current clinical overview of cutaneous melanoma.

    PubMed

    Lens, Marko

    This article reviews current evidence on epidemiology, diagnosis and management of cutaneous melanoma. Incidence of cutaneous melanoma is rising in all Caucasian populations across the world; thus, melanoma represents a significant public health burden. Although, incidence of melanoma is in continuous increase, a decrease of mortality and improved survival has been observed in most western European populations. Clinical characteristics of four major types of melanoma (superficial spreading, nodular, lentigo maligna melanoma and acral lentiginous melanoma) have been described. Surgical removal of melanoma remains the standard care in all primary melanomas. Current evidence suggests use of 1 to 2 cm excision margins. Wider margins may be necessary in patients with thicker melanomas with higher risk for local recurrence. In the treatment of regional lymph nodes elective lymphadenectomy has been surpassed by the sentinel lymph node biopsy (SLNB). However, although prognostic value of SLNB has been confirmed, its therapeutical benefit still needs to be evaluated. Currently there is no standard adjuvant therapy for melanoma although interferon-alpha has been the most widely used treatment in the adjuvant setting. The role of metastasectomy (removal of distant metastases) is still controversial. Chemotherapeutic agents have a limited activity in patients with metastatic melanoma with response rates up to 25%. Although different vaccines have been tested in melanoma patients their role still remain to be established in phase III trials. Progresses in molecular biology and genetics of melanoma may lead to the development of novel melanoma therapies.

  18. Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

    NASA Astrophysics Data System (ADS)

    Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

    2015-03-01

    Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

  19. Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience.

    PubMed

    Verbeek, Floris P R; Troyan, Susan L; Mieog, J Sven D; Liefers, Gerrit-Jan; Moffitt, Lorissa A; Rosenberg, Mireille; Hirshfield-Bartek, Judith; Gioux, Sylvain; van de Velde, Cornelis J H; Vahrmeijer, Alexander L; Frangioni, John V

    2014-01-01

    Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the sentinel lymph node (SLN) procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 mL of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of NIR fluorescence for SLN mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using (99)Technetium-colloid in all subjects and patent blue in 27 (28 %) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99 %) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean 1.9, range 1-5) were resected: 100 % NIR fluorescent, 88 % radioactive, and 78 % (of 40 nodes) blue. In 2 of 95 subjects (2.1 %), SLNs-containing macrometastases were found only by NIR fluorescence, and in one patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies.

  20. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    NASA Astrophysics Data System (ADS)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  1. Predicting non-sentinel lymph node status after positive sentinel biopsy in breast cancer: what model performs the best in a Czech population?

    PubMed

    Coufal, Oldrich; Pavlík, Tomás; Fabian, Pavel; Bori, Rita; Boross, Gábor; Sejben, István; Maráz, Róbert; Koca, Jaroslav; Krejcí, Eva; Horáková, Iva; Foltinová, Vendula; Vrtelová, Pavlína; Chrenko, Vojtech; Eliza Tekle, Wolde; Rajtár, Mária; Svébis, Mihály; Fait, Vuk; Cserni, Gábor

    2009-12-01

    Several models have previously been proposed to predict the probability of non-sentinel lymph node (NSLN) metastases after a positive sentinel lymph node (SLN) biopsy in breast cancer. The aim of this study was to assess the accuracy of two previously published nomograms (MSKCC, Stanford) and to develop an alternative model with the best predictive accuracy in a Czech population. In the basic population of 330 SLN-positive patients from the Czech Republic, the accuracy of the MSKCC and the Stanford nomograms was tested by the area under the receiver operating characteristics curve (AUC). A new model (MOU nomogram) was proposed according to the results of multivariate analysis of relevant clinicopathologic variables. The new model was validated in an independent test population from Hungary (383 patients). In the basic population, six of 27 patients with isolated tumor cells (ITC) in the SLN harbored additional NSLN metastases. The AUCs of the MSKCC and Stanford nomograms were 0.68 and 0.66, respectively; for the MOU nomogram it reached 0.76. In the test population, the AUC of the MOU nomogram was similar to that of the basic population (0.74). The presence of only ITC in SLN does not preclude further nodal involvement. Additional variables are beneficial when considering the probability of NSLN metastases. In the basic population, the previously published nomograms (MSKCC and Stanford) showed only limited accuracy. The developed MOU nomogram proved more suitable for the basic population, such as for another independent population from a mid-European country.

  2. Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin.

    PubMed Central

    Nip, J; Shibata, H; Loskutoff, D J; Cheresh, D A; Brodt, P

    1992-01-01

    Human melanoma is a highly metastatic cancer and the regional lymph nodes are generally the first site of metastasis. Adhesion to cryostat sections of human lymph nodes was therefore studied using two human melanoma models established from lymph node metastases, namely, MeWo cell lines of diverse metastatic potentials and a highly metastatic cell line of recent origin designated MIM/8. We found a good correlation between the metastatic potentials of the melanoma cells as measured in nude mice and their ability to adhere to cryostat sections of human lymph nodes. When adhesion to immobilized extracellular matrix proteins was measured, a significant increase in adhesion, which correlated with increased metastasis, was seen mainly on vitronectin and to a lesser extent on fibronectin. The adhesion to vitronectin and to the frozen sections were specifically blocked by an RGD-containing peptide, mAb 661 to vitronectin and mAb LM609 to integrin alpha v beta 3. FACS analysis revealed a significant and specific increase in cell surface expression of alpha v beta 3 on the metastatic cells as compared to the parent line. Together these results suggest that the adhesion of melanoma cells to lymph node vitronectin via the alpha v beta 3 receptor plays a role in the process of lymphatic dissemination. Images PMID:1383272

  3. Long-term multimodal imaging of tumor draining sentinel lymph nodes using mesoporous silica-based nanoprobes.

    PubMed

    Huang, Xinglu; Zhang, Fan; Lee, Seulki; Swierczewska, Magdalena; Kiesewetter, Dale O; Lang, Lixin; Zhang, Guofeng; Zhu, Lei; Gao, Haokao; Choi, Hak Soo; Niu, Gang; Chen, Xiaoyuan

    2012-06-01

    The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we report the development and application of mesoporous silica-based triple-modal nanoprobes that integrate multiple functional moieties to facilitate near-infrared optical, magnetic resonance (MR) and positron emission tomography (PET) imaging. After embedding near-infrared dye ZW800, the nanoprobe was labeled with T(1) contrast agent Gd(3+) and radionuclide (64)Cu through chelating reactions. High stability and long intracellular retention time of the nanoprobes was confirmed by in vitro characterization, which facilitate long-term in vivo imaging. Longitudinal multimodal imaging was subsequently achieved to visualize tumor draining SLNs up to 3 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate, amount of particles, and contrast between metastatic and contra-lateral sentinel lymph nodes were observed. These findings provide very helpful guidance for the design of robust multifunctional nanomaterials in SLNs' mapping and tumor metastasis diagnosis.

  4. Saccharide substituted zinc phthalocyanines: optical properties, interaction with bovine serum albumin and near infrared fluorescence imaging for sentinel lymph nodes.

    PubMed

    Lu, Li; Lv, Feng; Cao, Bo; He, Xujun; Liu, Tianjun

    2014-01-03

    Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(β-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed using nude mice as models. Results show that saccharide- substituted zinc phthalocyanines have favourable water solubility, good optical stability and high emission ability in the near infrared region. The interaction of lactose-substituted phthalocyanine with bovine serum albumin displays obvious differences to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in vivo.

  5. γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206)

    PubMed Central

    Azad, Abul K.; Rajaram, Murugesan V. S.; Metz, Wendy L.; Cope, Frederick O.; Blue, Michael S.; Vera, David R.

    2015-01-01

    γ-Tilmanocept (99mTc-labeled-tilmanocept or [99mTc]-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used that have high expression of the C-type lectin mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by small interfering RNA treatment and was increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR+ cells (macrophages and/or dendritic cells) in human sentinel lymph node tissues. Together these data provide strong evidence that CD206 is a major binding receptor for γ-tilmanocept. Identification of CD206 as the γ-tilmanocept–binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases. PMID:26202986

  6. Detection of sentinel lymph node in breast cancer recurrence may change adjuvant treatment decision in patients with breast cancer recurrence and previous axillary surgery.

    PubMed

    Cordoba, Octavi; Perez-Ceresuela, Francesc; Espinosa-Bravo, Martin; Cortadellas, Tomas; Esgueva, Antonio; Rodriguez-Revuelto, Robert; Peg, Vicente; Reyes, Victoria; Xercavins, Jordi; Rubio, Isabel T

    2014-08-01

    Use of sentinel lymph node dissection in patients with ipsilateral breast cancer recurrence is still controversial. The objective of this study is to evaluate the feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and whether the positivity had impact in the adjuvant treatment. Between 2008 and 2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We included 53 patients in a prospective study. Forty-three patients (81%) had a previous axillary lymph node dissection (ALND) and ten (19%) had a previous sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR. Adjuvant systemic treatment was given to all the patients with a positive SLNBR and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph node biopsy in breast tumor recurrence is feasible and significant differences were found in the use of radiation therapy in patients with a positive SLNBR.

  7. Spotlight on talimogene laherparepvec for the treatment of melanoma lesions in the skin and lymph nodes

    PubMed Central

    Orloff, Marlana

    2016-01-01

    On October 27, 2015, talimogene laherparepvec (T-VEC), a first in class intralesional oncolytic virotherapy, was granted the US Food and Drug Administration approval for the treatment of melanoma in the skin and lymph nodes. Its approval has added yet another therapeutic option to the growing list of effective therapies for melanoma. Though the Phase III OPTiM trial has demonstrated its efficacy as a single agent, the target patient population remains narrow. With numerous effective and tolerable treatments available for unresectable and metastatic melanoma, intralesional therapies such as T-VEC are still finding their niche. T-VEC is now widely accepted as option for treatment; however, its combination with various other agents in an effort to expand its use and synergize with other interventions is still being explored. This article will review the pre-clinical and clinical work that eventually led to the Food and Drug Administration approval of this first-in-class agent, as well as address concerns about clinical application and ongoing research. PMID:27785448

  8. Sentinel Lymph Node Dissection With and Without Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis: A Randomized Clinical Trial

    PubMed Central

    Giuliano, Armando E.; Hunt, Kelly K.; Ballman, Karla. V.; Beitsch, Peter D.; Whitworth, Pat W.; Blumencranz, Peter W.; Leitch, A. Marilyn; Saha, Sukamal; McCall, Linda M.; Morrow, Monica

    2017-01-01

    Context Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer. Objective To determine the impact of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer. Design and Setting The 115 sites participating in the American College of Surgeons Oncology Group Z0011 trial enrolled patients from May 1999 to December 2004. In this phase III noninferiority trial, patients with SLN metastasis were randomized to ALND or no further axillary treatment. Targeted enrollment was 1900 women, with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected. Patients Women with clinical T1–T2 invasive breast cancer, no palpable adenopathy, and 1–2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin and eosin staining on permanent section. Interventions All patients underwent lumpectomy and tangential whole-breast irradiation. Those randomized to ALND underwent dissection of ≥10 nodes. Systemic therapy was at the discretion of the treating physician. Main Outcome Measures Overall survival (OS) was the primary endpoint, with a noninferiority margin of a one-sided hazard ratio of 1.3 or less favoring ALND. Disease-free survival (DFS) was a secondary endpoint. Results Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up date 03/04/2010), 5-year OS was 91.8% (95% CI: 89.1 to 94.5) with ALND and 92.5% (95% CI: 90.0 to 95.1) with SLND alone; 5-year DFS was 82.2% (95% CI: 78.3 to 86.3) with ALND and 83.9% (95% CI: 80.2 to 87.9) with SLND alone. Hazard ratio for treatment-related OS was 0.79 (90% CI: 0.56 to 1.11) without adjustment and 0.87 (90% CI: 0.62 to 1.23) after adjusting for

  9. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Sinilkin, I.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Doroshenko, A.; Varlamova, N.; Skuridin, V.

    2016-08-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive 99mTc-Al2O3, and Group II patients (n = 30) received 99mTc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after 99mTc-Al2O3 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. The new radiopharmaceutical based on the 99mTc-Al2O3 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of 99mTc-Al2O3 were 100% for both SPECT and intraoperative gamma probe identification.

  10. Assessment of Risk Reduction for Lymphedema Following Sentinel Lymph Noded Guided Surgery for Primary Breast Cancer

    DTIC Science & Technology

    2006-10-01

    study uses SPECT scanning to localize lymphatics critical for arm drainage after surgical removal of axillary lymph nodes. The study has established...allows precise quantification of radiation dosimetry delivered to lymph nodes critical for arm drainage . The study will test the hypothesis that...Conduct a prospective cohort study to estimate the risk of lymphedema associated with radiation dosimetry to lymph node critical for arm drainage . (Months

  11. Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors

    PubMed Central

    Luke, Geoffrey P.; Myers, Jeffrey N.; Emelianov, Stanislav Y.; Sokolov, Konstantin V.

    2014-01-01

    Metastases rather than primary tumors are responsible for killing most cancer patients. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure - sentinel lymph node biopsy - is generally employed to identify metastatic cancer cells. Here we introduce a new approach for more sensitive in vivo detection of lymph node micrometastases, based on the use of ultrasound-guided spectroscopic photoacoustic (sPA) imaging of molecularly-activated plasmonic nanosensors (MAPS). Using a metastatic murine model of oral squamous cell carcinoma, we showed that MAPS targeted to the EGFR shifted their optical absorption spectrum to the red-near-infrared region after specific interactions with nodal metastatic cells, enabling their non-invasive detection by sPA. Notably, LN metastases as small as 50 μm were detected at centimeter-depth range with high sensitivity and specificity. Large sPA signals appeared in metastatic LN within 30 minutes of MAPS injection, in support of the clinical utility of this method. Our findings offer a rapid and effective tool to non-invasively identify micrometastases as an alternate to sentinal node biopsy analysis. PMID:25106426

  12. The Study of 99mTc-Aluminum Oxide Using for Sentinel Lymph Nodes Detection in Experiment

    NASA Astrophysics Data System (ADS)

    Medvedeva, A. A.; Sinilkin, I. G.; Zelchan, R. V.; Chernov, V. I.; Lyapunov, A. Yu.; Bragina, O. D.; Varlamova, N. V.; Skuridin, V. S.; Dergilev, A. P.

    2016-06-01

    The purpose of the study was a comparative research of the possibility of using the radiopharmaceuticals 99mTc-Al2O3 and 99mTc-Nanocis for visualizing sentinel lymph nodes in the experiment. Measurement of the sizes of 99mTc-Al2O3 and 99mTc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. Pharmacokinetics of 99mTc-Al2O3 and 99mTc-Nanocis was researched on 50 white male rats. The possibility of the use of 99mTc-Al2O3 and 99mTc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. Average dynamic diameter of the sol particle was 52-77 nm for 99mTc-Al2O3 and 16.7-24.5 nm for 99mTc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node - at 1 hour after administration the average uptake of 99mTc-Al2O3 was 8.6% in it and the accumulation of 99mTc-Nanocis was significantly lower - 1,8% (p <0,05). In all study point average uptake of 99mTc-Al2O3 in the lymph node was significantly higher 99mTc-Nanocis accumulation. The results dynamic scintigraphic studies in rats showed that 99mTc-Al2O3 and 99mTc-Nanocis actively accumulated into the lymphatic system. By using 99mTc-Al2O3 inguinal lymph node was determined in 5 minutes after injection and clearly visualize in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the 99mTc-Al2O3 accumulation reaches a plateau in a lymph node (average 10.5%) for 2 hour study and then its accumulation remains practically at the same level, slightly increasing to 12% at 24 hours. In the case of 99mTc-Nanocis inguinal lymph node visualized in all animals for 15 minutes when it was accumulated on the average 1.03% of the administered dose. Plateau of 99mTc-Nanocis accumulation in the lymph node (average 2.05%) occurred at 2 hour of the study and remained almost on the same level (in average 2.3%) to 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed

  13. Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study

    PubMed Central

    Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

    2016-01-01

    Purpose We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. Methods 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. Results The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. Conclusion 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings. PMID:27246977

  14. Sentinel lymph node biopsy using indigo carmine blue dye and the validity of '10% rule' and '4 nodes rule'.

    PubMed

    Nagao, Tomoya; Kinoshita, Takayuki; Hojo, Takashi; Kurihara, Hiroaki; Tsuda, Hitoshi

    2012-08-01

    This is the study which assessed sentinel lymph node biopsy (SNB) using indigo carmine blue dye and the validity of the '10% rule' and '4 nodes rule'. Patients (302) were performed SNB using the combined radioisotope (RI)/indigo carmine dye method. Excised SLNs were confirmed whether they were stained and numbered in order of RI count and the percentage of radioactivity as compared to the hottest node was calculated. The relationship between histological diagnosis, dyeing and RI count was assessed. All the patients were detected SLN. Positive nodes were identified in 84 (27.8%) patients and were identified up to the third degree of hottest. All the hottest positive nodes were stained by indigo carmine. From the results, removing the three most radioactive SLNs identified all cases of nodal metastasis without complications. These stopping rules were valid and useful under indigo carmine use too.

  15. Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy.

    PubMed

    Larson, Kelly J; Wittwer, Erica D; Nicholson, Wayne T; Weingarten, Toby N; Price, Daniel L; Sprung, Juraj

    2015-05-01

    Serotonin released in the nerve synapses is cleared through reuptake into presynaptic neurons and metabolism with monoamine oxidase (MAO). Therapy with selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors increases serotonin concentration in the synaptic cleft and may result in serotonin syndrome (SS). Our patient undergoing sentinel lymph node biopsy was on fluoxetine (SSRI) and intraoperatively developed SS after receiving fentanyl (200 μg) and methylene blue (MAO inhibitor), 7 mg subcutaneously into the scalp. Initial presentation was several episodes of generalized muscle activity, which was later diagnosed as lower extremity myoclonus consistent with SS. Upon awakening, the patient showed no evidence of encephalopathy, and the clonus was less intense. The patient was discharge home the next day. Our case suggests the possibility that even a small dose of methylene blue, when administered simultaneously with other serotoninergic medications, may be associated with serotonin toxicity.

  16. Sentinel lymph node biopsy in T1/T2 squamous cell carcinomas of the tongue: A prospective study.

    PubMed

    Sagheb, Keyvan; Sagheb, Kawe; Rahimi-Nedjat, Roman; Taylor, Kathy; Al-Nawas, Bilal; Walter, Christian

    2016-01-01

    Commonly used staging procedures often cannot predict the absence of cervical metastases (CM) in squamous cell carcinomas (SCCs) of the oral cavity. Due to the high incidence of occult CM in numerous N0 cases in the clinic, an elective neck dissection (ND) is performed. The sentinel lymph node biopsy (SNB) is a common concept in the modern surgical therapy of malignancies. The present study evaluates the applicability of this concept for T1/T2-SCC of the tongue. In a prospective clinical study, 10 consecutive patients with T1/T2-SCC of the tongue and cN0 necks, were enrolled. Following sentinel lymph node (SLN) scintigraphy, all patients underwent SNB with a γ-probe and a subsequent ND. SNB specimens were compared with histopathological assessments of surgical specimens from the ND. A total of 5 female and 5 male patients (mean age, 52 years; women, 62 years; men, 42 years), with a median follow-up time of 33.5 months (range, 10-40 months), were treated. All patients presented with detectable SLNs. In 7 cases, the SLN(s) and the residual ND were negative for CM. In 3 cases, the SLN(s) were positive without further CM in the other neck nodes. Furthermore, 1 patient showed additional CMs after 10 months in the contralateral neck and lung metastasis after 18 months, but none at the time of the initial treatment. The concept of an SNB appears to be applicable to the management of the cN0 neck in small SCC of the tongue. The role of SNB in the management of SCC requires further investigation by prospective trials with larger patient numbers.

  17. Is Sentinel Lymph Node Dissection Necessary in All Patients with Ductal Carcinoma In Situ Undergoing Total Mastectomy?

    PubMed

    Bonev, Valentina; De Paz Villanueva, Carlos Chavez; Solomon, Naveenraj; Senthil, Maheswari; Reeves, Mark E; Garberoglio, Carlos; Lum, Sharon S

    2016-10-01

    When ductal carcinoma in situ (DCIS) is found on core needle biopsy, rates of upgrade to invasive cancer of 25 per cent and nodal positivity of 10 per cent have been reported. Sentinel lymph node dissection (SLND) is recommended when mastectomy is performed for DCIS. We investigated the role of SLND in DCIS patients undergoing partial and total mastectomy (TM). During the study period 2004 to 2013, 170 patients with DCIS were identified with a median age of 60 years (range 26-84 years). Of these, 58.2 per cent had partial mastectomy (PM) alone, 10.6 per cent had PM with SLND, and 31.1 per cent had TM with or without contralateral prophylactic mastectomy with SLND. Overall, SLND identified positive nodes in 4.2 per cent of patients. Upgrade to invasive carcinoma on final breast pathology was found in 8.2 per cent of patients overall, including 4.0 per cent of patients undergoing PM alone, 22.2 per cent undergoing PM with SLND, and 11.3 per cent for TM with SLND (P = 0.8). In this study, patients diagnosed with DCIS on core needle biopsy had lower than expected rates of positive sentinel nodes and upgrade to invasive carcinoma. Surgeons and patients should revisit the necessity of SLND in DCIS patients undergoing mastectomy, which could lead to decreased health expenditure, resources, time, morbidity, and emotional impact on patients.

  18. In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

    PubMed

    Dar, Ume-Kalsoom; Khan, Irfanullah; Javed, Muhammad; Ali, Muhammad; Hyder, Syed Waqar; Murad, Sohail; Anwar, Jamil

    2013-03-01

    In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

  19. Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

    PubMed Central

    Shida, Atsuo; Mitsumori, Norio; Nimura, Hiroshi; Takano, Yuta; Iwasaki, Taizou; Fujisaki, Muneharu; Takahashi, Naoto; Yanaga, Katsuhiko

    2016-01-01

    Accurate prediction of lymph node (LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer (EGC). However, consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search, we identified several independent variables associated with LN metastasis in EGC, which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand, even if we use these promising parameters, we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN (SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review, we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition, we evaluated the history of sentinel node navigation surgery and the usefulness for EGC. PMID:27672266

  20. Lymphatic drainage of skin to a sentinel lymph node in a feline model.

    PubMed Central

    Wong, J H; Cagle, L A; Morton, D L

    1991-01-01

    To determine the feasibility of selective lymphadenectomy, the authors developed a feline model to identify and determine the utility of mapping dyes for this purpose. Adult cats were injected intradermally with a variety of mapping substances to determine whether the anatomic site of injection had a predictable pattern of drainage to a particular lymph node. Isosulfan blue provided the optimal mapping material. Injection of isosulfan blue intradermally into the skin of the medial thigh consistently led to coloration of the central lymph node, whereas intradermal abdominal wall injections and intradermal lateral thigh injections resulted in coloration of the lateral lymph node. Intradermal injections into skin about the perineum resulted in coloration of the most medial lymph node only. The feline model proved to a useful model to examine the utility of mapping dyes and to demonstrate dermal lymphatics. The predictable pattern of drainage of the skin in this feline model supports the feasibility of selective lymphadenectomy. Images Fig. 1. Fig. 2. PMID:1953118

  1. Axillary Irradiation as an Imperative Alternative to Axillary Dissection in Clinically Lymph Node-Negative but Sentinel Node-Positive Breast Cancer Patients?

    PubMed

    Nitsche, Mirko; Hermann, Robert

    2011-10-01

    At the moment, positive sentinel lymph node dissection (SLND) of the axilla is followed by axillary lymph node dissection (ALND) as standard of care. Recent data proves that omitting ALND after positive SLND in clinically lymph node-negative early stage breast cancer patients is feasible with low recurrence rates. The well known effect of radiotherapy to destroy occult tumor cells highly contributes to these results as a large extent of level I and II lymph nodes are unavoidably included in standard tangential radiation treatment fields. Reviewing the up to date published data on axillary lymph node treatment with radiotherapy, we hypothesize that full dosage coverage of level I and II of the axilla in early stage breast cancer will improve outcome and should be further evaluated.

  2. Is Sentinel Lymph Node Biopsy Necessary in Patients Undergoing Prophylactic Mastectomy? A Systematic Review and Meta-Analysis.

    PubMed

    Nagaraja, Vinayak; Edirimanne, Senarath; Eslick, Guy D

    2016-01-01

    The gain by performing sentinel lymph node biopsy (SLNB) during prophylactic mastectomy (PM) is debatable, and we performed a meta-analysis of existing literature to evaluate that the role of SLNB in subjects undergoing PM. A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. The search identified 11 relevant articles reporting on patients who underwent SLNB at the time of PM. Data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). We included 14 studies comprising of 2,708 prophylactic mastectomies. Among 2,708 prophylactic mastectomies, the frequency of occult invasive cancer (51 cases) was 1.8% and the rate of positive SLNs (33 cases) was 1.2%. In 25 invasive cancers at the time of PM were found to have negative SLNs which avoided axillary lymph node dissection (ALND). In seven cases with positive SLNBs were found not to have invasive cancer at the time of PM and needed a subsequent ALND. Most of the patients with positive SLNs had locally advanced disease in the contralateral breast. SLNB may be suitable for patients with ipsilateral, locally advanced breast cancer and is not recommend for all patients undergoing PM.

  3. Mucosal melanoma: an update.

    PubMed

    Ballester Sánchez, R; de Unamuno Bustos, B; Navarro Mira, M; Botella Estrada, R

    2015-03-01

    Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma.

  4. Diagnostic Efficacy of Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Meta-Analysis of 66 Studies

    PubMed Central

    Yang, Xihong

    2017-01-01

    Objectives The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC. Methods A systematic literature search for relevant literature published up to September 11, 2016 was conducted in PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials, and the reference lists of eligible studies were examined. Data from different studies were pooled to estimate the summary sentinel lymph node(SLN) identification rate, sensitivity, negative predictive value. Summary receiver operator characteristic curve(SROC) was plotted and area under the SROC curve (AUC) was calculated to evaluate the overall diagnostic efficacy. Threshold effect was assessed with use of the spearman correlation coefficient. Between-study heterogeneity was tested using the Q tests and the I2 statistics. Subgroup analyses were conducted in view of the greater effect of different study characteristics on diagnostic efficacy of SLN. Deeks’ funnel plot asymmetry test was performed to evaluate publication bias. Sensitivity analysis was evaluated through omitting studies one by one and comparing the pooled results of random-effects model and fixed-effects model. All analyses were performed using Review Manager (version 5.3.5), Meta-DiSc (version 1.4), Comprehensive Meta Analysis (version 2.0) and STATA (version 12). Results 66 studies comprising 3566 patients with cT1-2N0 OSCC were included in this meta-analysis. The pooled SLN identification rate was 96.3%(95% CI: 95.3%-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85–0.89), pooled negative predictive value was 0.94 (95% CI: 0.93–0.95), and AUC was 0.98 (95% CI: 0.97–0.99). Subgroup analyses indicated that SLN assessment with immunohistochemistry(IHC) achieved a significantly higher sensitivity than without IHC. Conclusions This meta-analysis suggests that

  5. Deep venous thromboembolism in patients undergoing inguinal lymph node dissection for melanoma

    SciTech Connect

    Arbeit, J.M.; Lowry, S.F.; Line, B.R.; Jones, D.C.; Brennan, M.F.

    1981-01-01

    Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p less than 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p less than 0.05).

  6. Deep venous thromboembolism in patients undergoing inguinal lymph node dissection for melanoma

    SciTech Connect

    Arbeit, J.M.; Lowry, S.F.; Line, B.R.

    1981-11-01

    Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p < 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p < 0.05).

  7. Intraoperative diagnosis of sentinel lymph node metastases in breast cancer treatment with one-step nucleic acid amplification assay (OSNA)

    PubMed Central

    Szychta, Paweł; Westfal, Bogusław; Maciejczyk, Rafał; Smolarz, Beata; Romanowicz, Hanna; Krawczyk, Tomasz

    2016-01-01

    Introduction The aim of the study was to evaluate the clinical usefulness of a one-step nucleic acid amplification assay (OSNA) for intraoperative detection of metastases to sentinel lymph nodes (SLNs) in comparison to examination of frozen sections, and to summarize the results of previous studies. Material and methods We enrolled 98 patients aged 58.13 ±10.74 years treated surgically for breast cancer, and 99 biopsies of SLNs were followed by analysis of 105 SLNs. The central 1 mm slice of SLN was used for examination of frozen sections, whereas 2 outer slices of SLNs were analyzed intraoperatively with OSNA. Detection of isolated tumor cells (ITC), micrometastases or macrometastases with OSNA extended surgery to axillary lymph node dissection. Congruency of results was assessed between OSNA and examination of frozen sections. Results One-step nucleic acid amplification assay detected metastases in 29/105 SLNs in surgery of 27/99 breasts, including ITC in 3/29 SLNs, micrometastases in 12/29 and macrometastases in 14/29. One-step nucleic acid amplification assay detected significantly more metastases to SLNs than examination of frozen sections (p < 0.0001). All 8 inconsistent results were positive in OSNA and negative in examination of frozen sections; ITC were identified in 2/8 SLNs and micrometastases in 6/8 SLNs. Sensitivity for OSNA was calculated as 100%, specificity as 90.47%, and κ was 79.16%. Conclusions One-step nucleic acid amplification assay analysis allows rapid and quantitative detection of mRNA CK19 with high specificity and a low rate of false positives. One-step nucleic acid amplification assay is a reliable tool for intraoperative diagnosis of whole SLNs during surgery of breast cancer. One-step nucleic acid amplification assay minimizes the need for secondary surgery and avoids delays in the adjuvant treatment. PMID:27904514

  8. Melanoma

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Melanoma KidsHealth > For Teens > Melanoma Print A A A ... to the moles on your skin. What Is Melanoma? Melanoma is a type of cancer that begins ...

  9. Melanoma

    MedlinePlus

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  10. Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells.

    PubMed

    González, Fermín E; Ortiz, Carolina; Reyes, Montserrat; Dutzan, Nicolás; Patel, Vyomesh; Pereda, Cristián; Gleisner, Maria A; López, Mercedes N; Gutkind, J Silvio; Salazar-Onfray, Flavio

    2014-07-01

    We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.

  11. Factors associated with involvement of four or more axillary nodes for sentinel lymph node-positive patients

    SciTech Connect

    Katz, Angela . E-mail: abkatz@partners.org; Niemierko, Andrzej; Gage, Irene; Evans, Sheila; Shaffer, Margaret; Smith, Frederick P.; Taghian, Alphonse; Magnant, Colette

    2006-05-01

    Purpose: Sentinel lymph node-positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields.

  12. Pemphigus vulgaris antigen mRNA quantification for the staging of sentinel lymph nodes in head and neck cancer

    PubMed Central

    Solassol, J; Burcia, V; Costes, V; Lacombe, J; Mange, A; Barbotte, E; de Verbizier, D; Cartier, C; Makeieff, M; Crampette, L; Boulle, N; Maudelonde, T; Guerrier, B; Garrel, R

    2009-01-01

    Background: Molecular diagnosis has been proposed to enhance the intra-operative diagnosis of sentinel lymph node (SLN) invasion in head and neck squamous cell carcinoma (HNSCC). Although cytokeratin (CK) mRNA quantification with real-time reverse transcriptase-PCR (QRT–PCR) has produced encouraging results, the more discriminating markers remain to be identified. Methods: Pemphigus vulgaris antigen (PVA), squamous cell carcinoma antigen (SCCA), and CK17 mRNA were quantified using QRT–PCR, and the results were compared with an extensive histopathological examination of the entire SLNs on 78 SLNs harvested from 22 patients with HNSCC. Results: SCCA and CK17 quantification showed significantly higher mRNA values for macrometastases (MAs) than for either negative or isolated tumour cell (ITC) SLNs (P<0.01). Pemphigus vulgaris antigen allowed the discrimination of all MAs and micrometastases from both negative and ITC SLNs (P<0.001). For the neck staging of patients, considering metastatic vs non-metastatic status, receiver-operating characteristic curve analysis found areas under the curve of 93.8, 97.9, and 100% for CK17, SCCA, and PVA, respectively. With PVA, a cutoff value of 562 copies per 100 ng of cDNA permitted the correct distinction between patients with positive as opposed to negative neck nodes in all cases. Conclusion: PVA seems to be a highly promising marker for accurate intra-operative SLN staging in HNSCC by QRT–PCR. PMID:19997107

  13. Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer

    PubMed Central

    Yang, Lu; Cheng, Juan; Chen, Yuli; Yu, Shengjie; Liu, Fengqiu; Sun, Yang; Chen, Yu; Ran, Haitao

    2017-01-01

    Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both in vitro and in vivo. Additionally, the CNPs are capable of staining lymph nodes, which can contribute significantly to the identification of LNs with naked eyes. With increased laser energy, the CNPs exhibit the high performance in killing the breast cancer cells both in vitro and in vivo, due to the photothermal effect induced from the CNs within CNPs. These results suggest that the developed multifunctional phase-transition nanodroplets have high potential to act as the theranostic agents in both SLNs detection and therapy of metastatic LNs. PMID:28338071

  14. 12-Chemokine Gene Signature Identifies Lymph Node-like Structures in Melanoma: Potential for Patient Selection for Immunotherapy?

    NASA Astrophysics Data System (ADS)

    Messina, Jane L.; Fenstermacher, David A.; Eschrich, Steven; Qu, Xiaotao; Berglund, Anders E.; Lloyd, Mark C.; Schell, Michael J.; Sondak, Vernon K.; Weber, Jeffrey S.; Mulé, James J.

    2012-10-01

    We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

  15. A cut-off of 2150 cytokeratin 19 mRNA copy number in sentinel lymph node may be a powerful predictor of non-sentinel lymph node status in breast cancer patients

    PubMed Central

    Terrenato, Irene; D’Alicandro, Valerio; Casini, Beatrice; Perracchio, Letizia; Rollo, Francesca; De Salvo, Laura; Di Filippo, Simona; Di Filippo, Franco; Pescarmona, Edoardo; Maugeri-Saccà, Marcello; Mottolese, Marcella

    2017-01-01

    Since 2007, one-step nucleic acid amplification (OSNA) has been used as a diagnostic system for sentinel lymph node (SLN) examination in patients with breast cancer. This study aimed to define a new clinical cut-off of CK19 mRNA copy number based on the calculation of the risk that an axillary lymph node dissection (ALND) will be positive. We analyzed 1529 SLNs from 1140 patients with the OSNA assay and 318 patients with positive SLNs for micrometastasis (250 copies) and macrometastasis (5000 copies) underwent ALND. Axillary non–SLNs were routinely examined. ROC curves and Youden’s index were performed in order to identify a new cut-off value. Logistic regression models were performed in order to compare OSNA categorical variables created on the basis of our and traditional cut-off to better identify patients who really need an axillary dissection. 69% and 31% of OSNA positive patients had a negative and positive ALND, respectively. ROC analysis identified a cut-off of 2150 CK19 mRNA copies with 95% sensitivity and 51% specificity. Positive and negative predictive values of this new cut-off were 47% and 96%, respectively. Logistic regression models indicated that the cut-off of 2150 copies better discriminates patients with node negative or positive in comparison with the conventional OSNA cut-off (p<0.0001). This cut-off identifies false positive and false negative cases and true-positive and true negative cases very efficiently, and therefore better identifies which patients really need an ALND and which patients can avoid one. This is why we suggest that the negative cut-off should be raised from 250 to 2150. Furthermore, we propose that for patients with a copy number that ranges between 2150 and 5000, there should be a multidisciplinary discussion concerning the clinical and bio-morphological features of primary breast cancer before any decision is taken on whether to perform an ALND or not. PMID:28187209

  16. Primary Tumor-Secreted Lymphangiogenic Factors Induce Pre-Metastatic Lymphvascular Niche Formation at Sentinel Lymph Nodes in Oral Squamous Cell Carcinoma

    PubMed Central

    Wakisaka, Naohiro; Hasegawa, Yasuhisa; Yoshimoto, Seiichi; Miura, Kouki; Shiotani, Akihiro; Yokoyama, Junkichi; Sugasawa, Masashi; Moriyama-Kita, Makiko; Endo, Kazuhira; Yoshizaki, Tomokazu

    2015-01-01

    Objectives The objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. Materials and Methods Forty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were evaluated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immunohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively. Results In 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metastasis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence). From the analyses of 140 SLNs without metastasis, LVDpodoplanin in 50 SLNs of metastasis-positive cases was significantly higher than that in 90 SLNs of metastasis-negative cases (p = 0.0025). HEVD was not associated with lymph node metastasis. The patients with VEGF-A-High or VEGF-D-High tumors had significantly higher LVDpodoplanin than patients with their Low counterparts (p = 0.0233 and p = 0.0209, respectively). In cases with lymph node metastasis, the VEGF-D-expression score was significantly higher than in those without lymph node metastasis (p = 0.0006). Conclusions These results suggest that lymph node lymphangiogenesis occurs before metastasis in OSCC. VEGF-A and VEGF-D play critical roles in this process. VEGF-D is a potential predictive marker of positive lymph node metastasis in cN0 patients. PMID:26630663

  17. Non-invasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-loaded Perfluorocarbon Nanoparticles

    PubMed Central

    Akers, Walter J.; Kim, Chulhong; Berezin, Mikhail; Guo, Kevin; Fuhrhop, Ralph; Lanza, Gregory M.; Fischer, Georg M.; Daltrozzo, Ewald; Zumbusch, Andreas; Cai, Xin; Wang, Lihong V.; Achilefu, Samuel

    2010-01-01

    The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle but significant ways. Design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime (FLT) imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods. PMID:21171567

  18. Quantitative investigation of a novel small field of view hybrid gamma camera (HGC) capability for sentinel lymph node detection

    PubMed Central

    Lees, John E; Bugby, Sarah L; Jambi, Layal K; Perkins, Alan C

    2016-01-01

    Objective: The hybrid gamma camera (HGC) has been developed to enhance the localization of radiopharmaceutical uptake in targeted tissues during surgical procedures such as sentinel lymph node (SLN) biopsy. To assess the capability of the HGC, a lymph node contrast (LNC) phantom was constructed to simulate medical scenarios of varying radioactivity concentrations and SLN size. Methods: The phantom was constructed using two clear acrylic glass plates. The SLNs were simulated by circular wells of diameters ranging from 10 to 2.5 mm (16 wells in total) in 1 plate. The second plate contains four larger rectangular wells to simulate tissue background activity surrounding the SLNs. The activity used to simulate each SLN ranged between 4 and 0.025 MBq. The activity concentration ratio between the background and the activity injected in the SLNs was 1 : 10. The LNC phantom was placed at different depths of scattering material ranging between 5 and 40 mm. The collimator-to-source distance was 120 mm. Image acquisition times ranged from 60 to 240 s. Results: Contrast-to-noise ratio analysis and full-width-at-half-maximum (FWHM) measurements of the simulated SLNs were carried out for the images obtained. Over the range of activities used, the HGC detected between 87.5 and 100% of the SLNs through 20 mm of scattering material and 75–93.75% of the SLNs through 40 mm of scattering material. The FWHM of the detected SLNs ranged between 11.93 and 14.70 mm. Conclusion: The HGC is capable of detecting low accumulation of activity in small SLNs, indicating its usefulness as an intraoperative imaging system during surgical SLN procedures. Advances in knowledge: This study investigates the capability of a novel small-field-of-view (SFOV) HGC to detect low activity uptake in small SLNs. The phantom and procedure described are inexpensive and could be easily replicated and applied to any SFOV camera, to provide a comparison between systems with clinically relevant

  19. Image-Guided Sentinel Lymph Node Mapping and Nanotechnology-Based Nodal Treatment in Lung Cancer using Invisible Near-Infrared Fluorescent Light

    PubMed Central

    Khullar, Onkar; Frangioni, John V.; Colson, Yolonda L.

