Biopsia del ganglio centinela en el melanoma: camino a la desaparición Sentinel lymph node biopsy for melanoma: bound to disappear

Directory of Open Access Journals (Sweden)

RE Achenbach

2011-03-01

Full Text Available La biopsia del ganglio centinela continúa siendo utilizada para la terapéutica del melanoma, sin fundamento científico comprobado. Los estudios prospectivos-randomizados han fracasado en demostrar beneficio alguno en el punto clave de los mismos, conocer si aumenta la sobrevida global del paciente con melanoma invasor. Se revisan algunos trabajos que demuestran que el punto de vista contrario a su uso rutinario, es el correcto con el fin de ofrecer al dermatólogo, amplitud de criterio en el momento de discutir con el paciente dicho estudio.Sentinel node biopsy and selective lymph node dissection are still a frequent tool for therapeutic management of melanoma without scientific support. Prospective-randomized trials have failed to show overall survival - the main goal in such trials in invasive melanoma. Some articles proving that the opposite point of view to its standard use is correct have been reviewed, in order to offer to the dermatologist the different alternatives so as to discuss such procedures with amplitude of criteria at the time of discussing such procedure with the potential patient.

Detection of sentinel lymph node in breast cancer and malignant melanoma - Influence of some factors on detection success rate

International Nuclear Information System (INIS)

Krafta, O.; Safarcika, K.; Stepien, A.

2004-01-01

Full text: The aim of this study was to compare three radiopharmaceuticals for sentinel lymph node detection in breast cancer and malignant melanoma patients. We examined 100 women and 2 men with breast cancer (average age 59.3 years) and 167 patients with malignant melanoma (69 men with mean age of 58.6 years and 98 women with mean age of 53.6 years). Lymphoscintigraphy was performed in all patients after injection of the radiotracer, either of the three: NANOCIS (average particle size 100 nm), SENTISCINT (particle size 100-600 nm), and NANOCOLL (particle size under 80 nm). Dynamic scintigraphy was performed in melanoma patients while breast cancer patients were subjected to stating imaging at 1-2 and 22 hours of injection. In patients with melanoma surgery was done on the same day, to remove the primary tumor, sentinel lymph node and other nodes, wherever required. In breast cancer patients, surgery, more or less, was done on the second day of radiotracer injection. In operation theatre isosulfan blue dye and gamma probe was used to detect sentinel lymph nodes. In breast cancer patients, scintigraphy detected a total of 231 lymph nodes but failed to show sentinel lymph node in 7 patients (success rate of lymphoscintigraphy 93.1 %). Using gamma probe 158 lymph nodes were detected in 89 patients but sentinel nodes were missed in 9 patients (success rate of probe was 89.9 %). 146 lymph nodes could be visualised using blue dye in 92 patients but were missed in 12 patients (detection rate by dye was 87 %). In 2 patients sentinel lymph node could not be detected by any method. In patients with melanoma, scintigraphy showed 304 lymph nodes. However, it did not detect sentinel lymph node in 9 patients (success rate of lymphoscintigraphy was 94.6 %). 104 patients were examined by means of gamma probe and 132 lymph nodes were detected and no lymph node was found in 13 patients (success rate of probe 87.5%). Using blue dye in 140 patients, 131 nodes were found but were

Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

DEFF Research Database (Denmark)

Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

2013-01-01

The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) perform......, essential to keep the morbidity and economic costs low, while keeping the quality of the procedure high....

The diagnostic value of adding dynamic scintigraphy to standard delayed planar imaging for sentinel node identification in melanoma patients

DEFF Research Database (Denmark)

Nielsen, Marie Kristina Rue; Chakera, Annette H; Hesse, Birger

2011-01-01

The aim of this study was to compare early dynamic imaging combined with delayed static imaging and single photon emission computed tomography (SPECT)/CT with delayed, planar, static imaging alone for sentinel node (SN) identification in melanoma patients.......The aim of this study was to compare early dynamic imaging combined with delayed static imaging and single photon emission computed tomography (SPECT)/CT with delayed, planar, static imaging alone for sentinel node (SN) identification in melanoma patients....

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

Science.gov (United States)

Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

2015-01-01

The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics

International Nuclear Information System (INIS)

Maza, S.; Valencia, R.; Geworski, L.; Zander, A.; Munz, D.L.; Draeger, E.; Winter, H.; Sterry, W.

2002-01-01

Detection of the ''true'' sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the skin leads to an

One-day or two-day procedure for sentinel node biopsy in melanoma?

International Nuclear Information System (INIS)

Chakera, A.H.; Drzewiecki, K.T.; Lock-Andersen, J.; Hesse, U.; Nuernberg, B.M.; Juhl, B.R.; Stokholm, K.H.; Hesse, B.

2009-01-01

We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings. We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis. The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy. This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs. (orig.)

Identification of the sentinel lymph node in patients with malignant melanoma: what are the reasons for mistakes?

International Nuclear Information System (INIS)

Vidal-Sicart, Sergi; Pons, Francesca; Puig, Susana; Vilalta, Antonio; Palou, J.M.; Castel, Teresa; Ortega, Marisa; Martin, Francisco; Rull, Ramon

2003-01-01

Scintigraphic identification of the sentinel lymph node is achievable in nearly all patients with malignant melanoma. However, in a very small number of cases the sentinel node fails to be detected, and sometimes recurrence appears during follow-up in patients who had previously tested negative for metastatic disease. The purpose of this study was to review our experience in order to isolate the reasons for erroneous sentinel lymph node identification. The evaluation involved 435 consecutive malignant melanoma patients with AJCC stages I and II (clinically negative nodes) and Breslow thickness >0.76 mm. Lymphoscintigraphy was performed the day before surgery by intradermal administration of technetium-99m labelled nanocolloid. Dynamic and static images were obtained. The sentinel node was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. After removal, routine histopathological examination with haematoxylin-eosin (H-E) and immunohistochemistry with S 100 and HMB45 (IHC) were performed. In those patients who developed regional recurrences during follow-up, sentinel nodes were further evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Lymphoscintigraphy visualised at least one sentinel node in 434 out of 435 patients (99.8%). Uptake in in-transit sentinel lymph nodes was observed in 32 patients (7.4%). During surgery, localisation and removal of sentinel nodes was successful in 430/435 patients (98.8%). A total of 790 sentinel lymph nodes were harvested, with a mean of 1.8 per patient. Routine histopathological examination with H-E or IHC revealed metastatic disease in 72 patients (16.8%). During a mean follow-up of 26 months, seven of those patients with a negative sentinel node developed regional lymph node metastases. In five of them RT-PCR was positive for micrometastases within the sentinel node. In conclusion, erroneous sentinel lymph node identification can be due to changes in the surgical team

Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with 'MCW Melanoma Cocktail' – A mixture of monoclonal antibodies to MART-1, melan-A, and tyrosinase

International Nuclear Information System (INIS)

Shidham, Vinod B; Qi, Dan; Rao, R Nagarjun; Acker, Scott M; Chang, Chung-Che; Kampalath, Bal; Dawson, Glen; Machhi, Jinobya K; Komorowski, Richard A

2003-01-01

MART-1, Melan-A, and Tyrosinase have shown encouraging results for evaluation of melanoma micrometastases in sentinel lymph nodes, as compared to conventionally used S-100 protein and HMB-45. To achieve higher sensitivity, some studies recommend evaluation of three sections, each at intervals of 200 μ. This would mean, routine staining of three adjacent sections in each of the three clusters at intervals of 200 μ, requiring nine slides resulting in added expense. If a cocktail of these antibodies could be used, only one section would be required instead of three generating significant cost savings. We prepared a combination of monoclonal antibodies to these three immunomarkers in optimized dilutions (MART-1, clone M2-7C10, dilution 1:500; Melan-A, clone A103, dilution 1:100; and Tyrosinase, clone T311, dilution 1:50) and designated it as 'MCW melanoma cocktail'. Formalin-fixed paraffin-embedded tissue sections of sentinel lymph nodes from patients with cutaneous melanoma, without macro-metastases were evaluated with this cocktail. Melanoma micrometastases were easily detectable with the cocktail in 41 out of 188 slices (8/24 cases). The diagnostic accuracy amongst five pathologists did not show statistically significant difference. Out of 188 slices, 78 had adjacent sections immunostained individually with MART-1 and Melan-A during our previous study. Of these 78 slices, 21 were positive for melanoma micrometastases with MART-1 and Melan-A individually. However, the adjacent section of these slices immunostained with the cocktail detected metastases in four additional slices. Thus, MART-1 and Melan-A could not detect melanoma micrometastases individually in 16% (4/25) of slices positive with the cocktail. Benign capsular nevi were immunoreactive for the cocktail in 4.8% (9/188) slices. All 81 slices of negative test controls (sentinel lymph nodes of mammary carcinoma) were interpreted correctly as negative for melanoma micrometastases. The melanoma

Contemporary Management of Early-Stage Melanoma: A Systematic Review.