    2011-01-01

    Current methods for sentinel lymph node (SLN) mapping and nodal treatment in lung cancer remain inadequate for routine clinical use. Here we discuss the potential for using the combination of invisible near-infrared (NIR) fluorescent light and nanotechnology for these applications. NIR fluorescence imaging has recently received significant attention for in vivo imaging applications because of its low tissue autofluorescence, high photon penetration into living tissue, and high signal-to-background ratio. Our large animal in vivo studies have been able to successfully identify sentinel lymph nodes in lung tissue and several clinical studies have examined the use of NIR fluorescence imaging systems for SLN mapping in breast and gastric cancer. Promising new nanoparticle technologies, when combined with NIR fluorescence imaging, offer the potential for image-guided treatment of lymph nodes at high risk for tumor recurrence. This review provides a theoretical and empirical framework for developing the next-generation of diagnostic and therapeutic agents for lung cancer. PMID:20226343

  20. Molecular staging by multimarker reverse transcriptase-polymerase chain reaction assay of lymphatic drainage and blood from melanoma patients after lymph node dissection.

    PubMed

    Rutkowski, Piotr; Nowecki, Zbigniew I; Kulik, Jadwiga; Ruka, Wlodzimierz; Siedlecki, Janusz A

    2008-08-01

    Reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated detection of melanoma cells may be a prognostic factor for disease outcome. We investigated the presence of melanoma cells in lymphatic drainage and blood in melanoma patients after lymph node dissection (LND) via the highly sensitive multimarker (MM) RT-PCR assay. We collected 24-h lymph fluid (LY) and peripheral blood (BL) from 107 stage III melanoma patients after radical LND (59 axillary and 48 ilioinguinal LND). Tyrosinase, MART1 and uMAGE mRNA levels were determined by RT-PCR to detect melanoma cells, and the presence of at least one marker signified a positive result. All patients underwent follow-up (median for survivors, 21 months, range: 4-37 months). Forty patients (37.4%) were positive for LY MM RT-PCR and 28 (26.2%) were positive based on BL MM RT-PCR. No differences for disease-free survival (DFS) curves according to BL MM RT-PCR were observed, but we found significant differences in the estimated 24-month DFS rate for patients with at least one marker and those without any marker in lymph fluid [18.9% (95% confidence interval: 1.4-37.5%) and 42.1% (95% confidence interval: 29.7-54.5%), median: 9.9 and 15.3 months, respectively] (P=0.04). Detection of multiple markers in lymph fluid correlated with shorter DFS. Approximately 37% of lymph fluid after radical LND were positive by MM RT-PCR, which correlated significantly with early melanoma recurrences and shorter survival. The LY MM RT-PCR seems to be an effective prognostic tool for stage III melanoma patients. The MM RT-PCR analysis of single peripheral blood sample in these patients did not have additional prognostic value.

  1. Optimal management and challenges in treatment of upper facial melanoma.

    PubMed

    Berdahl, John P; Pockaj, Barbara A; Gray, Richard J; Casey, William J; Woog, John J

    2006-12-01

    This study's purpose was to evaluate clinical and surgical outcomes in patients with upper facial melanoma. A sentinel lymph node (SLN) biopsy database review identified 43 patients receiving a diagnosis of upper facial melanoma between February 1997 and April 2005 at Mayo Clinic Arizona in Scottsdale. Patients underwent wide local excision (n = 40) or Mohs excision (n = 3) and SLN biopsy. Nine patients (21%) had positive margins requiring reexcision. SLN mapping identified the SLN in 39 patients (91%) and drainage to bilateral lymph node basins in 8 (21%). The SLN was positive for melanoma in 2 patients (5%). Recurrence in 33 patients with more than 1 year of follow-up (local in 5 [15%] and regional in 1 [3%]) was treated with salvage surgery; 1 patient developed metastatic disease. Two patients (5%) died, one of an unknown cause and the other of metastatic melanoma. We concluded that oncologic surgery can result in good local disease control in patients with upper facial melanoma.

  2. Risk of node metastasis of sentinel lymph nodes detected in level II/III of the axilla by single-photon emission computed tomography/computed tomography

    PubMed Central

    SHIMA, HIROAKI; KUTOMI, GORO; SATOMI, FUKINO; MAEDA, HIDEKI; TAKAMARU, TOMOKO; KAMESHIMA, HIDEKAZU; OMURA, TOSEI; MORI, MITSURU; HATAKENAKA, MASAMITSU; HASEGAWA, TADASHI; HIRATA, KOICHI

    2014-01-01

    In breast cancer, single-photon emission computed tomography/computed tomography (SPECT/CT) shows the exact anatomical location of sentinel nodes (SN). SPECT/CT mainly exposes axilla and partly exposes atypical sites of extra-axillary lymphatic drainage. The mechanism of how the atypical hot nodes are involved in lymphatic metastasis was retrospectively investigated in the present study, particularly at the level II/III region. SPECT/CT was performed in 92 clinical stage 0-IIA breast cancer patients. Sentinel lymph nodes are depicted as hot nodes in SPECT/CT. Patients were divided into two groups: With or without hot node in level II/III on SPECT/CT. The existence of metastasis in level II/III was investigated and the risk factors were identified. A total of 12 patients were sentinel lymph node biopsy metastasis positive and axillary lymph node dissection (ALND) was performed. These patients were divided into two groups: With and without SN in level II/III, and nodes in level II/III were pathologically proven. In 11 of the 92 patients, hot nodes were detected in level II/III. There was a significant difference in node metastasis depending on whether there were hot nodes in level II/III (P=0.0319). Multivariate analysis indicated that the hot nodes in level II/III and lymphatic invasion were independent factors associated with node metastasis. There were 12 SN-positive patients followed by ALND. In four of the 12 patients, hot nodes were observed in level II/III. Two of the four patients with hot nodes depicted by SPECT/CT and metastatic nodes were pathologically evident in the same lesion. Therefore, the present study indicated that the hot node in level II/III as depicted by SPECT/CT may be a risk of SN metastasis, including deeper nodes. PMID:25289038

  3. A new optical probe for the detection of the sentinel lymph node using patent blue V dye in breast cancer: A preliminary study.

    PubMed

    Tellier, F; Poulet, P; Ghnassia, J P; Wilt, M; Weitbruch, D; Rodier, J F

    2013-01-01

    The present study presents a novel near-infrared optical probe for the sentinel lymph node (SLN) detection in breast cancer patients, based on the recording of scattered photons. The aim of this study was to improve the detection of patent blue V (PBV), a dye routinely injected during clinical practice. A combined injection of the dye and radioactive colloid was used in the 24 patients enrolled in the study. The clinical results of the ex vivo detection of 70 dye-marked SLNs are reported, subsequent to the injection of various quantities of PBV (0.25-2 ml). The accuracy and success rate of an isotopic probe for the detection of radioactive colloid tracer, the eye visibility threshold of the surgeon and the use of a new optical probe were examined. The radio-labeled and dye-marked sentinel lymph nodes were all detected by the radio-isotopic probe, as opposed to the 75% detected by the eye visibility threshold of the surgeon. The optical probe detected all of the nodes, regardless of the volume of the dye injected. The relative PBV concentration computed by the probe facing SLNs with infravisible/visually undetectable dye-mark was relatively constant at 5.5±1.4 μmol/l. The optical detection of the sentinel lymph nodes using PBV and the probe presented in this study have the potential to reduce the false negative detection rate. This instrument is likely to provide surgeons with a simple diagnostic tool, without significantly changing their surgical procedures.

  4. A new optical probe for the detection of the sentinel lymph node using patent blue V dye in breast cancer: A preliminary study

    PubMed Central

    TELLIER, F.; POULET, P.; GHNASSIA, J.P.; WILT, M.; WEITBRUCH, D.; RODIER, J.F.

    2013-01-01

    The present study presents a novel near-infrared optical probe for the sentinel lymph node (SLN) detection in breast cancer patients, based on the recording of scattered photons. The aim of this study was to improve the detection of patent blue V (PBV), a dye routinely injected during clinical practice. A combined injection of the dye and radioactive colloid was used in the 24 patients enrolled in the study. The clinical results of the ex vivo detection of 70 dye-marked SLNs are reported, subsequent to the injection of various quantities of PBV (0.25–2 ml). The accuracy and success rate of an isotopic probe for the detection of radioactive colloid tracer, the eye visibility threshold of the surgeon and the use of a new optical probe were examined. The radio-labeled and dye-marked sentinel lymph nodes were all detected by the radio-isotopic probe, as opposed to the 75% detected by the eye visibility threshold of the surgeon. The optical probe detected all of the nodes, regardless of the volume of the dye injected. The relative PBV concentration computed by the probe facing SLNs with infravisible/visually undetectable dye-mark was relatively constant at 5.5±1.4 μmol/l. The optical detection of the sentinel lymph nodes using PBV and the probe presented in this study have the potential to reduce the false negative detection rate. This instrument is likely to provide surgeons with a simple diagnostic tool, without significantly changing their surgical procedures. PMID:24649137

  5. Case report and literature review: surgical treatment of a right atrial metastatic melanoma from a previously resected "advanced" primary site with regional lymph nodes involvement.

    PubMed

    Parissis, Haralabos; Al-Alao, Bassel Suffian; Young, Vincent K

    2012-10-01

    Although melanoma of the right atrium is a rare cardiac tumor, melanoma in general has a high propensity to involve the heart. Unfortunately, however, when the tumor is involving the heart, widespread metastasis ensues and hence surgery becomes a questionable option. We report a case of a young female who presented with an advanced skin primary melanoma and regional lymph node involvement and a metastasis into the right atrium. Postoperatively tumor dissemination was controlled with adjuvant chemotherapy. A vigorous attempt aiming at tumor clearance followed by adjuvant multimodality therapy along with a tumor surveillance program may improve survival even in advanced cases.

  6. The interplay between hospital and surgeon factors and the use of sentinel lymph node biopsy for breast cancer

    PubMed Central

    Yen, Tina W.F.; Li, Jianing; Sparapani, Rodney A.; Laud, Purushuttom W.; Nattinger, Ann B.

    2016-01-01

    Abstract Background: Several surgeon characteristics are associated with the use of sentinel lymph node biopsy (SLNB) for breast cancer. No studies have systematically examined the relative contribution of both surgeon and hospital factors on receipt of SLNB. Objective: To evaluate the relationship between surgeon and hospital characteristics, including a novel claims-based classification of hospital commitment to cancer care (HC), and receipt of SLNB for breast cancer, a marker of quality care. Data Sources/Study Design: Observational prospective survey study was performed in a population-based cohort of Medicare beneficiaries who underwent incident invasive breast cancer surgery, linked to Medicare claims, state tumor registries, American Hospital Association Annual Survey Database, and American Medical Association Physician Masterfile. Multiple logistic regression models determined surgeon and hospital characteristics that were predictors of SLNB. Results: Of the 1703 women treated at 471 different hospitals by 947 different surgeons, 65% underwent an initial SLNB. Eleven percent of hospitals were high-volume and 58% had a high commitment to cancer care. In separate adjusted models, both high HC (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.12–2.10) and high hospital volume (HV, OR 1.90, 95% CI 1.28–2.79) were associated with SLNB. Adding surgeon factors to a model including both HV and HC minimally modified the effect of high HC (OR 1.34, 95% CI 0.95–1.88) but significantly weakened the effect of high HV (OR 1.25, 95% CI 0.82–1.90). Surgeon characteristics (higher volume and percentage of breast cancer cases) remained strong independent predictors of SLNB, even when controlling for various hospital characteristics. Conclusions: Hospital factors are associated with receipt of SLNB but surgeon factors have a stronger association. Since regionalization of breast cancer care in the U.S. is unlikely to occur, efforts to improve the surgical care and

  7. Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study.

    PubMed

    Parada, David; Peña, Karla B; Riu, F Francesc; Aguilar, A Esther; Cohan, Sebastian

    2016-11-01

    Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the axillary lymph node status. However, insufficient evidence exists to support the recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to downsize tumours and allow for breast conservation surgery. The present study aimed to use molecular approaches to evaluate the feasibility and accuracy of SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50 consecutive patients with operable invasive breast carcinomas who had received prior NAC were assessed using the one-step nucleic acid amplification (OSNA) method. The rate of SLN identification was 100%. The OSNA assay showed that 29 patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19 of these 21 patients (90.48%), the SLN was the only positive lymph node. No axillary lymph nodes metastases were observed in patients with isolated tumour cells or with micrometastases. The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non-SLN metastases.

  8. Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study

    PubMed Central

    Parada, David; Peña, Karla B.; Riu, F. Francesc; Aguilar, A. Esther; Cohan, Sebastian

    2016-01-01

    Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the axillary lymph node status. However, insufficient evidence exists to support the recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to downsize tumours and allow for breast conservation surgery. The present study aimed to use molecular approaches to evaluate the feasibility and accuracy of SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50 consecutive patients with operable invasive breast carcinomas who had received prior NAC were assessed using the one-step nucleic acid amplification (OSNA) method. The rate of SLN identification was 100%. The OSNA assay showed that 29 patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19 of these 21 patients (90.48%), the SLN was the only positive lymph node. No axillary lymph nodes metastases were observed in patients with isolated tumour cells or with micrometastases. The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non-SLN metastases. PMID:27882235

  9. A grid matrix-based Raman spectroscopic method to characterize different cell milieu in biopsied axillary sentinel lymph nodes of breast cancer patients.

    PubMed

    Som, Dipasree; Tak, Megha; Setia, Mohit; Patil, Asawari; Sengupta, Amit; Chilakapati, C Murali Krishna; Srivastava, Anurag; Parmar, Vani; Nair, Nita; Sarin, Rajiv; Badwe, R

    2016-01-01

    Raman spectroscopy which is based upon inelastic scattering of photons has a potential to emerge as a noninvasive bedside in vivo or ex vivo molecular diagnostic tool. There is a need to improve the sensitivity and predictability of Raman spectroscopy. We developed a grid matrix-based tissue mapping protocol to acquire cellular-specific spectra that also involved digital microscopy for localizing malignant and lymphocytic cells in sentinel lymph node biopsy sample. Biosignals acquired from specific cellular milieu were subjected to an advanced supervised analytical method, i.e., cross-correlation and peak-to-peak ratio in addition to PCA and PC-LDA. We observed decreased spectral intensity as well as shift in the spectral peaks of amides and lipid bands in the completely metastatic (cancer cells) lymph nodes with high cellular density. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to create an automated smart diagnostic tool for bench side screening of sampled lymph nodes. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to develop an automated smart diagnostic tool for bench side screening of sampled lymph nodes supported by ongoing global research in developing better technology and signal and big data processing algorithms.

  10. Pathological controversies in breast cancer: classification of ductal carcinoma in situ, sentinel lymph nodes and low volume metastatic disease and reporting of neoadjuvant chemotherapy specimens.

    PubMed

    Provenzano, E; Brown, J P; Pinder, S E

    2013-02-01

    The pathological classification of breast cancer is constantly being updated to reflect the advances in our clinical and biological understanding of the disease. This overview examines new insights into the classification and molecular biology of ductal carcinoma in situ, the pathological handling of sentinel lymph node biopsies and the identification of low volume disease (micrometastases and isolated tumour cells) and the handling and reporting of specimens after neoadjuvant therapy. The molecular subtypes of invasive breast cancer are also represented in ductal carcinoma in situ. It is hoped that alongside traditional histological features, such as cytological grade and the presence of necrosis, this will lead to better classification systems with improved prediction of clinical behaviour, in particular the risk of progression to invasive cancer, and enable more targeted management. Sentinel lymph node biopsy is now the standard of care for early stage breast cancer in clinically node-negative patients. However, the handling and reporting of these specimens remains controversial, largely related to the uncertainties regarding the clinical significance of micrometastases and isolated tumour cells. The increasing use of neoadjuvant therapies has introduced challenges for the pathologist in the handling and interpretation of these specimens. Grading the tumour response, particularly the identification of a complete pathological response, is prognostically important. However, there is still marked variability in reporting these specimens in routine practice, and consensus guidelines for the histopathology reporting of breast cancers after neoadjuvant chemotherapy based on robust, validated evidence are presently lacking.

  11. Melanoma sentinel node biopsy and prediction models for relapse and overall survival

    PubMed Central

    Mitra, A; Conway, C; Walker, C; Cook, M; Powell, B; Lobo, S; Chan, M; Kissin, M; Layer, G; Smallwood, J; Ottensmeier, C; Stanley, P; Peach, H; Chong, H; Elliott, F; Iles, M M; Nsengimana, J; Barrett, J H; Bishop, D T; Newton-Bishop, J A

    2010-01-01

    Background: To optimise predictive models for sentinal node biopsy (SNB) positivity, relapse and survival, using clinico-pathological characteristics and osteopontin gene expression in primary melanomas. Methods: A comparison of the clinico-pathological characteristics of SNB positive and negative cases was carried out in 561 melanoma patients. In 199 patients, gene expression in formalin-fixed primary tumours was studied using Illumina's DASL assay. A cross validation approach was used to test prognostic predictive models and receiver operating characteristic curves were produced. Results: Independent predictors of SNB positivity were Breslow thickness, mitotic count and tumour site. Osteopontin expression best predicted SNB positivity (P=2.4 × 10−7), remaining significant in multivariable analysis. Osteopontin expression, combined with thickness, mitotic count and site, gave the best area under the curve (AUC) to predict SNB positivity (72.6%). Independent predictors of relapse-free survival were SNB status, thickness, site, ulceration and vessel invasion, whereas only SNB status and thickness predicted overall survival. Using clinico-pathological features (thickness, mitotic count, ulceration, vessel invasion, site, age and sex) gave a better AUC to predict relapse (71.0%) and survival (70.0%) than SNB status alone (57.0, 55.0%). In patients with gene expression data, the SNB status combined with the clinico-pathological features produced the best prediction of relapse (72.7%) and survival (69.0%), which was not increased further with osteopontin expression (72.7, 68.0%). Conclusion: Use of these models should be tested in other data sets in order to improve predictive and prognostic data for patients. PMID:20859289

  12. High nevus counts confer a favorable prognosis in melanoma patients.

    PubMed

    Ribero, Simone; Davies, John R; Requena, Celia; Carrera, Cristina; Glass, Daniel; Rull, Ramon; Vidal-Sicart, Sergi; Vilalta, Antonio; Alos, Lucia; Soriano, Virtudes; Quaglino, Pietro; Traves, Victor; Newton-Bishop, Julia A; Nagore, Eduardo; Malvehy, Josep; Puig, Susana; Bataille, Veronique

    2015-10-01

    A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.

  13. The first experience of using of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Doroshenko, A.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Varlamova, N.; Skuridin, V.; Dergilev, A.; Sinilkin, I.

    2016-06-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. Materials and methods. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n=34) were injected with radioactive 99mTc-Al203, and Group II patients (n=30) received 99mTc-labeled phytate colloid. Results. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. At 18 hours after 99mTc-Al203 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II patients, SLNs were detected in 27 patients. At 18 hours after injection of the phytate colloid, the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. Conclusion. The new radiopharmaceutical based on the 99mTc - Al203 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. Sensitivity and specificity of 99mTc - Al203 were 100% for both SPECT and intraoperative gamma probe identification.

  14. Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

    PubMed

    Nottegar, A; Veronese, N; Senthil, M; Roumen, R M; Stubbs, B; Choi, A H; Verheuvel, N C; Solmi, M; Pea, A; Capelli, P; Fassan, M; Sergi, G; Manzato, E; Maruzzo, M; Bagante, F; Koç, M; Eryilmaz, M A; Bria, E; Carbognin, L; Bonetti, F; Barbareschi, M; Luchini, C

    2016-07-01

    Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

  15. Sentinel Lymph Node Mapping with Pathologic Ultrastaging: A Valuable Tool for Assessing Nodal Metastasis in Low-Grade Endometrial Cancer with Superficial Myoinvasion

    PubMed Central

    Kim, Christine H.; Khoury-Collado, Fady; Barber, Emma L.; Soslow, Robert A.; Makker, Vicky; Leitao, Mario M.; Sonoda, Yukio; Alektiar, Kaled M.; Barakat, Richard R.; Abu-Rustum, Nadeem R.

    2013-01-01

    Objective To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging. Methods All patients from 9/2005-12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells. Results Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion. Conclusions Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases. PMID:24099838

  16. Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles.

    PubMed

    Liu, Zhiguo; Rong, Pengfei; Yu, Lun; Zhang, Xintong; Yang, Cejun; Guo, Fei; Zhao, Yanzhong; Zhou, Kechao; Wang, Wei; Zeng, Wenbin

    2015-09-08

    The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we developed an imaging contrast system based on fluorescent dye-loaded mesoporous silica nanoparticles (MSNPs) that integrate near-infrared (NIR) fluorescent and photoacoustic (PA) imaging modalities for efficient SLN mapping. By balancing the ratio of dye and nanoparticles for simultaneous optimization of dual-modality imaging (NIR and PA), the dye encapsulated MSNP platform was set up to generate both a moderate NIR emission and PA signals simultaneously. Moreover, the underlying mechanisms of the relevance between optical and PA properties were discovered. Subsequently, dual-modality imaging was achieved to visualize tumor draining SLNs up to 2 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate and contrast between metastatic and normal SLNs were observed both in vivo and ex vivo. Based on all these imaging data, it was demonstrated that the dye-loaded MSNPs allow detection of regional lymph nodes in vivo with time-domain NIR fluorescent and PA imaging methods efficiently.

  17. Intravital and whole-organ imaging reveals capture of melanoma-derived antigen by lymph node subcapsular macrophages leading to widespread deposition on follicular dendritic cells.

    PubMed

    Moalli, Federica; Proulx, Steven T; Schwendener, Reto; Detmar, Michael; Schlapbach, Christoph; Stein, Jens V

    2015-01-01

    Aberrant antigens expressed by tumor cells, such as in melanoma, are often associated with humoral immune responses, which may in turn influence tumor progression. Despite recent data showing the central role of adaptive immune responses on cancer spread or control, it remains poorly understood where and how tumor-derived antigen (TDA) induces a humoral immune response in tumor-bearing hosts. Based on our observation of TDA accumulation in B cell areas of lymph nodes (LNs) from melanoma patients, we developed a pre-metastatic B16.F10 melanoma model expressing a fluorescent fusion protein, tandem dimer tomato, as a surrogate TDA. Using intravital two-photon microscopy (2PM) and whole-mount 3D LN imaging of tumor-draining LNs in immunocompetent mice, we report an unexpectedly widespread accumulation of TDA on follicular dendritic cells (FDCs), which were dynamically scanned by circulating B cells. Furthermore, 2PM imaging identified macrophages located in the subcapsular sinus of tumor-draining LNs to capture subcellular TDA-containing particles arriving in afferent lymph. As a consequence, depletion of macrophages or genetic ablation of B cells and FDCs resulted in dramatically reduced TDA capture in tumor-draining LNs. In sum, we identified a major pathway for the induction of humoral responses in a melanoma model, which may be exploitable to manipulate anti-TDA antibody production during cancer immunotherapy.

  18. Visualisation of Sentinel Lymph Node with Indium-Based near Infrared Emitting Quantum Dots in a Murine Metastatic Breast Cancer Model

    PubMed Central

    Helle, Marion; Cassette, Elsa; Bezdetnaya, Lina; Pons, Thomas; Leroux, Agnès; Plénat, François; Guillemin, François; Dubertret, Benoît; Marchal, Frédéric

    2012-01-01

    Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near-infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS2/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma – mass spectroscopy (ICP-MS) as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer. PMID:22952979

  19. Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

    SciTech Connect

    Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil; Tang Gong; Johnson, Ronald; Ahrendt, Gretchen; Bonaventura, Marguerite; Soran, Atilla

    2009-11-15

    Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.

  20. Nodal combined blue nevus and benign nevus cells in multiple axillary sentinel nodes in a patient with breast carcinoma: report of a case.

    PubMed

    Begum, S M K Nahar; Lomme, Michele; Quddus, M Ruhul

    2014-09-01

    Combined blue nevus and benign nevus cells were identified in the same sentinel lymph node. Blue nevus alone was also present in an additional sentinel lymph node in the same axilla in a patient who underwent needle localization, wide local excision, and sentinel lymph node biopsy for her pT1cN1mi(sn)M(na) invasive duct carcinoma of the breast. Of the 4 sentinel lymph nodes, 1 showed micrometastasis and 2 other lymph nodes showed blue nevus involving the capsule and trabeculae of the nodes. The patient had no significant previous clinical history of any skin tumors and had a negative clinical examination for malignant melanoma or pigmented skin lesions after the diagnosis of nodal blue nevus. To our knowledge, this is the first case report of combined blue nevi involving multiple sentinel lymph nodes in the same axilla. An equally interesting finding is the presence of benign nonpigmented nevus cells in continuation with the blue nevus in the same node.

  1. Preparation of (99m)Tc-isosulfan blue for lymph node localization in rats (99m)Tc-isosulfan blue for lymph node localization.

    PubMed

    İlem-Özdemir, Derya; Yararbas, Ulkem; Zengel, Baha; Ertan, Gökhan; Asikoglu, Makbule

    2016-12-01

    The sentinel lymph node (SLN) is defined as the first regional lymph node to receive lymphatic drainage from a malignant tumor. Therefore, this node is a "sentinel" for second metastatic lymph node stations and for labeling regional tumor spread. For SLN detection, many surgeons preferred a combination of a preoperative injection of radiolabeled colloid and the intraoperative injection of blue dye. Under this combination protocol, nodes are considered to be "sentinel nodes" if they are radioactive and blue. The aim of this study is to develop a new single agent that combines both detection methods. For this purpose Isosulfan Blue (ISB) was radiolabeled by (99m)Tc with high labeling yield and stability. In vivo gamma scintigraphy studies were performed with rats. According to the scintigraphic studies, (99m)Tc-ISB shows rapid and high accumulation in both axillary (ALN) and popliteal lymph node (PLN). After the imaging study, extremity was opened and nodes were scanned for the radioactivity. According to performed study the lymph nodes were clearly seen to become blue and carried compound was sufficient to allow identification with a gamma probe. In conclusion, (99m)Tc-ISB has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for solid malignancies such as breast cancer and melanoma.

  2. Melanoma

    MedlinePlus

    ... flat or raised, large or small, light or dark, and can appear anywhere on our bodies. Sometimes, ... can still get melanoma even if they're dark skinned, young, and have no family history. Even ...

  3. Size Control of (99m)Tc-tin Colloid Using PVP and Buffer Solution for Sentinel Lymph Node Detection.

    PubMed

    Kim, Eun-Mi; Lim, Seok Tae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2015-06-01

    Colloidal particle size is an important characteristic that allows mapping sentinel nodes in lymphoscintigraphy. This investigation aimed to introduce different ways of making a (99m)Tc-tin colloid with a size of tens of nanometers. All agents, tin fluoride, sodium fluoride, poloxamer-188, and polyvinylpyrrolidone (PVP), were mixed and labeled with (99m)Tc. Either phosphate or sodium bicarbonate buffers were used to adjust the pH levels. When the buffers were added, the size of the colloids increased. However, as the PVP continued to increase, the size of the colloids was controlled to within tens of nanometers. In all samples, phosphate buffer added PVP (30 mg) stabilized tin colloid ((99m)Tc-PPTC-30) and sodium bicarbonate solution added PVP (50 mg) stabilized tin colloid ((99m)Tc-BPTC-50) were chosen for in vitro and in vivo studies. (99m)Tc-BPTC-50 (<20 nm) was primarily located in bone marrow and was then secreted through the kidneys, and (99m)Tc-PPTC-30 (>100 nm) mainly accumulated in the liver. When a rabbit was given a toe injection, the node uptake of (99m)Tc-PPTC-30 decreased over time, while (99m)Tc-BPTC-50 increased. Therefore, (99m)Tc-BPTC-50 could be a good candidate radiopharmaceutical for sentinel node detection. The significance of this study is that nano-sized tin colloid can be made very easily and quickly by PVP.

  4. The influence of postoperative lymph node radiation therapy on overall survival of patients with stage III melanoma, a National Cancer Database analysis

    PubMed Central

    Danish, Hasan H.; Patel, Kirtesh R.; Switchenko, Jeffrey M.; Gillespie, Theresa W.; Jhaveri, Jaymin; Chowdhary, Mudit; Abugideiri, Mustafa; Delman, Keith A.; Lawson, David H.; Khan, Mohammad K.

    2017-01-01

    Recently, TROG 02.01 results showed that in stage III melanoma patients with nodal metastasis, adjuvant radiation to lymph node basin after nodal dissection improves lymph node field relapse without an overall survival (OS) benefit. However, this trial was neither designed nor powered to detect an OS difference. In the present study, we analyzed patients in the National Cancer Database (NCDB) with stage III melanoma with pathologically involved nodes and compared survival outcomes of adjuvant radiation and no-radiation cohorts. Inclusion criteria were as follows: age at least 18 years; diagnosed 2003–2011; surgery to regional lymph nodes; pathologically involved lymph nodes; and American Joint Committee on Cancer stage (IIIA-C). We used propensity score matching analysis to compare the OS of patients with similar baseline demographic, clinical, and pathologic characteristics who received adjuvant radiation and no adjuvant radiation. Overall, 912 patients were analyzed with an average age at diagnosis of 54.4 years and a median follow-up time of 5.5 years. In this cohort, the 5-year OS was 69.0, 51.1, and 30.6% for stage IIIA, IIIB, and IIIC, respectively. On propensity score-adjusted multivariate analysis, we found that adjuvant radiation had no statistically significant impact on OS (hazard ratio: 1.09, 95% confidence interval: 0.75–1.58, P=0.640). Furthermore, age older than 60 years, number of nodes, increasing pathologic stage, and absence of immunotherapy correlated with worse OS. In this NCDB analysis, we found that the adjuvant radiotherapy for node-positive, stage III melanoma patients did not improve OS. This is consistent with TROG 02.01; however, there may be patient selection bias not accounted for by the NCDB. PMID:27575390

  5. 68Ga-labeled superparamagnetic iron oxide nanoparticles (SPIONs) for multi-modality PET/MR/Cherenkov luminescence imaging of sentinel lymph nodes

    PubMed Central

    Madru, Renata; Tran, Thuy A; Axelsson, Johan; Ingvar, Christian; Bibic, Adnan; Ståhlberg, Freddy; Knutsson, Linda; Strand, Sven-Erik

    2014-01-01

    The aim of this study was to develop 68Ga-SPIONs for use as a single contrast agent for dynamic, quantitative and high resolution PET/MR imaging of Sentinel Lymph Node (SLN). In addition 68Ga enables Cherenkov light emission which can be used for optical guidance during resection of SLN. SPIONs were labeled with 68Ga in ammonium acetate buffer, pH 5.5. The labeling yield and stability in human serum were determined using instant thin layer chromatography. An amount of 0.07-0.1 mL (~5-10 MBq, 0.13 mg Fe) of 68Ga-SPIONs was subcutaneously injected in the hind paw of rats. The animals were imaged at 0-3 h and 25 h post injection with PET/CT, 9.4 T MR and CCDbased Cherenkov optical systems. A biodistribution study was performed by dissecting and measuring the radioactivity in lymph nodes, kidneys, spleen, liver and the injection site. The labeling yield was 97.3 ± 0.05% after 15 min and the 68Ga-SPIONs were stable in human serum. PET, MR and Cherenkov luminescence imaging clearly visualized the SLN. Biodistribution confirmed a high uptake of the 68Ga-SPIONs within the SLN. We conclude that generator produced 68Ga can be labeled to SPIONs. Subcutaneously injected 68Ga-SPIONs can enhance the identification of the SLNs by combining sensitive PET and high resolution MR imaging. Clinically, hybrid PET/MR cameras are already in use and 68Ga-SPIONs have a great potential as a single-dose, tri-modality agent for diagnostic imaging and potential Cherenkov luminescent guided resection of SLN. PMID:24380046

  6. Multi-institutional comparison of non-sentinel lymph node predictive tools in breast cancer patients with high predicted risk of further axillary metastasis.

    PubMed

    Cserni, Gábor; Bori, Rita; Maráz, Róbert; Leidenius, Marjut H K; Meretoja, Tuomo J; Heikkila, Paivi S; Regitnig, Peter; Luschin-Ebengreuth, Gero; Zgajnar, Janez; Perhavec, Andraz; Gazic, Barbara; Lázár, György; Takács, Tibor; Vörös, András; Audisio, Riccardo A

    2013-01-01

    Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.

  7. The Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Initially Clinically Node-Negative Breast Cancer after Neoadjuvant Chemotherapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Geng, Chong; Chen, Xiao; Pan, Xiaohua; Li, Jiyu

    2016-01-01

    Background With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this study, we aimed to evaluate the feasibility and accuracy of SLNB for initially clinically node-negative breast cancer after NAC by conducting a systematic review and meta-analysis. Methods We searched PubMed, Embase, and the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on initially clinically node-negative breast cancer patients who underwent SLNB after NAC followed by axillary lymph node dissection (ALND). Results A total of 1,456 patients from 16 studies were included in this review. The pooled identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%-97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95% CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%-100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant differences were found in either the IR of an SLNB when different mapping methods were used (P = 0.180) or in the FNR between studies with and without immunohistochemistry (IHC) staining (P = 0.241). Conclusion Based on current evidence, SLNB is technically feasible and accurate enough for axillary staging in initially clinically node-negative breast cancer patients after NAC. PMID:27606623

  8. Optimization via specific fluorescence brightness of a receptor-targeted probe for optical imaging and positron emission tomography of sentinel lymph nodes.

    PubMed

    Qin, Zhengtao; Hall, David J; Liss, Michael A; Hoh, Carl K; Kane, Christopher J; Wallace, Anne M; Vera, David R

    2013-10-01

    The optical properties of a receptor-targeted probe designed for dual-modality mapping of the sentinel lymph node (SLN) was optimized. Specific fluorescence brightness was used as the design criterion, which was defined as the fluorescence brightness per mole of the contrast agent. Adjusting the molar ratio of the coupling reactants, IRDye 800CW-NHS-ester and tilmanocept, enabled us to control the number of fluorescent molecules attached to each tilmanocept, which was quantified by H1 nuclear magnetic resonance spectroscopy. Quantum yields and molar absorptivities were measured for unconjugated IRDye 800CW and IRDye 800CW-tilmanocept (800CW-tilmanocept) preparations at 0.7, 1.5, 2.3, 2.9, and 3.8 dyes per tilmanocept. Specific fluorescence brightness was calculated by multiplication of the quantum yield by the molar absorptivity and the number of dyes per tilmanocept. It predicted that the preparation with 2.3 dyes per tilmanocept would exhibit the brightest signal, which was confirmed by fluorescence intensity measurements using three optical imaging systems. When radiolabeled with Ga68 and injected into the footpads of mice, the probe identified SLNs by both fluorescence and positron emission tomography (PET) while maintaining high percent extraction by the SLN. These studies demonstrated the feasibility of 800CW-tilmanocept for multimodal SLN mapping via fluorescence and PET-computed tomography imaging.

  9. The first experience of using 99mTc-Al2O3-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-08-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  10. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-06-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3- based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (TlaNxMx- T2bNxMx) treated at the Tomsk Cancer Research Institute. At 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 were injected peritumorally, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3(the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac, obturator, presacral and retrosacral regions (they amounted to 14%, respectively),and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  11. Real-time sentinel lymph node biopsy guidance using combined ultrasound, photoacoustic, fluorescence imaging: in vivo proof-of-principle and validation with nodal obstruction

    PubMed Central

    Kang, Jeeun; Chang, Jin Ho; Kim, Sun Mi; Lee, Hak Jong; Kim, Haemin; Wilson, Brian C.; Song, Tai-Kyong

    2017-01-01

    Precise sentinel lymph node (SLN) identification is crucial not only for accurate diagnosis of micro-metastases at an early stage of cancer progression but also for reducing the number of SLN biopsies (SLNB) to minimize their severe side effects. Furthermore, it is desirable that an SLNB guidance should be as safe as possible in routine clinical use. Although there are currently various SLNB guidance methods for pre-operative or intra-operative assessment, none are ideal. We propose a real-time SLNB guidance method using contrast-enhanced tri-modal images (i.e., ultrasound, photoacoustic, and fluorescence) acquired by a recently developed hand-held tri-modal probe. The major advantage of tri-modal imaging is demonstrated here through an in vivo study of the technically-difficult case of nodal obstruction that frequently leads to false-negative results in patients. The results in a tumor model in rabbits and normal controls showed that tri-modal imaging is capable of clearly identifying obstructed SLNs and of indicating their metastatic involvement. Based on these findings, we propose an SLNB protocol to help surgeons take full advantage of the complementary information obtained from tri-modal imaging, including for pre-operative localization, intra-operative biopsy guidance and post-operative analysis. PMID:28327582

  12. Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node.

    PubMed

    Sun, Yun; Yu, Mengxiao; Liang, Sheng; Zhang, Yingjian; Li, Chenguang; Mou, Tiantian; Yang, Wenjiang; Zhang, Xianzhong; Li, Biao; Huang, Chunhui; Li, Fuyou

    2011-04-01

    Rare-earth-based nanoparticles have attracted increasing attention for their unique optical and magnetic properties. However, their application in bioimaging has been limited to photoluminescence bioimaging and magnetic resonance imaging. To facilitate their use in other bioimaging techniques, we developed a simple, rapid, efficient and general synthesis strategy for (18)F-labeled rare-earth nanoparticles through a facile inorganic reaction between rare-earth cations and fluoride ions. The (18)F-labeling process based on rare-earth elements was achieved efficiently in water at room temperature with an (18)F-labeling yield of >90% and completed within 5 min, with only simple purification by aqueous washing and centrifugation, and without the use of organic agents. The effectiveness of (18)F-labeled rare-earth nanoparticles was further evaluated by positron emission tomography (PET) imaging of their in vivo distribution and application in lymph monitoring. In addition, this strategy is proposed for the creation of a dual-model bioimaging technique, combining upconversion luminescence bioimaging and PET imaging.

  13. A 10-Year Trend Analysis of Sentinel Lymph Node Frozen Section and Completion Axillary Dissection for Breast Cancer: Are These Procedures Becoming Obsolete?

    PubMed Central

    Weber, Walter P.; Barry, Mitchel; Stempel, Michelle M.; Junqueira, Manuela J.; Eaton, Anne A.; Patil, Sujata M.; Morrow, Monica; Cody, Hiram S.

    2013-01-01

    Background Recent results from the ACOSOG Z0011 trial question the use of intraoperative frozen section (FS) during sentinel lymph node (SLN) biopsy and the role of axillary dissection (ALND) for SLN-positive breast cancer patients. Here we present a 10-year trend analysis of SLN-FS and ALND in our practice. Methods We reviewed our prospective SLN database over 10 years (1997–2006, 7509 SLN procedures) for time trends and variation between surgeons in the use of SLN-FS and ALND in patients with cN0 invasive breast cancer. Results Use of SLN-FS decreased from 100% to 62% (P < 0.0001) and varied widely by surgeon (66% to 95%). There were no statistically significant trends in the performance of ALND for patients with SLN metastases detected by FS (n = 1370, 99–99%) or routine hematoxylin and eosin (H&E) (n = 333; 69–77%), but only for those detected by serial section H&E with or without immunohistochemistry (n = 438; 73–48%; P = 0.0054) or immunohistochemistry only (n = 294; 48–28%; P < 0.0001). These trends coincided with an increase in the proportion of completion versus immediate ALND (30–40%; P = 0.0710). Conclusions Over 10 years, we have observed a diminishing rate of SLN-FS and, for patients with low-volume SLN metastases, fewer ALND, trends that suggest a more nuanced approach to axillary management. If the Z0011 selection criteria had been applied to our cohort, 66% of SLN-FS (4159 of 6327) and 48% of ALND (939 of 1953) would have been avoided, sparing 13% of all patients the morbidity of ALND. PMID:21647763

  14. The detection of sentinel lymph nodes in laparoscopic surgery for uterine cervical cancer using 99m-technetium-tin colloid, indocyanine green, and blue dye

    PubMed Central

    Tanaka, Tomohito; Ohmichi, Masahide

    2017-01-01

    Objective Our objective was to determine the feasibility and detection rates and clarify the most effective combination of injected tracer types for sentinel lymph node (SLN) mapping in uterine cervical cancer in patients who have undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). Methods A total of 119 patients with cervical cancer underwent SLN biopsy at radical hysterectomy using three types of tracers. The various factors related to side-specific detection rate, sensitivity, and false negative (FN) rate were analyzed. Results The SLN detection rates using 99m-technetium (99mTc)-tin colloid, indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%, respectively. The patients with ≥2-cm-diameter tumors and those who received NAC had lower detection rates than those with <2-cm-diameter tumors (75.7% vs. 91.5%, p<0.01) and those who did not receive NAC (67.9% vs. 86.3%, p<0.01), respectively. Laparoscopic procedures had a higher detection rate than laparotomy (100.0% vs. 77.1%, p<0.01). No factors significantly affected the sensitivity; however, the patients with ≥2-cm-diameter tumors (86.0% vs. 1.4%, p<0.01), NAC (19.4% vs. 2.2%, p<0.01), and those who underwent laparotomy (7.4% vs. 0%, p<0.01) had an unfavorable FN rate. Conclusion Among the examined tracers, 99mTc had the highest detection of SLN mapping in patients with uterine cervical cancer. Patients with local advanced cervical cancer with/without NAC treatment might be unsuited for SLN mapping. SLN mapping is feasible and results in an excellent detection rate in patients with <2-cm-diameter cervical cancer. Laparoscopic surgery is the best procedure for SLN detection in patients with early-stage disease. PMID:27894166

  15. Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status.

    PubMed

    Dürst, Matthias; Hoyer, Heike; Altgassen, Christoph; Greinke, Christiane; Häfner, Norman; Fishta, Alba; Gajda, Mieczyslaw; Mahnert, Ute; Hillemanns, Peter; Dimpfl, Thomas; Lenhard, Miriam; Petry, K Ulrich; Runnebaum, Ingo B; Schneider, Achim

    2015-09-08

    Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 - 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 - 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.

  16. The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping

    PubMed Central

    Troyan, Susan L.; Kianzad, Vida; Gibbs-Strauss, Summer L.; Gioux, Sylvain; Matsui, Aya; Oketokoun, Rafiou; Ngo, Long; Khamene, Ali; Azar, Fred; Frangioni, John V.

    2009-01-01

    Background Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE™ imaging system overcomes this major obstacle. Methods Color video was acquired simultaneously, and in real-time, along with two independent channels of NIR fluorescence. Grayscale NIR fluorescence images were converted to visible “pseudo-colors” and overlaid onto the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final pre-clinical validation of the imaging system. A 6-patient pilot study was conducted in women undergoing sentinel lymph node (SLN) mapping for breast cancer. Subjects received 99mTc-sulfur colloid lymphoscintigraphy. In addition, 12.5 µg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer. Results The FLARE™ system permitted facile positioning in the operating room. NIR light did not change the look of the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated in swine using clinically available NIR fluorophores and the dual NIR capabilities of the system. In the pilot clinical trial, a total of 9 SLNs were identified by 99mTc-lymphoscintigraphy and 9 SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered. Conclusions We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery. PMID:19582506

  17. Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy.

    PubMed

    Chu, Maoquan; Hai, Wangxi; Zhang, Zheyu; Wo, Fangjie; Wu, Qiang; Zhang, Zefei; Shao, Yuxiang; Zhang, Ding; Jin, Lu; Shi, Donglu

    2016-06-01

    The use of non-toxic or low toxicity materials exhibiting dual functionality for use in sentinel lymph node (SLN) mapping and cancer therapy has attracted considerable attention during the past two decades. Herein, we report that the natural black sesame melanin (BSM) extracted from black sesame seeds (Sesamum indicum L.) shows exciting potential for SLN mapping and cancer photothermal therapy. Aqueous solutions of BSM under neutral and alkaline conditions can assemble into sheet-like nanoparticles ranging from 20 to 200 nm in size. The BSM nanoparticles were encapsulated by liposomes to improve their water solubility and the encapsulated and bare BSM nanoparticles were both non-toxic to cells. Furthermore, the liposome-encapsulated BSM nanoparticles (liposome-BSM) did not exhibit any long-term toxicity in mice. The liposome-BSM nanoparticles were subsequently used to passively target healthy and tumor-bearing mice SLNs, which were identified by the black color of the nanoparticles. BSM also strongly absorbed light in the near-infrared (NIR) range, which was rapidly converted to heat energy. Human esophagus carcinoma cells (Eca-109) were killed efficiently by liposome-BSM nanocomposites upon NIR laser irradiation. Furthermore, mouse tumor tissues grown from Eca-109 cells were seriously damaged by the photothermal effects of the liposome-BSM nanocomposites, with significant tumor growth suppression compared with controls. Given that BSM is a safe and nutritious biomaterial that can be easily obtained from black sesame seed, the results presented herein represent an important development in the use of natural biomaterials for clinical SLN mapping and cancer therapy.

  18. Metastasis Detection in Sentinel Lymph Nodes: Comparison of a Limited Widely Spaced (NSABP protocol B-32) and a Comprehensive Narrowly Spaced Paraffin Block Sectioning Strategy

    PubMed Central

    Weaver, Donald L.; Le, U. Phuong; Dupuis, Stacey L.; Weaver, Katherine A. E.; Harlow, Seth P.; Ashikaga, Takamaru; Krag, David N.

    2009-01-01

    The NSABP B-32 trial is examining whether patients with initially negative sentinel lymph nodes (SLNs) who have occult metastases detected on deeper levels and cytokeratin immunohistochemistry (CK-IHC) stains are at risk for regional or distant metastases. The experimental B-32 protocol was designed to detect metastases larger than 1.0 mm by examining sections approximately 0.5 and 1.0 mm deeper into the paraffin blocks (2 levels; wide spacing). This pilot quality assurance study compares detection rates to a comprehensive protocol designed to detect metastases larger than 0.2 mm (multilevel; narrow spacing). All SLNs were sectioned grossly at close to 2.0 mm and all sections embedded in paraffin blocks. For clinical treatment, a single H&E section was examined from each block. For 54 cases with 1–5 SLNs and all SLNs negative, additional CK-IHC sections were evaluated every 0.18 mm through the block until no tissue remained. 20 of 176 (11.4%) blocks harbored occult metastases; the B-32 protocol detected metastases in 11 blocks (6.3%) and 9 additional blocks (5.1%) with metastases were detected on sections that would not have been evaluated (p=0.002; correlated proportions). Median number of levels examined per block on the comprehensive protocol was 11 (range 3–26); the B-32 protocol was fixed at 2 levels (median 2; range 1–2). Median thickness of node sections in the block was 2.1 mm (range 0.7–4.8 mm) and the modal thickness was 2.3 mm. Although more comprehensive sectioning of SLNs detects additional micrometastases, the data suggest diminishing returns and reduced cost effectiveness for the comprehensive strategy. PMID:19730364

  19. Role of patient and tumor characteristics in sentinel lymph node metastasis in patients with luminal early breast cancer: an observational study.

    PubMed

    La Verde, Nicla; Biagioli, Elena; Gerardi, Chiara; Cordovana, Andrea; Casiraghi, Chiara; Floriani, Irene; Bernardin, Elena; Farina, Gabriella; Di Cosimo, Serena; Dazzani, Maria Chiara; Gherardi, Giorgio

    2016-01-01

    Predicting the risk of sentinel lymph node (SLN) metastasis is important for clinical decision-making in the setting of early breast cancer (EBC). This study is aimed to identify tumor and patient characteristics that influenced the SLN metastatic involvement, with a focus on luminal subtypes. An observational study including women treated for EBC from 2005 to 2013 was conducted. Regression analyses were used to assess the association between SLN metastasis and age, menopausal status, tumor size, histological grading, presence of extensive "in situ" carcinoma components, lymphovascular invasion (LVI), and expression of Ki-67, hormone receptors, and HER2. Of 345 women, 84 (24.3 %) had at least one SLN metastasis; 63.1 % were macrometastases. Among all patients, 31.6 % exhibited LVI. In univariate analyses, tumor size, histological grade, and LVI were associated with SLN metastasis. The multivariate model confirmed only the association between LVI and SLN status (OR 3.27, 95 % CI 1.85-5.68; p < 0.0001). Luminal subtypes were detected in 86.1 % of women. In this subgroup, the multivariate model confirmed a significant relationship between LVI and SLN status (OR 3.47, 95 % CI 1.90-6.33; p < 0.0001). Since a proper histopathological assessment of LVI is not possible prior to surgery, this factor cannot be used to guide decisions on performing SLN biopsies. Nevertheless, when a SLN biopsy is refused or contraindicated, an LVI assessment on an excisional biopsy of the tumor could facilitate prognosis determination and treatment management.

  20. Lack of XAGE-1b and NY-ESO-1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients.

    PubMed

    Mori, Mariko; Funakoshi, Takeru; Kameyama, Kaori; Kawakami, Yutaka; Sato, Eiichi; Nakayama, Eiichi; Amagai, Masayuki; Tanese, Keiji

    2017-01-20

    The cancer-testis antigens (CTA) are a large family of tumor-associated antigens expressed by a variety of cancer cells and primitive germ cells of the adult testis and placenta. These tumor-restricted expressing patterns suggest that CTA would be ideal targets for tumor-specific immunotherapy. XAGE-1 is a CTA that was originally identified by computer-based screening, and four transcription variants, XAGE-1a, -1b, -1c and -1d, have been characterized to date. Although the presence of XAGE-1 transcripts has been reported in various cancers, the expression of XAGE-1b in melanoma has not been fully characterized. In this study, we performed immunohistochemical staining of XAGE-1b together with NY-ESO-1, a well-known CTA, in 113 melanoma samples obtained from 84 patients and evaluated their expression in tumor cells. The effects of expression on tumor progression and patient prognosis were analyzed. Both XAGE-1b and NY-ESO-1 were expressed at high levels in lymph node metastasis and skin metastasis samples compared with the primary site (P < 0.01 in XAGE-1b and P < 0.05 in NY-ESO-1). In a subgroup analysis of 22 patients with stage III lymph node metastasis, overall survival was significantly higher in the XAGE-1b and NY-ESO-1 double-negative group than in the other groups (P < 0.05). These results suggest that lack of XAGE-1b and NY-ESO-1 expression could have a positive influence on clinical outcome in patients with melanoma.

  1. A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis

    PubMed Central

    Duvall, Eric; Grasmick, Zachary; Haedicke, Kay

    2017-01-01

    Background Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma. Methods Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML), developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes. Results DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor. Conclusion The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease. PMID:28146572

  2. Sentinel node in cancer diagnosis with surgical probes

    NASA Astrophysics Data System (ADS)

    Kazandjian, Anne; Prat, Vincent; Simon, Herve; Ricard, Marcel; Bede, Jessica

    1999-10-01

    A probe system has been designed for the accurate location of areas of increased radionuclide uptake. Different type of applications are possible i.e. when precise position or even identification of the radionuclide is needed, like in wound investigation. In this paper, we restrict ourself to a system incorporating two probes, for the identification of `hot' lymph nodes, close to the surface of the body. Axillary lymph node involvement is a major prognostic indicator and treatment planning factor in both melanoma and breast cancer. However, sentinel node localization is relatively difficult often due to close proximity of the primary tumor. The developed instrument has a very sensitive detector, with good spatial resolution, able to discriminate between primary and scattered radiations.

  3. [Case of primary amelanotic malignant melanoma of the female urethra].

    PubMed

    Yoshii, Takahiko; Horiguchi, Akio; Shirotake, Suguru; Tobe, Musashi; Tasaki, Shinsuke; Hayakawa, Masamichi; Sumitomo, Makoto; Asano, Tomohiko

    2010-09-01

    We report a rare case of primary amelanotic malignant melanoma of the female urethra. A 58-year-old female with complaint of nodule on the external urethral meatus was referred to our hospital. Pathological diagnosis of the biopsy specimen from the nodule was malignant melanoma. Computed tomography of the chest and abdomen as well as bone scan showed no evidence of metastasis. Sentinel biopsy from the inguinal lymph nodes revealed no metastasis. Thereafter, the patient underwent radical urethrectomy, whose limits of resection were the bulbocavernosal muscles bilaterally, the arch of the pubic symphysis anteriorly, the anterior vaginal wall posteriorly, and the urethra up to the level of the bladder neck superiorly. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received six cycles of DAV-Feron (dacarbazine, nimustine, vincristine, and interferon-beta) in an adjuvant setting, and there is no sign of recurrence 25 months after operation.

  4. Malignant melanoma arising in an in vitro fertilisation pregnancy: A case report.

    PubMed

    Pabuccu, Recai; Kiseli, Mine; Kahyaoğlu, Inci; Cağlar, Gamze Sinem; Yılmaz, Müşerref Banu

    2013-01-01

    Malignant melanoma diagnosed during pregnancy results in confusion about staging and management. In this case report, a 39-year-old pregnant woman, who had undergone conception via in vitro fertilisation, was diagnosed with malignant melanoma of a growing lesion on her back in the 20th week of gestation. She delivered her baby by caesarean section in the 38th week. Metastasis was not found by chest X-ray, ultrasonography and positron emission tomography after delivery. She has been disease free for 6 months postpartum. Surgical resection of malignant melanoma and postponing of the sentinel lymph node biopsy has been proposed. Risk of adverse perinatal outcomes has not been increased; but the prognosis of malignant melanoma is known to be poorer when diagnosed during pregnancy. As a conclusion, any pigmentary change in the nevi should be assessed carefully during pregnancy.

  5. Association of occult metastases in sentinel lymph nodes and bone marrow with survival of women with early-stage invasive breast cancer

    PubMed Central

    Giuliano, Armando E.; Hawes, Debra; Ballman, Karla V.; Whitworth, Pat W.; Blumencranz, Peter W.; Reintgen, Douglas S.; Morrow, Monica; Leitch, A. Marilyn; Hunt, Kelly K.; McCall, Linda M.; Abati, Andrea; Cote, Richard

    2017-01-01

    Context Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathologic or clinical examination. Objective To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow from patients with early-stage breast cancer. Design, Setting, and Patients From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1–T2, N0, M0 invasive breast carcinoma in a prospective observational study. Interventions All patients underwent breast-conserving surgery and SLN dissection; bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). SLN specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results. Main Outcome Measures Overall survival (primary end point) and disease-free survival (a secondary end point). Results Of 5119 (98.3%) SLN specimens, 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were tumor-positive. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7% (95% CI, 95.0%–96.5%) for immunohistochemical positive and 95.1% (95% CI, 92.7%–97.5% for immunohistochemical negative disease, P=0.64), unadjusted hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.59–1.39; P=.64). Bone marrow metastases were associated with decreased overall survival (5-year rates: 95.0% (95% CI, 94.3%–95.8%) and 90.1% (95% CI, 84.5%–96.1%), respectively (P=.01) (unadjusted

  6. Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Stoeckli, Sandro J; Alkureishi, Lee W T; Ross, Gary L

    2009-06-01

    The appearance of lymph node metastases represents the most important adverse prognostic factor in head and neck squamous cell carcinoma. Therefore, accurate staging of the cervical nodes is crucial in these patients. The management of the clinically and radiologically negative neck in patients with early oral and oropharyngeal squamous cell carcinoma is still controversial, though most centers favor elective neck dissection for staging of the neck and removal of occult disease. As only approximately 30% of patients harbor occult disease in the neck, most of the patients have to undergo elective neck dissection with no benefit. The sentinel node biopsy concept has been adopted from the treatment of melanoma and breast cancer to early oral and oropharyngeal squamous cell carcinoma during the last decade with great success. Multiple validation studies in the context of elective neck dissections revealed sentinel node detection rates above 95% and negative predictive values for negative sentinel nodes of 95%. Sentinel node biopsy has proven its ability to select patients with occult lymphatic disease for elective neck dissection, and to spare the costs and morbidity to patients with negative necks. Many centers meanwhile have abandoned routine elective neck dissection and entered in observational trials. These trials so far were able to confirm the high accuracy of the validation trials with less than 5% of the patients with negative sentinel nodes developing lymph node metastases during observation. In conclusion, sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma can be considered as safe and accurate, with success rates in controlling the neck comparable to elective neck dissection. This concept has the potential to become the new standard of care in the near future.

  7. Prognostic differences across sexes in melanoma patients: what has changed from the past?

    PubMed

    Sanlorenzo, Martina; Ribero, Simone; Osella-Abate, Simona; Zugna, Daniela; Marenco, Federica; Macripò, Giuseppe; Fierro, Maria T; Bernengo, Maria G; Quaglino, Pietro

    2014-12-01

    Differences across the sexes include epidemiological trends, distribution of clinical features and prognostic relevance in melanoma patients. The aims of this single-institution hospital-based cohort study were as follows: to assess the trends over time of the male/female ratio; to analyse the clinicopathologic features according to sex and their modifications following the introduction in 1999 of sentinel lymph node biopsy; to ascertain the metastatic pathways across sexes and the prognostic role of sex in the disease-free interval (DFI), disease-specific survival (DSS) and survival after recurrence. The patient population included 4310 stage I-II melanoma patients, diagnosed, treated and followed up in our institution from 1975. Patients were divided into two groups on the basis of the introduction of sentinel lymph node biopsy in 1999. A female prevalence was observed until 1999; thereafter, the male/female ratio approached 1 (period 1999-2003), with a subsequent increasing trend suggesting a potential male prevalence. Longer DFI and DSS were observed after 1999 and men showed greater improvement compared with women. In multivariate analyses, sex showed a lower impact on DFI and survival after recurrence following the introduction on sentinel lymph node biopsy. No sex-related differences in terms of DSS were observed before and after 1999 among patients with melanoma located on the trunk. However, among patients with primary lesions not located on the trunk, sex maintained a significant prognostic role in both groups. The results of this study suggest that in the last few years, the prognosis of men could have improved more than that in women. The changing surgical/therapeutic interventions can influence sex disparities in melanoma.

  8. Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II*

    PubMed Central

    Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2016-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779

  9. Thin Melanoma: A Generic Term Including Four Histological Subtypes of Cutaneous Melanoma.

    PubMed

    Roncati, Luca; Pusiol, Teresa; Piscioli, Francesco

    2016-12-01

    Today, the scientific community is focusing on the prognostic significance of different histological subtypes of thin melanoma (1). The current staging system for melanoma of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute: melanomas with up to 1 mm thickness is defined as thin, because they present a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin ≥1 cm (2). There is a significant interaction between mitotic rate and Breslow depth, so the predictive value of the mitotic rate on sentinel lymph node (SLN) positivity can be dependent on Breslow thickness (3). Cutaneous melanoma generally evolves through three clearly discernible progression stages. At first, transformed melanocytes proliferate above the epidermal basement membrane (the in situ or epidermal radial growth phase); they then invade the papillary dermis (the micro-invasive radial growth phase); and subsequently acquire the capacity to grow as a well-known malignant tumor (the invasive vertical growth phase). More specifically, micro-invasive melanoma is a non-tumorigenic radial growth phase of cutaneous melanoma, which invades the superficial dermis without forming a tumor nodule or papule, in absence of regression (3). In contrast, the micro-invasive radial growth phase of cutaneous melanoma with regression will rarely metastasize and, for this reason, the lesion should be recognized and could also be categorized as a 'micro-invasive radial growth phase of uncertain tumorigenic potential' (4). The early vertical growth phase of tumorigenic melanoma is characterized by the presence of a cell cluster in the dermis that is larger than the largest cluster in the epidermis (5). This feature is typical of tumorigenicity, while the mitogenicity is documented by the observation of mitotic figures in dermal melanoma cells (5,6). The early vertical growth phase and the radial growth phase with regression

  10. Melanoma of the Umbilicus: A Patient Report, Precaution in Operative Strategy, and the First Histopathological Review of Published Cases

    PubMed Central

    Suzuki, Shuji; Yoshida, Yuichi; Shiomi, Tatsushi; Yanagihara, Shigeto; Kimura, Ryoko; Yamamoto, Osamu

    2016-01-01

    Umbilical melanoma is extremely rare. Among the past English reports on umbilical melanoma, there are only 8 reports in which histopathology was described in detail, and there has been no report with a review of the histopathology of previously reported cases. We experienced a case of umbilical melanoma and reviewed previously reported cases including our case. Because of the anatomical location, it is difficult to become aware of the umbilical melanoma unless there are some concomitant symptoms such as discharge or swelling. Even with these symptoms, patients tend to postpone a hospital visit for unknown reasons, resulting in increased risk of tumor growth and metastasis. When performing resection of umbilical melanoma, a portion of the peritoneum should also be removed. Sentinel lymph nodes can be axilla or inguinal lymph nodes. There is a possibility of metastasis to the preoperative abdominal cavity or to nearby skin through hematogenous spread. Preoperative evaluation of tumor spread and postoperative observation are important for umbilical melanoma in order to detect recurrence or metastasis because of its unique anatomical location. PMID:27493491

  11. The sentinel node in gynaecological malignancies

    PubMed Central

    Balega, J; Van Trappen, P O

    2006-01-01

    As lymph node metastasis is one of the earliest features of tumour cell spread in most human cancers, assessment of the regional lymph nodes is required for tumour staging, determining prognosis and planning adjuvant therapeutic strategies. However, complete lymph node dissections are frequently associated with significant complications. Conjugating the diagnostic advantages with decreased morbidity, the sentinel node concept represents one of the most recent advances in surgical oncology. In this review we briefly highlight the historical background of the development of the sentinel node concept, the anatomical evidence for applying the sentinel node concept in pelvic gynaecological cancers and the technical aspects of sentinel node detection. We discuss recent studies in vulval, cervical and endometrial cancer. PMID:16520291

  12. Cost comparison of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. A national study based on a prospective multi-institutional series of 985 patients ‘on behalf of the Group of Surgeons from the French Unicancer Federation’

    PubMed Central

    Classe, J. M.; Baffert, S.; Sigal-Zafrani, B.; Fall, M.; Rousseau, C.; Alran, S.; Rouanet, P.; Belichard, C.; Mignotte, H.; Ferron, G.; Marchal, F.; Giard, S.; Tunon de Lara, C.; Le Bouedec, G.; Cuisenier, J.; Werner, R.; Raoust, I.; Rodier, J.-F.; Laki, F.; Colombo, P.-E.; Lasry, S.; Faure, C.; Charitansky, H.; Olivier, J.-B.; Chauvet, M.-P.; Bussières, E.; Gimbergues, P.; Flipo, B.; Houvenaeghel, G.; Dravet, F.; Livartowski, A.

    2012-01-01

    Background: Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients. Patients and methods: We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery. Results: Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€2947 (σ = 580) versus €3331 (σ = 902); P = 0.0001]. Conclusion: ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources. PMID:21896543

  13. A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance.

    PubMed

    Wernicke, A Gabriella; Goodman, Robert L; Turner, Bruce C; Komarnicky, Lydia T; Curran, Walter J; Christos, Paul J; Khan, Imraan; Vandris, Katherine; Parashar, Bhupesh; Nori, Dattatreyudu; Chao, K S Clifford

    2011-02-01

    We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I-II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3-15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0-50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1-5) in cohort SLND and 18 (range 7-36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent

  14. Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma.

    PubMed

    Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, Lyn M

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  15. Immunomodulation by imiquimod in patients with high-risk primary melanoma

    PubMed Central

    Narayan, Rupa; Nguyen, Hong; Bentow, Jason J.; Moy, Lauren; Lee, Diana K.; Greger, Stephanie; Haskell, Jacquelyn; Vanchinathan, Veena; Chang, Pei-Lin; Tsui, Shanli; Konishi, Tamiko; Comin-Anduix, Begonya; Dauphine, Christine; Vargas, Hernan I.; Economou, James S.; Ribas, Antoni; Bruhn, Kevin W.; Craft, Noah

    2011-01-01

    Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80–100% cure rate of lentigo maligna, but studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLN), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A*0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted. PMID:21850019

  16. KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.

    PubMed

    Campillo, José A; Legaz, Isabel; López-Álvarez, M Rocío; Bolarín, José Miguel; Las Heras, Beatriz; Muro, Manuel; Minguela, Alfredo; Moya-Quiles, María R; Blanco-García, Rosa; Martínez-Banaclocha, Helios; García-Alonso, Ana M; Alvarez-López, M Rocío; Martínez-Escribano, Jorge A

    2013-05-01

    Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (Pc = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (Pc = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.

  17. Large-scale synthesis of bioinert tantalum oxide nanoparticles for X-ray computed tomography imaging and bimodal image-guided sentinel lymph node mapping.

    PubMed

    Oh, Myoung Hwan; Lee, Nohyun; Kim, Hyoungsu; Park, Seung Pyo; Piao, Yuanzhe; Lee, Jisoo; Jun, Samuel Woojoo; Moon, Woo Kyung; Choi, Seung Hong; Hyeon, Taeghwan

    2011-04-13

    Ever since Au nanoparticles were developed as X-ray contrast agents, researchers have actively sought alternative nanoparticle-based imaging probes that are not only inexpensive but also safe for clinical use. Herein, we demonstrate that bioinert tantalum oxide nanoparticles are suitable nanoprobes for high-performance X-ray computed tomography (CT) imaging while simultaneously being cost-effective and meeting the criteria as a biomedical platform. Uniformly sized tantalum oxide nanoparticles were prepared using a microemulsion method, and their surfaces were readily modified using various silane derivatives through simple in situ sol-gel reaction. The silane-modified surface enabled facile immobilization of functional moieties such as polyethylene glycol (PEG) and fluorescent dye. PEG was introduced to endow the nanoparticles with biocompatibility and antifouling activity, whereas immobilized fluorescent dye molecules enabled simultaneous fluorescence imaging as well as X-ray CT imaging. The resulting nanoparticles exhibited remarkable performances in the in vivo X-ray CT angiography and bimodal image-guided lymph node mapping. We also performed an extensive study on in vivo toxicity of tantalum oxide nanoparticles, revealing that the nanoparticles did not affect normal functioning of organs.

  18. Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity.

    PubMed

    Pons, Thomas; Pic, Emilie; Lequeux, Nicolas; Cassette, Elsa; Bezdetnaya, Lina; Guillemin, François; Marchal, Frédéric; Dubertret, Benoit

    2010-05-25

    Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II-VI and IV-VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR ( approximately 800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS(2)/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS(2)/ZnS QDs than for their Cd-containing counterparts.

  19. Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma.

    PubMed

    Ma, Qing; Zhou, Dapeng; DeLyria, Elizabeth S; Wen, Xiaoxia; Lu, Wei; Thapa, Prakash; Liu, Chengwen; Li, Dan; Bassett, Roland L; Overwijk, Willem W; Hwu, Patrick; Li, Chun

    2017-01-01

    There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8 T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%±16.9% of the injected PG-CpG dose versus 4.72%±2.61% of free CpG remained at the tumor, and 1.53%±1.22% of the injected PG-CpG versus 0.37%±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.

  20. Sentinel Network

    Cancer.gov

    The Sentinel Network is an integrated, electronic, national medical product safety initiative that compiles information about the safe and effective use of medical products accessible to patients and healthcare practitioners.

  1. Sentinel node in cancer diagnosis with surgical probes

    NASA Astrophysics Data System (ADS)

    Fougères, Paul; Kazandjian, Anne; Prat, Vincent; Simon, Hervé; Ricard, Marcel; Bede, Jessica

    2001-02-01

    A probe system has been designed for the accurate location of areas of increased radionuclide uptake. Different types of applications are possible, i.e. when the precise position or even identification of the radionuclide is needed, like in wound investigation. In this paper, we restrict ourselves to a system incorporating two probes, for the identification of "hot" lymph nodes, close to the surface of the body. Axillary lymph node involvement is a major prognostic indicator and treatment planning factor in both melanoma and breast cancer. However, sentinel node localisation is relatively difficult often due to close proximity of the primary tumour. The developed instrument has a very sensitive detector, with good spatial resolution, able to discriminate between primary and scattered radiation. In the first part of the paper the instrument arrangement will be presented, including the two probes, CdTe /CZT and CsI(Tl) coupled to a photodiode. In the second part results will be given, demonstrating the performance of the system.

  2. Lymph nodes

    MedlinePlus Videos and Cool Tools

    ... and conveying lymph and by producing various blood cells. Lymph nodes play an important part in the ... the microorganisms being trapped inside collections of lymph cells or nodes. Eventually, these organisms are destroyed and ...

  3. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma.

    PubMed

    Hauschild, Axel; Weichenthal, Michael; Rass, Knuth; Linse, Ruthild; Ulrich, Jens; Stadler, Rudolf; Volkenandt, Matthias; Grabbe, Stephan; Proske, Ulrike; Schadendorf, Dirk; Brockmeyer, Norbert; Vogt, Thomas; Rompel, Rainer; Kaufmann, Roland; Kaatz, Martin; Näher, Helmut; Mohr, Peter; Eigentler, Thomas; Livingstone, Elisabeth; Garbe, Claus

    2009-07-20

    PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.

  4. Fluorescence guided lymph node biopsy in large animals using direct image projection device

    NASA Astrophysics Data System (ADS)

    Ringhausen, Elizabeth; Wang, Tylon; Pitts, Jonathan; Akers, Walter J.

    2016-03-01

    The use of fluorescence imaging for aiding oncologic surgery is a fast growing field in biomedical imaging, revolutionizing open and minimally invasive surgery practices. We have designed, constructed, and tested a system for fluorescence image acquisition and direct display on the surgical field for fluorescence guided surgery. The system uses a near-infrared sensitive CMOS camera for image acquisition, a near-infra LED light source for excitation, and DLP digital projector for projection of fluorescence image data onto the operating field in real time. Instrument control was implemented in Matlab for image capture, processing of acquired data and alignment of image parameters with the projected pattern. Accuracy of alignment was evaluated statistically to demonstrate sensitivity to small objects and alignment throughout the imaging field. After verification of accurate alignment, feasibility for clinical application was demonstrated in large animal models of sentinel lymph node biopsy. Indocyanine green was injected subcutaneously in Yorkshire pigs at various locations to model sentinel lymph node biopsy in gynecologic cancers, head and neck cancer, and melanoma. Fluorescence was detected by the camera system during operations and projected onto the imaging field, accurately identifying tissues containing the fluorescent tracer at up to 15 frames per second. Fluorescence information was projected as binary green regions after thresholding and denoising raw intensity data. Promising results with this initial clinical scale prototype provided encouraging results for the feasibility of optical projection of acquired luminescence during open oncologic surgeries.

  5. History of sentinel node and validation of the technique

    PubMed Central

    Tanis, Pieter J; Nieweg, Omgo E; Valdés Olmos, Renato A; Th Rutgers, Emiel J; Kroon, Bin BR

    2001-01-01

    Sentinel node biopsy is a minimally invasive technique to select patients with occult lymph node metastases who may benefit from further regional or systemic therapy. The sentinel node is the first lymph node reached by metastasising cells from a primary tumour. Attempts to remove this node with a procedure based on standard anatomical patterns did not become popular. The development of the dynamic technique of intraoperative lymphatic mapping in the 1990s resulted in general acceptance of the sentinel node concept. This hypothesis of sequential tumour dissemination seems to be valid according to numerous studies of sentinel node biopsy with confirmatory regional lymph node dissection. This report describes the history and the validation of the technique, with particular reference to breast cancer. PMID:11250756

  6. Lymphatic mapping and sentinel node location with magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Jung, Chu W.; Rogers, James M.; Groman, Ernest V.