Science.gov (United States)

Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

2017-05-01

The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

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

Science.gov (United States)

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. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Preoperative 18F-FDG-PET/CT imaging and sentinel node biopsy in the detection of regional lymph node metastases in malignant melanoma.

Science.gov (United States)

Singh, Baljinder; Ezziddin, Samer; Palmedo, Holger; Reinhardt, Michael; Strunk, Holger; Tüting, Thomas; Biersack, Hans-Jürgen; Ahmadzadehfar, Hojjat

2008-10-01

The objective of this study was to evaluate the role of preoperative 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning, preoperative lymphoscintigraphy (LS), and sentinel lymph node biopsy in patients with malignant melanoma. Fifty-two patients (36 men: 16 women; mean age 55.0+/-13.0 years; median age 61 years; range 17-76 years) with malignant melanoma were selected. According to the latest version of the American Joint Committee on Cancer staging system, the disease in the study patients was initially classified as either stage I or II. The other primary tumor characteristics were mean Breslow depth=2.87 mm and median=2 mm; range 1-12.0 mm and Clarks levels III-V. None of the study patients had clinical or radiological evidence of regional lymph node metastatic disease. At least one sentinel node was identified in all patients. Preoperative LS detected a total of 111 sentinel lymph nodes (average 2.13 sentinel lymph node per patient) and demonstrated a single nodal draining basin in 38 (73%) patients and multiple (2-3 draining basins) in the remaining 14 (27%) patients. Fourteen out of the 52 patients (27%) had at least one involved sentinel node. Positron emission tomography was true positive in two patients with a sentinel node greater than 1 cm and false positive in two other patients. In this study, the detection of sentinel lymph node by LS and gamma probe had a sensitivity of 100%. In contrast, 18F-FDG-PET imaging demonstrated very low sensitivity (14.3%; 95% CI, 2.5 to 44%) and positive predictive value (50%; 95% CI, 9 to 90%) for localizing the subclinical nodal metastases. The specificity, net present value, and diagnostic accuracy were 94.7, 75, and 73%, respectively. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography imaging is not able to substitute LS/sentinel lymph node biopsy in patients at stage I or II.

Lymphatic mapping and sentinel node biopsy in early stage melanoma: study of the first 100 cases in Institut Gustave Roussy

International Nuclear Information System (INIS)

Buffard, V.; Duvillard, P.; Mamelle, G.; Lumbroso, J.; Ricard, M.; Kolb, F.; Sleilati, F.; Spatz, A.

2005-01-01

Introduction: We report the data of the first 100 patients who underwent sentinel lymph node biopsy (SLND) in our institution using lymphoscintigraphy only. Patients and methods: From 1998 to 2000, 100 consecutive patients (53 men and 47 women) with stage I or II melanoma (mean Breslow: 3.11 mm) underwent a SLND. Localisation of the sentinel node was performed by preoperative lymphoscintigraphy and hand held gamma probe detection. The sentinel node was examined by routine histology and immunohistochemistry for PS100 and HMB-45. If the sentinel node contained tumor cells, a complete lymphadenectomy was performed. Results: Lymphoscintigraphy was performed for 97 patients. The SLN was identified in 97% of cases (94/97) and excised in 95% of cases (92/97). The rate of SLN metastasis was 19/92 patients (21%), correlated with Breslow index ( 4 mm: 46%). A mean number of 1.81 lymph node per patient was analysed. The mean follow-up was 26 months with a relapse in 14 patients, 5 of them having a metastatic sentinel node. Three patients had a recurrence at the site of the SLND although they had initially a negative sentinel node. Conclusion: The identification and metastatic rates of sentinel nodes are similar to those of the literature. More studies are needed to determine whether lymphoscintigraphy alone is efficient for successful SLND in melanoma. (author)

Sentinel lymphoscintigraphy in malignant melanoma and Merkel cell carcinoma

International Nuclear Information System (INIS)

Dekova, M.; Kirov, V.; Donchev, M.; Slavova, M.; Tsarovska, T.

2013-01-01

Full text:Introduction: The concept of a biopsy of the sentinel lymph node (SLN) was developed by Mortan in 1992, using blue dye. In 1993. Alex and Krag identified SLN with radiocolloid and gamma probe in case of malignant melanoma. Today, both methods are applied separately or together with a success rate above 90% and false negative rate of 5 %. Materials and Methods: The study includes 10 patients, 9 of whom have been diagnosed with malignant melanoma and 1 – with Merkel cancer. All patients were of a higher risk of lymphatic metastases without distinct clinical symptoms. Lymphoscintigraphy was performed with double-headed SPECT gamma camera Toshiba CGA 7200 UI. The visualized lymph nodes were projected and marked on the skin by a point radioactive source under monitoring. The marked lymph nodes were verified during the operation by staining and patent Blau then removed and studies histopathologically. Results: In all patients the Lymphoscintigraphy visualized SLN, which were surgically found just below the skin markers and removed. In the SLN of one patient a diffuse metastasis was found. In the SLN of nine patients no evidence for metastatic process was found. Conclusion: The technique of marking the SLN with subsequent biopsy is a minimally invasive method for the detection of lymph node metastases in patients with malignant melanoma and Merkel carcinoma with a high degree of reliability of the results

Sentinel lymph node biopsy: is it possible to reduce false negative rates by excluding patients with nodular melanoma?

LENUS (Irish Health Repository)

Corrigan, M A

2012-02-03

OBJECTIVE: The aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to delineate whether patients with nodular melanoma are more likely to develop nodal recurrence despite negative SLNB. METHODS: Consecutive patients with cutaneous melanoma undergoing SLNB were identified from a departmental database between 1997 and 2005. Factors including demographic data, site, histological subtype, depth and outcome were examined. RESULTS: Of 131 patients, 103 were node negative and eligible for study. The median age was 53 (16-82) years with 46 patients being male (45%) and 57 female (55%). Primary melanoma sites included lower limb (49; 48%), upper limb (29; 28%), head (12; 11%), trunk (7; 7%) and back (6; 6%). The median Breslow thickness was 2mm. Superficial spreading accounted for 43% of melanoma with nodular accounting for 42%. Median follow-up was 40 (3-90) months. Of 20 relapses, seven recurred in the same nodal basin, three were satellite recurrences, one recurred with both satellite and nodal lesions simultaneously, and nine experienced haematogenous spread. Of the eight patients who developed recurrence in the same nodal basin, four were of nodular histological subtype (p=NS). All of the three patients with satellite lesions had nodular melanoma histologically (p=0.02). When nodal and satellite recurrences were combined, eight of 11 were histologically nodular (p=0.01). CONCLUSIONS: This study indicates that lymphatic recurrence occurs more often in SLNB negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel node biopsy is warranted.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

A biópsia de linfonodo sentinela não deve ser recomendada para pacientes portadores de melanoma espesso Sentinel node biopsy should not be recommended for patients with thick melanoma

Directory of Open Access Journals (Sweden)