    1999-04-01

    Subcutaneously administered magnetite nanoparticles were used to locate sentinel lymph nodes in normal rats. Nanoparticles sequestered in brachial and axillary lymph nodes produced magnetic susceptibility artifacts in gradient recall echo magnetic resonance images. The artifact sizes enabled the determination of nanoparticle nodal uptake rates and lymphatic drainage patterns. These studies were confirmed by use of 59Fe labeled magnetite nanoparticles.

  7. Balloon cell melanoma: a case report with polarized and non-polarized dermatoscopy and dermatopathology

    PubMed Central

    Maher, James; Cameron, Alan; Wallace, Sharon; Acosta-Rojas, Rafael; Weedon, David; Rosendahl, Cliff

    2014-01-01

    Balloon cell melanoma is a rare melanoma subtype, with only one previous case with dermatoscopy published. It is often non-pigmented, leading to diagnostic difficulty, and there is a tendency for lesions to be thick at diagnosis. We report a case of balloon cell melanoma on the forearm of a 61-year-old man with both polarized and non-polarized dermatoscopy and dermatopathology. It presented as a firm pale nodule with focal eccentric pigmentation. The clinical images evoke a differential diagnosis of dermatofibroma, dermal nevus, Spitz nevus and basal cell carcinoma as well as melanoma. This melanoma was partially pigmented due to a small, pigmented superficial spreading component on the edge of the non-pigmented balloon cell nodule, prompting further evaluation. In retrospect there was the clue to malignancy of polarizing-specific white lines (chrysalis structures) and polymorphous vessels, including a pattern of dot vessels. The reticular lines exclude basal cell carcinoma, polarizing-specific white lines are inconsistent with the diagnosis of dermal nevus and their eccentric location is inconsistent with both Spitz nevus and dermatofibroma. Excision biopsy was performed, revealing a superficial spreading melanoma with two distinct invasive components, one of atypical non-mature epithelioid cells and the other an amelanotic nodular component, comprising more than 50% of the lesion, characterized by markedly distended epithelioid melanocytes showing pseudo-xanthomatous cytoplasmic balloon cell morphology. A diagnosis of balloon cell melanoma, Breslow thickness 1.9 mm, mitotic rate 3 per square millimeter was rendered. Wide local excision was performed, as was sentinel lymph node biopsy, which was negative. PMID:24520518

  8. Measuring the quality of melanoma surgery - Highlighting issues with standardization and quality assurance of care in surgical oncology.

    PubMed

    Pasquali, S; Sommariva, A; Spillane, A J; Bilimoria, K Y; Rossi, C R

    2017-03-01

    In an attempt to ensure high standards of cancer care, there is increasing interest in determining and monitoring the quality of interventions in surgical oncology. In recent years, this has been particularly the case for melanoma surgery. The vast majority of patients with melanoma undergo surgery. Usually, this is with combinations of wide excision, sentinel lymph node biopsy and lymphadenectomy. The indications for these procedures evolved during a time when no effective systemic adjuvant therapy was available, and whilst the rationale has been sound, the justification for differences in extent and thoroughness has generally been supported by inadequate or low-level evidence. This has led to a substantial variation among melanoma centres or even among surgeons within a centre in how these procedures are done. With recent rapid progress in the efficacy of systemic treatments that are impacting on overall survival, the prospect of long-term survival in these previously high risk patients means that more than ever long-term locoregional control of melanoma is imperative. Furthermore, the understanding of effects of systemic therapy on locoregional disease will only be interpretable if surgeons use standardized, high quality techniques. This article focuses on standardization and evolution of quality indicators for melanoma surgery and how these might have a positive impact on patient care.

  9. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  10. Sentinel node detection and radioguided occult lesion localization in breast cancer.

    PubMed

    Trifirò, Guiseppe; Lavinia Travaini, Laura; De Cicco, Concetta; Paganelli, Giovanni

    2006-01-01

    Sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 breast cancer patients and represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. In our Institute, Radioguided Occult Lesion Localization is the standard method to locate non-palpable breast lesions and the gamma probes is very effective in assisting intra-operative localization and removal, as in sentinel node biopsy. The rapid spread of sentinel lymph node biopsy has led to its use in clinical settings previously considered contraindications to sentinel lymph node biopsy. In this contest, we evaluated in a large group of patients possible factors affecting sentinel node detection and the reliability of sentinel lymph node biopsy carried out after large excisional breast biopsy. Our data confirm that a previous breast surgery does not prohibit efficient sentinel lymph node localization and sentinel lymph node biopsy can correctly stage the axialla in these patients.

  11. A Note of Caution: Variable Cytokeratin Staining in Sentinel Node Metastases.

    PubMed

    Zeng, Jennifer; Alexander, Melissa Ann; Nimeh, Diana; Darvishian, Farbod

    2015-10-01

    Sentinel lymph node biopsy is the current standard procedure used to stage patients with breast cancer. The best histological method in evaluating sentinel nodes is highly debated among institutions and is thus not standardized. The optimal histological analysis is a balance between comprehensive evaluation of the sentinel nodes and cost effectiveness. One commonly used approach is serial sectioning and alternately staining with hemotoxylin and eosin and AE1/AE3 cytokeratin immunohistochemistry analysis. We report 2 cases of metastatic carcinoma demonstrating negative staining for AE1/AE3. This observation highlights a rare but potential pitfall to this commonly used strategy in assessing sentinel lymph node biopsies in breast cancer.

  12. Value of DNA Ploidy and S-Phase Fraction as Prognostic Factors in Stage III Cutaneous Melanoma

    PubMed Central

    Martin, Ginette; Halwani, Fawaz; Shibata, Henry; Meterissian, Sarkis

    2000-01-01

    Objective To determine the prognostic value of flow cytometric analysis (S-phase fraction and DNA index) performed on lymph-node metastases of patients with stage III melanoma. Design A retrospective chart review with flow cytometric analysis of paraffin-embedded tissues. Setting A university teaching hospital. Patients Among 332 patients with cutaneous melanoma, 33 with stage III were identified. Distant metastases developed in 16 patients; 17 had no further recurrence. Charts were reviewed to obtain clinicopathologic parameters such as sex, age, location of the primary tumour, histologic features, presence or absence of ulceration, and Clark’s and Breslow’s levels. Intervention DNA ploidy and S-phase fraction were determined on the paraffin-embedded nodes. Main outcome measures The groups with or without recurrence were compared in terms of disease-free survival (DFS) and overall survival (OS). These survival parameters were correlated with DNA ploidy and S-phase fraction. Results By univariate analysis, clinicopathologic factors did not predict OS. A higher Clark’s level of invasion and more than 3 positive lymph nodes were associated with shorter DFS (p < 0.05). Tumour thickness and S-phase fraction did not correlate with either DFS or OS. Patients with diploid lymph-node metastases had an 87% 12-month survival compared with 41% for those with aneuploid tumours. Conclusions DNA ploidy may be used as a prognostic index in patients with lymph-node metastases. This could be particularly useful in the context of sentinel lymph-node mapping by which more patients are being identified with single microscopic lymph-node involvement. PMID:10714254

  13. Treatment plan for breast cancer with sentinel node metastasis

    PubMed Central

    Abreu, Efrén Bolívar; Martinez, Pedro; Betancourt, Luis; Romero, Gabriel; Godoy, Ali; Bergamo, Laura

    2014-01-01

    Lymph node involvement is considered to be one of the most important independent prognostic factors in breast cancer. In patients without palpable lymphadenopathies, the method of choice for determining this involvement is the sentinel lymph node biopsy. In the presence of macrometastases, the current standard is to perform axillary lymph node dissection in spite of the knowledge that the involvement of non-sentinel lymph nodes is approximately 50%. When lymph node involvement is micrometastasic, the decision as to whether or not to proceed with lymphadenectomy remains in dispute. We set out, on the basis of the current scientific evidence and our own experience, to create guidelines that allow us to individualise each case and decide whether or not to perform a lymphadenectomy. We will discuss the arguments that support our position. PMID:24478806

  14. The Danish Melanoma Database

    PubMed Central

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva; Schmidt, Grethe; Gad, Dorte; Svane, Inge Marie; Schmidt, Henrik; Lorentzen, Henrik Frank; Ibfelt, Else Helene

    2016-01-01

    Aim of database The aim of the database is to monitor and improve the treatment and survival of melanoma patients. Study population All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. Main variables The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. Descriptive data The DMD is an old research database, but new as a clinical quality register. The coverage is high, and the performance in the five Danish regions is quite similar due to strong adherence to guidelines provided by the Danish Melanoma Group. The list of monitored indicators is constantly expanding, and annual quality reports are issued. Several important scientific studies are based on DMD data. Conclusion DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment and research. PMID:27822097

  15. Adjuvant Treatment of Melanoma

    PubMed Central

    Moreno Nogueira, J. A.; Valero Arbizu, M.; Pérez Temprano, R.

    2013-01-01

    Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50–80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon-α2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas. PMID:23476798

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

    PubMed Central

    2010-01-01

    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. PMID:20478045

  17. Axillary Silicone Granulomas in Patients With Melanoma.

    PubMed

    Fernández Canedo, M I; Blázquez Sánchez, N; Valdés Solís, P; de Troya Martín, M

    2016-05-01

    Subcutaneous lesions may be detected during follow-up of patients with melanoma. The main entities that should be contemplated in the differential diagnosis in such cases are in-transit and regional lymph node metastases. We describe 2 cases of women with breast implants who developed palpable subcutaneous lesions in the axillary region during follow-up of melanoma. In both cases, the ultrasound study showed diffuse hyperechoic signals forming the characteristic snowstorm sign in the subcutaneous tissue. Ultrasound proved to be a key diagnostic tool for ruling out melanoma-related disease, such as in-transit metastases and regional lymph node metastases.

  18. Sentinel node biopsy (image)

    MedlinePlus

    Sentinel node biopsy is a technique which helps determine if a cancer has spread (metastasized), or is contained locally. When a ... is closest to the cancer site. Sentinel node biopsy is used to stage many kinds of cancer, ...

  19. Lymph system

    MedlinePlus

    Lymphatic system ... Dains JE, Flynn JA, Solomon BS, Stewart RW. Lymphatic system. In: Ball JW, Dains JE, Flynn JA, Solomon ... 2015:chap 9. Hall JE. The microcirculation and lymphatic system: capillary fluid exchange, interstitial fluid, and lymph flow. ...

  20. Nodal staging of colorectal carcinomas and sentinel nodes

    PubMed Central

    Cserni, G

    2003-01-01

    This review surveys the staging systems used for the classification of colorectal carcinomas, including the TNM system, and focuses on the assessment of the nodal stage of the disease. It reviews the quantitative requirements for a regional metastatic work up, and some qualitative features of lymph nodes that may help in the selection of positive and negative lymph nodes. Identification of the sentinel lymph nodes (those lymph nodes that have direct drainage from the primary tumour site) is one such qualitative feature that is claimed to allow the upstaging of colorectal carcinomas via an oriented, enhanced pathological work up. Current evidence in favour of a change in the requisite of assessing as may lymph nodes as is possible, and concentrating the efforts on only a selected number of lymph nodes, is weak. PMID:12719450

  1. Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma.

    PubMed

    Chevolet, I; Speeckaert, R; Schreuer, M; Neyns, B; Krysko, O; Bachert, C; Hennart, B; Allorge, D; van Geel, N; Van Gele, M; Brochez, L

    2015-03-01

    In melanoma, both the induction of immunosuppression by tumor cells and the inflammatory antitumor response can induce an upregulation of counter-regulatory mechanisms such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1) and CTLA-4(+) regulatory T-cells (Tregs) in the tumor microenvironment. Even though these immunosuppressive mediators are targets for immunotherapy, research investigating their expression in the peripheral blood is lacking. We therefore, performed flow cytometry on PBMCs of stage I-IV melanoma patients. IDO expression was detected in plasmacytoid dendritic cells (pDC) and monocytic myeloid-derived suppressor cells (mMDSC), and increased in advanced disease stage (p = 0.027). Tryptophan breakdown confirmed the functional activity of IDO and was linked with increased PD-L1+ cytotoxic T-cells (p = 0.009), relative lymphopenia (p = 0.036), and a higher mDC/pDC ratio (p = 0.002). High levels of circulating PD-L1+ cytotoxic T-cells were associated with increased CTLA-4 expression by Tregs (p = 0.005) and MDSC levels (p = 0.033). This illustrates that counter-regulatory immune mechanisms in melanoma should be considered as one interrelated signaling network. Moreover, both increased PD-L1+ T-cells and CTLA-4 expression in Tregs conferred a negative prognosis, indicating their in vivo relevance. Remarkably, circulating CTLA-4, IDO, and pDC levels were altered according to prior invasion of the sentinel lymph node and IDO expression in the sentinel was associated with more IDO+ PBMCs. We conclude that the expression of IDO, PD-L1, and CTLA-4 in the peripheral blood of melanoma patients is strongly interconnected, associated with advanced disease and negative outcome, independent of disease stage. Combination treatments targeting several of these markers are therefore likely to exert a synergistic response.

  2. History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture.

    PubMed

    Mansel, R E; Khonji, N I; Clarke, D

    2000-01-01

    The word Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.

  3. Sensor sentinel computing device

    DOEpatents

    Damico, Joseph P.

    2016-08-02

    Technologies pertaining to authenticating data output by sensors in an industrial environment are described herein. A sensor sentinel computing device receives time-series data from a sensor by way of a wireline connection. The sensor sentinel computing device generates a validation signal that is a function of the time-series signal. The sensor sentinel computing device then transmits the validation signal to a programmable logic controller in the industrial environment.

  4. The history of sentinel node biopsy in head and neck cancer: From visualization of lymphatic vessels to sentinel nodes.

    PubMed

    de Bree, Remco; Nieweg, Omgo E

    2015-09-01

    The aim of this report is to describe the history of sentinel node biopsy in head and neck cancer. Sentinel node biopsy is a minimally invasive technique to select patients for treatment of metastatic lymph nodes in the neck. Although this procedure has only recently been accepted for early oral cancer, the first studies on visualization of the cervical lymphatic vessels were reported in the 1960s. In the 1980s mapping of lymphatic drainage from specific head and neck sites was introduced. Sentinel node biopsy was further developed in the 1990s and after validation in this century the procedure is routinely performed in early oral cancer in several head and neck centers. New techniques may improve the accuracy of sentinel node biopsy further, particularly in difficult subsites like the floor of mouth.

  5. Conjunctival melanoma: a review of conceptual and treatment advances

    PubMed Central

    Lim, Li-Anne; Madigan, Michele C; Conway, R Max

    2013-01-01

    The aim of this study was to review the available literature and identify recent advances in the classification and management of conjunctival melanoma (CM) for clinicians working in this field. English-based articles were identified using the MEDLINE® database, and additional cited works not detected in the initial search were also obtained. Articles were assessed according to the Australian National Health and Medical Research Council levels of evidence criteria. Review of the literature indicated that the current classification and management of CM is predominantly based upon primarily nonrandomized, single-institution, retrospective case series. While these studies provide the basis for the recent seventh edition of the tumor node metastasis staging classification, this classification more accurately reflects the current knowledge of prognostic factors for CM. Application of this revised classification system together with prospective trials will provide the opportunity for future consistent and comparable data collection across centers, and it will improve the quality of evidence upon which current classification and management of CM is based. Furthermore, the high risk of local recurrence with current standard management suggests that adjuvant therapy, particularly mitomycin C and/or brachytherapy, may improve outcomes regardless of clinical staging. Finally, the use of sentinel lymph node biopsy may have significant benefit for a select group of CM patients. PMID:23515569

  6. Primary "flat" melanoma of the trachea.

    PubMed

    Mori, K; Cho, H; Som, M

    1977-02-01

    A 47-yr-old woman, complaining of shortness of breath, had a chest X-ray showing a right parahilar mass and bronchoscopic examination disclosed a bluish flat lesion on the posterior wall of the trachea at the level of the fifth and sixth rings. Histological examination of the resected segment of trachea and an adjacent lymph-node revealed a primary tracheal melanoma with lymph-node metastasis. Review of five reported cases and of the literature on mucosal melanomas disclosed that the flat configuration of the tumour and the abundance of melanophages observed in the present case were unique. Possible relationships to mucosal melanosis and squamous metaplasia were briefly discussed.

  7. Identification and resection of the clipped node decreases the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy – results from ACOSOG Z1071 (Alliance)

    PubMed Central

    Boughey, Judy C.; Ballman, Karla V.; Le-Petross, Huong T.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Taback, Bret; Feliberti, Eric C.; Hunt, Kelly K.

    2015-01-01

    Background The American College of Surgeons Oncology Group Z1071 trial reported a false negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery. Methods Z1071 was a multi-institutional trial in which women with clinical T0-4,N1-2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated. Results A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (CI:1.9–16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI:5.4–41.9%). In cases without a clip placed (n=355) and those where clipped node location was not confirmed at surgery (n=29), the FNR was 13.4% and 14.3%, respectively. Conclusion Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when performing SLN surgery in this setting. PMID:26649589

  8. Sentinel-1 Instrument Overview

    NASA Astrophysics Data System (ADS)

    Snoeij, Paul; Torres, Ramon; Geudtner, Dirk; Brown, Michael; Deghaye, Patrick; Navas-Traver, Ignacio; Ostergaard, Allan; Rommen, Bjorn; Floury, Nicolas; Davidson, Malcolm

    2013-03-01

    The forthcoming European Space Agency (ESA) Sentinel-1 (S-1) C-band SAR constellation will provide continuous all-weather day/night global coverage, with six days exact repetition time (near daily coverage over Europe and Canada) and with radar data delivery within 3 to 24 hours. These features open new possibilities for operational maritime services. The Sentinel-1 space segment has been designed and is being built by an industrial consortium with Thales Alenia Space Italia as prime contractor and EADS Astrium GmbH as C-SAR instrument responsible. It is expected that Sentinel-1A be launched in 2013. This paper will provide an overview of the Sentinel-1 system, the status and characteristics of the technical implementation. The key elements of the system supporting the maritime user community will be highlighted.

  9. A large retrospective multicenter study of vaginal melanomas: implications for new management.

    PubMed

    Vaysse, Charlotte; Pautier, Patricia; Filleron, Thomas; Maisongrosse, Veronique; Rodier, Jean-François; Lavoue, Vincent; Reyal, Fabien; Thomas, Laurence; de la Fouchardière, Arnaud; Delannes, Martine

    2013-04-01

    The outcome of patients presenting with vaginal melanoma has been assessed in a large multicentric retrospective study. The databases of 12 French institutions were searched for primary vaginal melanomas managed between 1990 and 2007. Among the 54 patients recorded, 46 were managed with a curative intent and included in the study. The clinical characteristics, treatments, and detection of c-KIT protein expression have been studied. The median age of the patients was 63.5 years (42-88). Twenty-eight patients were classified as International Federation of Gynecology and Obstetrics (FIGO) stage I, five as stage II, six as stage III, and one as stage IVA. c-KIT protein was overexpressed in 80% of the patients. Forty-two patients underwent surgical resection of the tumor, nine patients received local adjuvant treatment, and 10 received systemic adjuvant therapy. The median relapse-free survival was 10.9 months. c-KIT-negative status (P=0.01) and stage I (P=0.02) were associated with locoregional recurrence. The rate of metastasis was increased for advanced FIGO stages (P<0.01). The median overall survival (OS) was 28.4 months. The finding of lymph node metastasis adversely affected OS (P<0.01). Conservative surgery and radiotherapy were associated with a decrease in metastasis-free and OS (P<0.01) compared with surgery alone, this group of patients presenting with advanced FIGO stages (P=0.02). Despite the use of limited data, conservative surgery combined with a sentinel lymph node procedure, followed by adjuvant radiotherapy could be proposed to patients with early FIGO stage in the absence of validated management. c-KIT negativity by immunochemistry appears to be a poor prognosis marker in terms of locoregional recurrences but not for metastatic spread nor survival. Further assessment of the role of c-KIT expression in this disease is thus mandatory to select patients for targeted therapy.

  10. [Sentinel node biopsy in breast cancer: techniques and indications].

    PubMed

    Haid, Anton; Knauer, Michael; Köberle-Wührer, Roswitha; Wenzl, Etienne

    2005-02-01

    Sentinel node biopsy (SNB) has proved to be a useful and accurate procedure for lymph node staging in breast cancer and melanoma and should be standard of care in the treatment of these tumors. In other malignancies (colon, rectum, stomach, esophagus, head and neck and thyroid, cervix uteri) it is still under investigation. SNB in breast cancer was accepted as a sole and reliable diagnostic method in breast cancer from the panel of distinguished experts at the 8th international conference of primary therapy of early breast cancer 2003 in St. Gallen. Combination of the current techniques with radiocolloids and blue dye, applicated superficially (intradermal, subdermal, peri- and subareolar) and deeply (peritumoral, intratumoral, subtumoral) enables high identification rates and negative predictive values. It should be performed by teams consisting of surgeons, pathologists and nuclear medicine specialists with appropriate training and experience. Accepted indications are uni- and multifocal tumors smaller than 3 cm without suspicious findings in the axilla, furthermore SNB is indicated in patients with large ductal carcinoma in situ (>2cm) and/or with assumed microinvasion. Albeit SNB could be shown to be safe after preoperative chemotherapy and in multicentric breast cancer, due to lack of sufficient data it is still under discussion in these cases. Expedience of this procedure in other lymph node basins, along the mammaria interna vessels or in the infra- and supraclavicular region is considered to be at an investigative stage as well. SNB allows the pathologist to focus on a small number of nodes most likely to contain metastases. Application of serial sectioning and immunhistochemistry results in a more accurate staging than routine examination. Detection of additional micrometastases that are found in 10-15% leads to an upgrading from N0 to N1. Broad application and refurbishment led to scientific discussion of prognostic importance of micrometastases and its

  11. Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma-detecting probe.

    PubMed

    Alazraki, N P; Styblo, T; Grant, S F; Cohen, C; Larsen, T; Aarsvold, J N

    2000-01-01

    Sentinel node staging for breast cancer is increasingly used in place of axillary lymph node dissection but is not yet universally accepted. The problems of non-standardized methodologies and lack of consensus on the optimum techniques to identify sentinel nodes are being addressed. Complementary use of radionuclide imaging before surgery, intraoperative probe detection, and blue dye have yielded the best reported sensitivities for finding a sentinel node (94%). The importance of imaging is summarized as identifying sentinel node(s), distinguishing sentinel from secondary nodes, guiding surgical incision planning, and facilitating lower doses. The learning curve phenomenon, which applies to the surgeon and the nuclear medicine physician, has been recognized; measures to minimize it are being implemented. Radiation exposure to operating room and pathology personnel is very low; estimates of exposure to the surgeon's hands are 0.2% of the annual whole body dose received by every human being from natural background and cosmic sources.

  12. The role of ultrasound and lymphoscintigraphy in the assessment of axillary lymph nodes in patients with breast cancer

    PubMed Central

    Dobruch-Sobczak, Katarzyna; Wareluk, Paweł; Gumińska, Anna; Białek, Ewa; Cacko, Marek; Królicki, Leszek

    2016-01-01

    Breast cancer is the most common malignancy and the leading cause of death due to cancer in European women. Mammography screening programs aimed to increase the detection of early cancer stages were implemented in numerous European countries. Recent data show a decrease in mortality due to breast cancer in many countries, particularly among young women. At the same time, the number of sentinel node biopsy procedures and breast-conserving surgeries has increased. Intraoperative sentinel lymph node biopsy preceded by lymphoscintigraphy is used in breast cancer patients with no clinical signs of lymph node metastasis. Due to the limited sensitivity and specificity of physical examination in detecting metastatic lesions, developing an appropriate diagnostic algorithm for the preoperative assessment of axillary lymph nodes seems to be a challenge. The importance of ultrasound in patient qualification for sentinel lymph-node biopsy has been discussed in a number of works. Furthermore, different lymphoscintigraphy protocols have been compared in the literature. The usefulness of novel radiopharmaceuticals as well as the methods of image acquisition in sentinel lymph node diagnostics have also been assessed. The aim of this article is to present, basing on current guidelines, literature data as well as our own experience, the diagnostic possibilities of axillary lymph node ultrasound in patient qualification for an appropriate treatment as well as the role of lymphoscintigraphy in sentinel lymph node biopsy. PMID:27103998

  13. [Choroidal melanoma].

    PubMed

    Desjardins, Laurence

    2016-03-01

    Choroidal melanoma is the most common form of eye cancer in adults. Treatments enabling the tumour to be destroyed or removed while preserving the eye socket are mainly based on surgery, proton therapy and brachytherapy.

  14. Fluorescence imaging to study cancer burden on lymph nodes

    NASA Astrophysics Data System (ADS)

    D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; 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 along with a cancer targeting tracer, Affibody labeled with IRDYE800CW 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.

  15. Distribution of Prostate Sentinel Nodes: A SPECT-Derived Anatomic Atlas

    SciTech Connect

    Ganswindt, Ute; Schilling, David; Mueller, Arndt-Christian; Bares, Roland; Bartenstein, Peter; Belka, Claus

    2011-04-01

    Purpose: The randomized Radiation Therapy Oncology Group 94-13 trial revealed that coverage of the pelvic lymph nodes in high-risk prostate cancer confers an advantage (progression-free survival and biochemical failure) in patients with {>=}15% risk of lymph node involvement. To facilitate an improved definition of the adjuvant target volume, precise knowledge regarding the location of the relevant lymph nodes is necessary. Therefore, we generated a three-dimensional sentinel lymph node atlas. Methods and Materials: In 61 patients with high-risk prostate cancer, a three-dimensional visualization of sentinel lymph nodes was performed using a single photon emission computed tomography system after transrectal intraprostatic injection of 150 to 362 (median 295) mega becquerel (MBq) {sup 99m}Technetium-nanocolloid (1.5-3h after injection) followed by an anatomic functional image fusion. Results: In all, 324 sentinel nodes in 59 of 61 patients (96.7%) were detected, with 0 to 13 nodes per patient (median 5, mean 5.3). The anatomic distribution of the sentinel nodes was as follows: external iliac 34.3%, internal iliac 17.9%, common iliac 12.7%, sacral 8.6%, perirectal 6.2%, left paraaortic 5.3%, right paraaortic 5.3%, seminal vesicle lymphatic plexus 3.1%, deep inguinal 1.5%, superior rectal 1.2%, internal pudendal 1.2%, perivesical 0.9%, inferior rectal 0.9%, retroaortic 0.3%, superficial inguinal 0.3%, and periprostatic 0.3%. Conclusions: The distribution of sentinel nodes as detected by single photon emission computed tomography imaging correlates well with the distribution determined by intraoperative gamma probe detection. A lower detection rate of sentinels in close proximity to the bladder and seminal vesicles is probably caused by the radionuclide accumulation in the bladder. In regard to intensity-modulated radiotherapy techniques, the presented anatomic atlas may allow optimized target volume definitions.

  16. Tuberculosis axillary lymph node coexistent breast cancer in adjuvant treatment: case report

    PubMed Central

    Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório

    2015-01-01

    Coexistence of breast cancer and tuberculosis is rare. In most cases, involvement by tuberculosis occurs in axillary lymph nodes. We report a case of a 43-years-old patient who had undergone adenomastectomy and left sentinel lymph node biopsy due to a triple negative ductal carcinoma. At the end of adjuvant treatment, the patient had an atypical lymph node in the left axilla. Lymph node was excised, and after laboratory analysis, the diagnosis was ganglion tuberculosis. The patient underwent treatment for primary tuberculosis. The development of these two pathologies can lead to problems in diagnosis and treatment. An accurate diagnosis is important to avoid unnecessary surgical procedures. PMID:26018148

  17. Reticulin and NM23 staining in the interpretation of lymph nodal nevus rests.

    PubMed

    Kanner, William A; Barry, Catherine I; Smart, Chandra N; Frishberg, David P; Binder, Scott W; Wick, Mark R

    2013-06-01

    Melanocytic nevus rests in lymph nodes are a known diagnostic challenge, especially in patients with a history of melanoma. Reticulin and NM23 have been studied in this context. The pattern of reticulin staining in melanomas surrounds groups/nests of melanocytes but individual cells in benign nevi. NM23, a metastasis-suppressor gene, has an association with metastatic potential in melanomas and some carcinomas. Twenty-eight cases (14 cases of metastatic melanoma to lymph nodes and 14 cases of lymph node nevus rests, all confirmed with Melan-A staining) were stained with reticulin and NM23. The pattern of reticulin staining was reported as surrounding groups if staining was noted in approximately 5-10 melanocytes in greater than 50% of the lesion but was otherwise reported as surrounding individual melanocytes. Cytoplasmic staining was considered to represent reactivity for NM23. Reticulin staining around groups of melanocytes was identified in all 14 cases of metastatic melanoma. Regarding nodal nevus rest cases, 12 of 14 cases (86%) demonstrated staining around individual melanocytes, whereas in 2 cases, reticulin surrounded melanocytic groups. NM23 staining was equivocal in all cases. Reticulin staining reliably invests groups of melanocytes in cases of metastatic melanoma, whereas in nodal nevus rests, it predominantly surrounds individual melanocytes. NM23 demonstrated no discriminatory value in this analysis. In cases in which a collection of melanocytes is present within a lymph node, reticulin deposition around individual melanocytes supports a diagnosis of lymph nodal nevus rest.

  18. Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats.

    PubMed

    Herring, Erin S; Smith, Mark M; Robertson, John L

    2002-09-01

    A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

  19. Significantly high lymphatic vessel density in cutaneous metastasizing melanoma

    PubMed Central

    Špirić, Z; Erić, M; Eri, Ž; Skrobić, M

    2015-01-01

    Background Cutaneous melanoma has the propensity to early metastatic spread via the lymphatic vessels. Recent studies have found a positive correlation between an increased number of tumor-associated lymphatics and lymph node metastasis. The aim of this study was to determine whether there was a difference in the lymphatic vessel density (LVD) when cutaneous metastasizing melanomas were compared with nonmetastasizing melanomas and nevi. Methods Ninety-five melanoma specimens (45 with lymph node metastasis, 50 nonmetastasizing) and 22 nevi specimens (7 compound, 5 intradermal, 4 blue, and 6 dysplastic) were investigated by immunostaining for the lymphatic endothelial marker D2-40. The quantification of lymphatics was conducted by computer-assisted morphometric analysis. Metastasizing and nonmetastasizing melanoma specimens were matched according to their thickness into three classes ≤2.0 mm, 2.01 – 4.0 mm, >4.0 mm. Results Metastasizing melanomas thick 2.01–4.0 mm and thicker than 4.0 mm, showed a significantly higher intratumoral and peritumoral LVD compared with nonmetastasizing melanomas (2.01–4.0 mm, p =0.006 and p =0.032, respectively; >4.0 mm, p =0.045 and p =0.026, respectively). No significant difference in intratumoral and peritumoral LVD was found between metastasizing and nonmetastasizing melanomas of thickness ≤2.0 mm. Metastasizing melanomas showed a significantly higher intratumoral LVD compared with compound, intradermal, blue and dysplastic nevi p <0.001, p =0.002, p =0.002 and p <0.001, respectively), and significantly higher peritumoral LVD compared with compound nevi (p=0.039). Total average LVD was significantly higher in metastasizing melanomas than in nonmetastasizing melanomas (p <0.001), compound, intradermal, blue and dysplastic nevi (p <0.001, p <0.001, p =0.001 and p <0.001, respectively). Conclusions This study shows higher LVD in metastasizing melanomas compared with nonmetastasizing melanomas and nevi. In melanomas with

  20. Clinical and morphological characteristics of cutaneous melanoma.

    PubMed

    Balaban, Jagoda; Ninković Baroš, Djuka; Grujić, Dragana; Starović, Dragana; Ćelić, Milanka

    2014-01-01

    The incidence of cutaneous melanoma has increased significantly worldwide over the last several decades. The aim of this study is to determine clinical and morphology characteristics of primary melanoma, since some of them are important prognostic factors. This retrospective study included 172 patients. The data were collected by the Consulting team for malignant skin tumors in the Banja Luka Clinical Centre from 2009 to 2011. We did not use dermoscopy as a diagnostic tool in our investigation. We determined that melanoma occurs equally commonly in both sexes, in women in the sixth decade and the seventh in men. The most common sub-type was nodular melanoma (59.5%, P<0.05), followed by superficial spreading (27.8%) and acral lentiginous melanoma (11.4%). The most common localization was on the back in men (34.3%) and on the legs in women (P<0.05). More than half of our patients (55.8%) had melanoma thickness from 1.0 to 4.0 mm, and 38% had a melanoma thicker than 4.0 mm. The average Breslow thickness is 4.6 mm. More women than men had melanoma thicker than 4 mm (P<0.05). Spread of the primary tumor localization was found in 31.4% of patients, more frequently in men than in women (P<0.05). In most cases it was abstraction of lymph nodes (P<0.05). The average thickness of the melanoma in our patients is much higher than the average in the world and the countries of Europe. The results of this study indicate a need for better unique regional registry in this part of Bosnia and Herzegovina and improvement of preventive measures in the early diagnosis of melanoma.

  1. Melanoma Diagnosis

    NASA Astrophysics Data System (ADS)

    Horsch, Alexander

    The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

  2. Nano-imaging of the lymph network structure with quantum dots

    NASA Astrophysics Data System (ADS)

    Hikage, Makoto; Gonda, Kohsuke; Takeda, Motohiro; Kamei, Takashi; Kobayashi, Masaki; Kumasaka, Masutaka; Watanabe, Mika; Satomi, Susumu; Ohuchi, Noriaki

    2010-05-01

    Sentinel lymph node diagnosis contributes to operative strategy in cancer surgery. During lymph node metastasis, cancer cells first reach the sentinel lymph node (SLN) via lymph flow. To perform SLN biopsy effectively, it is important that cancer cells are detected with high sensitivity in SLN connected to the tumor site. Here we present a method to visualize a high-risk area in the SLN for lymph node metastasis with a high degree of accuracy. Quantum dots (QDs), bright fluorescent nanoparticles, were endoscopically injected into the gastrointestinal wall of pigs, and their signal was specifically detected in the SLN with a laparoscopic device. Single-particle imaging under a confocal microscope showed that the QDs were distributed heterogeneously in the SLN and that their distribution marked the inflow locus of afferent lymphatic vessels where lymph node metastasis begins. Moreover, we developed a method using cellular marker conjugated QDs that visualizes specific cells in SLNs, suggesting that this method can be applied for the detection of cancer cells in sentinel lymph nodes using tumor-specific-molecular conjugated QDs. These results show that our method might significantly increase the detection rate of cancer metastasis in SLNs.

  3. Uveal Melanoma

    PubMed Central

    Papastefanou, Vasilios P.; Cohen, Victoria M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future. PMID:21773036

  4. Antioxidants can increase melanoma metastasis in mice.

    PubMed

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-07

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression.

  5. Cutaneous melanoma of the breast.

    PubMed

    Papachristou, D N; Kinne, D W; Rosen, P P; Ashikari, R; Fortner, J G

    1979-03-01

    A study of 115 cutaneous melanomas of the breast demonstrated that these neoplasms follow different metastatic patterns than do primary carcinomas of the breast and require a different therapuetic approach. Lesions located below a 3 cm from the clavicle metastasized exclusively to the axillary nodes regardless of location. None of 19 internal mammary node chains examined histologically contained tumor deposits. Microstaging of the primary lesion correlated closely with prognosis and lymph node metastasis. Treatment by mastectomy (radical, modified, extended radical) offered no advantage over local excision of the primary plus axillary dissection. The latter procedure is recommended for all cutaneous melanomas of the breast which require node dissection. Mastectomy is not indicated unless the breast is in the field of wide local excision. Internal mammary node dissections are not indicated.

  6. Assessment of lymph node involvement in colorectal cancer

    PubMed Central

    Ong, Mark L H; Schofield, John B

    2016-01-01

    Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed. PMID:27022445

  7. Role of parathymic lymph nodes in metastatic tumor development.

    PubMed

    Banfalvi, Gaspar

    2012-06-01

    Parathymic lymph nodes as potential sites of tumor progression have been neglected in humans. We have established a rat renal capsule-parathymic lymph node model to study in vivo metastasis. Epithelial liver carcinoma (HeDe) and mesenchymal mesoblastic nephroma (NeDe) cell lines have been established after inducing chemical carcinogenesis in newborn Fisher 344 inbred rats by N-nitrosodimethylamine. Implanting the exact number of tumor cells (HeDe, NeDe) under the renal capsule allowed the standardization and timing of metastatic development. Tumor cells released from the primary tumor in the peritoneal cavity were drained to the parathymic lymph nodes (PTNs) as sentinel lymph nodes. Similarly, tumor cells injected i.p. were engulfed by macrophages, drained through the transdiaphragmatic channels, and transported to the thoracal lymphatics, primarily to PTNs. Tumor cells after transdiaphragmic drainage can enter both anterior mammary and parathymic sentinel lymph nodes. The potential common origin can shed new light on the metastatic cell progression of PTNs and mammary tumors.

  8. Sentinel-2 Mission status

    NASA Astrophysics Data System (ADS)

    Hoersch, Bianca; Colin, Olivier; Gascon, Ferran; Arino, Olivier; Spoto, Francois; Marchese, Franco; Krassenburg, Mike; Koetz, Benjamin

    2016-04-01

    Copernicus is a joint initiative of the European Commission (EC) and the European Space Agency (ESA), designed to establish a European capacity for the provision and use of operational monitoring information for environment and security applications. Within the Copernicus programme, ESA is responsible for the development of the Space Component, a fully operational space-based capability to supply earth-observation data to sustain environmental information Services in Europe. The Sentinel missions are Copernicus dedicated Earth Observation missions composing the essential elements of the Space Component. In the global Copernicus framework, they are complemented by other satellites made available by third-parties or by ESA and coordinated in the synergistic system through the Copernicus Data-Access system versus the Copernicus Services. The Copernicus Sentinel-2 mission provides continuity to services relying on multi-spectral high-resolution optical observations over global terrestrial surfaces. Sentinel-2 capitalizes on the technology and the vast experience acquired in Europe and the US to sustain the operational supply of data for services such as forest monitoring, land cover changes detection or natural disasters management. The Sentinel-2 mission offers an unprecedented combination of the following capabilities: ○ Systematic global coverage of land surfaces: from 56°South to 84°North, coastal waters and Mediterranean sea; ○ High revisit: every 5 days at equator under the same viewing conditions with 2 satellites; ○ High spatial resolution: 10m, 20m and 60m; ○ Multi-spectral information with 13 bands in the visible, near infra-red and short wave infra-red part of the spectrum; ○ Wide field of view: 290 km. The data from the Sentinel-2 mission are available openly and freely for all users with online easy access since December 2015. The presentation will give a status report on the Sentinel-2 mission, and outlook for the remaining ramp-up Phase, the

  9. SNAP (Sentinel Application Platform) and the ESA Sentinel 3 Toolbox

    NASA Astrophysics Data System (ADS)

    Zuhlke, Marco; Fomferra, Norman; Brockmann, Carsten; Peters, Marco; Veci, Luis; Malik, Julien; Regner, Peter

    2015-12-01

    ESA is developing three new free open source Toolboxes for the scientific exploitation of the Sentinel-1, Sentinel-2 and Sentinel-3 missions. The Toolboxes are based on a common software platform, namely the Sentinel Application Platform (SNAP). SNAP is an evolution of the proven ESA BEAM/NEST architecture inheriting all current BEAM and NEST functionality including multi-mission support for SAR and optical missions to support ESA and third party missions for years to come. The Sentinel-3 Toolbox includes generic function for visualisation and analysis of Sentinel-3 OLCI and SLSTR Level 1 and Level 2 data, as well as specific processing tools such as cloud screening, water constituent retrieval and SST retrieval. The Toolbox will put emphasis on access to remote in-situ databases such as Felyx or MERMAID, and exploitation of the data-uncertainty information which is included in the Sentinel-3 data products. New image classification, segmentation and filtering methods, as well as interoperability with the ORFEO Toolbox and the GDAL libraries will be additional new tools. New challenges stemming from Sentinel-3 sensors, such as raster data in different resolutions within a single dataset, will be supported gracefully. The development of SNAP and the Sentinel Toolboxes is funded through the “Scientific Exploitation of Operational Missions (SEOM)” programme, a new programme element of ESA’s fourth period of the Earth Observation Envelope Programme (2013-2017).

  10. Swollen lymph nodes

    MedlinePlus

    ... lymph nodes, including: Seizure medicines such as phenytoin Typhoid immunization Which lymph nodes are swollen depends on ... hard, irregular, or fixed in place. You have fever, night sweats, or unexplained weight loss. Any node ...

  11. Lymph node biopsy

    MedlinePlus

    ... Performed The test is used to diagnose cancer, sarcoidosis, or an infection (such as tuberculosis): When you ... of lymph nodes and other organs and tissues ( sarcoidosis ) Risks Lymph node biopsy may result in any ...

  12. Completion of axillary dissection for a positive sentinel node: necessary or not?

    PubMed

    Erb, Kathleen M; Julian, Thomas B

    2009-01-01

    Sentinel node excision has been widely accepted as the initial surgical step for evaluating the axilla for metastatic breast cancer. When the nodes are positive, the standard of care is to complete the axillary node dissection, a more extended procedure that carries an increased risk for morbidity. This article reviews data from sentinel lymph node trials, case series reports of outcomes when axillary node dissection was not performed in the setting of positive sentinel nodes, models for predicting the status of nonsentinel nodes, and the morbidity associated with axillary operations. Despite an approximate 10% false-negative rate, early results indicate that there is a much lower local recurrence rate after sentinel node excision alone and that systemic therapy may sterilize the axilla. In selected patients, it may be appropriate to forgo an axillary node dissection, although there are no randomized clinical trial data to support or refute this suggestion.

  13. (Neo)adjuvant systemic therapy for melanoma.

    PubMed

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  14. Noninvasive and label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    NASA Astrophysics Data System (ADS)

    Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Wei, Xunbin

    2015-03-01

    Melanoma is a malignant tumor of melanocytes. Circulating melanoma cell has high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC). PAFC is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. In our research, we developed in vitro experiments to prove the ability of PAFC system of detecting PA signals from melanoma cells. For in vivo experiments, we constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells B16F10 with subcutaneous injection. PA signals were detected in the blood vessels of mouse ears in vivo. By counting circulating melanoma cells termly, we obtained the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation. Our PAFC system is an efficient tool to monitor melanoma metastases, cancer recurrence and therapeutic efficacy.

  15. [Vulvar melanoma].

    PubMed

    Chokoeva, A; Tchernev, G; Wollina, U

    2015-01-01

    Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist < 5% of all cases of melanoma in females, as the ratio of its manifestation, compared with the cutaneous melanoma is 1:71. Higher risk of developing melanoma of the vulva is established in white women, as the peak of the incidence is between 60 and 70 years of age. Clinically, MM of the vulva manifests as asymptomatic pigmented, rarely a pigmented lesion, as the usual clinical form is superficial spreading MM and much less common nodular MM, which is associated with a poorer prognosis in. general. The diagnosis is confirmed by histological examination. Conduction of PCR and DNA analysis for detection of BRAF mutations, NRAS mutations and KIT amplification is also appropriate. Advanced age, black race, tumor size, tumor thickness, ulceration, presence of satellite lesions, involvement of adjacent organs (vagina, urethra), and the presence of regional or distant metastases are identified as the most important prognostic markers. Radical wide excision followed by bilateral lymphadenectomy id considered as the optimal therapeutic approach.

  16. Sentinel-3 for Science

    NASA Astrophysics Data System (ADS)

    Benveniste, J.; Regner, P.; Desnos, Y. L.

    2015-12-01

    The Scientific Exploitation of Operational Mission (SEOM) programme element (http://seom.esa.int/) is part of the ESA's Fourth Earth Observation Envelope Programme (2013-2017). The prime objective is to federate, support and expand the international research community that the ERS, ENVISAT and the Envelope programmes have built up over the last 25 years. It aims to further strengthen the leadership of the European Earth Observation research community by enabling them to extensively exploit future European operational EO missions. SEOM is enabling the science community to address new scientific research that are opened by free and open access to data from operational EO missions. The Programme is based on community-wide recommendations for actions on key research issues, gathered through a series of international thematic workshops and scientific user consultation meetings such as the Sentinel-3 for Science Workshop held last June in Venice, Italy (see http://seom.esa.int/S3forScience2015). The 2015 SEOM work plan includes the launch of new R&D studies for scientific exploitation of the Sentinels, the development of open-source multi-mission scientific toolboxes, the organization of advanced international training courses, summer schools and educational materials, as well as activities for promoting the scientific use of EO data, also via the organization of Workshops. This paper will report the recommendations from the International Scientific Community concerning the Sentinel-3 Scientific Exploitation, as expressed in Venice, keeping in mind that Sentinel-3 is an operational mission to provide operational services (see http://www.copernicus.eu).

  17. What Does Melanoma Look Like?

    MedlinePlus

    ... Skin Cancer Skin Cancer Screening Research What Does Melanoma Look Like? Melanoma is a type of cancer ... melanoma is itchy, tender, or painful. Photos of Melanoma A large, asymmetrical melanoma with an uneven color ...

  18. Melanomas of unknown primary have a mutation profile consistent with cutaneous sun-exposed melanoma.

    PubMed

    Dutton-Regester, Ken; Kakavand, Hojabr; Aoude, Lauren G; Stark, Mitchell S; Gartside, Michael G; Johansson, Peter; O'Connor, Linda; Lanagan, Cathy; Tembe, Varsha; Pupo, Gulietta M; Haydu, Lauren E; Schmidt, Christopher W; Mann, Graham J; Thompson, John F; Scolyer, Richard A; Hayward, Nicholas K

    2013-11-01

    Melanoma of unknown primary (MUP) is an uncommon phenomenon whereby patients present with metastatic disease without an evident primary site. To determine their likely site of origin, we combined exome sequencing from 33 MUPs to assess the total rate of somatic mutations and degree of UV mutagenesis. An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11. Results showed that the majority of MUPs exhibited high somatic mutation rates, high ratios of C>T/G>A transitions, and a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas. These data suggest that a significant proportion of MUPs arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin.

  19. [Update to the recommendations for management of melanoma stages I to III].

    PubMed

    Guillot, B; Dalac, S; Denis, M G; Dupuy, A; Emile, J-F; De La Fouchardière, A; Hindie, E; Jouary, T; Lassau, N; Mirabel, X; Piperno Neumann, S; De Raucourt, S; Vanwijck, R

    2016-10-01

    As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3years) is recommended for patients, but with greater emphasis on imaging.

  20. Whole proteome analysis of mouse lymph nodes in cutaneous anthrax.

    PubMed

    Popova, Taissia G; Espina, Virginia; Zhou, Weidong; Mueller, Claudius; Liotta, Lance; Popov, Serguei G

    2014-01-01

    This study aimed to characterize a soluble proteome of popliteal lymph nodes during lymphadenitis induced by intradermal injection of Bacillus anthracis Sterne spores in mice using tandem LC-MS/MS and reverse-phase protein microarray with antibodies specific to epitopes of phosphorylated proteins. More than 380 proteins were detected in the normal intra-nodal lymph, while the infectious process resulted in the profound changes in the protein abundances and appearance of 297 unique proteins. These proteins belong to an array of processes reflecting response to wounding, inflammation and perturbations of hemostasis, innate immune response, coagulation and fibrinolysis, regulation of body fluid levels and vascular disturbance among others. Comparison of lymph and serum revealed 83 common proteins. Also, using 71 antibodies specific to total and phosphorylated forms of proteins we carried initial characterization of circulating lymph phosphoproteome which brought additional information regarding signaling pathways operating in the lymphatics. The results demonstrate that the proteome of intra-nodal lymph serves as a sensitive sentinel of the processes occurring within the lymph nodes during infection. The acute innate response of the lymph nodes to anthrax is accompanied by cellular damage and inflammation with a large number of up- and down-regulated proteins many of which are distinct from those detected in serum. MS data are available via ProteomeXchange with identifier PXD001342.

  1. Whole Proteome Analysis of Mouse Lymph Nodes in Cutaneous Anthrax

    PubMed Central

    Zhou, Weidong; Mueller, Claudius; Liotta, Lance; Popov, Serguei G.

    2014-01-01

    This study aimed to characterize a soluble proteome of popliteal lymph nodes during lymphadenitis induced by intradermal injection of Bacillus anthracis Sterne spores in mice using tandem LC-MS/MS and reverse-phase protein microarray with antibodies specific to epitopes of phosphorylated proteins. More than 380 proteins were detected in the normal intra-nodal lymph, while the infectious process resulted in the profound changes in the protein abundances and appearance of 297 unique proteins. These proteins belong to an array of processes reflecting response to wounding, inflammation and perturbations of hemostasis, innate immune response, coagulation and fibrinolysis, regulation of body fluid levels and vascular disturbance among others. Comparison of lymph and serum revealed 83 common proteins. Also, using 71 antibodies specific to total and phosphorylated forms of proteins we carried initial characterization of circulating lymph phosphoproteome which brought additional information regarding signaling pathways operating in the lymphatics. The results demonstrate that the proteome of intra-nodal lymph serves as a sensitive sentinel of the processes occurring within the lymph nodes during infection. The acute innate response of the lymph nodes to anthrax is accompanied by cellular damage and inflammation with a large number of up- and down-regulated proteins many of which are distinct from those detected in serum. MS data are available via ProteomeXchange with identifier PXD001342. PMID:25329596

  2. Sentinel Node Biopsy in Early Breast Cancer.

    PubMed

    Basso, Stefano M M; Chiara, Giordano B; Lumachi, Franco

    2016-01-01

    The approach to the axilla is an evolving paradigm, and recognition of the complexity of breast cancer (BC) biology is changing treatment options. The sentinel lymph node biopsy (SLNB) technique is based on the excision and histological examination of the axillary lymph nodes(s), which is assumed to be the first one draining from the primary tumor. SLNB can accurately stage the axilla, and several trials have shown that there are no significant differences in local recurrence and overall survival between patients treated with or without axillary node dissection (ALND) after a negative SLNB. Surgical morbidity was significantly reduced in terms of rates of lymphedema and neuropathy, with reduced hospital stay and better quality of life after the SLNB procedure. ALND can safely be omitted in patients with ≥2 positive nodes who received conservative surgery and radiotherapy, while ALND is still recommended in clinically N1 BCs, in case of ≥3 positive nodes, and when the number of positive nodes would be crucial for the choice of chemotherapy. Micrometastatic disease can be safely managed with SLNB alone, and additional identification of micrometastases with immunohistochemistry does not affect disease-free survival or overall survival. An appropriate management of the axilla is crucial for the outcome of patients with early BC, and SLNB introduction into the clinical practice dramatically changed the surgical treatment, reducing morbidity without decreasing survival. A tailored approach should be suggested in each patient with BC, considering the biology of the tumor rather than nodal involvement.

  3. Sentinel-3 For Land Applications

    NASA Astrophysics Data System (ADS)

    Goryl, Philippe; Gobron, Nadine; Mecklenburg, Susanne; Donlon, Craig; Bouvet, Marc; Buongiorno, Alessandra; Wilson, Hilary

    2016-07-01

    The Copernicus Programme, being Europe's Earth Observation and Monitoring Programme led by the European Union, aims to provide, on a sustainable basis, reliable and timely services related to environmental and security issues. The Sentinel-3 mission forms part of the Copernicus Space Component. Its main objectives, building on the heritage and experience of the European Space Agency's (ESA) ERS and ENVISAT missions, are to measure sea-surface topography, sea- and land-surface temperature and ocean- and land-surface colour in support of ocean forecasting systems, and for environmental and climate monitoring. The series of Sentinel-3 satellites will ensure global, frequent and near-real time ocean, ice and land monitoring, with the provision of observation data in a routine, long-term (up to 20 years of operations) and continuous fashion, with a consistent quality and a high level of reliability and availability. The launch of Sentinel-3 was successful last February 2016. The Sentinel-3 missions are jointly operated by ESA and EUMETSAT. ESA will be responsible for the operations, maintenance and evolution of the Sentinel-3 ground segment on land related products and EUMETSAT on the marine products and the satellite monitoring and control. All facilities supporting the Sentinel-3 operations are in place. The Sentinel-3 ground segment systematically acquires, processes and distributes a set of pre-defined core data products to the users. For a detailed description of the core data products please see https://earth.esa.int/web/sentinel/missions/sentinel-3/data-products. On request from the European Commission, ESA and EUMETSAT are presently assessing the possibility to include further core data products, in particular on aerosol optical depth, fire monitoring and synergistic products over land. This paper will provide an update on the status of the mission operations after the initial months in orbit and provide in particular an overview on the status of the Sentinel-3

  4. Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Inguinal Node Metastases in Patients With Anal Cancer

    SciTech Connect

    Mistrangelo, Massimiliano; Pelosi, Ettore; Bello, Marilena; Castellano, Isabella; Cassoni, Paola; Ricardi, Umberto; Munoz, Fernando; Racca, Patrizia; Contu, Viviana; Beltramo, Giancarlo; Morino, Mario; Mussa, Antonio

    2010-05-01

    Background: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. Methods and Materials: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. Results: PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. Conclusions: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.

  5. Innovation in early breast cancer surgery: radio-guided occult lesion localization and sentinel node biopsy.

    PubMed

    Paganelli, G; Veronesi, U

    2002-07-01

    The surgical management of non-palpable breast lesions remains controversial. At the European Institute of Oncology we have introduced a new technique, radio-guided occult lesion localization (ROLL) to replace standard methods and overcome their disadvantages. Regarding axillary dissection, probe-guided biopsy of the sentinel node (SN) is easy to apply, and the whole procedure is associated to a low risk of false negatives. We suggest that the SN technique should be widely adopted to stage the axilla in patients with breast cancer with clinically negative lymph nodes. Large-scale implementation of the sentinel node technique will reduce the cost of treatment as a result of shorter hospitalization times.

  6. Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo

    NASA Astrophysics Data System (ADS)

    Jung, Yeongri; Zhi, Zhongwei; Wang, Ruikang K.

    2010-09-01

    Sentinel lymph nodes (SLNs) are the first lymph nodes to drain wastes originated from cancerous tissue. There is a need for an in vivo imaging method that can image the intact SLN to further our understanding of its normal as well as abnormal functions. We report the use of ultrahigh sensitive optical microangiography (UHS-OMAG) to image functional microvascular and lymphatic vessel networks that innervate the intact lymph node in mice in vivo. The promising results show a potential role of UHS-OMAG in the future understanding and diagnosis of the SLN involvement in cancer development.

  7. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  8. Cutaneous Melanoma in Asians

    PubMed Central

    Kim, Sang Yub

    2016-01-01

    Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians. PMID:27689028

  9. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  10. Augmented reality visualization in head and neck surgery: an overview of recent findings in sentinel node biopsy and future perspectives.

    PubMed

    Profeta, Andrea Corrado; Schilling, Clare; McGurk, Mark

    2016-07-01

    "Augmented reality visualisation", in which the site of an operation is merged with computer-generated graphics, provides a way to view the relevant part of the patient's body in better detail. We describe its role in relation to sentinel lymph node biopsy (SLNB), current advancements, and future directions in the excision of tumours in early-stage cancers of the head and neck.

  11. Revisiting determinants of prognosis in cutaneous melanoma.

    PubMed

    Weiss, Sarah A; Hanniford, Douglas; Hernando, Eva; Osman, Iman

    2015-12-01

    The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma.

  12. Genetic and morphologic features for melanoma classification

    PubMed Central

    Broekaert, Sigrid M.C.; Roy, Ritu; Okamoto, Ichiro; van den Oord, Joost; Bauer, Jürgen; Garbe, Claus; Barnhill, Raymond L.; Busam, Klaus J.; Cochran, Alistair J.; Cook, Martin G.; Elder, David E.; McCarthy, Stanley W.; Mihm, Martin C; Schadendorf, Dirk; Scolyer, Richard A.; Spatz, Alain; Bastian, Boris C.

    2011-01-01

    Summary Melanoma is comprised of biologically distinct subtypes. The defining clinical, histomorphologic and molecular features are not fully established. This study sought to validate the association between genetic and histomorphologic features previously described, determine their reproducibility, and association with important clinical variables. Detailed clinical and histomorphologic features of 365 primary cutaneous melanomas were assessed by 11 pathologists and correlated with mutation status of BRAF and NRAS. There was substantial agreement in the quantitative assessment of histomorphologic features showing similar or better interobserver reproducibility than the established WHO classification scheme. We confirmed that melanomas with BRAF mutations showed characteristic morphologic features (p<0.0001) and metastasized more frequently to regional lymph nodes (p=0.046). Importantly, melanomas without mutations were a heterogeneous group, with a subset having very similar features clinical and morphological features than those with BRAF mutation raising the possibility that they are biologically related. Our study confirms an association between histomorphologic features, mutation status and pattern of metastasis, providing criteria for a refined melanoma classification aimed at defining biologically homogeneous disease subgroups. PMID:20874733

  13. Sentinel-3 Mission Overview

    NASA Astrophysics Data System (ADS)

    Klein, U.; Berruti, B.; Donlon, C.; Frerick, J.; Mavrocordatos, C.; Nieke, J.; Seitz, B.; Stroede, J.; Rebhan, H.

    2009-04-01

    The series of Sentinel-3 satellites will provide global, frequent and near-realtime ocean, ice and land monitoring. Sentinel-3 will be particularly devoted to the provision of observation data in routine, long term (20 years of operations) and continuous fashion with a consistent quality and a very high level of availability. It will continue the successful observations of similar predecessor instruments onboard Envisat from 2012 onwards. The Ocean and Land Colour Instrument (OLCI) is based on the Envisat MEdium Resolution Imaging Spectrometer Instrument (MERIS) instrument. It fulfils ocean-colour and land-cover objectives with a larger swath and additional spectral bands. The Sea and Land Surface Temperature radiometer (SLSTR) is based on Envisat's Advanced Along Track Scanning Radiometer (AATSR). SLSTR has a double-scanning mechanism, yielding a wider swath and a complete overlap with OLCI. This enables the generation of a synergy product with a total of 30 spectral bands, fully co-registered for new and innovative ocean and land products. The topography mission has the primary objective of providing accurate, closely spaced altimetry measurements from a high-inclination orbit with a long repeat cycle. It will complement the Jason ocean altimeter series monitoring mid-scale circulation and sea levels. The altimeter will be operated in two different modes, a classical low resolution mode and a synthetic aperture mode similar to CryoSat for increased along-track resolution and improved performance. Accompanying the altimeter will be a Precise Orbit Determination system and microwave radiometer (MWR) for removing the errors related to the altimeter signals being delayed by water vapour in the atmosphere. The altimeter will track over a variety of surfaces: Open ocean, coastal zones, sea ice and inland waters. The conceptual designs of the major instruments and their basic performance parameters will be introduced together with the expected accuracies of the main

  14. Near-infrared-fluorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives.

    PubMed

    Toyota, Taro; Fujito, Hiromichi; Suganami, Akiko; Ouchi, Tomoki; Ooishi, Aki; Aoki, Akira; Onoue, Kazutaka; Muraki, Yutaka; Madono, Tomoyuki; Fujinami, Masanori; Tamura, Yutaka; Hayashi, Hideki

    2014-01-15

    Liposomally formulated indocyanine green (LP-ICG) has drawn much attention as a highly sensitive near-infrared (NIR)-fluorescence probe for tumors or lymph nodes in vivo. We synthesized ICG derivatives tagged with alkyl chains (ICG-Cn), and we examined NIR-fluorescence imaging for lymph nodes in the lower extremities of mice by using liposomally formulated ICG-Cn (LP-ICG-Cn) as well as conventional liposomally formulated ICG (LP-ICG) and ICG. Analysis with a noninvasive preclinical NIR-fluorescence imaging system revealed that LP-ICG-Cn accumulates in only the popliteal lymph node 1h after injection into the footpad, whereas LP-ICG and ICG accumulate in the popliteal lymph node and other organs like the liver. This result indicates that LP-ICG-Cn is a useful NIR-fluorescence probe for noninvasive in vivo bioimaging, especially for the sentinel lymph node.

  15. Chondroitin sulfate proteoglycan-4: a biomarker and a potential immunotherapeutic target for canine malignant melanoma.

    PubMed

    Mayayo, Saray Lorda; Prestigio, Simone; Maniscalco, Lorella; La Rosa, Giuseppe; Aricò, Arianna; De Maria, Raffaella; Cavallo, Federica; Ferrone, Soldano; Buracco, Paolo; Iussich, Selina

    2011-11-01

    Chondroitin sulfate proteoglycan-4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is a membrane-bound chondroitin sulfate proteoglycan highly expressed by human melanoma cells. This phylogenetically conserved tumour antigen plays an important biological role in human melanoma, where it is used as a marker to diagnose forms with unusual characteristics, such as desmoplastic melanoma, and to detect melanoma cells in lymph nodes and peripheral blood, and as a target for immunotherapy because of its restricted distribution in normal tissues. To identify suitable targets to develop novel approaches of treating canine melanoma, CSPG4 was studies to see whether it is expressed in canine malignant melanomas. Immunohistochemical staining of 65 canine malignant melanomas with an anti-human CSPG4-specific antibody detected CSPG4 in 37 cases (56.9%). Positive staining was more frequent, albeit not significantly, in amelanotic compared to melanotic tumours and was statistically associated with tumours having both melanin and the epithelioid histotype. The frequency of CSPG4 expression was similar to that of other melanoma antigens used as diagnostic markers for canine malignant melanoma, such as Melan A and the protein recognized by the PNL2 monoclonal antibody. The results suggest that CSPG4 constitutes a new potential immunohistochemical marker of canine malignant melanoma and may represent an immunotherapeutic target as in humans.

  16. Blood and Lymph Diseases

    MedlinePlus

    ... in direct contact with the external environment, the circulatory system acts as a transport system for these cells. Two distinct fluids move through the circulatory system: blood and lymph. Blood carries oxygen and nutrients ...

  17. Lymph node culture

    MedlinePlus

    Culture - lymph node ... or viruses grow. This process is called a culture. Sometimes, special stains are also used to identify specific cells or microorganisms before culture results are available. If needle aspiration does not ...

  18. Drugs Approved for Melanoma

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  19. Melanoma - neck (image)

    MedlinePlus

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  20. Molecular Classification of Melanoma

    Cancer.gov

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  1. Intramammary lymph nodes.

    PubMed Central

    Jadusingh, I. H.

    1992-01-01

    AIMS: To determine the prevalence and pathology of intramammary lymph nodes in breast specimens. METHODS: All breast specimens examined by a single pathologist over 70 months in a large teaching hospital were studied retrospectively. All the surgical pathology reports were reviewed. Relevant glass slides from cases in which intramammary lymph nodes were identified were also reexamined. RESULTS: Breast specimens (n = 682) were examined. Seven lymph nodes were found in five patients. The specimens comprised 533 biopsy specimens, 29 segmental resections, 22 reduction mammoplasties, 77 modified radical mastectomies and 20 gynecomastia mastectomies. No clinically relevant microscopical abnormalities were found in four lymph nodes and slight sinus histiocytosis was seen in two nodes. One node contained metastatic adenocarcinoma and benign glandular epithelial inclusions. CONCLUSION: Although rare, intramammary lymph nodes may be detected by careful gross examination of breast specimens even in the absence of clinical identification. They can occur in any quadrant of the breast and can display a variety of pathological conditions. Pathologists should be alert to the existence and potential importance of these lymph nodes. Images PMID:1452776

  2. Melanoma to the heart

    PubMed Central

    Hall, James A.; Fidone, Erica J.; Mack, Ryan; Metting, Austin L.

    2016-01-01

    Malignant melanoma is the third most common skin cancer yet has the highest mortality rate due to its predilection for metastasis. While the diagnosis of antemortem melanoma with cardiac metastasis is relatively uncommon, diagnosing malignant melanoma itself by first identifying a cardiac metastasis is even more rare. This vignette describes an antemortem diagnosis of melanoma in a 50-year-old woman through identification of metastasis to multiple sites, including the tricuspid valve. PMID:27695188

  3. Melanoma to the heart.

    PubMed

    Durham, Charis G; Hall, James A; Fidone, Erica J; Mack, Ryan; Metting, Austin L

    2016-10-01

    Malignant melanoma is the third most common skin cancer yet has the highest mortality rate due to its predilection for metastasis. While the diagnosis of antemortem melanoma with cardiac metastasis is relatively uncommon, diagnosing malignant melanoma itself by first identifying a cardiac metastasis is even more rare. This vignette describes an antemortem diagnosis of melanoma in a 50-year-old woman through identification of metastasis to multiple sites, including the tricuspid valve.

  4. ORAL AMELANOTIC MELANOMA

    PubMed Central

    Adisa, A.O.; Olawole, W.O.; Sigbeku, O.F.

    2012-01-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399

  5. Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2017-01-18

    Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  6. Hybrid tracers for sentinel node biopsy.

    PubMed

    Van Den Berg, N S; Buckle, T; Kleinjan, G I; Klop, W M; Horenblas, S; Van Der Poel, H G; Valdés-Olmos, R A; Van Leeuwen, F I

    2014-06-01

    Conventional sentinel node (SN) mapping is performed by injection of a radiocolloid followed by lymphoscintigraphy to identify the number and location of the primary tumor draining lymph node(s), the so-called SN(s). Over the last decade research has focused on the introduction of new imaging agents that can further aid (surgical) SN identification. Different tracers for SN mapping, with varying sizes and isotopes have been reported, most of which have proven their value in a clinical setting. A major challenge lies in transferring this diagnostic information obtained at the nuclear medicine department to the operating theatre thereby providing the surgeon with (image) guidance. Conventionally, an intraoperative injection of vital blue dye or a fluorescence dye is given to allow intraoperative optical SN identification. However, for some indications, the radiotracer-based approach remains crucial. More recently, hybrid tracers, that contain both a radioactive and fluorescent label, were introduced to allow for direct integration of pre- and intraoperative guidance technologies. Their potential is especially high when they are used in combination with new surgical imaging modalities and navigation tools. Next to a description of the known tracers for SN mapping, this review discusses the application of hybrid tracers during SN biopsy and how the introduction of these new techniques can further aid in translation of nuclear medicine information into the operating theatre.

  7. Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

    ClinicalTrials.gov

    2014-05-20

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  8. The Evolving Role of Radiation Therapy in the Management of Malignant Melanoma

    SciTech Connect

    Khan, Niloufer; Khan, Mohammad K.; Almasan, Alex; Singh, Arun D.; Macklis, Roger

    2011-07-01

    The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotactic radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.

  9. Dormancy of Growth-Stunted Malignant Melanoma: Sustainable and Smoldering Patterns

    PubMed Central

    Piérard-Franchimont, Claudine; Hermanns-Lê, Trinh; Delvenne, Philippe; Piérard, Gerald E.

    2014-01-01

    The presentations of primary and metastatic cutaneous malignant melanoma (CMM) are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the so-called CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocyte-mediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear. PMID:25992239

  10. Disorders of lymph flow.

    PubMed

    Witte, C L; Witte, M H

    1995-04-01

    Disturbances in blood capillary exchange of fluid, macromolecules, and cells across intact and abnormal microvessels and deranged lymphatic transport are integral, interacting components in disorders of tissue swelling. Lymphedema or low-output failure of the lymph circulation is often indolent for many years before lymphatic insufficiency (failure) and tissue swelling emerge and persist. Superimposed occult or overt infection (lymphangitis) are probably major contributors to progressive limb deformity (elephantiasis). Long-standing lymphedema is characterized by trapping in the skin and subcutaneous tissue of fluid, extravasated plasma proteins, and other macromolecules: impaired immune cell trafficking; abnormal processing of autologous and foreign antigens; heightened susceptibility to superimposed infection; local immunodysregulation; defective lymphatic (lymphangion) propulsion from an imbalance of mediators regulating vasomotion; soft-tissue overgrowth; scarring and hypertrophy; and exuberant angiogenesis occasionally culminating in vascular tumors (Fig. 8). In contrast to the blood circulation, where flow depends primarily on the propulsive force of the myocardium, lymph propulsion depends predominately on intrinsic truncal contraction, a phylogenetic vestige of amphibian lymph hearts. Whereas venous "plasma" flows rapidly (2-3 l/min) against low vascular resistance, lymph flows slowly (1-2 ml/min) against high vascular resistance. On occasion, impaired transport of intestinal lymph may be associated with reflux and accumulation and leakage of intestinal chyle in a swollen leg. Although the term "lymphedema" is usually reserved for extremity swelling, the pathogenesis of a wide variety of visceral disorders also may be traceable to defective tissue fluid and macromolecular circulation and impaired cell trafficking of lymphocytes and macrophages. Thus, lymph stasis, with impaired tissue fluid flow, underlies or complicates an indolent subclinical course with

  11. Sentinel 2 global reference image

    NASA Astrophysics Data System (ADS)

    Dechoz, C.; Poulain, V.; Massera, S.; Languille, F.; Greslou, D.; de Lussy, F.; Gaudel, A.; L'Helguen, C.; Picard, C.; Trémas, T.

    2015-10-01

    Sentinel-2 is a multispectral, high-resolution, optical imaging mission, developed by the European Space Agency (ESA) in the frame of the Copernicus program of the European Commission. In cooperation with ESA, the Centre National d'Etudes Spatiales (CNES) is responsible for the image quality of the project, and will ensure the CAL/VAL commissioning phase. Sentinel-2 mission is devoted the operational monitoring of land and coastal areas, and will provide a continuity of SPOT- and Landsat-type data. Sentinel-2 will also deliver information for emergency services. Launched in 2015 and 2016, there will be a constellation of 2 satellites on a polar sun-synchronous orbit, imaging systematically terrestrial surfaces with a revisit time of 5 days, in 13 spectral bands in visible and shortwave infra-red. Therefore, multi-temporal series of images, taken under the same viewing conditions, will be available. So as to ensure for the multi-temporal registration of the products, specified to be better than 0.3 pixels at 2σ, a Global Reference Image (GRI) will be produced during the CAL/VAL period. This GRI is composed of a set of Sentinel-2 acquisitions, which geometry has been corrected by bundle block adjustment. During L1B processing, Ground Control Points will be taken between this reference image and the sentinel-2 acquisition processed and the geometric model of the image corrected, so as to ensure the good multi-temporal registration. This paper first details the production of the reference during the CALVAL period, and then details the qualification and geolocation performance assessment of the GRI. It finally presents its use in the Level-1 processing chain and gives a first assessment of the multi-temporal registration.

  12. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    ClinicalTrials.gov

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  13. [Eye and lymph drainage].

    PubMed

    Grüntzig, J; Schicha, H; Huth, F

    1979-06-01

    Up to now lymphatics in the eye could not be pointed out. An ocular lymph drainage is denied. Földi succeeded in producing experimentally the syndrome of "lymphostatic encephalopathy and ophthalmopathy" by operative blockade of the cervical lymphatics in animals. In the first part of the present paper a historical view considering the subject "Eye and lymphatic system" is given. In the second part it is entered into the particulars of own experimental studies. As to our own investigations, rabbits have been injected 99mTc-sulfur-colloid, 99mTc-microcolloid, 99mTc-Albumin and 198Au-colloid into the retrobulbar space, anterior chamber, vitreous body and subconjuctival space of one eye. Measurements of the activity's distribution have been made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after section with a sodium iodine crystal well counter (Clinimat-200, Picker). In some animals the investigation has been combined with a bilateral dissection of the cervical lymph nodes. After injection in the retrobulbar space a significant concentration of the activity could be observed for the most part in the equilateral Lymphonodulus cervicalis profundus. By the cervical lymph blockade the removal of lymphoctopic substances from the retrobulbar space was largely inhibited. After injection in the anterior chamber a significant concentration could be observed for the most part in the equilateral Lymphonodulus cervicalis superficialis. After intravitreal injection a drainage to the bilateral deep cervical lymph nodes could be observed. After injection into the subconjunctival space a significant accumulation of activity could be registered in the equilateral Lymphonoduli mandibulares and cervicales superficiales. The data substantiate a segmental lymph drainage from the eye: vitreous body and retrobulbar space for the most part into the Lymphonoduli cervicales profundi, anterior chamber and subconjunctival space for the most part into

  14. Cutaneous Melanoma in Women

    PubMed Central

    Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin

    2015-01-01

    The incidence of cutaneous melanoma (CM) continues to increase in the Caucasian population in the United States. In 2014, women only accounted for 42% of the 76,100 new melanoma cases and only 33% of the 9,710 deaths associated with CM in the US.1 These trends are consistently observed in populations around the world. Indeed, gender disparity in melanoma outcome is so consistently observed that gender has been suggested as an important prognostic factor in melanoma, despite not being formerly incorporated in staging algorithms.2 The source of this gender disparity in melanoma remains unclear but likely represents both biological and behavioral etiologies. Herein, we review the current knowledge of how melanoma differs between men and women. PMID:25844396

  15. [Targeted therapies for melanoma].

    PubMed

    Leiter, U; Meier, F; Garbe, C

    2014-07-01

    Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

  16. Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma.

    PubMed

    Siiskonen, Hanna; Poukka, Mari; Bykachev, Andrey; Tyynelä-Korhonen, Kristiina; Sironen, Reijo; Pasonen-Seppänen, Sanna; Harvima, Ilkka T

    2015-12-01

    The role of mast cells in cutaneous melanoma remains unclear. Tryptase and chymase are serine proteinases and major proteins in mast cell secretory granules. Therefore, this study aimed to investigate the presence of tryptase and chymase mast cells in benign and malignant cutaneous melanocytic lesions and in lymph node metastases of melanomas. The presence of positively stained mast cells was correlated with clinicopathological characteristics in invasive melanomas. Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm) invasive melanomas and 30 lymph node metastases were immunohistochemically stained for mast cell tryptase and chymase, and immunopositive cells were counted using the hotspot counting method. The mean count of tryptase and chymase mast cells was lower in invasive melanomas compared with in-situ melanomas and dysplastic and benign nevi. In deeply invasive melanomas, the difference was statistically significant compared with dysplastic nevi (P=0.003 for tryptase and P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of tryptase mast cells were associated with poor overall survival (P=0.031) in deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in superficially invasive melanomas. Low numbers of chymase mast cells were associated with microsatellites (P=0.017) in deeply invasive melanomas. The results suggest that these serine proteinases of mast cells may be protective in the pathogenesis of melanoma.