Renato Santos de Oliveira Filho

2013-04-01

Full Text Available OBJETIVO: verificar se há alguma relação entre o estado histopatológico do linfonodo sentinela, a recorrência e a mortalidade decorrente do melanoma espesso em pacientes submetidos à BLS ao longo de um seguimento significante. MÉTODOS: Oitenta e seis pacientes portadores de melanoma espesso submetidos à BLS foram selecionados de um banco de dados prospectivo. A linfocintilografia, o mapeamento linfático e a detecção gama intraoperatória foram realizados em todos pacientes. O linfonodo sentinela (LS foi analisado por HE e por imunoistoquímica. Linfadenectomia total foi indicada para os pacientes com LS positivo. O estado histopatológico do LS foi relacionado à taxa de recorrência e de mortalidade por melanoma. RESULTADOS: Cento e sessenta e seis LS foram retirados dos 86 pacientes. As idades variaram de 18 a 73 anos. Havia 47 mulheres e 39 homens. Micrometástases foram encontradas em 44 pacientes. Quarenta e dois pacientes foram submetidos à linfadenectomia total. Sete pacientes tiveram outro linfonodo positivo. Entre os 44 pacientes com LS positivo houve 20 recorrências e 15 mortes. Houve 18 recidivas e 12 mortes no grupo de LS negativo. A espessura de Breslow não apresentou correlação com o estado histopatológico do LS. O estado histopatológico do LS não interferiu nas taxas de recorrência e de mortalidade (teste de Fisher, p=1.00. A mediana de seguimento foi 69 meses. CONCLUSÃO: Considerando a falta de evidência de benefício, a BLS não deve ser indicada para pacientes com melanoma espesso fora de estudos clínicos.OBJECTIVE: To ascertain whether there is any relationship between the state of the sentinel lymph node histopathology, recurrence and mortality from thick melanoma in patients undergoing SLNB over a long follow-up. METHODS: Eighty-six patients with thick melanoma undergoing SLNB were selected from a prospective database. Lymphoscintigraphy, lymphatic mapping and intraoperative gamma probe detection were

EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology

DEFF Research Database (Denmark)

Riber-Hansen, Rikke; Hastrup, N; Clemmensen, O.

2010-01-01

EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology......EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology...

Sentinel node biopsy for early-stage melanoma - Accuracy and morbidity in MSLT-I, an international multicenter trial

NARCIS (Netherlands)

Morton, DL; Cochran, AJ; Thompson, JF; Elashoff, R; Essner, R; Glass, EC; Mozzillo, N; Nieweg, OE; Roses, DF; Hoekstra, HJ; Karakousis, CP; Reintgen, DS; Coventry, BJ; Wang, HJ

Objective:The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. Summary

Role of the technologist in the lymphoscintigraphy and the identification of sentinel node in malignant skin melanoma

International Nuclear Information System (INIS)

Barbier, D.

2002-01-01

The biopsy of the first tumor-draining lymph node (sentinel node) is bound to become the procedure of choice in regional staging of skin melanoma patients. In our department, we do successively: lymphoscintigraphy; identification of sentinel node by γ probe before surgery; identification during surgery of sentinel node with γ probe. During those different steps, the technologist has an important role. The different steps of the technologist's work are: Preparation of radiopharmaceutical Tc 99m Nanocolloides (Nanocis Cis Bio Int); Control of radio chemical purity(RCP) by thin-layer chromatography (TLC); Programming of acquisition protocol on the γ camera; Acquisition of dynamic and static images; Identification percutaneous of the sentinel node with the γ probe and Co 57 pencil; Processing of scintigraphic images; At least identification with surgeon of the sentinel node. After excision of the lymph node, we have to verify the disappearing of radioactivity. Those steps will be illustrated by different clinical cases. Conclusion: Sentinel node identification is: New useful technique for patient: not very much invasive; screening of patients with high risk factors; great parameters of prognosis; Interest for technologist: narrow collaboration with nuclearist and surgeon; psychological role close to the patient; various competency of technologist; diagnostic and therapeutic participations

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

Science.gov (United States)

Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Comparison of 99mTc-MIBI scanning and sentinel node biopsy in the detection of occult melanoma lymph node metastases

International Nuclear Information System (INIS)

Alonso, O.; Lago, G.; Lopes de Amorim, M.C.; Juri, C.; Larre Borges, A.; Martinez, M.; De Boni, D.; Espasandin, J.; Priario, J.

2002-01-01

Aim: Sentinel node biopsy (SNB) is a highly accurate technique for detecting occult metastatic disease in the regional lymph nodes. Our group has reported that 99m Tc-MIBI scintigraphy is an imaging technique that can detect clinically undetectable metastases. This prospective study shows preliminary results on the comparison of both techniques for the detection of lymph node invasion. Material and Methods: Twenty-two consecutive patients (15 women, 7 men; mean age, 55 years) with primary melanoma > 1.0 mm thick were enrolled (mean 2.6 mm). Patients underwent 99m Tc-MIBI scintigraphy of regional lymph nodes 1-2 weeks before surgery, acquiring 10-minute planar images with a LFOV gamma camera. A preoperative lymphoscintigraphy using 99m Tc-colloidal (Re) sulphide was performed the day before surgery, using a dose of 74-93 MBq. Radio guided SNB was performed with a hand-held gamma probe. Lymph nodes were examined histologically and immunostained for S-100 and HMB-45. Results: The sentinel node (SN) was identified in 21/22 patients. An average of 1.6 SN/lesion were harvested from melanomas located in the following regions: head and neck (n=3), trunk (n=6), extremities (n=12). All patients with negative SN (n=11) were also negative with MIBI. In 10 cases the SN demonstrated metastatic involvement, whereas 99m Tc-MIBI was positive in 8 of them (80%). In cases with positive SN/negative 99m Tc-MIBI, the pathology report revealed micro metastatic disease. Conclusion: These preliminary results suggest that 99m Tc-MIBI scanning has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

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Boada, Aram; Tejera-Vaquerizo, Antonio; Ribero, Simone; Puig, Susana; Moreno-Ramírez, David; Descalzo-Gallego, Miguel A; Fierro, María T; Quaglino, Pietro; Carrera, Cristina; Malvehy, Josep; Vidal-Sicart, Sergi; Bennássar, Antoni; Rull, Ramón; Alos, Llucìa; Requena, Celia; Bolumar, Isidro; Traves, Víctor; Pla, Ángel; Fernández-Figueras, María T; Ferrándiz, Carlos; Pascual, Iciar; Manzano, José L; Sánchez-Lucas, Marina; Giménez-Xavier, Pol; Ferrandiz, Lara; Nagore, Eduardo

2018-02-01

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. © 2017 UICC.

Advanced malignant melanoma during pregnancy: technical description of sentinel lymph node biopsy followed by radical lymph node dissection

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Alberto Julius Alves Wainstein

2015-12-01

Full Text Available Abstract Introduction: melanoma is a very aggressive cancer, with increasing incidence, and is currently the fifth most common cancer in men and the sixth most common in women in the United States. Melanoma is not unusual in pregnancy, with an estimated occur-rence rate of 1:1.000. Although not the most common cancer in pregnancy, melanoma is the tumor with the highest incidence ofplacenta and fetus metastases. Description: a 29-year-old lady, 4 weeks after conception underwent resection of an atypical pigmented lesion after a diagnosis of stage T4b melanoma. At 16 weeks she underwent a broad local excision and sentinel lymph node (SLN biopsy. SLN was evaluated histologically and tested positive for melanoma. A radical axillary lymphadenectomy was performed on the patient without evidence of metas-tasis in any other LN. In the 40th week of pregnancy, labor was induced and a healthy newborn was deli-vered via cesarean. Discussion: melanoma management in pregnancy is more complex and requires multidisciplinary coor-dination, as well as extensive discussion with the patient and her family. We present a case report description in which treatment recommendations are established according to no pregnancy experience.

Diagnosis of sentinel lymph nodal metastases in malignant melanoma. Usefulness of genetic diagnosis by reverse transcriptase-polymerase chain reaction

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Isoda, Hideka; Mori, Tomoko; Nishio, Daisuke; Tokura, Yoshiki; Yasuda, Hiroshi

2005-01-01

Sentinel lymph node (SLN) biopsy has been performed in 25 patients with malignant melanoma for the last four years at the Department of Dermatology, University of Occupational and Environmental Health. SLNs were identified by using both patent blue dye and redionucleotide-labeled colloid methods. The removed SLNs were subjected to routine haematoxylin-eosin staining and immunohistochemical stainings for Melan-A, S-100 protein and HMB45, and 10 of 25 cases had positive SLN metastases. In 8 cases, mRNA for malignant melanoma related molecules, gp100, MART-1 and tyrosinase, was analyzed by RT-PCR, and 7 of 8 cases gave agreement with the histopathological results. One case had negative SLN metastasis on histopathological examination but exhibited amplification of mRNA for the melanoma-related molecules on RT-PCR analysis. (author)

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

International Nuclear Information System (INIS)

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

2011-01-01

Aim. to compare 18 F-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

Is the identification of in-transit sentinel lymph nodes in malignant melanoma patients really necessary?