  17. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  18. Sentinel-3 SAR Altimetry Toolbox

    NASA Astrophysics Data System (ADS)

    Benveniste, Jerome; Lucas, Bruno; DInardo, Salvatore

    2015-04-01

    The prime objective of the SEOM (Scientific Exploitation of Operational Missions) element is to federate, support and expand the large international research community that the ERS, ENVISAT and the Envelope programmes have build up over the last 20 years for the future European operational Earth Observation missions, the Sentinels. Sentinel-3 builds directly on a proven heritage of ERS-2 and Envisat, and CryoSat-2, with a dual-frequency (Ku and C band) advanced Synthetic Aperture Radar Altimeter (SRAL) that provides measurements at a resolution of ~300m in SAR mode along track. Sentinel-3 will provide exact measurements of sea-surface height along with accurate topography measurements over sea ice, ice sheets, rivers and lakes. The first of the two Sentinels is expected to be launched in early 2015. The current universal altimetry toolbox is BRAT (Basic Radar Altimetry Toolbox) which can read all previous and current altimetry mission's data, but it does not have the capabilities to read the upcoming Sentinel-3 L1 and L2 products. ESA will endeavour to develop and supply this capability to support the users of the future Sentinel-3 SAR Altimetry Mission. BRAT is a collection of tools and tutorial documents designed to facilitate the processing of radar altimetry data. This project started in 2005 from the joint efforts of ESA (European Space Agency) and CNES (Centre National d'Etudes Spatiales), and it is freely available at http://earth.esa.int/brat. The tools enable users to interact with the most common altimetry data formats, the BratGUI is the front-end for the powerful command line tools that are part of the BRAT suite. BRAT can also be used in conjunction with Matlab/IDL (via reading routines) or in C/C++/Fortran via a programming API, allowing the user to obtain desired data, bypassing the data-formatting hassle. BRAT can be used simply to visualise data quickly, or to translate the data into other formats such as netCDF, ASCII text files, KML (Google Earth

  19. Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

    2016-03-01

    Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. The raw signal detected from target cells often contains some noise caused by electronic devices, such as background noise and thermal noise. We choose the Wavelet denoising method to effectively distinguish the target signal from background noise. Processing in time domain and frequency domain would be combined to analyze the signal after denoising. This algorithm contains time domain filter and frequency transformation. The frequency spectrum image of the signal contains distinctive features that can be used to analyze the property of target cells or particles. The processing methods have a great potential for analyzing signals accurately and rapidly. By counting circulating melanoma cells termly, we obtain the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.

  20. Primary leptomeningeal melanoma.

    PubMed

    Xie, Zhao-Yu; Hsieh, Kevin Li-Chun; Tsang, Yuk-Ming; Cheung, Wing-Keung; Hsieh, Chen-Hsi

    2014-06-01

    Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature.

  1. Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats.

    PubMed

    Kaminskas, Lisa M; McLeod, Victoria M; Ascher, David B; Ryan, Gemma M; Jones, Seth; Haynes, John M; Trevaskis, Natalie L; Chan, Linda J; Sloan, Erica K; Finnin, Benjamin A; Williamson, Mark; Velkov, Tony; Williams, Elizabeth D; Kelly, Brian D; Owen, David J; Porter, Christopher J H

    2015-02-02

    The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.

  2. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  3. Copernicus POD Service: Ready for Sentinel-3

    NASA Astrophysics Data System (ADS)

    Peter, H.; Fernández, J.; Escobar, D.; Féménias, P.; Flohrer, C.; Otten, M.

    2015-12-01

    The Copernicus POD Service is part of the Copernicus PDGS Ground Segment of the Sentinel missions. A GMV-led consortium is operating the Copernicus POD Service being in charge of generating precise orbital products and auxiliary data files for their use as part of the processing chains of the respective Sentinel PDGS. The Sentinel-1, -2 & -3 missions have different but very demanding requirements in terms of orbital accuracy and timeliness. Orbital products in Near Real Time (latency: 30 min), Short Time Critical (1.5 days) and Non-time Critical (20-30 days) are required. The accuracy requirements are very challenging, targeting 5 cm in 3D for Sentinel-1 and 2-3 cm in radial direction for Sentinel-3. Sentinel-3A carries, in addition to a GPS receiver a laser retro reflector and a DORIS receiver. On the one hand, the three different techniques GPS, SLR and DORIS make POD more complex but, on the other hand, it is very helpful to have independent techniques available for validation of the orbit results. The successful POD processing for Sentinel-1A is a good preparation for Sentinel-3A due to the similar demanding orbit accuracy requirements. The Copernicus POD Service is ready for Sentinel-3A and the service will process GPS and SLR data routinely and has the capacity to process DORIS in NTC and reprocessing campaigns. The three independent orbit determination techniques on Sentinel-3 offer big potential for scientific exploitation. Carrying all three techniques together makes the satellite, e.g., very useful for combining all the techniques on observation level as it could only be done for Jason-2 until now. The Sentinel POD Quality Working Group strongly supporting the CPOD Service delivers additional orbit solutions to validate the CPOD results independently. The recommendations from this body guarantee that the CPOD Service is updated following state-of-the-art algorithms, models and conventions. The QWG also focuses on the scientific exploitation of the

  4. The sentinel behaviour of Arabian babbler floaters

    PubMed Central

    Heifetz, Aviad

    2017-01-01

    The sentinel behaviour of 38 Arabian babbler adult floaters, who lived alone within a territory belonging to a foreign group, was studied and compared with their own sentinel behaviour in the past, when they were group members. All floaters acted as sentinels and uttered ‘alarm calls’. This suggests that sentinel activity is due at least, in part, to selfish motives. Floaters sentinelled less than they did as group members, with the decrease in sentinel activity sharper for ex-dominants than for ex-subordinates. One possible explanation for these differences is that sentinel activity is aimed not only at detecting predators, but also at detecting foreign conspecifics. Within a group, the latter incentive is stronger for breeding dominants than for subordinates, whereas all floaters alike may be trying to detect the owners of the territory in which they were roaming but also to avoid being detected by them. Other possible explanations are that floaters have less time and energy for sentinel activity because they are weaker or because foraging is more difficult in a foreign territory. This may be especially so for dominants who used to enjoy privileged access to food in their group. No significant difference was found in the rate of sentinels' ‘alarm calls’ between floaters and group members, suggesting that their main purpose is predator–prey communication, of which warning groupmates may be a side benefit. PMID:28386429

  5. The Sentinel-2 Mission Products

    NASA Astrophysics Data System (ADS)

    Gascon, Ferran

    2012-04-01

    In the framework of the Global Monitoring for Environment and Security (GMES) programme, the European Space Agency (ESA) in partnership with the European Commission (EC) is developing the Sentinel-2 optical imaging mission devoted to the operational monitoring of land and coastal areas. This system will deliver a new generation of optical data products designed to directly feed downstream services acting in several domains such as land management, agricultural industry, forestry, food security, or disaster control management following floods, volcanic eruptions, landslides, etc. The Sentinel-2 mission designed to generate products with accurate radiometric and geometric performances (including multi-temporal imagery co-registration). To maximize the products suitability and readiness to downstream usage for the majority of applications, the Sentinel-2 PDGS will systematically generate and archive Level-1C products, which will provide Top of Atmosphere (TOA) reflectance images, orthorectified using a global DEM and UTM projection. A Level-1B product will also be available for expert users and will provide the radiometrically corrected pixels in sensor geometry with the geometric model appended. Finally, a complementary atmospheric correction and enhanced cloud screening algorithm is being prototyped in parallel with the goal of providing some initial capabilities to the users, by means of a specific software toolbox operated on their platforms, to translate the Level-1C TOA reflectance image into Bottom of Atmosphere (BOA) reflectance.

  6. Uveal melanoma: estimating prognosis.

    PubMed

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  7. Bronchial malignant melanoma.

    PubMed

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  8. Acid Ceramidase in Melanoma

    PubMed Central

    Realini, Natalia; Palese, Francesca; Pizzirani, Daniela; Pontis, Silvia; Basit, Abdul; Bach, Anders; Ganesan, Anand; Piomelli, Daniele

    2016-01-01

    Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells. High AC expression was also observed in biopsies from human subjects with Stage II melanoma. Immunofluorescence studies revealed that the subcellular localization of AC differs between melanocytes (where it is found in both cytosol and nucleus) and melanoma cells (where it is primarily localized to cytosol). In addition to having high AC levels, melanoma cells generate lower amounts of ceramides than normal melanocytes do. This down-regulation in ceramide production appears to result from suppression of the de novo biosynthesis pathway. To test whether AC might contribute to melanoma cell proliferation, we blocked AC activity using a new potent (IC50 = 12 nm) and stable inhibitor. AC inhibition increased cellular ceramide levels, decreased sphingosine 1-phosphate levels, and acted synergistically with several, albeit not all, antitumoral agents. The results suggest that AC-controlled sphingolipid metabolism may play an important role in the control of melanoma proliferation. PMID:26553872

  9. Melanoma International Foundation

    MedlinePlus

    ... Jason J. Luke, MD January 07, 2016 Surgical Management of Melanoma: A 2015 Primer Presented by Jeffrey Gershenwald, MD May 09, 2015 Our Awards Melanoma International Foundation Our Mission: To develop personalized strategies with patients so they may live longer, better ...

  10. Melanoma with gastric metastases

    PubMed Central

    Wong, Katherine; Serafi, Sam W.; Bhatia, Abhijit S.; Ibarra, Irene; Allen, Elizabeth A.

    2016-01-01

    An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations. PMID:27609722

  11. The Role of Intralesional Therapies in Melanoma.

    PubMed

    Agarwala, Sanjiv S

    2016-05-01

    The US Food and Drug Administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. Recently, it approved the first intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. Several other intralesional therapies (PV-10, interleukin-12 electroporation, coxsackievirus A21 [CVA21]) are entering later-stage testing. Locally injected agents have clearly shown their ability to produce local responses that can be durable. The possibility that they also stimulate a regional and even systemic immune response is exciting, as this potential effect may have utility in combination regimens; such regimens are an area of active research. Favorable responses with minimal toxicities in monotherapy trials have led to the first melanoma studies of T-VEC in combination with the cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab and, separately, with the programmed death 1-blocking antibody pembrolizumab. Studies of PV-10 with pembrolizumab and of CVA21 with pembrolizumab are also being initiated. Preliminary analyses of the results of the first combination trials, which show higher response rates than with either agent alone, offer some optimism that these locoregional therapies will find application--as treatment for patients who cannot tolerate systemic immunotherapies, to alleviate locoregional morbidity, and perhaps even to "prime" the immune system.

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

    PubMed

    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.

  13. Lymph node extramedullary hematopoiesis in breast cancer patients receiving neoadjuvant therapy: a potential diagnostic pitfall.

    PubMed

    Prieto-Granada, Carlos; Setia, Namrata; Otis, Christopher N

    2013-06-01

    Extramedullary hematopoiesis (EMH) develops as a compensatory mechanism associated with hematologic processes but it may occur in association with chemotherapy. Three cases of EMH arising in axillary lymph nodes following neoadjuvant therapy for breast carcinoma are reported herein. Three women ranging in age from 41 to 47 years presented with unilateral breast masses measuring 0.6 to 4.0 cm in greatest dimension and were diagnosed with infiltrating ductal carcinoma, grade III by core needle biopsies. Two of the tumors were triple negative and one was estrogen receptor positive. All patients subsequently received neoadjuvant therapy followed by lumpectomies. No residual carcinoma was identified in postchemotherapy breast resection specimens. One patient underwent a sentinel lymph node procedure, the second patient an axillary lymph node dissection, and the third patient had a core biopsy of an enlarged axillary lymph node. The patient that underwent axillary lymph node dissection had metastatic carcinoma in one of her lymph nodes. Foci of EMH consisting of myeloid, erythroid, and megakaryocytic precursors were present within the nodal parenchyma and/or subcapsular sinuses of axillary lymph nodes of all three cases. Megakaryocytes were immunoreactive with factor VIII, erythroid elements with Glycophorin and myeloid precursors with myeloperoxidase. With increasing use of neoadjuvant therapy for breast carcinoma, EMH within lymph nodes is more likely to be encountered. Hematopoietic precursors present in lymph nodes may potentially be misdiagnosed as metastatic tumor cells, particularly as lobular carcinoma or metaplastic carcinoma. Therefore, caution should be exercised when evaluating axillary lymph nodes in the clinical setting of neoadjuvant therapy for breast carcinoma.

  14. Primary malignant melanoma of prostate.

    PubMed

    Doublali, M; Chouaib, A; Khallouk, A; Tazi, M F; El Fassi, M J; Farih, My H; Elfatmi, H; Bendahou, M; Benlemlih, A; Lamarti, O

    2010-05-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

  15. Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

    PubMed

    Jahn, Stephan W; Kashofer, Karl; Halbwedl, Iris; Winter, Gerlinde; El-Shabrawi-Caelen, Laila; Mentzel, Thomas; Hoefler, Gerald; Liegl-Atzwanger, Bernadette

    2015-07-01

    Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.

  16. Etiology of melanoma.

    PubMed

    Koh, H K; Sinks, T H; Geller, A C; Miller, D R; Lew, R A

    1993-01-01

    Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over

  17. Dormancy of metastatic melanoma

    PubMed Central

    Ossowski, Liliana; Aguirre-Ghiso, Julio A.

    2010-01-01

    Summary Metastatic dormancy of melanoma has not received sufficient attention, most likely because once detectable, metastasis is almost invariably fatal and, understandably, the focus has been on finding ways to prolong life of patients with overt recurrences. Nevertheless, analysis of the published clinical and experimental data on melanoma indicates that some aspect of melanoma biology imitate traits recently associated with dormancy in other solid cancers. Among them the ability of some melanomas to disseminate early during primary tumor progression and once disseminated, to remain undetected (dormant) for years. Comparison of cutaneous and uveal melanoma indicates that, in spite of being of the same origin, they differ profoundly in their clinical progression. Importantly for this discussion, between 40 and 50% of uveal melanoma remain undetected for longer than a decade, while less than 5% of cutaneous melanoma show this behavior. Both types of melanoma have activating oncogene mutations that provide autonomous pro-proliferative signals, yet the consensus is that those are not sufficient for tumor progression. If that is the case, it is possible to envision that signals from outside the tumor cell, (microenvironment) shape the fate of an individual disseminated cell, regardless of an oncogene mutation, to progress or to pause in a state of dormancy. To stimulate further debate and inquiry we describe here a few examples of potential signals that might modify the fate of disseminated cell and provide brief description of the current knowledge on dormancy in other cancers. Our hope is to convince the reader that disseminated melanoma cells do enter periods of prolonged dormancy and that finding ways to induce it, or to prolong it, might mean an extension of symptoms-free life for melanoma patients. Ultimately, understanding the biology of dormancy and the mechanisms of dormant cell survival, might allow for their specific targeting and elimination. PMID

  18. Quantitative imaging of lymph function.

    PubMed

    Sharma, Ruchi; Wang, Wei; Rasmussen, John C; Joshi, Amit; Houston, Jessica P; Adams, Kristen E; Cameron, Arlin; Ke, Shi; Kwon, Sunkuk; Mawad, Michel E; Sevick-Muraca, Eva M

    2007-06-01

    Functional lymphatic imaging was demonstrated in the abdomen and anterior hindlimb of anesthetized, intact Yorkshire swine by using near-infrared (NIR) fluorescence imaging following intradermal administration of 100-200 microl of 32 microM indocyanine green (ICG) and 64 microM hyaluronan NIR imaging conjugate to target the lymph vascular endothelial receptor (LYVE)-1 on the lymph endothelium. NIR fluorescence imaging employed illumination of 780 nm excitation light ( approximately 2 mW/cm(2)) and collection of 830 nm fluorescence generated from the imaging agents. Our results show the ability to image the immediate trafficking of ICG from the plexus, through the vessels and lymphangions, and to the superficial mammary, subiliac, and middle iliac lymph nodes, which were located as deep as 3 cm beneath the tissue surface. "Packets" of ICG-transited lymph vessels of 2-16 cm length propelled at frequencies of 0.5-3.3 pulses/min and velocities of 0.23-0.75 cm/s. Lymph propulsion was independent of respiration rate. In the case of the hyaluronan imaging agent, lymph propulsion was absent as the dye progressed immediately through the plexus and stained the lymph vessels and nodes. Lymph imaging required 5.0 and 11.9 microg of ICG and hyaluronan conjugate, respectively. Our results suggest that microgram quantities of NIR optical imaging agents and their conjugates have a potential to image lymph function in patients suffering from lymph-related disorders.

  19. Analysis of tumor mitotic rate in thin metastatic melanomas compared with thin melanomas without metastasis using both the hematoxylin and eosin and anti-phosphohistone 3 IHC stain.

    PubMed

    Thareja, Sumeet; Zager, Jonathan S; Sadhwani, Divya; Thareja, Shalini; Chen, Ren; Marzban, Suroosh; Jukic, Drazen M; Glass, Lewis F; Messina, Jane

    2014-01-01

    Studies have suggested that elevated tumor mitotic rate (MR) is linked to overall survival in thin melanoma. Recently, promising data regarding anti-phosphohistone 3 (pHH3) immunohistochemistry and its ability to aid in calculation of MR have emerged. The authors retrospectively analyzed original biopsies from 13 thin melanomas with positive sentinel node (SN) status and 16 thin melanomas with negative SN status. Both anti-pHH3 immunohistochemistry and the hematoxylin and eosin (H&E) stain were used to evaluate MR by 2 dermatopathologists blinded to SN status using the "hot spot" method. Intraclass coefficient values were attained to measure interobserver concordance and reliability of the pHH3 stain. By generating a receiver operating characteristic curve and analyzing the overall area under the curve, pHH3 was found to have good interobserver reliability. The relationship between MR and SN involvement was also evaluated, but this correlation was not statistically significant.

  20. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    PubMed Central

    Odashiro, Macanori; Hans Filho, Gunter; Pereira, Patricia Rusa; Castro, Ana Rita Coimbra Motta; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors. PMID:26131861

  1. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  2. Sentinel node biopsy in the surgical management of breast cancer: experience in a general hospital with a dedicated surgical team.

    PubMed

    Merson, M; Fenaroli, P; Gianatti, A; Virotta, G; Giuliano, L G; Bonasegale, A; Bambina, S; Pericotti, S; Guerra, U; Tondini, C

    2004-06-01

    The aims of this study were to analyse the feasibility and accuracy of the sentinel lymph node biopsy (SLNB) procedure as performed in a general hospital compared with the literature results; to report on the organizational aspects of planning surgical time with higher accuracy of pathological analysis; and to verify that there is a real advantage of SLNB in the surgical management of breast cancer. From October 1999 to September 2000, 371 consecutive patients with T1-2N0 breast lesions underwent SLNB. The immunoscintigraphic method of sentinel node identification was the main one used, the blue dye method being used only when the lymphoscintigraphic method was unsuccessful in identifying sentinel nodes. SLNB was done under either general or local anaesthesia, depending on how the surgical procedure was organized and clinically planned. SLNB was successful in 99% of these T1-2N0 breast cancer cases, and in 71% no metastases were found in the sentinel node. In 47% of cases with axillary metastasis only the sentinel node was involved. Nodal involvement was not present in any case of microinvasive or in situ carcinoma. In T1 cancers nodal involvement was present in 21%; in T2 cases the corresponding rate reached 51%. The results obtained with the SLNB procedure at Bergamo Hospital are similar to the literature data. When a dedicated surgical team, the nuclear medicine department and the pathology department work together, a general hospital can provide breast cancer patients with appropriate surgical treatment.

  3. Discovering Sentinel Rules for Business Intelligence

    NASA Astrophysics Data System (ADS)

    Middelfart, Morten; Pedersen, Torben Bach

    This paper proposes the concept of sentinel rules for multi-dimensional data that warns users when measure data concerning the external environment changes. For instance, a surge in negative blogging about a company could trigger a sentinel rule warning that revenue will decrease within two months, so a new course of action can be taken. Hereby, we expand the window of opportunity for organizations and facilitate successful navigation even though the world behaves chaotically. Since sentinel rules are at the schema level as opposed to the data level, and operate on data changes as opposed to absolute data values, we are able to discover strong and useful sentinel rules that would otherwise be hidden when using sequential pattern mining or correlation techniques. We present a method for sentinel rule discovery and an implementation of this method that scales linearly on large data volumes.

  4. NF1 Mutations Are Common in Desmoplastic Melanoma.

    PubMed

    Wiesner, Thomas; Kiuru, Maija; Scott, Sasinya N; Arcila, Maria; Halpern, Allan C; Hollmann, Travis; Berger, Michael F; Busam, Klaus J

    2015-10-01

    Desmoplastic melanoma (DM) is a rare variant of melanoma with distinct clinical, histopathologic, and immunohistochemical features. Clinically, DM differs from conventional melanoma by a higher propensity for local recurrence and less frequent metastatic spread to regional lymph nodes. In its pure form, DM has a distinct appearance displaying a low density of fusiform melanocytes in a collagen-rich matrix. Whereas a number of mutations have been identified in primary melanoma, including BRAF, NRAS, GNAQ, GNA11, and KIT, and the occurrence of these mutations has been found to correlate to some extent with the histopathologic features, anatomic site, and/or mode of sun exposure, no distinct set of mutations has so far been reported for DM. To study the potential association of neurofibromin (NF1) mutations with DM, we examined 15 desmoplastic and 20 non-DMs by next-generation sequencing. Mutations of the NF1 gene were found in 14 of 15 (93%) DMs and 4 of 20 (20%) non-DMs. The high frequency of NF1 mutations in DMs suggests an important role for NF1 in the biology of this type of melanoma.

  5. How Is Melanoma Skin Cancer Diagnosed?

    MedlinePlus

    ... Cancer Early Detection, Diagnosis, and Staging Tests for Melanoma Skin Cancer Most melanomas are brought to a ... New in Melanoma Skin Cancer Research? Biopsies of melanoma that may have spread Biopsies of areas other ...

  6. Management of the Regional Lymph Nodes Following Breast-Conservation Therapy for Early-Stage Breast Cancer: An Evolving Paradigm

    SciTech Connect

    Warren, Laura E.G.; Punglia, Rinaa S.; Wong, Julia S.; Bellon, Jennifer R.

    2014-11-15

    Radiation therapy to the breast following breast conservation surgery has been the standard of care since randomized trials demonstrated equivalent survival compared to mastectomy and improved local control and survival compared to breast conservation surgery alone. Recent controversies regarding adjuvant radiation therapy have included the potential role of additional radiation to the regional lymph nodes. This review summarizes the evolution of regional nodal management focusing on 2 topics: first, the changing paradigm with regard to surgical evaluation of the axilla; second, the role for regional lymph node irradiation and optimal design of treatment fields. Contemporary data reaffirm prior studies showing that complete axillary dissection may not provide additional benefit relative to sentinel lymph node biopsy in select patient populations. Preliminary data also suggest that directed nodal radiation therapy to the supraclavicular and internal mammary lymph nodes may prove beneficial; publication of several studies are awaited to confirm these results and to help define subgroups with the greatest likelihood of benefit.

  7. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma.

    PubMed

    Jarrett, Stuart G; Novak, Marian; Harris, Nathan; Merlino, Glenn; Slominski, Andrezj; Kaetzel, David M

    2013-01-01

    Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of <5 % for patients presenting with metastatic disease. Mechanisms underlying metastatic spread of UVR-induced melanoma are not well understood, in part due to a paucity of animal models that accurately recapitulate the disease in its advanced forms. We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis. Crossing of the nm23-h1/nm23-h2 knockout in hemizygous-null form ([m1m2](+/-)) to a transgenic mouse strain (hepatocyte growth factor/scatter factor-overexpressing, or HGF(+) strain) vulnerable to poorly-metastatic, UVR-induced melanomas resulted in UVR-induced melanomas with high metastatic potential. Metastasis to draining lymph nodes was seen in almost all cases of back skin melanomas, while aggressive metastasis to lung, thoracic cavity, liver and bone also occurred. Interestingly, no differences were observed in the invasive characteristics of primary melanomas of HGF(+) and HGF(+) × [m1m2](+/-) strains, with both exhibiting invasion into the dermis and subcutis, indicating factors other than simple invasive activity were responsible for metastasis of HGF(+) × [m1m2](+/-) melanomas. Stable cell lines were established from the primary and metastatic melanoma lesions from these mice, with HGF(+) × [m1m2](+/-) lines exhibiting increased single cell migration and genomic instability. These studies demonstrate for the first time in vivo a potent metastasis suppressor activity of NM23 in UVR-induced melanoma, and have provided new tools for identifying molecular mechanisms that underlie melanoma metastasis.

  8. What's New in Research and Treatment of Melanoma Skin Cancer?

    MedlinePlus

    ... Melanoma Skin Cancer About Melanoma Skin Cancer What’s New in Melanoma Skin Cancer Research? Research into the ... Cancer? Key Statistics for Melanoma Skin Cancer What’s New in Melanoma Skin Cancer Research? More In Melanoma ...

  9. Anorectal melanoma. An update.

    PubMed

    Reina, Angel; Errasti, José; Espín, Eloy

    2014-10-01

    Anorectal melanoma is an uncommon and aggressive disease. Because the patients often present with non specific complaints, a high clinical suspicion is important to avoid a delayed diagnosis. Patients undergoing radical surgery have no significant survival difference compared to those undergoing wide local excision. Abdominoperineal resection should be reserved for selected patients in whom local excision is not technically possible or cannot obtain a clear margin. The indiscriminate use of groin dissection is not advisable in anorectal melanoma and should be use in selected cases. Systemic chemotherapy is generally a non effective treatment and continues be studied. Radiation therapy can be used as hypofractionated radiation therapy combined with local excision or in a palliative setting. The oncological outcomes in anorectal melanoma are very poor. The aim of the present study is to review clinicopathology features and management of anorectal melanoma.

  10. Melanoma of the eye

    MedlinePlus

    Small melanomas may be treated with: Surgery Laser Radiation therapy (such as Gamma Knife , CyberKnife , brachytherapy) Surgery to remove the eye (enucleation) may be needed. Other treatments that may be used ...

  11. LCP nanoparticle for tumor and lymph node metastasis imaging

    NASA Astrophysics Data System (ADS)

    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

  12. Booster Vaccination in Preventing Disease Recurrence in Previously Vaccinated Patients With Melanoma That Has Been Removed By Surgery

    ClinicalTrials.gov

    2015-01-23

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  13. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    ClinicalTrials.gov

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  14. [Lung cancer and lymph drainage].

    PubMed

    Riquet, M

    2007-01-01

    Lung cancer is lymphophile and may involve lymph nodes (LN) belonging to lung lymph drainage. LN metastases are figured within stations numbered 1 to 14. These stations are located along lymph vessels. The lymph vessels and the LN are forming together anatomical chains. Lymph vessels are valved and pulsatile and travel to the cervical venous confluence where they pour the lung lymph into the blood circulation. They may be totally or partly nodeless along their travel, anastomose with each other around the trachea, and connect with the thoracic duct within the mediastinum. Within the anatomical LN chains, LN are variable in number and in size from one individual to another. They may be absent from one or several stations of the international mapping. Stations are located along the anatomical chains: pulmonary ligament (9), tracheal bifurcation(8 and 7), right paratracheal (4R, 2R and 1), preaortic (5 and 6), left paratracheal (4L, 2L and 1). Station 3 is located on 2 differents chains (phrenic and right esophagotracheal). Station 10 are located at the beginning of the mediastinal lymph nodes chains. Each chain connects with the blood circulation, anastomoses with he neighbouring chains and behave as an own entity whatever the number of its LN. International station mapping misknowns this anatomy and occults the true pronostic value of lung lymph drainage.

  15. Targeted therapy in melanoma.

    PubMed

    Kudchadkar, Ragini R; Smalley, Keiran S M; Glass, L Frank; Trimble, James S; Sondak, Vernon K

    2013-01-01

    Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.

  16. Axillary ultrasound and fine-needle aspiration in preoperative staging of axillary lymph nodes in patients with invasive breast cancer*

    PubMed Central

    Rocha, Rafael Dahmer; Girardi, André Ricardo; Pinto, Renata Reis; de Freitas, Viviane Aguilera Rolim

    2015-01-01

    Objective To propose an algorithm to determine the necessity for ultrasonography-guided fine-needle aspiration (US-FNA) in preoperative axillary lymph node staging of patients with invasive breast cancer. Materials and Methods Prospective study developed at National Cancer Institute. The study sample included 100 female patients with breast cancer referred for axillary staging by US-FNA. Results The overall US-FNA sensitivity was set at 79.4%. The positive predictive value was calculated to be 100%, and the negative predictive value, 69.5%. The US-FNA sensitivity for lymph nodes with normal sonographic features was 0%, while for indeterminate lymph nodes it was 80% and, for suspicious lymph nodes, 90.5%. In the assessment of invasive breast tumors stages T1, T2 and T3, the sensitivity was respectively 69.6%, 83.7% and 100%. US-FNA could avoid sentinel node biopsy in 54% of cases. Conclusion Axillary ultrasonography should be included in the preoperative staging of all patients with invasive breast cancer. The addition of US-FNA in cases of lymph nodes suspicious for malignancy may prevent more than 50% of sentinel lymphadenectomies, significantly shortening the time interval to definitive therapy. PMID:26811550

  17. Terahertz imaging of metastatic lymph nodes using spectroscopic integration technique

    PubMed Central

    Park, Jae Yeon; Choi, Hyuck Jae; Cheon, Hwayeong; Cho, Seong Whi; Lee, Seungkoo; Son, Joo-Hiuk

    2017-01-01

    Terahertz (THz) imaging was used to differentiate the metastatic states of frozen lymph nodes (LNs) by using spectroscopic integration technique (SIT). The metastatic states were classified into three groups: healthy LNs, completely metastatic LNs, and partially metastatic LNs, which were obtained from three mice without infection and six mice infected with murine melanoma cells for 30 days and 15 days, respectively. Under histological examination, the healthy LNs and completely metastatic LNs were found to have a homogeneous cellular structure but the partially metastatic LNs had interfaces of the melanoma and healthy tissue. THz signals between the experimental groups were not distinguished at room temperature due to high attenuation by water in the tissues. However, a signal gap between the healthy and completely metastatic LNs was detected at freezing temperature. The signal gap could be enhanced by using SIT that is a signal processing method dichotomizing the signal difference between the healthy cells and melanoma cells with their normalized spectral integration. This technique clearly imaged the interfaces in the partially metastatic LNs, which could not be achieved by existing methods using a peak point or spectral value. The image resolution was high enough to recognize a metastatic area of about 0.7 mm size in the partially metastatic LNs. Therefore, this pilot study demonstrated that THz imaging of the frozen specimen using SIT can be used to diagnose the metastatic state of LNs for clinical application. PMID:28271007

  18. Lymph drainage in pregnant women.

    PubMed

    Cataldo Oportus, Sylvia; de Paiva Rodrigues, Lilian; Pereira de Godoy, José Maria; Guerreiro Godoy, Maria de Fátima

    2013-01-01

    Aim. The aim of this study was to evaluate the efficacy of lymph drainage to reduce edema of pregnant women. Method. Pregnant women (30 limbs) from the Obstetrics Outpatient Clinic of the Medical School of Santa Casa in São Paulo in the period December 2009 to May 2010 were enrolled in this quantitative, prospective study. The patients, in the 5th to 8th months of gestation, were submitted to one hour of manual lymph drainage of the legs. The volume of the legs was measured by water displacement volumetry before and after one hour of drainage using the Godoy & Godoy manual lymph drainage technique. The paired t-test was used for statistical analysis with an alpha error of 5% being considered significant. Results. Manual lymph drainage significantly reduced swelling of the legs of pregnant women during the day (P = 0.04). Conclusion. Manual lymph drainage helps to reduce limb size during the day of pregnant women.

  19. Sexually selected sentinels? Evidence of a role for intrasexual competition in sentinel behavior

    PubMed Central

    Walker, Lindsay A.; York, Jenny E.

    2016-01-01

    Although the evolutionary mechanisms that favor investment in cooperative behaviors have long been a focus of research, comparatively few studies have considered the role that sexual selection may play. For example, evolutionary explanations for sentinel behavior (where 1 individual assumes an elevated position and scans the surroundings while other group members forage nearby) have traditionally focused on the inclusive fitness benefits arising from its effects on predation risk, while its potential role in defense against intrasexual competitors remains largely unexplored. Here, we provide experimental evidence of a role for sentinel behavior in intrasexual competition, in a cooperatively breeding songbird, the white-browed sparrow weaver (Plocepasser mahali). First, dominant males sentinel substantially more than other group members (even when controlling for variation in age and body condition), consistent with a role for sentineling in intrasexual competition for mates and/or territory. Second, experimental playback of an unfamiliar male’s solo song elicited a marked increase in sentineling by the dominant male, and the vocal response to the playback also positively predicted his sentinel effort following the simulated intrusion. A second experiment also suggests that sentineling may facilitate mounting rapid anti-intruder responses, as responses to intruder-playback occurred significantly earlier when the dominant male was sentineling rather than foraging at playback onset. Together, our findings provide rare support for the hypothesis that sentinel behavior plays a role in intrasexual competition, and so highlight the potential for sexually selected direct benefits to shape its expression in this and other social vertebrates. PMID:27656086

  20. Biokinetics of 99mTc-labeled gold nanoparticles conjugated to mannose for specific sentinel node detection

    NASA Astrophysics Data System (ADS)

    Ocampo-García, B. E.; Ferro-Flores, G.; de M. Ramírez, F.; De León-Rodríguez, L. M.; Santos-Cuevas, C. L.; Morales-Avila, E.; de Murphy, C. Arteaga; Pedraza-López, M.; Medina, L. A.; López-Rodríguez, V.

    2010-12-01

    The aim of this research was to evaluate the biological behavior in Wistar rats of a multifunctional system of gold nanoparticles (AuNP) conjugated to 99mTc-HYNIC-GGC and mannose for sentinel lymph node (SLN) specific detection. The radiolabeled nanoconjugate, characterized by TEM and UV-vis, vibrational, XPS and Fluorescence spectroscopic analyses, was administered in rats (footpad) and the radioactivity levels in the popliteal and inguinal lymph nodes determined at different times from 30 min to 24 h. Results showed that 21% of the injected radio-AuNP-mannose was retained in the first lymph node (popliteal) during 24 h. 99mTc-HYNIC-GGC-AuNP-Mannose is a potential target-specific tracer for SLN detection in breast cancer patients.

  1. Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and Tissues.

    PubMed

    Krizkova, Sona; Fabrik, Ivo; Adam, Vojtech; Kukacka, Jiri; Prusa, Richard; Chavis, Grace J; Trnkova, Libuse; Strnadel, Jan; Horak, Vratislav; Kizek, Rene

    2008-05-10

    In the paper we utilized the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothioneins (MT) in melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of patients with malignant melanoma. Primarily we attempted to investigate the influence of dilution of real sample on MT electrochemical response. Dilution of samples of 1 000 times was chosen the most suitable for determination of MT level in biological samples. Then we quantified the MT level in the melanoma cells, the animal melanoma tissues and the blood serum samples. The MT content in the cells varied within the range from 4.2 to 11.2 μM. At animal melanoma tissues (melanomas localized on abdomen, back limb and dorsum) the highest content of MT was determined in the tumour sampled on the back of the animal and was nearly 500 μg of MTs per gram of a tissue. We also quantified content of MT in metastases, which was found in liver, spleen and lymph nodes. Moreover the average MT level in the blood serum samples from patients with melanoma was 3.0 ± 0.8 μM. MT levels determined at melanoma samples were significantly (p < 0.05) higher compared to control ones at cells, tissues and blood serum.

  2. Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and Tissues

    PubMed Central

    Krizkova, Sona; Fabrik, Ivo; Adam, Vojtech; Kukacka, Jiri; Prusa, Richard; Chavis, Grace J.; Trnkova, Libuse; Strnadel, Jan; Horak, Vratislav; Kizek, Rene

    2008-01-01

    In the paper we utilized the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothioneins (MT) in melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of patients with malignant melanoma. Primarily we attempted to investigate the influence of dilution of real sample on MT electrochemical response. Dilution of samples of 1 000 times was chosen the most suitable for determination of MT level in biological samples. Then we quantified the MT level in the melanoma cells, the animal melanoma tissues and the blood serum samples. The MT content in the cells varied within the range from 4.2 to 11.2 μM. At animal melanoma tissues (melanomas localized on abdomen, back limb and dorsum) the highest content of MT was determined in the tumour sampled on the back of the animal and was nearly 500 μg of MTs per gram of a tissue. We also quantified content of MT in metastases, which was found in liver, spleen and lymph nodes. Moreover the average MT level in the blood serum samples from patients with melanoma was 3.0 ± 0.8 μM. MT levels determined at melanoma samples were significantly (p < 0.05) higher compared to control ones at cells, tissues and blood serum. PMID:27879868

  3. What Is Melanoma Skin Cancer?

    MedlinePlus

    ... melanomas do not make melanin and can appear pink, tan, or even white. Melanomas can develop anywhere ... Cancer Society is a qualified 501(c)(3) tax-exempt organization. Cancer.org is provided courtesy of ...