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Vidal-Sicart, Sergi; Pons, Francesca; Fuertes, Silvia; Ortega, Marisa; Vilalta, Antonio; Puig, Susana; Palou, Josep M.; Castel, Teresa; Rull, Ramon

2004-01-01

The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called ''in-transit nodes'' or ''interval nodes'' and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of 99m Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary. (orig.)

Sentinel lymph node biopsy: clinical relevance

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Howman-Giles, R.

2002-01-01

Sentinel lymph node biopsy (SLNB) has become an important technique in the management of patients with intermediate level melanoma, clinical operable breast cancer and some other cancers. The technique relies on lymphatic mapping to define the lymph drainage from a primary tumour with the premise that the lymph nodes, which directly drain from that area, will reflect the tumour status of the remainder of the node field. Current techniques use lymphoscintigraphy where a radioactive labelled particle and / or blue dye are injected intradermally or intraparenchymally to map the lymph drainage, often in conjunction with a radioactive gamma probe at surgery. In patients with melanoma the SLNB has improved the staging and prognostic information by more accurate determination of whether regional lymph nodes have metastatic spread. This has a major impact on patient management as those patients with negative nodes do not require regional lymph node dissection and have a significantly better prognosis. In our experience of over 3000 patients the combined sentinel node biopsy technique localised accurately 98% of sentinel lymph nodes. Lymphoscintigraphy in patients with melanoma to locate the sentinel lymph nodes involves the intradermal injection of a radiocolloid around the melanoma site or the excision biopsy site. Injections of 5 -10 MBq in 0.05-0.1ml/inj are used and typically 4 injections are usually required. Following tracer injection dynamic imaging is performed to follow the lymphatic collecting vessels until they reach the draining sentinel nodes. An image should be acquired as the vessels reach the node field so that the sentinel nodes directly receiving the channels can be identified and distinguished from any second tier nodes which may sometimes be seen. Delayed scans are performed 2 hours later at which time all regions which can possible drain the primary melanoma site are examined with 5-10 minute static images. The surface location of all sentinel nodes is

Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

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Yamamoto, Maki; Fisher, Kate J; Wong, Joyce Y; Koscso, Jonathan M; Konstantinovic, Monique A; Govsyeyev, Nicholas; Messina, Jane L; Sarnaik, Amod A; Cruse, C Wayne; Gonzalez, Ricardo J; Sondak, Vernon K; Zager, Jonathan S

2015-05-15

Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (Pthick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma. © 2015 American Cancer Society.

Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

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Gerrit Cornelis Langhout

2014-01-01

Full Text Available 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.

Advantages of preoperative ultrasound in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph nodes: a retrospective analysis in 221 patients with malignant melanoma AJCC Stages I and II.

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Stoffels, I; Dissemond, J; Poeppel, T; Klötgen, K; Hillen, U; Körber, A; Schadendorf, D; Klode, J

2012-01-01

Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions as it is a surgical intervention with potential morbidity. The present retrospective study seeks to clarify the reliability of preoperative ultrasonography (US) in direct comparison to the result of SLNE and seeks to identify potential advantages of preoperative ultrasound if performed in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph node (SLN). We retrospectively analysed data from 221 patients with primary malignant melanoma with a Breslow index of ≥ 1.0 mm. Of the 221 patients, 77.4% (n = 171) had a negative SLN. In 50 patients (22.6%), the histopathological investigation of 71 excised lymph nodes resulted in a positive SLN. The US examination demonstrated a sensitivity of 13.6%, a specificity of 96.9%, a positive predictive value of 97.2% and a negative predictive value of 12.6%. SLNE alone shows a sensitivity of 94%, a specificity of 98.6%, a positive predictive value of 100% and a negative predictive value of 98.3%. Preoperative US in conjunction with dynamic lymphoscintigraphy, followed by SLNE, demonstrated a detecting ratio of 100% (n = 28) for micrometastases and 98.6% (n = 42/43) for macrometastases. In conclusion, this study confirms that preoperative US alone cannot replace the vital information obtained during dynamic lymphoscintigraphy. But preoperative US is an important component of the staging procedure in melanoma patients and has clear advantages when performed in conjunction with dynamic lymphoscintigraphy. Therefore, we recommend preoperative US before every SLNE. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Discordance in histopathologic evaluation of melanoma sentinel lymph node biopsy with clinical follow-up: results from a prospectively collected database.

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Dandekar, Monisha; Lowe, Lori; Fullen, Douglas R; Johnson, Timothy M; Sabel, Michael S; Wong, Sandra L; Patel, Rajiv M

2014-10-01

Sentinel lymph node (SLN) status currently represents the single most important prognostic factor in clinically localized melanoma and is widely used in patients with melanoma at significant risk for nodal micrometastasis. Although several studies have looked at the rates and implications of inaccuracies in the histopathologic diagnosis of melanocytic lesions, accuracy in the histologic interpretation of the SLN in melanoma has not been addressed. The goal of this study was to determine the rates of discordance in the histopathologic evaluation of the SLN and the potential clinical impact on patients referred to a comprehensive melanoma center. A prospectively collected database was queried for melanoma patients who had SLN biopsies performed at outside institutions before referral to the University of Michigan Multidisciplinary Melanoma Program between 2006 and 2009. These cases were reviewed and clinical follow-up obtained. After internal review of the SLN material, 13 (8 %) of 167 cases had major discrepancies in diagnosis that impacted patient management and prognosis. The disease of five patients was subsequently downstaged and the disease of eight patients was upstaged after internal review of the SLNs and reversal in diagnoses. There appears to be a small yet significant rate of discordance in diagnosis of the SLN for melanoma after expert histopathologic review. The implications of this discordance and revision of diagnosis is substantial. Expert histopathologic review of the SLN warrants consideration to provide the most accurate prognostic information and optimal patient care.

Lymph-scintigraphic identification of sentinel lymph nodes in breast carcinoma and malignant melanoma patients

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Sergieva, S; Bajchev, G.; Aleksandrova, E.

1999-01-01

It is the purpose of the study to assay the possibilities of lymphoscintigraphy (LS) in evaluating local lymphatic drainage and sentinel lymph nodes (SLNs) location in patients presenting breast carcinoma and malignant melanoma. Twenty-nine women with breast carcinoma (TI-IIa clinical stage, age range 31 to 74 y) and 7 patients with malignant melanoma (Clark III-V) are scanned in the period 1997 through 1998. 99m Tc-sulphur colloid (Solco Lymphoscint, SORIN) with mean size of particles 50 nm is used. Planar images are obtained at 20 and 120-180 min after sc injection in the region of primary tumor, at mean radioactivity 20 MBq per injection site in a volume 0.2-0.3 ml. In the breast cancer patients Patent Blue V or Mitoxantrone is injected around the tumor twice - 20 and 3 to 1/2 hours prior to surgery. In malignant melanoma patients immunoscintigraphy using 740 MBq 99m Tc-anti-melanoma monoclonal antibodies (Technemab-K-1) is carried out before lymph node dissection. SLNs are visualized in 25 patients (86.2%) with breast cancer. In 21 (72%) patients to 4 SLNs are scanned in level I of the local axillary region, in 4 cases (14%) - in the region of axillary level II, in one female patient (3%) - at axillary level III, and in 3 patients (10%) i psilateral internal mammary lymph nodes are scanned. Two patients are suspected for the so-called s kip t ype of tumor lymphatic dissemination. In 4 patients no SLN images are visible. In breast carcinoma patients SLN are additionally stained blue and following intraoperative revision, evidence of metastatic involvement is established in 12 instances (41.3%). In 3 patients with melanoma in the abdomen and back SLNs are located in the region of inguinal and axillary lymph node groups, while in 3 patients presenting lesions to the surface of extremities only local lymph nodes draining the melanoma are visualized. Immunoscintigraphy shows enhanced uptake in the region of SLNs in 3 cases with the metastatic changes in them

Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

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Kucher, Cynthia; Zhang, Paul J; Acs, Geza; Roberts, Shelley; Xu, Xiaowei

2006-09-01

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

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Stoffels, Ingo; Leyh, Julia; Schadendorf, Dirk; Klode, Joachim [University of Duisburg-Essen, Department of Dermatology, Venerology and Allergology, University-Hospital Essen, Essen (Germany); Mueller, Markus [University of Duisburg-Essen, Department of Medical controlling, University-Hospital Essen, Essen (Germany); Geisel, Marie Henrike [University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University-Hospital Essen, Essen (Germany); Poeppel, Thorsten [University of Duisburg-Essen, Department of Nuclear Medicine, University-Hospital Essen, Essen (Germany)

2014-09-15

Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified. Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of EUR 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was EUR 1,619.7 (Q1;Q3 EUR 1,317.0;2,603.4) and of SLNE without SPECT/CT was EUR 2,330.2 (EUR 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared

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

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

2016-04-15

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

Sentinel lymph node and its applications in cancer. Review of literature

International Nuclear Information System (INIS)

Leon A, L.; Vigil R, C.; Velarde G, R.; Abugattas S, J.; Leon R, M.; Caceres G, E.; Cano P, R.; Morales G, R.; Aguilar R, C.

2001-01-01

In the human body, the lymph nodes groups like in the groin, axilla, neck and others regions, receive the lymphatic drainage from a determined corporal territory, and the first node to receive it is called the sentinel node and as the name suggest, it is the most likely node to contain metastases if present; in the axilla the sentinel node is usually localized in level I. The presence of regional lymph node involvement remains the most reliable prognostic factor and provides accurate nodal staging for woman with epithelial cancers. The most commonly use indicator of prognosis for patients with operable carcinoma of the breast is the histological presence or absence of axillary lymph node metastases. The sentinel node biopsy is a new procedure composed of two steps: the first is the lymphatic mapping where the sentinel node can be identified in the preoperative period by lymphoscintigraphy, and in the operating room by injection of a vital blue dye, and with technetium labeled sulfur colloid injected into the same area as the vital blue dye or in place of the blue dye. In the second step the extracted and a rigorous assessment of the accuracy by pathological examination. Multiple studies have showed that if the sentinel lymph node is negative for metastatic disease, the remaining lymph nodes are also likely to be negative. The value of the sentinel lymph node biopsy is based in the pathologic diagnosis, when it is negative it is possible to avoid axillary dissection. The technique of identification of sentinel lymph node is applied to different types of cancers and distinct localizations, in the penis, malignant melanoma, breast, head and neck (oral cavity, epidermoid carcinoma, malignant melanoma), vulva, gastric, colorectal, 'non small cell lung cancer' and for merkel cell carcinoma. This publication regarding the sentinel lymph node technique and its applications in cancer, represents the routine followed in the Department of Breast Bone and Mixed Tumours of the

Sentinel lymph node molecular ultrastaging in patients with melanoma: a systematic review and meta-analysis of prognosis.

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Mocellin, Simone; Hoon, Dave S B; Pilati, Pierluigi; Rossi, Carlo R; Nitti, Donato

2007-04-20

Molecular biology-based ultrastaging of cancer is already part of the standard management of patients with hematologic malignancies, whereas the evidence for solid tumors is much more debated. Polymerase chain reaction (PCR) -based detection of melanoma cells in sentinel lymph nodes (SLN) of patients with melanoma represents an appealing prognostic tool. However, no consensus exists on the clinical implementation of this prognostic indicator for the management of these patients. Twenty-two studies enrolling 4,019 patients who underwent SLN biopsy for clinical stage I to II cutaneous melanoma were reviewed. Correlation of PCR status with TNM stage, disease recurrence rates, and survival was assessed by means of association statistics and formal meta-analysis, respectively. PCR status correlated with both TNM stage (stage I to II v III; PCR positivity, 95.1% v 46.6%; P < .0001) and disease recurrence (PCR positive v negative; relapse rate, 16.8% v 8.7%; P < .0001). PCR positivity was also associated with worse overall (hazard ratio [HR], 5.08; 95% CI, 1.83 to 14.08; P = .002) and disease-free (HR, 3.41; 95% CI, 1.86 to 6.24; P < .0001) survival. Statistical heterogeneity was significant, underscoring the variability among overall effect estimates across studies; metaregression and subgroup analysis did not identify clear-cut sources of heterogeneity, although some study design variables were suggested as potential causes. PCR status of SLN appears to have a clinically valuable prognostic power in patients with melanoma. Although the heterogeneity of the studies so far published warrants caution to avoid overestimating the favorable results of pooled data, our findings strongly support additional investigation in this field.

Lymphatic mapping and sentinel node biopsy in early stage melanoma: study of the first 100 cases in Institut Gustave Roussy; Lymphoscintigraphie et biopsie du ganglion sentinelle dans les melanomes cutanes primitifs: analyse des 100 premiers cas a l'Institut Gustave Roussy

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Buffard, V.; Duvillard, P. [Institut Gustave Roussy, Service de Dermatologie, 94 - Villejuif (France); Mamelle, G. [Institut Gustave Roussy, Service de Chirurgie Cervico-faciale, 94 - Villejuif (France); Lumbroso, J.; Ricard, M. [Institut Gustave Roussy, Service de Medecine Nucleaire et de Physique Medicale, 94 - Villejuif (France); Kolb, F.; Sleilati, F. [Institut Gustave Roussy, Service de Chirurgie Plastique, 94 - Villejuif (France); Spatz, A. [Institut Gustave Roussy, Service d' Histopathologie, 94 - Villejuif (France)

2005-01-15

Introduction: We report the data of the first 100 patients who underwent sentinel lymph node biopsy (SLND) in our institution using lymphoscintigraphy only. Patients and methods: From 1998 to 2000, 100 consecutive patients (53 men and 47 women) with stage I or II melanoma (mean Breslow: 3.11 mm) underwent a SLND. Localisation of the sentinel node was performed by preoperative lymphoscintigraphy and hand held gamma probe detection. The sentinel node was examined by routine histology and immunohistochemistry for PS100 and HMB-45. If the sentinel node contained tumor cells, a complete lymphadenectomy was performed. Results: Lymphoscintigraphy was performed for 97 patients. The SLN was identified in 97% of cases (94/97) and excised in 95% of cases (92/97). The rate of SLN metastasis was 19/92 patients (21%), correlated with Breslow index (< 1.5 mm: 5%, 1.5-4 mm: 15%, > 4 mm: 46%). A mean number of 1.81 lymph node per patient was analysed. The mean follow-up was 26 months with a relapse in 14 patients, 5 of them having a metastatic sentinel node. Three patients had a recurrence at the site of the SLND although they had initially a negative sentinel node. Conclusion: The identification and metastatic rates of sentinel nodes are similar to those of the literature. More studies are needed to determine whether lymphoscintigraphy alone is efficient for successful SLND in melanoma. (author)

The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma

International Nuclear Information System (INIS)

Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

2015-01-01

Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation

The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma.

Science.gov (United States)

Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

2015-01-01

Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation.

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

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Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

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Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

2010-12-01

This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

The diagnostic value of adding dynamic scintigraphy to standard delayed planar imaging for sentinel node identification in melanoma patients

International Nuclear Information System (INIS)

Nielsen, Kristina Rue; Nielsen, Michael B.; Chakera, Annette H.; Hesse, Birger; Oturai, Peter S.; Scolyer, Richard A.; Stretch, Jonathan F.; Thompson, John F.; Uren, Roger F.