  4. Uveal melanoma: Estimating prognosis

    PubMed Central

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-01-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538

  5. The Sentinel-3 Missions Overview

    NASA Astrophysics Data System (ADS)

    Donlon, C.; Berruti, B.; Becklenberg, S.; Nieke, J.; Rebhan, H.; Klein, U.; Buongiorno, A.; Mavrocordatos, C.; Frerick, J.; Seitz, B.; Goryl, P.; Femenias, P.; Stroede, J.; Sciarra, R.

    2012-03-01

    ESA is currently implementing the Sentinel-3 mission [3], [4] as part of the European Global Monitoring for Environment and Security (GMES) program. It is designed as a constellation of two identical polar orbiting satellites, separated by 180 deg, for the provision of longterm operational marine and land monitoring services. These services include the generation of land and ocean colour products, sea and land surface temperature, vegetation products and sea, ice and land surface topography. The first satellite has a planned launch in late 2013 and will provide valuable information for scientists and policy makers in the European Union and its Member States for the next decade. The operational character of this mission implies a high level of availability of the data products and fast delivery time, which have been important design drivers for the mission.

  6. Primary malignant melanoma of prostate

    PubMed Central

    Doublali, M.; Chouaib, A.; Khallouk, A.; Tazi, M. F.; El Fassi, M. J.; Farih, My. H.; Elfatmi, H.; Bendahou, M.; Benlemlih, A.; Lamarti, O.

    2010-01-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate. PMID:20882159

  7. Comparison between one day and two days protocols for sentinel node mapping of breast cancer patients.

    PubMed

    Ali, Jangijoo; Alireza, Rezapanah; Mostafa, Mehrabibahar; Naser, Forghani Mohammad; Bahram, Memar; Ramin, Sadeghi

    2011-01-01

    Sentinel node biopsy can decrease the morbidity of breast cancer treatment significantly by sparing many patients of axillary lymph node dissection and resulting arm lymphedema. Despite widespread use of sentinel node mapping for breast cancer patients almost all aspects of this procedure are controversial; such as: type of the radiotracer, eligibility, time of injection, etc. One of these controversial issues is the efficacy of 2 days protocol (injection of the tracer on one day and sentinel node mapping and surgery on the following day). The main reason to perform 2 days protocol is the ease of operation room scheduling the patient does not need to complete injection and imaging in the nuclear medicine department. Despite widespread use of 2 days protocol for sentinel node mapping, very few studies have specifically evaluated this protocol in comparison to 1 day protocol and also the false negative rate which is the better index of sentinel node mapping success. Most of the above studies used tracers with large particle size such as (99m)Tc-sulfur colloid. Tracers with small particle size can theoretically be washed out from the real sentinel nodes and move to the second echelon nodes, so some recommended using large particle size radiotracers for the 2 days protocol. In this study, we compared the false negative rate of sentinel node mapping between 1 and 2 days protocols using intradermal injection of (99m)Tc-antimony sulfide colloid ((99m)Tc-SbSC) which has very small particle size. Eighty patients with early stage breast cancer (clinical stages of I and II) were evaluated. The diagnosis of the breast cancer was established by either excisional or core needle biopsy. The patients didn't take any chemotherapeutic drug before surgery and were divided into two groups: 1 day (Group I) and 2 days (Group II) protocols (45 in Group I and 35 in Group II). For Group I, periareolar intradermal injections of 0.5Bq/0.2mL (99m)Tc-SbSC were applied for patients without

  8. Methods of Melanoma Detection.

    PubMed

    Leachman, Sancy A; Cassidy, Pamela B; Chen, Suephy C; Curiel, Clara; Geller, Alan; Gareau, Daniel; Pellacani, Giovanni; Grichnik, James M; Malvehy, Josep; North, Jeffrey; Jacques, Steven L; Petrie, Tracy; Puig, Susana; Swetter, Susan M; Tofte, Susan; Weinstock, Martin A

    2016-01-01

    Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed.

  9. Prevention of malignant melanoma

    PubMed Central

    Chaidemenos, G; Stratigos, A; Papakonstantinou, M; Tsatsou, F

    2008-01-01

    The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts. PMID:18923759

  10. Genotyping of cutaneous melanoma.

    PubMed

    Glitza, Isabella C; Davies, Michael A

    2014-09-01

    Until recently, treatment options for patients with metastatic melanoma were very limited. This landscape has evolved dramatically since the discovery of activating mutations in the BRAF gene in ~45% of cutaneous melanomas. Vemurafenib, dabrafenib, and trametinib have all received regulatory approval for the treatment of metastatic melanoma patients with a BRAF(V600) mutation. Based on the necessity to document the presence of a BRAF(V600) mutation to prescribe these agents, molecular testing is now the standard of care in this disease. However, the options and rationale for testing are evolving rapidly due to an improved understanding of the molecular drivers and heterogeneity of melanoma. Such testing may identify rational combinatorial approaches to prevent or overcome resistance for the approved BRAF inhibitors. In addition, new clinical strategies have been identified for a number of other molecular changes that are detected in this disease, including somatic changes in NRAS, PTEN, CDKN2A, and c-KIT, among others. This review summarizes the current understanding of the genetic landscape of mutations in melanoma, their associations with clinicopathological features, and their implications for clinical testing and treatment.

  11. Targeted Therapy for Melanoma

    SciTech Connect

    Quinn, Thomas; Moore, Herbert

    2016-12-05

    The research project entitled,” Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  12. Melanoma-restricted genes

    PubMed Central

    Wang, Ena; Panelli, Monica C; Zavaglia, Katia; Mandruzzato, Susanna; Hu, Nan; Taylor, Phil R; Seliger, Barbara; Zanovello, Paola; Freedman, Ralph S; Marincola, Francesco M

    2004-01-01

    Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets. PMID:15488140

  13. The SENTINEL-3 Mission: Overview and Status

    NASA Astrophysics Data System (ADS)

    Benveniste, J.; Mecklenburg, S.

    2015-12-01

    The Copernicus Programme, being Europe's Earth Observation and Monitoring Programme led by the European Union, aims to provide, on a sustainable basis, reliable and timely services related to environmental and security issues. The Sentinel-3 mission forms part of the Copernicus Space Component. Its main objectives, building on the heritage and experience of the European Space Agency's (ESA) ERS and ENVISAT missions, are to measure sea-surface topography, sea- and land-surface temperature and ocean- and land-surface colour in support of ocean forecasting systems, and for environmental and climate monitoring. The series of Sentinel-3 satellites will ensure global, frequent and near-real time ocean, ice and land monitoring, with the provision of observation data in routine, long term (up to 20 years of operations) and continuous fashion, with a consistent quality and a high level of reliability and availability. The Sentinel-3 missions will be jointly operated by ESA and EUMETSAT. ESA will be responsible for the operations, maintenance and evolution of the Sentinel-3 ground segment on land related products and EUMETSAT for the marine products. The Sentinel-3 ground segment systematically acquires, processes and distributes a set of pre-defined core data products. Sentinel-3A is foreseen to be launched at the beginning of November 2015. The paper will give an overview on the mission, its instruments and objectives, the data products provided, the mechanisms to access the mission's data, and if available first results.

  14. Detection and capture of single circulating melanoma cells using photoacoustic flowmetry

    NASA Astrophysics Data System (ADS)

    O'Brien, Christine; Mosley, Jeffrey; Goldschmidt, Benjamin S.; Viator, John A.

    2010-02-01

    Photoacoustic flowmetry has been used to detect single circulating melanoma cells in vitro. Circulating melanoma cells are those cells that travel in the blood and lymph systems to create secondary tumors and are the hallmark of metastasis. This technique involves taking blood samples from patients, separating the white blood and melanoma cells from whole blood and irradiating them with a pulsed laser in a flowmetry set up. Rapid, visible wavelength laser pulses on the order of 5 ns can induce photoacoustic waves in melanoma cells due to their melanin content, while surrounding white blood cells remain acoustically passive. We have developed a system that identifies rare melanoma cells and captures them in 50 microliter volumes using suction applied near the photoacoustic detection chamber. The 50 microliter sample is then diluted and the experiment is repeated using the new sample until only a melanoma cell remains. We have tested this system on dyed microspheres ranging in size from 300 to 500 microns. Capture of circulating melanoma cells may provide the opportunity to study metastatic cells for basic understanding of the spread of cancer and to optimize patient specific therapies.

  15. 1H NMR Metabolomics Study of Metastatic Melanoma in C57BL/6J Mouse Spleen

    PubMed Central

    Wang, Xuan; Hu, Mary; Feng, Ju; Liu, Maili; Hu, Jian Zhi

    2014-01-01

    Melanoma is a malignant tumor of melanocytes. Although extensive investigations have been done to study metabolic changes in primary melanoma in vivo and in vitro, little effort has been devoted to metabolic profiling of metastatic tumors in organs other than lymph nodes. In this work, NMR-based metabolomics combined with multivariate data analysis is used to study metastatic B16-F10 melanoma in C57BL/6J mouse spleen. Principal Component Analysis (PCA), an unsupervised multivariate data analysis method, is used to detect possible outliers, while Orthogonal Projection to Latent Structure (OPLS), a supervised multivariate data analysis method, is employed to find important metabolites responsible for discriminating the control and the melanoma groups. Two different strategies, i.e. spectral binning and spectral deconvolution, are used to reduce the original spectral data before statistical analysis. Spectral deconvolution is found to be superior for identifying a set of discriminatory metabolites between the control and the melanoma groups, especially when the sample size is small. OPLS results show that the melanoma group can be well separated from its control group. It is found that taurine, glutamate, aspartate, O-Phosphoethanolamine, niacinamide,ATP, lipids and glycerol derivatives are decreased statistically and significantly while alanine, malate, xanthine, histamine, dCTP, GTP, thymidine, 2′-Deoxyguanosine are statistically and significantly elevated. These significantly changed metabolites are associated with multiple biological pathways and may be potential biomarkers for metastatic melanoma in spleen. PMID:25383071

  16. Postlumpectomy Focal Brachytherapy for Simultaneous Treatment of Surgical Cavity and Draining Lymph Nodes

    SciTech Connect

    Hrycushko, Brian A.; Li Shihong; Shi Chengyu; Goins, Beth; Liu Yaxi; Phillips, William T.; Otto, Pamela M.; Bao, Ande

    2011-03-01

    Purpose: The primary objective was to investigate a novel focal brachytherapy technique using lipid nanoparticle (liposome)-carried {beta}-emitting radionuclides (rhenium-186 [{sup 186}Re]/rhenium-188 [{sup 188}Re]) to simultaneously treat the postlumpectomy surgical cavity and draining lymph nodes. Methods and Materials: Cumulative activity distributions in the lumpectomy cavity and lymph nodes were extrapolated from small animal imaging and human lymphoscintigraphy data. Absorbed dose calculations were performed for lumpectomy cavities with spherical and ellipsoidal shapes and lymph nodes within human subjects by use of the dose point kernel convolution method. Results: Dose calculations showed that therapeutic dose levels within the lumpectomy cavity wall can cover 2- and 5-mm depths for {sup 186}Re and {sup 188}Re liposomes, respectively. The absorbed doses at 1 cm sharply decreased to only 1.3% to 3.7% of the doses at 2 mm for {sup 186}Re liposomes and 5 mm for {sup 188}Re liposomes. Concurrently, the draining sentinel lymph nodes would receive a high focal therapeutic absorbed dose, whereas the average dose to 1 cm of surrounding tissue received less than 1% of that within the nodes. Conclusions: Focal brachytherapy by use of {sup 186}Re/{sup 188}Re liposomes was theoretically shown to be capable of simultaneously treating the lumpectomy cavity wall and draining sentinel lymph nodes with high absorbed doses while significantly lowering dose to surrounding healthy tissue. In turn, this allows for dose escalation to regions of higher probability of containing residual tumor cells after lumpectomy while reducing normal tissue complications.

  17. [Place of indocyanine green coupled with fluorescence imaging in research of breast cancer sentinel node].

    PubMed

    Vermersch, Charlotte; Raia Barjat, Tiphaine; Perrot, Marianne; Lima, Suzanne; Chauleur, Céline

    2016-04-01

    The sentinel node has a fundamental role in the management of early breast cancer. Currently, the double detection of blue and radioisotope is recommended. But in common practice, many centers use a single method. However, with a single detection, the risk of false negatives and the identification failure rate increase to a significant extent and the number of sentinel lymph node detected and removed is not enough. Furthermore, the tracers used until now show inconveniences. The purpose of this work is to present a new method of detection, using the green of indocyanine coupled with fluorescence imaging, and to compare it with the already existing methods. The method combined by fluorescence and isotopic is reliable, sure, of fast learning and could constitute a good strategy of detection. The major interest is to obtain a satisfactory number of sentinel nodes. The profit could be even more important for overweight patients. The fluorescence used alone is at the moment not possible. Wide ranging studies are necessary. The FLUOTECH, randomized study of 100 patients, comparing the isotopic method of double isotope technique and fluorescence, is underway to confirm these data.

  18. The EANM clinical and technical guidelines for lymphoscintigraphy and sentinel node localization in gynaecological cancers.

    PubMed

    Giammarile, Francesco; Bozkurt, M Fani; Cibula, David; Pahisa, Jaume; Oyen, Wim J; Paredes, Pilar; Olmos, Renato Valdes; Sicart, Sergi Vidal

    2014-07-01

    The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board.

  19. Nivolumab for Metastatic Melanoma.

    PubMed

    Gupta, A K; Daigle, D

    2016-03-01

    Melanoma is an aggressive skin cancer with a generally poor prognosis at Stage III-IV disease. Traditionally, metastatic melanoma was treated by surgical resection, when possible, and with systemic chemotherapy. New developments in molecular biology have led to the identification of immune checkpoints which are exploited by malignant cells, allowing them to go undetected by the immune system. Nivolumab (Opdivo®) is a human monoclonal antibody which prevents immune inhibition by interacting with PD-1 on tumor cells; thus, increasing tumor-specific T cell proliferation. Nivolumab has demonstrated efficacy superior to that of standard chemotherapy and relative safety in clinical trials. Indeed, the outcomes for patients with advanced melanoma are being improved by novel biologic agents such as nivolumab.

  20. Targeted therapies for cutaneous melanoma.

    PubMed

    Kee, Damien; McArthur, Grant

    2014-06-01

    Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.

  1. Vitamins and Melanoma

    PubMed Central

    Russo, Irene; Caroppo, Francesca; Alaibac, Mauro

    2015-01-01

    A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamins in chemoprevention and therapy of melanoma could be encouraged if supported by pre-clinical and clinical evidence. PMID:26213971

  2. Use of computed body tomography in malignant melanoma

    SciTech Connect

    Kostrubiak, I.; Whitley, N.O.; Aisner, J.; Goose, P.; DeLuca, R.R.; Didolkar, M.S.; Elias, E.G.

    1988-05-20

    Malignant melanoma has no predictable clinical behavior. The Breslow depth and Clark's level of invasion are important prognostic factors, but their prognostic values are overshadowed by the presence of regional lymph node metastasis (stage III disease). The authors reviewed the CT scans and charts of 67 patients who had a confirmed diagnosis of malignant melanoma. Excluding patients with stage I disease, all others had histological evidence of metastatic disease shown in one or more sites by biopsy or necropsy specimens. In addition, in some patients metastatic disease was documented by clinical course and follow-up study in sites such as the brain, lung, and liver, where biopsies were not performed. They tried to ascertain any change in the extent of disease or any alteration in therapy that was based on the findings on the CT scan.

  3. Melanoma associated retinopathy: A new dimension using adaptive optics.

    PubMed

    Dabir, Supriya; Mangalesh, Shwetha; Govindraj, Indu; Mallipatna, Ashwin; Battu, Rajani; Shetty, Rohit

    2015-01-01

    We report a 56-year-old male patient, complaining of metamorphopsia in his left eye nevertheless visual acuity, slit lamp, and fundus examinations were within normal limits. Microperimetry (MAIA, Centervue, Italy) revealed central field loss and spectral domain optical coherence tomography (Spectralis, Heidelberg, Germany) showed disrupted cone outer segment tip layer. The patient had a diagnosis of cutaneous melanoma in his foot for which an excision biopsy with lymph node dissection was performed 5 months earlier. Our clinical diagnosis was melanoma-associated retinopathy. Electrophysiology confirmed the diagnosis. Adaptive optics retinal imaging (Imagine eyes, Orsay) was performed to assess the cone mosaic integrity across the central retina. This is the first report on the investigation of autoimmune retinopathy using adaptive optics ophthalmoscopy. This case highlights the viability of innovative diagnostic modalities that aid early detection and subsequent management of vision threatening retinal.

  4. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  5. Activation of latent metastases in the lung after resection of a metastatic lymph node in a lymph node metastasis mouse model.

    PubMed

    Shao, Lenan; Ouchi, Tomoki; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

    2015-05-08

    Iatrogenic induction of regional and distant cancer metastases is a risk associated with clinical resection of tumor-positive sentinel lymph nodes. However, there have been no studies of this risk in a mouse model of cancer metastasis. Here, we report that resection of a tumor-bearing subiliac lymph node (SiLN) enhanced lung metastasis in a mouse model of lymph node metastasis. Bioluminescence imaging revealed that metastatic tumor cells in the secondary lymph node continued to grow after resection of the SiLN, and that the probability of metastasis to the lungs was increased when the interval between SiLN inoculation and resection was reduced. Futhermore, histological analysis demonstrated that latents in the lung were stimulated to grow after resection of the SiLN. Fluorescence imaging indicated that the route of tumor cell dissemination from SiLN to the lung was the venous system located over the SiLN. We speculate that our mouse model will be useful for studying the mechanisms of tumor cell latency, with a view to improving the detection and treatment of latent metastases.

  6. Management of non-melanoma skin cancer in immunocompromised solid organ transplant recipients.

    PubMed

    Bangash, Haider K; Colegio, Oscar R

    2012-09-01

    The management of non-melanoma skin cancers (NMSCs) in solid organ transplant recipients (OTRs) presents a variety of clinical challenges for physicians. OTRs are at a 65-fold increased risk for developing cutaneous squamous cell carcinomas (SCC), the most common NMSC that develops after transplantation. Risk factors contributing to the development of NMSCs in OTRs include a past medical history of any previous skin cancer, a personal history of significant sun exposure and a fair skin complexion or phototype. Further, greater immunosuppressive medication levels lead to an increased risk of NMSCs. Among immunosuppressants, specific older agents such as azathioprine and cyclosporine may increase the risk of developing NMSCs in contrast to newer agents such as sirolimus. Early skin biopsy and treatment of premalignant and malignant lesions are essential for treating these patients successfully. In this regard, the concept of field cancerization has been instructive in broadening treatments to include entire affected areas rather than individual lesions given that the areas with significant ultraviolet irradiation will continue to develop numerous individual precancerous and cancerous lesions. Field therapy with photodynamic therapy or topical 5-fluorouracil, imiquimod or diclofenac is often used in OTRs according to individual patient tolerability. Prompt excision or Mohs micrographic surgery is the standard of care of primary, uncomplicated squamous cell and basal cell carcinomas. For patients with in-transit or metastatic squamous cell carcinomas, adjuvant radiation, chemotherapy, and staging by sentinel lymph node dissection may be employed. For patients who develop numerous SCC per year, chemoprophylaxis can be effective in limiting the burden of disease. In consultation with the multidisciplinary transplant team, the immunosuppressive regimen can be revised to lower overall immunosuppression or altered to include newer drugs that have decreased oncogenic

  7. Lymphoscintigraphy and triangulated body marking for morbidity reduction during sentinel node biopsy in breast cancer

    PubMed Central

    Krynyckyi, Borys R; Shafir, Michail K; Kim, Suk Chul; Kim, Dong Wook; Travis, Arlene; Moadel, Renee M; Kim, Chun K

    2005-01-01

    Current trends in patient care include the desire for minimizing invasiveness of procedures and interventions. This aim is reflected in the increasing utilization of sentinel lymph node biopsy, which results in a lower level of morbidity in breast cancer staging, in comparison to extensive conventional axillary dissection. Optimized lymphoscintigraphy with triangulated body marking is a clinical option that can further reduce morbidity, more than when a hand held gamma probe alone is utilized. Unfortunately it is often either overlooked or not fully understood, and thus not utilized. This results in the unnecessary loss of an opportunity to further reduce morbidity. Optimized lymphoscintigraphy and triangulated body marking provides a detailed 3 dimensional map of the number and location of the sentinel nodes, available before the first incision is made. The number, location, relevance based on time/sequence of appearance of the nodes, all can influence 1) where the incision is made, 2) how extensive the dissection is, and 3) how many nodes are removed. In addition, complex patterns can arise from injections. These include prominent lymphatic channels, pseudo-sentinel nodes, echelon and reverse echelon nodes and even contamination, which are much more difficult to access with the probe only. With the detailed information provided by optimized lymphoscintigraphy and triangulated body marking, the surgeon can approach the axilla in a more enlightened fashion, in contrast to when the less informed probe only method is used. This allows for better planning, resulting in the best cosmetic effect and less trauma to the tissues, further reducing morbidity while maintaining adequate sampling of the sentinel node(s). PMID:16277655

  8. Raman spectroscopy detects melanoma and the tissue surrounding melanoma using tissue-engineered melanoma models

    PubMed Central

    Yorucu, Ceyla; Lau, Katherine; Mittar, Shweta; Green, Nicola H.; Raza, Ahtasham; Rehman, Ihtesham Ur; MacNeil, Sheila

    2016-01-01

    ABSTRACT Invasion of melanoma cells from the primary tumor involves interaction with adjacent tissues and extracellular matrix. The extent of this interaction is not fully understood. In this study Raman spectroscopy was applied to cryo-sections of established 3D models of melanoma in human skin. Principal component analysis was used to investigate differences between the tumor and normal tissue and between the peri-tumor area and the normal skin. Two human melanoma cells lines A375SM and C8161 were investigated and compared in 3D melanoma models. Changes were found in protein conformations and tryptophan configurations across the entire melanoma samples, in tyrosine orientation and in more fluid lipid packing only in tumor dense areas, and in increased glycogen content in the peri-tumor areas of melanoma. Raman spectroscopy revealed changes around the perimeter of a melanoma tumor as well as detecting differences between the tumor and the normal tissue. PMID:27158185

  9. Importance of recognizing sentinel headache

    PubMed Central

    Pereira, Júlio Leonardo Barbosa; de Albuquerque, Lucas Alverne Freitas; Dellaretti, Marcos; de Carvalho, Gervásio Teles Cardoso; Vieira Junior, Gerival; Rocha, Marcella Israel; Loures, Laize Luzia Andrade; Christo, Paulo Pereira; de Sousa, Atos Alves

    2012-01-01

    Background: Sentinel headache (SH) is a kind of secondary headache and is characterized as sudden, intense, and persistent, preceding spontaneous subarachnoid hemorrhage (SAH) by days or weeks. Methods: Eighty-nine consecutive patients with a diagnosis of spontaneous SAH were evaluated following admission to the Neurosurgical Service at Santa Casa Hospital, Belo Horizonte, between December 2009 and December 2010. Results: Out of the 89 patients, 64 (71.9%) were women. Mean age was 48.9 years (SD ± 13.4, ranging from 18 to 85 years). Twenty-four patients (27.0%) presented SH, which occurred, in average, 10.6 days (SD ± 13.5) before a SAH. No statistically significant differences were observed between the presence of SH and gender, arterial hypertension and migraine (P > 0.05), Glasgow Comma Scale (GCS) and World Federation of Neurological Surgeons (WFNS) scale at admission. Conclusion: The prevalence of SH was 27% in this study but no related factors were identified. Therefore, further clarification of this important entity is required so as to facilitate its recognition in emergency services and improve the prognosis of patients with cerebral aneurysms. PMID:23372978

  10. Melanoma Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Congenital uveal melanoma?

    PubMed

    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V

    2016-01-01

    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma.

  12. [Immunotherapy of melanoma].

    PubMed

    Dréno, Brigitte

    2010-10-01

    This article describes current concepts and future challenges in non specific immunotherapy, vaccination, and antigen-specific adoptive immunotherapy of melanoma. If these treatments are to realize their full potential, it will be essential to understand how the tumor induces immune tolerance.

  13. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  14. The curious incident of 3 melanomas and their possible origins—A case report and review of literature

    PubMed Central

    Sin, Eliza I-Lin; Tan, Benita Kiat Tee; Lau, Kah Weng; Teo, Melissa Ching-Ching

    2016-01-01

    Background We describe an unusual case of 2 intra-parenchymal breast melanomas with a concomitant subcutaneous melanoma in the ipsilateral upper limb and no definite primary lesion. Case report Our patient is a 40-year-old Chinese female who presented with a breast lump in her left breast for which excision biopsy showed melanoma. A PET-CT revealed a second lesion in her breast. A left upper arm nodule with no overlying skin changes was also noted. She underwent a mastectomy and excision biopsy of the upper arm nodule. Histology showed that the second breast lesion was also a melanoma, while the arm nodule contained melanoma cells within a fibrous capsule. Conclusion The presence of a melanoma in the breast should prompt a close and meticulous search for a primary lesion and potential signs of metastasis. Encapsulated subcutaneous nodules can be attributed to replaced lymph nodes or subcutaneous melanoma which can be either primary dermal melanoma or metastasis from an unknown primary. PMID:27100953

  15. Proceedings of GLaSS: Global Lakes Sentinel Services

    NASA Astrophysics Data System (ADS)

    Peters, Steef; Hommersom, Annelies; Alikas, Krista; Heege, Thomas; Schenk, Karin; Ruescas, Ana; Eleveld, Marieke; Giardino, Claudia; Koponen, Sampsa; Kallio, Kari; Philipson, Petra

    2015-12-01

    Global Lakes Sentinel Services (GLaSS) is developing a prototype Sentinel service infrastructure to ingest and process Sentinel-2 and Sentinel-3 data into validated ecological water quality parameters for lakes, plus training material. GLaSS is an EU-funded R&D project within the Copernicus framework. The project is well on its way to reach its goals. Some results on comparisons on atmospheric correction methods for inland waters are presented here.

  16. Clinics, prognosis and new therapeutic options in patients with mucosal melanoma

    PubMed Central

    Schaefer, Tim; Satzger, Imke; Gutzmer, Ralf

    2017-01-01

    Abstract Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites. We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department. The primary melanomas were located in the head/neck region (n = 32), the FGT (n = 24), and the anorectal region (n = 19). The median age of the patients was 66 years. At initial diagnosis the primary melanoma was not completely resectable in 11 (15%) patients, 18 (24%) patients had regional lymph node metastases, and 7 (9%) patients distant metastases. During follow-up, 22 (29%) patients suffered from a local recurrence, in particular patients with primary melanoma in the head/neck region without postoperative radiotherapy. By multivariate analysis location of the primary melanoma in the head/neck area or anorectal region and presence of metastases at time of diagnosis represented poor prognostic factors for recurrence-free survival. In 62 tested individuals 7 KIT mutations were found, 2 BRAF mutations in 57 tested patients. Four patients received targeted therapies, 14 checkpoint inhibitors, 4 (1/1 on vemurafenib, 1/7 on ipilimumab, and 2/7 on PD-1 inhibitors) patients showed responses of more than 100 days duration. Mucosal melanomas are often locally advanced or metastatic at initial diagnosis, thus they require extensive staging procedures. The high rate of local recurrences in the head/neck region can be significantly reduced by postoperative radiotherapy. For the potential use of medical treatment a mutation analysis for KIT and BRAF genes should be performed. The use of new immunologic and targeted

  17. CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma.

    PubMed

    Fernández-Figueras, M T; Ariza, A; Calatrava, A; Puig, L; Fernández-Vasalo, A; Ferrándiz, C

    1996-04-01

    CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied. According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.

  18. Decreased Expression of Nuclear p300 Is Associated with Disease Progression and Worse Prognosis of Melanoma Patients

    PubMed Central

    Rotte, Anand; Bhandaru, Madhuri; Cheng, Yabin; Sjoestroem, Cecilia; Martinka, Magdalena; Li, Gang

    2013-01-01

    Background Genomic instability due to UV radiation is one of the leading causes for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA repair and maintenance of genomic integrity. The present study was performed to analyze the correlation between p300 expression, melanoma progression and patient survival. Methods Tissue microarray and immunohistochemical analysis was employed to study the expression of p300 in melanoma patients. A total of 358 melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis, and receiver-operating characteristic curves, were used to elucidate the prognostic significance of p300 expression. Results Our results demonstrate that p300 is expressed in both nucleus and cytoplasm but the nuclear expression of p300 is predominant. The progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma was associated with decreased nuclear and increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain in cytoplasmic p300 was correlated with the progression of melanoma from AJCC stage II to stage III, which requires the migration and metastasis of cancer cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and increase in cytoplasmic p300 expression correlated with worse survival of melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the patient survival independent of AJCC stage, age and gender. Conclusion Loss of nuclear p300 expression is an indicator of worse patient survival and is an independent prognostic marker for melanoma. PMID:24098694

  19. Melanoma risk loci as determinants of melanoma recurrence and survival

    PubMed Central

    2013-01-01

    Background Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested. Methods We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics. Results We identified significant associations for rs7538876 (RCC2) with RFS (HR = 1.48, 95% CI = 1.20-1.83, p = 0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR = 1.43, 95% CI = 1.07-1.91, p = 0.01, HR = 1.52, 95% CI = 1.09-2.12, p = 0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC = 82%) compared to histological type and stage alone (AUC = 78%). Conclusions We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication. PMID:24188633

  20. The Scientist as Sentinel (Invited)

    NASA Astrophysics Data System (ADS)

    Oreskes, N.

    2013-12-01

    Scientists have been warning the world for some time about the risks of anthropogenic interference in the climate system. But we struggle with how, exactly, to express that warning. The norms of scientific behavior enjoin us from the communication strategies normally associated with warnings. If a scientist sounds excited or emotional, for example, it is often assumed that he has lost his capac¬ity to assess data calmly and therefore his conclusions are suspect. If the scientist is a woman, the problem is that much worse. In a recently published article my colleagues and I have shown that scientists have systematically underestimated the threat of climate change (Brysse et al., 2012). We suggested that this occurs for norma¬tive reasons: The scientific values of rationality, dispassion, and self-restraint lead us to demand greater levels of evidence in support of surprising, dramatic, or alarming conclusions than in support of less alarming conclusions. We call this tendency 'err¬ing on the side of least drama.' However, the problem is not only that we err on the side of least drama in our assessment of evidence, it's also that we speak without drama, even when our conclusions are dramatic. We speak without the emotional cadence that people expect to hear when the speaker is worried. Even when we are worried, we don't sound as if we are. In short, we are trying to act as sentinels, but we lack the register with which to do so. Until we find those registers, or partner with colleagues who are able to speak in the cadences that communicating dangers requires, our warnings about climate change will likely continue to go substantially unheeded.

  1. Experimental models of uveal melanoma.

    PubMed

    Blanco, Paula L; Caissie, Amanda L; Burnier, Miguel N

    2004-06-01

    Over the past several decades, considerable effort has been directed toward developing suitable experimental models for the study of uveal melanoma. Animal models of uveal melanoma have undergone many improvements, leading to the development of experimental systems that better represent the disease in human beings. A major advance has come from the use of human uveal melanoma cell lines capable of inducing tumour growth and metastatic disease in immunodeficient hosts. Knowledge gained from the use of experimental models will ultimately be translated into better diagnostic and therapeutic strategies for patients with uveal melanoma. In this review the authors describe the current state-of-the-art designs of experimental models of uveal melanoma, highlighting the advantages and disadvantages of the available models. Novel findings from a rabbit model of uveal melanoma are also presented.

  2. Correlation Between SUVmax and CT Radiomic Analysis Using Lymph Node Density in PET/CT-Based Lymph Node Staging.

    PubMed

    Giesel, Frederik L; Schneider, Florian; Kratochwil, Clemens; Rath, Daniel; Moltz, Jan; Holland-Letz, Tim; Kauczor, Hans-Ulrich; Schwartz, Lawrence H; Haberkorn, Uwe; Flechsig, Paul

    2017-02-01

    In patients with lung cancer (LC), malignant melanoma (MM), gastroenteropancreatic neuroendocrine tumors (GEP NETs), and prostate cancer (PCA), lymph node (LN) staging is often performed by (18)F-FDG PET/CT (LC and MM), (68)Ga-DOTATOC PET/CT (GEP NET), and (68)Ga-labeled prostate-specific membrane antigen PET/CT (PCA) but is sometimes not accurate because of indeterminate PET findings. To better evaluate malignant LN infiltration, additional surrogate parameters, especially in cases with indeterminate PET findings, would be helpful. The purpose of this study was to evaluate whether SUVmax in the PET examination might correlate with semiautomated density measurements of LNs in the CT component of the PET/CT examination.

  3. SENTINEL-1 Image Matching Using Strong Scatters

    NASA Astrophysics Data System (ADS)

    Ghannadi, M. A.; Saadatseresht, M.; Motagh, M.

    2015-12-01

    The availability of new radar spaceborne sensors offers new interesting potentialities for the geomatics application: spatial and temporal change detection, generation of Digital Elevation Model(DEM) using radargrametry and interferometry. Since the start of the sentinel-1 mission to take images from different regions all over the world, the ability to use these images in variety domains has been treasured. This paper suggests a method for image matching using strong scatters. all the experiments are done on sentinel-1 stereo images from Jam, Bushehr, Iran.

  4. Outcomes by Ethnicity: Sentinel Lymph Node Status in Women with Breast Cancer

    DTIC Science & Technology

    2006-04-01

    Current and Emerging Treatment Strategies 4-18-05 Update in the Prevention and Treatment of DVT and PE : Factor XA Inhibitors 4-5-05...Differences in health-seeking behaviors, socioeconomic disparities, cultural influences, stage at diagnosis , estrogen receptor status, treatment and tumor...backgrounds.1-2 Differences in health-seeking behaviors, socioeconomic disparities, cultural influences, stage at diagnosis , estrogen receptor status

  5. Detection of Genetic Alterations in Breast Sentinel Lymph Node by Array-CGH

    DTIC Science & Technology

    2005-10-01

    razor blade to ensure minimal contamination of normal or stromal cells. The DNA is extracted from these sections (average 5 slides with 5mM sections per...M. Ribeiro,3 Cicero A. Urban,4 Rubens S. de Lima,4 Iglenir J. Cavalli,3 Bassem R. Haddad.1 Georgetown University Medical Center,1 Washington, DC

  6. The prognostic value of sentinel lymph node micrometastases in patients with invasive breast carcinoma.

    PubMed

    Cipolla, Calogero; Graceffa, Giuseppa; La Mendola, Roberta; Fricano, Salvatore; Fricano, Martina; Vieni, Salvatore

    2015-01-01

    Il significato prognostico delle micrometastasi nel linfonodo sentinella nelle pazienti affette da carcinoma della mammella è ancora ampiamente dibattuto. Anche se, in assenza di univoche linee guida, nella pratica clinica la linfadenectomia ascellare in queste pazienti non viene più eseguita di routine. Abbiamo condotto uno studio retrospettivo su 746 patienti affette da carcinoma invasivo della mammella con linfonodi ascellari negativi, sottoposte a chirurgia conservativa o a mastectomia totale con biopsia del linfonodo sentinella. Le pazienti in cui è stata diagnostica la presenza di micrometastasi del linfonodo sentinella sono state considerate in due diversi gruppi. In un primo gruppo, trattato con linfadenectomia ascellare totale è stata valutata l’incidenza di metastasi a carico dei rimanenti linfonodi ascellari. Un secondo gruppo non ha ricevuto alcun trattamento aggiuntivo dell’ascella e le pazienti sono state seguite con controlli periodici clinico strumentali. In entrambi i gruppi è stata valutata l’incidenza di eventuali recidive ascellari. All’esame istologico estemporaneo ed al successivo esame istologico definitivo del linfonodo sentinella, in 51 pazienti (6,83%) sono state evidenziate micrometastasi, in 8 pazienti (1,07%) erano presenti cellule tumorali isolate. Quindici di queste pazienti sono state sottoposte a linfadenectomia ascellare totale. Solo in 2 casi (13,33%) sono state ritrovate metastasi a carico dei rimanenti linfonodi ascellari. Quarantaquattro pazienti non hanno ricevuto alcun trattamento aggiuntivo dell’ascella. In queste pazienti nessuna recidiva ascellare è stata registrata durante un follow-up medio di 65,3±9,65 mesi (range 42-78 mesi). Sulla base dei risultati ottenuti in questo studio ed in linea con alcuni recenti trials randomizzati si ci sentiamo di concludere che la linfadenectomia ascellare può essere evitata nei casi con micrometastasi nel linfonodo sentinella. Una sua eventuale indicazione può essere valutata caso per caso considerando come fattori di rischio per la recidiva ascellare alcune caratteristiche biomorfologiche del tumore primitivo.