2011-01-01

The aim of this study was to compare early dynamic imaging combined with delayed static imaging and single photon emission computed tomography (SPECT)/CT with delayed, planar, static imaging alone for sentinel node (SN) identification in melanoma patients. Three hundred and seven consecutive melanoma patients referred for SN biopsy (SNB) were examined using combined imaging. Secondary interpretation of only the delayed static images was subsequently performed. In 220 patients (72%), complete surgical and pathological information relating to the SNB was available. The number of SNs identified and number of patients with positive SNs were compared between the two interpretations of the imaging studies and, when available, related to pathology data. A slightly higher number of SNs (mean 0.12/patient) was identified when interpreting only delayed static images compared to combined imaging. In a direct patient-to-patient comparison, the number of SN(s) identified on the combined vs static images only showed moderate agreement (kappa value 0.56). In 38 patients (17%), positive SNs were identified by the combined procedure compared to 35 (16%) by static imaging only. Thus by static imaging only, tumour-positive SNs were not identified in 3 of 38 patients (8%). For SN identification in melanoma patients, dynamic imaging combined with delayed static imaging and SPECT/CT is superior to delayed static imaging only because the latter is more likely to fail to identify SNs containing metastases. (orig.)

Sentinel lymph node imaging in breast cancer

International Nuclear Information System (INIS)

Kim, Byung Tae

1999-01-01

Currently, dissection of the axillary or regional lymph nodes is considered the standard staging procedure in breast cancer. However, accumulating evidence is becoming available that the sentinel node concept may provide the same or even better staging information. In the case of melanoma, it is proven that the histological characteristics of the sentinel node reflect the histological characteristics of the distal part of the lymphatic basin. Morbidity can be reduced significantly by the use of sentinel node dissection as several authors have reported successful introduction of this technique into clinical practice. But in breast cancer patients, there are significant differences in practice relating to the technology, such as radiopharmaceuticals, injection sites, volume of injectate, combination with vital blue dye, preoperative lymphoscintigraphy, etc. Valuable reports on these topics appeared in recent journals. This review is a summary of those reports for nuclear physicians interested in sentinel node detection by lymphoscintigraphy in breast cancer patients

Persistent postoperative pain and sensory changes following lymph node excision in melanoma patients

DEFF Research Database (Denmark)

Slagelse, Charlotte; Petersen, Karin L; Dahl, Jørgen B

2014-01-01

Studies on complications related to chronic nerve injury following sentinel lymph node biopsy (SLNB) and complete lymph node dissection (CLND) for melanoma are sparse. This review summarizes the existing literature on pain and neuropathic complications in melanoma patients undergoing SLNB...

Preliminary evaluation of intraoperative gamma probe detection of the sentinel node

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Sierralta, M P; Jofre, M J [Nuclear Medicine Department, Military Hospital, Santiago (Chile); Iglesis, R; Schwartz, R; Gomez, L; Velez, R [Surgery Department, Military Hospital, Santiago (Chile); Sandoval, R [Pathology Department, Military Hospital, Santiago (Chile)

2002-09-01

Introduction: The resurgence of the lymphoscintigraphy with the sentinel node concept and the availability of the intraoperative gamma probe have been proposed to avoid the morbidity of an unnecessary regional node dissection. The aim of the study was to evaluate the intraoperative gamma probe use after lymphoscintigraphy for the localization of the sentinel node. Material and methods: Twenty-nine patients were studied, 18 females (62%), mean age 60 {+-} 19 y.o. (range 24-86 y.o.) at the Military Hospital Nuclear Medicine Department. The reference diagnoses were 66% malignant melanoma, 21 % breast cancer, 10 % head and neck cancer and 3% vulvae cancer. Lymphoscintigraphs were performed with Tc99m-Dextran injected intradermally in four points around the primary lesion or around the biopsy site (for melanoma 500 microCi each one; for breast and head and neck 200 microCi each one). Afterwards, dynamic images were taken, followed by intraoperative gamma probe investigations in order to localize and remove the sentinel node. Additionally, isosulfan blue was injected before the surgery was made. Results: Lymphoscintigraphy was positive to detect sentinel node(s) in 20 patients (69%). During the surgery, 40 sentinel nodes were detected. In 33 cases, the intraoperative gamma probe was performed, of which 88 % were radioactives. In 35 nodes, the isosulfan blue was injected, of which 80 % were dyed. The correlation between both techniques was 75 %. The histology study of 37 samples demonstrated that 86% (n=32) were truly ganglionar nodes. Conclusion: The intraoperative gamma probe after lymphoscintigraphy is a useful technique for the localization of the sentinel node.

Preliminary evaluation of intraoperative gamma probe detection of the sentinel node

International Nuclear Information System (INIS)

Sierralta, M.P.; Jofre, M.J.; Iglesis, R.; Schwartz, R.; Gomez, L.; Velez, R.; Sandoval, R.

2002-01-01

Introduction: The resurgence of the lymphoscintigraphy with the sentinel node concept and the availability of the intraoperative gamma probe have been proposed to avoid the morbidity of an unnecessary regional node dissection. The aim of the study was to evaluate the intraoperative gamma probe use after lymphoscintigraphy for the localization of the sentinel node. Material and methods: Twenty-nine patients were studied, 18 females (62%), mean age 60 ± 19 y.o. (range 24-86 y.o.) at the Military Hospital Nuclear Medicine Department. The reference diagnoses were 66% malignant melanoma, 21 % breast cancer, 10 % head and neck cancer and 3% vulvae cancer. Lymphoscintigraphs were performed with Tc99m-Dextran injected intradermally in four points around the primary lesion or around the biopsy site (for melanoma 500 microCi each one; for breast and head and neck 200 microCi each one). Afterwards, dynamic images were taken, followed by intraoperative gamma probe investigations in order to localize and remove the sentinel node. Additionally, isosulfan blue was injected before the surgery was made. Results: Lymphoscintigraphy was positive to detect sentinel node(s) in 20 patients (69%). During the surgery, 40 sentinel nodes were detected. In 33 cases, the intraoperative gamma probe was performed, of which 88 % were radioactives. In 35 nodes, the isosulfan blue was injected, of which 80 % were dyed. The correlation between both techniques was 75 %. The histology study of 37 samples demonstrated that 86% (n=32) were truly ganglionar nodes. Conclusion: The intraoperative gamma probe after lymphoscintigraphy is a useful technique for the localization of the sentinel node

Contrast enhanced ultrasound of sentinel lymph nodes

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XinWu Cui

2013-03-01

Full Text Available Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient’s prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue®, Sonazoid® and Definity®. This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node.

New Safety Margins for Melanoma Surgery: Nice Possibility for Drinking of "Just That Cup of Coffee"?

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Tchernev, Georgi; Chokoeva, Anastasiya Atanasova

2017-06-15

The American Joint Committee on Cancer (AJCC's) skin melanoma surgical treatment recommendations from 2011 are characterised by a prima facie "freedom of choice" regarding how extensive should be the excisions for melanomas with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the recommended surgical security margins vary between 0.5 and 1 cm for melanoma in situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range of variation is also between 1 and 2 cm, without specifying when the surgical field should be broader and, narrower, accordingly. This "uncertainty or lack of intent" of the guilders often leads to the same surgical approach to melanomas at different stages, or to a different approach in cases of melanomas at the same stage, in contrast. Therefore, this should be defined as wrong, logically. We present 3 patients with cutaneous melanomas, treated with similar fields of surgical security. Current issues, generated within the framework of melanoma's surgery guided by the recommendations of the AJCC are also discussed. A new surgical approach in patients with melanoma is recommended, discussed for the first time in world literature. We hypothesize that the introduction of a certain recommendations for a 2 cm surgical field in all directions during the initial excision, combined with the parallel performance of a sentinel lymph node biopsy, will lead in fact to several important advantages: 1) avoiding of the secondary excision in at least 70% - 90% of the patients (depending on the tumor thickness), 2) minimizing the risk of lymphatic effusion change and misinterpretation of the sentinel lymph node biopsy's results in patients with secondary excision; 3) optimization of the surgical team's work; 4) minimizing the possibility of unprepared/uninformed personnel to take part in decisions for treating a specific disease such as skin melanoma, 4) facilitating the appropriate patients' group selection at the appropriate

Methodology of sentinel node detection

International Nuclear Information System (INIS)

Maublant, J.

2000-01-01

The isotopic localisation of the sentinel node, i.e., the first functional lymph node in a tumor basin, is probably the fastest growing field ever experienced in nuclear medicine. Although based on the simple concept of the lymphatic migration of Tc-labeled colloids, the choice of the optimal technique remains controversial. We review and discuss the role of the colloids, of the site of injection, of the injected volume, of early imaging and of the colorimetric approach. Initially applied to melanoma and breast cancer, the sentinel node detection is now tested in other types of cancer such as lung, colon and prostate. It could become one of the leading tools in minimally invasive surgical oncology. The nuclear medicine physician has to remain aware of the rapid evolutions in this field in order to be able to answer to a rapidly growing demand. (author)

Selective Sentinel Lymphadenectomy for Breast Cancer in the United States

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Stanley P.L. Leong

2004-10-01

Full Text Available Lymph node status is the most reliable prognostic indicator for breast cancer patients. Sentinel lymph nodes (SLNs are the first draining lymph nodes for metastatic breast cancer to spread from the primary site. Although the therapeutic role of selective sentinel lymphadenectomy (SSL in breast cancer has not been determined, the practical significance is that it is being used as a staging procedure, so that a negative SLN can spare a patient more extensive axillary lymph node dissection (ALND with its associated morbidity. If the SLN is negative, the negative predictive value of the remaining nodal basin for breast cancer exceeds 95%. SSL selects out one or a few SLNs and permits more extensive study of the nodes by the pathologist. Such extensive examination would not be practical for the many nodes yielded by a standard ALND. SSL is rapidly evolving into a standard approach for staging primary breast cancer in the United States, without the maturation of results from clinical trials.

Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma.

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Mocellin, Simone; Ambrosi, Alessandro; Montesco, Maria Cristina; Foletto, Mirto; Zavagno, Giorgio; Nitti, Donato; Lise, Mario; Rossi, Carlo Riccardo

2006-08-01

Currently, approximately 80% of melanoma patients undergoing sentinel node biopsy (SNB) have negative sentinel lymph nodes (SLNs), and no prediction system is reliable enough to be implemented in the clinical setting to reduce the number of SNB procedures. In this study, the predictive power of support vector machine (SVM)-based statistical analysis was tested. The clinical records of 246 patients who underwent SNB at our institution were used for this analysis. The following clinicopathologic variables were considered: the patient's age and sex and the tumor's histological subtype, Breslow thickness, Clark level, ulceration, mitotic index, lymphocyte infiltration, regression, angiolymphatic invasion, microsatellitosis, and growth phase. The results of SVM-based prediction of SLN status were compared with those achieved with logistic regression. The SLN positivity rate was 22% (52 of 234). When the accuracy was > or = 80%, the negative predictive value, positive predictive value, specificity, and sensitivity were 98%, 54%, 94%, and 77% and 82%, 41%, 69%, and 93% by using SVM and logistic regression, respectively. Moreover, SVM and logistic regression were associated with a diagnostic error and an SNB percentage reduction of (1) 1% and 60% and (2) 15% and 73%, respectively. The results from this pilot study suggest that SVM-based prediction of SLN status might be evaluated as a prognostic method to avoid the SNB procedure in 60% of patients currently eligible, with a very low error rate. If validated in larger series, this strategy would lead to obvious advantages in terms of both patient quality of life and costs for the health care system.

Radioguided sentinel node biopsy with 99mTc colloidal (Re) sulphide: Our experience

International Nuclear Information System (INIS)

Lago, G.; Alonso, O.; Aizen, B.; Juri, C.

2004-01-01

Full text: It has been demonstrated that nodal metastases from different solid tumors are not random events. Tumour spread within the regional draining basin has been shown to progress in an orderly fashion with first draining basin (sentinel node) most likely to have metastatic involvement. Thus, the sentinel node examination accurately reflects the histology of the remainder of the lymphatic basin. Sentinel node biopsy (SLB) with previous lymphatic mapping by means of radiocolloid lymphoscintraphy has been proposed by many authors as a routine method for staging the regional lymph nodes in patients with cutaneous melanoma and breast cancer. A positive SLB is found to carry high prognostic significance and identifies those patients who might benefit from early therapeutic lymph node dissection and adjuvant treatment. The aim of this retrospective study was to evaluate our experience with radioguided SLB in patients with different tumours. We studied 154 patients between 1998-2003, with clinically localized breast cancer (n=45), melanoma (n=82), cervix carcinoma (n=22) and penis carcinoma (n=5). Lymphoscintigraphy was performed 6-18 hours before surgery using a LFOV gamma camera equipped with a LEHR collimator. A dose of 111-185 MBq of 99mTc colloidal sulphide (Nanocis, Cis bio international, Gif-Sur-Yvette, France) was injected around the primary lesion (melanoma, breast cancer, and penis carcinoma) and into the four quadrants of the cervix (cervix carcinoma). All basins identified by lymphoscintigraphy were explored through incisions directed by the use of a gamma probe. Radioactivity (counts /sec) of the sentinel node(s) and the adjacent tissues was measured in-vivo and verified ex-vivo after removal. A signal to background ratio higher than 2 to 3 in-vivo and higher than 10 ex-vivo was considered significant. Blue dye mapping was performed in all cases of breast cancer but left at discretion of the surgeon for the remaining tumours. Serial sections of the

Cutaneous melanoma – guidelines for diagnostics and therapy in 2016

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Piotr Rutkowski

2016-02-01

Full Text Available Dermoscopy is currently the standard method for clinical differential diagnosis of cutaneous melanoma and for qualifying a lesion for excisional biopsy. Full thickness excisional biopsy of suspicious melanomatous skin lesions likely to be diagnosed as early melanomas is crucial in establishing the diagnosis and defining prognostic factors. Early diagnosis and surgical removal of cutaneous melanoma not only improves patients’ prognosis but is also associated with approximately 90% likelihood of cure. The next steps in the therapeutic management of cutaneous melanoma following excisional biopsy are radical scar excision with adequate margins and sentinel lymph node biopsy. Radical lymph node dissection is recommended in the case of regional lymph node metastases. High-risk patients (lymph node involvement and/or ulcerated primary lesion should be advised to participate in prospective clinical trials on adjuvant therapy. Melanoma patients with distant metastases are still characterized by poor outcomes. In patients with metastatic disease testing for the presence of BRAF gene mutation is mandatory. Patients with metastatic disease should be considered for participation in clinical trials. Long-term survival is confined to a selected group of patients undergoing resection of isolated metastatic lesions. In systemic – mainly first-line – therapy of patients with BRAF V600 mutation the BRAF inhibitor vemurafenib or dabrafenib (preferentially in combination with a MEK inhibitor may be employed and independently of mutational status immunotherapy with anti-PD-1 antibodies (nivolumab or pembrolizumab and eventually ipilimumab (anti-CTLA4 antibody may be used.

Lymphoscintigraphy with intraoperative gamma probe sentinel node detection: clinical impact in patients with head and neck melanomas

International Nuclear Information System (INIS)

Maccauro, M.; Villano, C.; Aliberti, G.; Ferrani, L.; Castellani, M.R.; Bombardieri, E.; Patuzzo, R.; Santinami, M.; Tshering, D.

2005-01-01

Aim. The aims of this paper were to evaluate the clinical relevance of lymphoscintigraphy with intraoperative gamma-probe detection in identifying sentinel nodes (SNs) and to study the prognostic value of SN biopsy in head and neck melanoma patients. Methods. Sixty-one patients had lymphoscintigraphy with intradermal injections of 99m Tc-Nanocoll (40 MBq), 24 h before surgery. Tumor-positive SNs patients underwent total lymph node dissection Postoperative histological examination was performed. Patients were followed up for 1 to 5 years (median 3 years). The tumor relapses and the overall survival were evaluated by means of statistical methods. Results. Lymphoscintigraphy showed lymphatic distribution to more than one basin in 45 patients (74%), in 15 patients one basin was visualized and no basin in 1 patient. In 41 patients the SN was negative for metastases, while in 20 was positive. In a high percentage of patients (30%), metastatic involvement occurred in more than one lymph node basin. During follow-up in the negative SN group, 40 patients remained disease free and 1 relapsed. In the positive SN group, 10 patients remained disease free and 10 relapsed. Recurrence time ranged from 6 to 11 months. The overall survival of the SNs negative group was significantly higher than the positive SN group. Conclusion. This approach was able to distinguish: a) patients with tumor-negative SNs with a favorable clinical course (98% did not relapse, P<0.001); b) patients with tumor-positive SNs with a high rate of tumor relapse (50%, P<0.001). Therefore SN biopsy may give information about prognosis in head and neck melanoma patients

EANM-EORTC general recommendations for sentinel node diagnostics in melanoma

DEFF Research Database (Denmark)

Chakera, Annette H; Hesse, Birger; Burak, Zeynep

2009-01-01

-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...