  7. [Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

    PubMed

    Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

    2014-01-01

    Antecedentes: en pacientes con carcinoma ductal in situ la biopsia de ganglio centinela es motivo de controversia porque se reportan ganglios positivos en 1.4-12.5% debido al carcinoma invasor oculto en la pieza quirúrgica. Objetivo: conocer la frecuencia de metástasis en ganglio centinela en pacientes con carcinoma ductal in situ e identificar las diferencias entre los casos positivos y negativos. Material y métodos: estudio retrospectivo, transversal, analítico de pacientes con carcinoma ductal in situ a quienes se realizó una biopsia de ganglio centinela por requerir mastectomía, tener un tumor palpable, lesión radiológica = 5 cm, inadecuada relación mama-tumor o porque la escisión pudiera afectar el flujo linfático. Resultados: de 168 carcinomas in situ, se incluyeron 50 casos con carcinoma ductal in situ y biopsia de ganglio centinela, de pacientes con edad promedio de 51.6 años, 30 (60%) de ellas asintomáticas. Los signos reportados fueron: nódulo palpable (18%), secreción por el pezón (12%) o ambos (8%). Predominaron las microcalcificaciones (72%), comedonecrosis (62%) y grado histológico -2 (44%) con 28% de receptores hormonales negativos. En el estudio transoperatorio 4 (8%) pacientes tuvieron ganglio centinela positivo y un caso en estudio histopatológico definitivo (60% micrometástasis, 40% macrometástasis), todos con carcinoma invasor en la pieza quirúrgica. Las pacientes con ganglio centinela transoperatorio positivo eran más jóvenes (44.5 vs 51 años), con más tumores palpables (50 vs 23.1%), más grandes (3.5 vs 2 cm), más comedonecrosis (75 vs 60.8%), más indiferenciados (75% vs 39.1%) y menos receptores hormonales (50 vs 73.9%), que las que tenían ganglio centinela negativo, sin que estas diferencias tuvieran significación estadística. Conclusiones: puesto que 1 de cada 12 pacientes con carcinoma ductal in situ tiene afectación ganglionar en el ganglio centinela, se recomienda seguir tomando la biopsia para evitar segundas cirugías por un carcinoma invasor oculto.

  8. Outcomes by Ethnicity: Sentinel Lymph Node Status in Women With Breast Cancer

    DTIC Science & Technology

    2005-04-01

    race/ethnicity a Descriptive analysis "I Annual Summary W81XH-04-1-042901 Hassett, Mary A. Funding Sources * http://cdmrp.army.mil a Nursing ... organizations YOU CAN DO IT I * Private Industry e Non-profit organizations o Institution-based 4.! 2.’ I\\ / . • , "Annual Summary W81XH-04-1-042901 Hassett

  9. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    PubMed

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog.

  10. AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

    ClinicalTrials.gov

    2015-06-01

    Acral Lentiginous Malignant Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Intraocular Melanoma; Iris Melanoma; Lentigo Maligna Malignant Melanoma; Recurrent Melanoma; Stage, Intraocular Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  11. Oncogenes in melanoma: an update.

    PubMed

    Kunz, Manfred

    2014-01-01

    Melanoma is a highly aggressive tumour with poor prognosis in the metastatic stage. BRAF, NRAS, and KIT are three well-known oncogenes involved in melanoma pathogenesis. Targeting of mutated BRAF kinase has recently been shown to significantly improve overall survival of metastatic melanoma patients, underscoring the particular role of this oncogene in melanoma biology. However, recurrences regularly occur within several months, which supposedly involve further oncogenes. Moreover, oncogenic driver mutations have not been described for up to 30% of all melanomas. In order to obtain a more complete picture of the mutational landscape of melanoma, more recent studies used high-throughput DNA sequencing technologies. A number of new oncogene candidates such as MAPK1/2, ERBB4, GRIN2A, GRM3, RAC1, and PREX2 were identified. Their particular role in melanoma biology is currently under investigation. Evidence for the functional relevance of some of these new oncogene candidates has been provided in in vitro and in vivo experiments. However, these findings await further validation in clinical studies. This review provides an overview on well-known melanoma oncogenes and new oncogene candidates, based on recent high-throughput sequencing studies. The list of genes discussed herein is of course not complete but highlights some of the most significant of recent findings in this area. The new candidates may support more individualized treatment approaches for metastatic melanoma patients in the future.

  12. Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases

    ClinicalTrials.gov

    2016-03-09

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Liver Metastases; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  13. Metabolic rewiring in melanoma

    PubMed Central

    Ratnikov, Boris I.; Scott, David A.; Osterman, Andrei L.; Smith, Jeffrey W.; Ronai, Ze’ev A.

    2016-01-01

    Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the MAPK pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1α, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy. PMID:27270434

  14. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  15. Autochthonous primary and metastatic melanomas in Hgf-Cdk4 R24C mice evade T-cell-mediated immune surveillance.

    PubMed

    Landsberg, Jennifer; Gaffal, Evelyn; Cron, Mira; Kohlmeyer, Judith; Renn, Marcel; Tüting, Thomas

    2010-10-01

    Genetically engineered mouse models offer new opportunities to investigate the role of cell-mediated immunity in the natural progression of melanoma in an immunocompetent host. Here we report that Hgf-Cdk4(R24C) mice spontaneously develop a spectrum of primary melanomas with high penetrance during their first year of life. Malignant transformation proceeds in a stepwise manner from multiple melanocytic nevi to single nodular melanomas and disseminated metastases in most mice. Migrating melanoma cells invade the draining lymph nodes without activating the immune system. Autochthonous primary tumors are destroyed following experimental introduction of immune surveillance using an adoptive lymphocyte transfer approach. However, some tumor cells are able to survive, evade immune cell control, and recur both locally and systemically. Immune tolerance in recurring tumors may be supported by immunosuppressive Gr1(+) myeloid cells. Taken together, our results demonstrate that primary and metastatic melanomas developing spontaneously in Hgf-Cdk4(R24C) mice effectively evade cellular immune surveillance.

  16. miR-125b induces cellular senescence in malignant melanoma

    PubMed Central

    2014-01-01

    Background Micro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory. Methods We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization. Results In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours. Conclusions Our results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma. PMID:24762088

  17. Evaluating Biomarkers in Melanoma

    PubMed Central

    Karagiannis, Panagiotis; Fittall, Matthew; Karagiannis, Sophia N.

    2015-01-01

    The incidence of cutaneous melanoma has more than doubled over the last decades making it one of the fastest rising cancers worldwide. Improved awareness and early detection of malignant moles now permit earlier diagnosis aiming to decrease the likelihood of recurrence. However, it is difficult to identify those patients initially diagnosed with localized melanoma who subsequently develop metastatic disease. For this group, prognosis remains poor and clinical outcomes are variable and challenging to predict. Considerable efforts have focused on the search for novel prognostic tools, with numerous markers evaluated in the circulation and in tumor lesions. The most reliable predictors of patient outcome are the clinical and histological features of the primary tumor such as Breslow thickness, ulceration status, and mitotic rate. Elevated serum levels of the enzyme lactate dehydrogenase, likely to indicate active metastatic disease, are also routinely used to monitor patients. The emergence of novel immune and checkpoint antibody treatments for melanoma and increasing appreciation of key roles of the immune system in promoting or halting cancer progression have focused attention to immunological biomarkers. Validation of the most promising of these may have clinical applications in assisting prognosis, assessing endpoints in therapy, and monitoring responses during treatment. PMID:25667918

  18. Beyond BRAF in melanoma.

    PubMed

    Daud, Adil; Bastian, Boris C

    2012-01-01

    Recent progress in the analysis of genetic alterations in melanoma has identified recurrent mutations that result in the activation of critical signaling pathways promoting growth and survival of tumors cells. Alterations in the RAS-RAF-MAP kinase and PI3-kinase signaling pathways are commonly altered in melanoma. Mutations in BRAF, NRAS, KIT, and GNAQ occur in a mutually exclusive pattern and lead to MAP-kinase activation. Loss of PTEN function, primarily by deletion, is the most common known genetic alteration in the PI3-kinase cascade, and is commonly associated with BRAF mutations (Curtin et al., N Engl J Med 353:2135-2147, 2005; Tsao et al., Cancer Res 60:1800-1804, 2000, J Investig Dermatol 122:337-341, 2004). The growth advantage conveyed by the constitutive activation of these pathways leads to positive selection of cells that have acquired the mutations and in many instances leads to critical dependency of the cancer cells on their activation. This creates opportunities for therapeutic interventions targeted at signaling components within these pathways that are amenable for pharmacological inhibition. This concept follows the paradigm established by the landmark discovery that inhibition of the fusion kinase BCR-ABL can be used to treat chronic myelogenous leukemia (Druker et al., N Engl J Med 344:1031-037, 2001). The review will focus primarily on kinases involved in signaling that are currently being evaluated for therapeutic intervention in melanoma.

  19. Desmoplastic melanoma: a review.

    PubMed

    Chen, Lucy L; Jaimes, Natalia; Barker, Christopher A; Busam, Klaus J; Marghoob, Ashfaq A

    2013-05-01

    Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis, and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of DM and nondesmoplastic melanoma. This has led to the separation of DM into 2 histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors, and examine the current literature on disease progression and management.

  20. Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation.

    PubMed

    Tormo, Damia; Ferrer, Aleix; Gaffal, Evelyn; Wenzel, Jörg; Basner-Tschakarjan, Etiena; Steitz, Julia; Heukamp, Lukas C; Gütgemann, Ines; Buettner, Reinhard; Malumbres, Marcos; Barbacid, Mariano; Merlino, Glenn; Tüting, Thomas

    2006-08-01

    Currently, novel mouse models of melanoma are being generated that recapitulate the histopathology and molecular pathogenesis observed in human disease. Impaired cell-cycle control, which is a hallmark of both familial and sporadic melanoma, promotes slowly growing carcinogen-induced melanomas in the skin of mice carrying a mutated cyclin-dependent kinase 4 (CDK4(R24C)). Deregulated receptor tyrosine kinase signaling, which is another important feature of human melanoma, leads to spontaneous development of metastatic melanoma after a long latency period in mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF mice). Here we report that treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate induced metastatic melanomas in all HGF/SF mice on the C57BL/6 background, which histologically resemble human melanoma. Importantly, mutant CDK4 dramatically increased the number and the growth kinetics of carcinogen-induced primary melanomas in the skin and promoted the growth of spontaneous metastases in lymph nodes and lungs in all HGF/SF mice within the first 3 months of life. Apart from very few skin papillomas, we did not observe tumors of other histology in carcinogen-treated HGF/SF x CDK4(R24C) mice. This new experimental mouse model can now be exploited to study further the biology of melanoma and evaluate new treatment modalities.

  1. Data mining tools for Sentinel 1 and Sentinel 2 data exploitation

    NASA Astrophysics Data System (ADS)

    Espinoza Molina, Daniela; Datcu, Mihai

    2016-10-01

    With the new planned Sentinel missions, the availability of Earth Observation data is increasing everyday offering a larger number of applications that can be created using these data. Currently, three of the five missions were launched and they are delivering a wealth of data and imagery of the Earth's surface as, for example, the Sentinel-1 carries an advanced radar instrument to provide an all-weather, day-and-night supply of Earth imagery. The second mission, the Sentinel-2, carries an optical instrument payload that will sample 13 spectral bands at different resolutions. Even though, we count on tools for automated loading and visual exploration of the Sentinel data, we still face the problem of extracting relevant structures from the images, finding similar patterns in a scene, exploiting the data, and creating final user applications based on these processed data. In this paper, we present our approach for processing radar and multi-spectral Sentinel data. Our approach is mainly composed of three steps: 1) the generation of a data model that explains the information contained in a Sentinel product. The model is formed by primitive descriptors and metadata entries, 2) the storage of this model in a database system, 3) the semantic definition of the image content based on machine learning algorithms and relevance feedback methods.

  2. Patch-Based Image Classification For Sentinel-1 and Sentinel-2 Earth Resolution EO Data

    NASA Astrophysics Data System (ADS)

    Georgescu, Florin-Andrei; Tanase, Radu; Datcu, Mihai; Raducanu, Dan

    2016-08-01

    In an era where the satellite image collections are in a continuous growth, Earth Observation (EO) image annotation and classification is becoming an important component of data exploitation. In this paper we present how feature extraction methods such as Gabor (G) and Weber Local Descriptor (WLD) are performing in a patch- based approach in the frame of Sentinel-1 and Sentinel-2 image data analysis. Having the goal to develop an application capable to join feature extraction and classification algorithms, in our assessment, we performed supervised support vector machines (SVM) and k-Nearest Neighbors (k-NN) classifications to extract a few generic classes from synthetic aperture radar (SAR), multispectral (MSI) and data fusion (DFI) images. The result of this study is intended to establish the optimum number of classes that can be found in the Sentinel-1 and Sentinel-2 images when using patch based image classification techniques. Also another important objective of this paper is to determine the best patch sizes suitable for this classification type in order to return best results for Sentinel-1 and Sentinel-2 EO images.

  3. Permian insect wing from antarctic sentinel mountains.

    PubMed

    Tasch, P; Riek, E F

    1969-06-27

    A homopterous insect wing was found in micaceous graywacke from the Polarstar Formation, Sentinel Mountains. The unusual venation is reminiscent of family Stenoviciidae known from the Permian and Triassic of Eastern Australia and elsewhere. This first documented account of Paleozoic insects in Antarctica bears on drift questions.

  4. Land science with Sentinel-2 and Sentinel-3 data series synergy

    NASA Astrophysics Data System (ADS)

    Moreno, Jose; Guanter, Luis; Alonso, Luis; Gomez, Luis; Amoros, Julia; Camps, Gustavo; Delegido, Jesus

    2010-05-01

    Although the GMES/Sentinel satellite series were primarily designed to provide observations for operational services and routine applications, there is a growing interest in the scientific community towards the usage of Sentinel data for more advanced and innovative science. Apart from the improved spatial and spectral capabilities, the availability of consistent time series covering a period of over 20 years opens possibilities never explored before, such as systematic data assimilation approaches exploiting the time-series concept, or the incorporation in the modelling approaches of processes covering time scales from weeks to decades. Sentinel-3 will provide continuity to current ENVISAT MERIS/AATSR capabilities. The results already derived from MERIS/AATRS will be more systematically exploited by using OLCI in synergy with SLST. Particularly innovative is the case of Sentinel-2, which is specifically designed for land applications. Built on a constellation of two satellites operating simultaneously to provide 5 days geometric revisit time, the Sentinel-2 system will providing global and systematic acquisitions with high spatial resolution and with a high revisit time tailored towards the needs of land monitoring. Apart from providing continuity to Landsat and SPOT time series, the Sentinel-2 Multi-Spectral Instrument (MSI) incorporates new narrow bands around the red-edge for improved retrievals of biophysical parameters. The limitations imposed by the need of a proper cloud screening and atmospheric corrections have represented a serious constraint in the past for optical data. The fact that both Sentinel-2 and 3 have dedicated bands to allow such needed corrections for optical data represents an important step towards a proper exploitation, guarantying consistent time series showing actual variability in land surface conditions without the artefacts introduced by the atmosphere. Expected operational products (such as Land Cover maps, Leaf Area Index

  5. Improved regeneration of autologous transplanted lymph node fragments by VEGF-C treatment.

    PubMed

    Sommer, Tanja; Buettner, Manuela; Bruns, Frank; Breves, Gerhard; Hadamitzky, Catarina; Pabst, Reinhard

    2012-05-01

    Secondary lymphedema is a common complication after removal of lymph nodes in combination with radiation therapy in the treatment of breast cancer, cervical cancer, and melanomas. Only symptomatic therapies are available at the moment, and lymphedema is for most patients a lifelong condition involving psychological and physical disabilities. Animal models exist to study the pathophysiology of lymphedema but not to study surgical treatments. The aim of this study was to show that regeneration of autologous transplanted lymph node fragments is possible in rats that were irradiated previously locally in the groin and to examine the effects of vascular endothelial growth factor (VEGF)-C injections on the rate of regeneration of transplanted lymph nodes. In all of the animals, inguinal and popliteal lymph nodes and adjacent lymphatic vessels were unilaterally removed and the inguinal region irradiated by a single dose of 15 Gy. Afterward, lymph node fragments were transplanted subcutaneously in the irradiated region. Half of the animals were treated by local VEGF-C injections after transplantation. Four weeks after transplantation, drainage of the leg was tested by injection of blue dye, and the transplanted fragments were removed and examined immunohistologically. We could show that regeneration of autologous transplanted lymph node fragments is possible in areas treated with radiotherapy in the rat. We also documented that transplants can achieve a connection to the lymphatic collectors of the leg. The results suggest that the outcome of regeneration can be improved by injection of VEGF-C in the transplantation area. Thus, lymph node fragment regeneration may be relevant for lymphedema prevention and therapy.

  6. Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

    PubMed Central

    Ayhan, Ali; Celik, Husnu; Dursun, Polat

    2008-01-01

    Although it does not have a long history of sentinel node evaluation (SLN) in female genital system cancers, there is a growing number of promising study results, despite the presence of some aspects that need to be considered and developed. It has been most commonly used in vulvar and uterine cervivcal cancer in gynecological oncology. According to these studies, almost all of which are prospective, particularly in cases where Technetium-labeled nanocolloid is used, sentinel node detection rate sensitivity and specificity has been reported to be 100%, except for a few cases. In the studies on cervical cancer, sentinel node detection rates have been reported around 80–86%, a little lower than those in vulva cancer, and negative predictive value has been reported about 99%. It is relatively new in endometrial cancer, where its detection rate varies between 50 and 80%. Studies about vulvar melanoma and vaginal cancers are generally case reports. Although it has not been supported with multicenter randomized and controlled studies including larger case series, study results reported by various centers around the world are harmonious and mutually supportive particularly in vulva cancer, and cervix cancer. Even though it does not seem possible to replace the traditional approaches in these two cancers, it is still a serious alternative for the future. We believe that it is important to increase and support the studies that will strengthen the weaknesses of the method, among which there are detection of micrometastases and increasing detection rates, and render it usable in routine clinical practice. PMID:18492253

  7. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  8. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

    PubMed Central

    2009-01-01

    Background Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180. Methods Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells. Results Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes. Conclusion Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells. PMID:19698142

  9. Geocoding uncertainty analysis for the automated processing of Sentinel-1 data using Sentinel-1 Toolbox software

    NASA Astrophysics Data System (ADS)

    Dostálová, Alena; Naeimi, Vahid; Wagner, Wolfgang; Elefante, Stefano; Cao, Senmao; Persson, Henrik

    2016-10-01

    One of the major advantages of the Sentinel-1 data is its capability to provide very high spatio-temporal coverage allowing the mapping of large areas as well as creation of dense time-series of the Sentinel-1 acquisitions. The SGRT software developed at TU Wien aims at automated processing of Sentinel-1 data for global and regional products. The first step of the processing consists of the Sentinel-1 data geocoding with the help of S1TBX software and their resampling to a common grid. These resampled images serve as an input for the product derivation. Thus, it is very important to select the most reliable processing settings and assess the geocoding uncertainty for both backscatter and projected local incidence angle images. Within this study, selection of Sentinel-1 acquisitions over 3 test areas in Europe were processed manually in the S1TBX software, testing multiple software versions, processing settings and digital elevation models (DEM) and the accuracy of the resulting geocoded images were assessed. Secondly, all available Sentinel-1 data over the areas were processed using selected settings and detailed quality check was performed. Overall, strong influence of the used DEM on the geocoding quality was confirmed with differences up to 80 meters in areas with higher terrain variations. In flat areas, the geocoding accuracy of backscatter images was overall good, with observed shifts between 0 and 30m. Larger systematic shifts were identified in case of projected local incidence angle images. These results encourage the automated processing of large volumes of Sentinel-1 data.

  10. Axillary Lymph Nodes and Breast Cancer

    MedlinePlus

    ... more likely to affect arm function and cause lymphedema. For this reason, sentinel node biopsy is the ... OR supraclavicular (above the clavicle) nodes have cancer Lymphedema Lymphedema [lim-fa-DEE-ma] is a build- ...

  11. Sentinel-1 Mission Overview and Implementation Status

    NASA Astrophysics Data System (ADS)

    Davidson, M.; Attema, E.; Snoeij, P.; Levrini, G.

    2009-04-01

    Sentinel-1 is an imaging radar mission at C-band consisting of a constellation of two satellites aimed at providing continuity of all-weather day-and-night supply of imagery for user services. Special emphasis is placed on services identified in ESA's GMES service elements program and on projects funded by the European Union Framework Programmes. Three priorities (fast-track services) for the mission have been identified by user consultation working groups of the European Union: Marine Core Services, Land Monitoring and Emergency Services. These cover applications such as: - Monitoring sea ice zones and the arctic environment - Surveillance of marine environment - Monitoring land surface motion risks - Mapping of land surfaces: forest, water and soil, agriculture - Mapping in support of humanitarian aid in crisis situations. The Sentinel 1 space segment will be designed and built by an industrial consortium with Thales Alenia Space Italia as prime contractor and EADS Astrium GmbH as C-SAR instrument responsible. Data products from current and previous ESA missions including ERS-1, ERS-2 and Envisat missions form the basis for many of the pilot GMES services. Consequently Sentinel-1 data maintain data quality levels of the Agency‘s previous SAR missions in terms of spatial resolution, sensitivity, accuracy, polarization and wavelength. Nonetheless, the Sentinel-1 synthetic aperture radar (SAR) constellation represents a completely new approach to SAR mission design by ESA in direct response to the operational needs for SAR data expressed under the EU-ESA Global Monitoring for Environment and Security (GMES) programme. The Sentinel-1 constellation is expected to provide near daily coverage over Europe and Canada, global coverage all independent of weather with delivery of radar data within 1 hour of acquisition - all vast improvements with respect to the existing SAR systems. The continuity of C-band SAR data combined with the greatly improved data provision is

  12. ESA Sentinel-1 Mission and Products

    NASA Astrophysics Data System (ADS)

    Floury, Nicolas; Attema, Evert; Davidson, Malcolm; Levrini, Guido; Rommen, Björn; Rosich, Betlem; Snoeij, Paul

    The global Monitoring for Environment and Security (GMES) space component relies on existing and planned space assets by European States, the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT), and the European Space Agency (ESA), as well as new complementary developments by ESA. The new developments are implemented in terms of five families of satellites called Sentinels. The Sentinel-1 mission is an imaging synthetic aperture radar (SAR) mission at C-band designed to supply all-weather day-and-night imagery to a number of operational Earth observation based services. Three priorities (fasttrack services) for the mission have been identified by user consultation working groups of the European Union: Marine Core Services, Land Monitoring and Emergency Services. These cover applications such as: - monitoring sea ice zones and the arctic environment, - surveillance of marine environment, - monitoring land surface motion risks, - mapping of land surfaces: forest, water and soil, agriculture, - mapping in support of humanitarian aid in crisis situations. Sentinel-1 has been designed to address medium resolution applications. It includes a main mode of operation that features a wide swath (250 km) and a medium resolution (5 m x 20 m). The two-satellite constellation offers six days exact repeat and the conflict-free operations based on the main operational mode allow exploiting every single data take. This paper describes the Sentinel-1 mission, provides an overview of the mission requirements, and presents some of the key user driven information products, the crucial requirements for operational sustainable services being continuity of data supply, frequent revisit, geographical coverage and timeliness. As data products from the Agency‘s successful ERS-1, ERS-2 and Envisat missions form the basis for many of the pilot GMES services, Sentinel-1 data products need to maintain and in some ways to improve data quality levels of the Agency

  13. Proteomic Findings in Melanoma

    PubMed Central

    Sengupta, Deepanwita; Tackett, Alan J

    2016-01-01

    Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate. PMID:27274624

  14. Melanoma and pregnancy.

    PubMed

    Morton, Sarah Kym; Morton, Adam Park

    2017-02-10

    Melanoma is the most common cancer in women during their reproductive years and kills more young Australians than any other single cancer. Care of women whose pregnancy is complicated by a diagnosis of malignancy is complex. The risk of delaying treatment to the mother, the short-term and long-term risks of premature delivery to the child, and the immediate risks to the foetus and long-term risks to the child of maternal treatment with surgery, radiotherapy or medical therapies must be considered.

  15. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    ClinicalTrials.gov

    2017-04-04

    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  16. Histopathology of the Lymph Nodes

    PubMed Central

    Elmore, Susan A.

    2007-01-01

    Lymph nodes function as filters of tissues and tissue fluids and are sites of origin and production of lymphocytes for normal physiological functions. As part of this normal function, they react to both endogenous and exogenous substances with a variety of specific morphological and functional responses. Lesions can be both proliferative and nonproliferative, and can be treatment-related or not. The histological evaluation of lymph nodes is necessary in order to understand the immunotoxic effects of chemicals with the resulting data providing an important component of human risk assessment. It is the challenge of the toxicologic pathologist to interpret the pathology data within the complete clinical evaluation of the entire animal. Daily insults, ageing and toxins can alter the normal histology and primary function of lymph nodes. Therefore it is important to distinguish and differentiate lesions that occur naturally during normal development and ageing from those that are induced by xenobiotics. To achieve this goal, comparison with strain- age- and sex-matched controls is crucial. PMID:17067938

  17. Sentinel Mission: Forest Fire Products Evaluation over China

    NASA Astrophysics Data System (ADS)

    Garcia, M.; Sanz, J.; Salvador, P.; Molina, V.; Cassanova, J.-P.; Qin, Xianlin

    2016-08-01

    Sentinel-2a and Sentinel-3a were launch the 23 June 2015 and 16 February 2016 respectively. These two platforms constitute a great improvement in the surface monitoring, especially in forest fires emergency management, evaluation and recovery.The multispectral sensor on board Sentinel-2a is a perfect tool to delineate burnt areas and identify severity with great spatial and temporal resolution while the surface thermal information provided by Sea and Land Surface Temperature Radiometer (SLSTR) on board Sentinel-3a constitute a source of hotspots. Both platforms will be complemented with their respective twins Sentinel-2b and Sentinel-3b in order to improve temporal resolution.This work tries to evaluate the constellation capacity to provide reliable forest fires products over China by comparison with Earth Observing System (EOS) and Landsat constellation products.

  18. Clinicopathologic subtypes and compromise of lymph nodes in patients with breast cancer

    PubMed Central

    Jaime Jans, B; Nicolás Escudero, M; Dahiana Pulgar, B; Francisco Acevedo, C; César Sánchez, R; Camus, A Mauricio

    2014-01-01

    Breast cancer (BC) is currently a heterogeneous disease with variations in clinical behaviour. Classification according to subtypes has allowed progress in the individualisation of treatment. The objective of this study is to evaluate the risk of axillary node compromise in patients with BC, according to clinicopathologic subtypes. Materials and methods are a retrospective, descriptive-analytical study. All patients that had undergone surgery for invasive BC were included, with the study of sentinel lymph nodes (SLNs) at Hospital Clínico de la Pontificia Universidad Católica, between May 1999 and December 2012. The results showed 632 patients fulfilled the inclusion criteria, with the median age being 55 years (range: 28–95), and 559 (88.4%) patients presented with estrogen receptor and/or progesterone receptor positive tumours. Luminal A: 246 patients (38.9%), luminal B: 243 (38.4%), luminal not otherwise specified: 70 (11.1%) triple negative (TN): 60 (9.5%) and over expression of epidermal growth factor type 2 receptor (HER2 positive): 13 (2.1%). Luminal tumours displayed a greater risk of metastasis in the SLNs, but this difference was not statistically significant (p = 0.67). TN and HER2 positive tumours presented the greatest proportion of metastatic compromise in non-sentinel lymph nodes (non-SLNs) (57.1% and 50%, respectively). The presence of macrometastasis (MAM) in the SLN was associated with a greater risk of compromise of the non-SLN. Conclusions: Luminal tumours are the most frequent and present a greater proportion of axillary lymph node compromise, without being statistically significant. TN and HER2 positive tumours tend to have a higher axillary compromise; however, this was not statistically significant in either. Only the presence of MAM in SLNs displayed a statistically significantly association in the compromise of non-SLNs. PMID:25114720

  19. Sentinel node navigation in gastric cancer: new horizons for personalized minimally invasive surgical oncology?

    PubMed Central

    Hasemaki, Natasha; Vaggelis, Georgios; Karampa, Anastasia; Anastasiadi, Zoi; Lianou, Aikaterini; Papanikolaou, Sarantis; Floras, Grigorios; Bali, Christina D.; Lekkas, Epameinondas; Katsios, Christos; Mitsis, Michail

    2016-01-01

    Complete (R0) resection and regional lymph nodes (LNs) dissection represent undoubtedly the basic surgical tools for patients with gastric cancer. It is reported that the LN metastasis rate in patients with early gastric cancer (EGC) is approximately 15–20%. Therefore, the innovative clinical application of sentinel node navigation surgery (SNNS) for EGC might be able to prevent unnecessary LN dissection as well as to reduce significantly the volume of gastric resection. Recent evidence suggests that double tracer methods appear superior compared to single tracer techniques. However, the researchers’ interest is now focused on the identification of new LN detection methods utilizing sophisticated technology such as infrared ray endoscopy, fluorescence imaging and near-infrared technology. Despite its notable limitations, hematoxylin-eosin is still considered the mainstay staining for assessing the metastatic status of LNs. In this review, we summarize the current evidences and we provide the latest scientific information assessing safety, efficacy and potential limitations of the innovative sentinel node (SN) navigation technique for gastric cancer. We try also to provide a “view” towards a future potential application of personalized minimally invasive surgery in gastric cancer field. PMID:28138656

  20. Slug Expression during Melanoma Progression

    PubMed Central

    Shirley, Stephanie H.; Greene, Victoria R.; Duncan, Lyn M.; Torres Cabala, Carlos A.; Grimm, Elizabeth A.; Kusewitt, Donna F.

    2012-01-01

    Slug (Snai2), a member of the Snail family of zinc finger transcription factors, plays a role in the epithelial-to-mesenchymal transformation (EMT) that occurs during melanocyte emigration from the neural crest. A role for Slug in the EMT-like loss of cell adhesion and increased cell motility exhibited during melanoma progression has also been proposed. Our immunohistochemical studies of melanoma arrays, however, revealed that Slug expression was actually higher in nevi than in primary or metastatic melanomas. Moreover, Slug expression in melanomas was not associated with decreased expression of E-cadherin, the canonical Slug target in EMT. Comparisons of endogenous Slug and E-cadherin expression in cultured normal human melanocytes and melanoma cell lines supported our immunohistochemical findings. Expression of exogenous Slug in melanocytes and melanoma cells in vitro, however, suppressed E-cadherin expression, enhanced N-cadherin expression, and stimulated cell migration and invasion. Interestingly, both in tumors and cultured cell lines, there was a clear relationship between expression of Slug and MITF, a transcription factor known to regulate Slug expression during development. Taken together, our findings suggest that Slug expression during melanomagenesis is highest early in the process and that persistent Slug expression is not required for melanoma progression. The precise role of Slug in melanomagenesis remains to be elucidated and may be related to its interactions with other drivers of EMT, such as Snail. PMID:22503751

  1. Malignant melanoma of the skin

    PubMed Central

    Armstrong, B. K.; Holman, C. D. J.

    1987-01-01

    Ultra-violet radiation (UVR) in sunlight is thought to be the main cause of malignant melanoma in lightly-pigmented populations. Individuals with fair skin, fair hair, blue eyes and/or a tendency to burn rather than tan when exposed to the sun are at particularly high risk of melanoma and should be given special attention in primary prevention programmes. Intermittent exposure to the sun, as in recreational exposure, may be a more potent cause of melanoma than more continuous exposure. Primary prevention offers the best prospects for a substantial reduction in mortality from malignant melanoma. However, there is little evidence available to judge the effectiveness of primary prevention of melanoma through reduction of exposure to the sun. Education for reducing exposure to the sun is common in high-risk populations but has never been evaluated adequately. Mortality from melanoma could also possibly be reduced by earlier diagnosis through education or screening of high-risk groups. Regular screening of patients with the familial dysplastic naevus syndrome should reduce their mortality from melanoma. PMID:3301043

  2. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  3. Enhanced SAR Data Compressor for Sentinel-1

    NASA Astrophysics Data System (ADS)

    Algra, T.; Bierens, L.

    2007-08-01

    This paper presents a new on-board SAR data compressor which outperforms the conventionally used Block Adaptive Quantization (BAQ) compressor. The system applies improved entropy-constrained block adaptive quantization of raw Synthetic Aperture Radar (SAR) data in the frequency domain. For advanced multi-mode satellite SAR instruments, such as the one to be implemented on-board of Sentinel- , the average compression ratio can be doubled as compared to BAQ. Space borne implementation with a high-speed data throughput is feasible due to the advent of advanced space FPGA's and ASIC's including the powerFFT, a fast FFT-oriented DSP. The complete compressor module can be implemented on a 6U Eurocard that fits in the SAR Electronics System crate of Sentinel-1.

  4. Sentinel-1 Support in the GAMMA Software

    NASA Astrophysics Data System (ADS)

    Wegmuller, Urs; Werner, Charles; Stroozzi, Tazio; Wiesmann, Andreas; Frey, Othmar; Santoro, Maurizio

    2015-05-01

    First results using the new Sentinel-1 SAR look very promising but the special interferometric wide-swath data acquired in the TOPS mode makes InSAR processing challenging. The steep azimuth spectra ramp in each burst results in very stringent co-registration requirements. Combining the data of the individual bursts and sub-swaths into consistent mosaics requires careful “book-keeping” in the handling of the data and meta data and the large file sizes and high data throughputs require also a good performance. Considering these challenges good support from software is getting increasingly important. In this contribution we describe the Sentinel-1 support in the GAMMA Software, a high-level software package used by researchers, service providers and operational users in their SAR, InSAR and PSI work.

  5. Immunotherapy of melanoma.

    PubMed

    Kee, D; McArthur, G

    2017-03-01

    Immunotherapy for advanced melanoma has progressed dramatically in the last five years with the approval of immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets can break cancer-immune tolerance and result in durable objective responses with significantly improved tolerability over cytokine-based immunotherapy. Ipilimumab is an inhibitor of CTLA-4 and the first-in-class immune checkpoint inhibitor to demonstrate an improvement in overall survival in melanoma. Pembrolizumab and nivolumab target PD-1 and have improved single agent activity and tolerability in comparison to ipilimumab. The combination of nivolumab and ipilimumab results in even better response rates, reductions in tumor volume and progression free survival but at the expense of considerable autoimmune effects. Autoimmune side-effects and non-standard response kinetics represent a new challenge associated with cancer therapies that practitioners will have to become more familiar with as checkpoint inhibitors increasingly become part of mainstream oncological practice. Ongoing areas of investigation include drug development against novel immune targets; alternative treatment modalities, such as genetically modified oncolytic viruses; optimization of immunotherapy combination strategies; and the identification of reliable biomarkers to better guide treatment selection.

  6. Prognostic models in melanoma.

    PubMed

    Halpern, A C; Schuchter, L M

    1997-02-01

    Predicting which patients with primary melanoma are at risk of developing metastastic disease is important for making rational therapeutic decisions. Tumor thickness alone is the most commonly used predictor of survival, but other clinical and pathologic variables also play an important role. We have developed two multivariate logistic regression models to predict survival in patients who have primary melanoma. The first of these models assigns patients to two groups based on radial or vertical growth phase. The probability of survival for those patients with vertical growth phase tumors was further determined based on a model using six variables (mitotic rate, tumor infiltrating lymphocytes, tumor thickness, anatomic site of the primary tumor, sex, and histologic regression) that have the greatest strength as independent predictors of survival. This model is 89% accurate for predicting survival in patients with vertical growth phase tumors. A second model has been developed that uses readily available clinical parameters to predict survival. Four variables (tumor thickness, anatomic site, age, and sex) entered into the model as powerful independent predictors. Clinical algorithms for assessing patient risk are provided.

  7. Melanoma survival: sex does matter, but we do not know how.

    PubMed

    Crocetti, Emanuele; Fancelli, Laura; Manneschi, Gianfranco; Caldarella, Adele; Pimpinelli, Nicola; Chiarugi, Alessandra; Nardini, Paolo; Buzzoni, Carlotta

    2016-09-01

    The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population-based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow's thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86-89%) for women and 80% (78-82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56-0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown.

  8. Photoacoustic detection of induced melanoma in vitro using a mouse model

    NASA Astrophysics Data System (ADS)

    Gupta, Sagar; Bhattacharya, Kiran; Newton, Jessica R.; Quinn, Thomas P.; Viator, John A.

    2012-03-01

    Metastasis is a life threatening complex physiological phenomenon that involves the movement of cancer cells from one organ to another by means of blood and lymph. An understanding about metastasis is extremely important to device diagnostic systems to detect and monitor its spread within the body. For the first time we report rapid photoacoustic detection of the induced metastatic melanoma in mice in vitro using photoacoustic flowmetry. A new photoacoustic flow system is developed, that em