[The validity of the sentinel node concept in gastrointestinal cancers].

Science.gov (United States)

Kitagawa, Y; Fujii, H; Mukai, M; Ando, N; Kubota, T; Ikeda, T; Ohgami, M; Watanabe, M; Otani, Y; Ozawa, S; Hasegawa, H; Furukawa, T; Nakahara, T; Kubo, A; Kumai, K; Kitajima, M

2000-03-01

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell death in cultured melanoma cells.

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Lewies, Angélique; Wentzel, Johannes Frederik; Miller, Hayley Christy; Du Plessis, Lissinda Hester

2018-01-01

Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells present with altered energy metabolism which is associated with elevated reactive oxygen species (ROS) generation. This is also evident for melanoma, the leading cause of skin cancer related deaths. Altered mechanisms affecting mitochondrial bioenergetics pose attractive targets for novel anticancer therapies. Antimicrobial peptides have been shown to exhibit selective anticancer activities. In this study, the anti-melanoma potential of the antimicrobial peptide, nisin Z, was evaluated in vitro. Nisin Z was shown to induce selective toxicity in melanoma cells compared to non-malignant keratinocytes. Furthermore, nisin Z was shown to negatively affect the energy metabolism (glycolysis and mitochondrial respiration) of melanoma cells, increase reactive oxygen species generation and cause apoptosis. Results also indicate that nisin Z can decrease the invasion and proliferation of melanoma cells demonstrating its potential use against metastasis associated with melanoma. As nisin Z seems to place a considerable extra burden on the energy metabolism of melanoma cells, combination therapies with known anti-melanoma agents may be effective treatment options. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy

International Nuclear Information System (INIS)

Zambo, Katalin; Schmidt, Erzsebet; Dehghani, Babak; Hartmann, Tamas; Bodis, Jozsef; Kornya, Laszlo; Tinneberg, Hans Rudolf

2002-01-01

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy. (orig.)

Popliteal lymphadenectomy for treating metastatic melanoma: case report

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Sergio Renato Pais Costa

Full Text Available CONTEXT: Regional lymph node involvement in patients with malignant melanomas has been associated with poor prognosis. In-transit metastases also lead to poor long-term survival. Whereas for nodal disease only regional lymphadenectomy offers adequate locoregional control, for in-transit metastasis both local excision and isolated limb perfusion with chemotherapy plus tumor necrosis factor-alpha can be used for disease control. In cases of tumors located in the distal region of the legs, the lymphatic dissemination most commonly observed is to the inguinal chain. Consequently, therapeutic inguinal lymphadenectomy or even selective lymphadenectomy (sentinel lymph node biopsy have been recommended. On the other hand, involvement of the popliteal chain is very rare. When this occurs, popliteal lymphadenectomy should be indicated. Local excision may be the logical approach for a few small in-transit metastases because of the low morbidity in this procedure, when compared with isolated limb perfusion. CASE REPORT: A case of melanoma of the heel with popliteal chain involvement and in-transit metastases is presented. This was treated by means of regional lymphadenectomy plus in-transit metastases excision, with a good postoperative course.

Geocoding uncertainty analysis for the automated processing of Sentinel-1 data using Sentinel-1 Toolbox software

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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.

Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis.

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González, Óscar; Zafon, Carles; Caubet, Enric; García-Burillo, Amparo; Serres, Xavier; Fort, José Manuel; Mesa, Jordi; Castell, Joan; Roca, Isabel; Ramón Y Cajal, Santiago; Iglesias, Carmela

2017-10-01

Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Introducing navigation during melanoma-related sentinel lymph node procedures in the head-and-neck region.

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KleinJan, Gijs H; Karakullukçu, Baris; Klop, W Martin C; Engelen, Thijs; van den Berg, Nynke S; van Leeuwen, Fijs W B

2017-08-17

Intraoperative sentinel node (SN) identification in patients with head-and-neck malignancies can be challenging due to unexpected drainage patterns and anatomical complexity. Here, intraoperative navigation-based guidance technologies may provide outcome. In this study, gamma camera-based freehandSPECT was evaluated in combination with the hybrid tracer ICG- 99m Tc-nanocolloid. Eight patients with melanoma located in the head-and-neck area were included. Indocyanine green (ICG)- 99m Tc-nanocolloid was injected preoperatively, whereafter lymphoscintigraphy and SPECT/CT imaging were performed in order to define the location of the SN(s). FreehandSPECT scans were generated in the operation room using a portable gamma camera. For lesion localization during surgery, freehandSPECT scans were projected in an augmented reality video-view that was used to spatially position a gamma-ray detection probe. Intraoperative fluorescence imaging was used to confirm the accuracy of the navigation-based approach and identify the exact location of the SNs. Preoperatively, 15 SNs were identified, of which 14 were identified using freehandSPECT. Navigation towards these nodes using the freehandSPECT approach was successful in 13 nodes. Fluorescence imaging provided optical confirmation of the navigation accuracy in all patients. In addition, fluorescence imaging allowed for the identification of (clustered) SNs that could not be identified based on navigation alone. The use of gamma camera-based freehandSPECT aids intraoperative lesion identification and, with that, supports the transition from pre- to intraoperative imaging via augmented reality display and directional guidance.

Selective sentinel lymph node biopsy in male breast cancer.

Science.gov (United States)

Martin-Marcuartu, J J; Alvarez-Perez, R M; Sousa Vaquero, J M; Jimenez-Hoyuela García, J M

To evaluate the reproducibility of the sentinel lymph node (SLN) technique in male breast cancer. We retrospectively analysed 21 male patients diagnosed with breast cancer in our hospital from 2008 to 2016 with, at least, 18 months follow-up. Fifteen patients underwent selective sentinel lymph node biopsy (SLNB) following the usual protocols with peritumoral injection of 18.5-111MBq of 99m Tc-nanocoloides and acquisition of planar images 2hours after the injection. In 2 cases it was necessary to perform a SPECT/CT to locate the SLN. Immunohistochemistry and molecular techniques (OSNA) were used for their analysis. Six patients did not undergo SLNB because they had pathological nodes or distant disease at the time of diagnosis. SLNB was performed in 15 patients. The SLN was negative in 6 patients and positive in the remaining 9. Three patients with positive SLNB did not need axillary lymphadenectomy because of the low number of copies by molecular analysis OSNA. Axillary lymphadenectomy was performed in the remaining 6 patients with the result of 4 positive axillary lymphadenectomies and 2 that did not show further extension of the disease. According to our experience, SLNB in males is a reproducible, useful, safe and reliable technique which avoids unnecessary axillary lymphadenectomy and prevents the appearance of undesirable effects. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

Directory of Open Access Journals (Sweden)

Joana R. Viola

2013-01-01

Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

Radioiodinated methylene blue for melanoma targeting: Chemical characterisation and tumour selectivity of labelled components

International Nuclear Information System (INIS)

Blower, Philip J.; Clark, Katherine; Link, Eva M.

1997-01-01

Radioiodinated methylene blue contains a mixture of components showing selective uptake in human pigmented melanoma, and it has potential for imaging and therapy. Nuclear magnetic resonance and mass spectroscopic studies show that the majority of the radioactivity (85%) is in the form of monoiodinated methylene blue, 4-iodo-3-methylamino-7-dimethylaminophenaza thionium chloride. The amino group ortho-to iodine has become demethylated to a mono-methylamino group. The remainder (15%) of the mixture is the doubly labelled 4,5-diiodo-3,7-bis(methylamino) phenazathionium chloride. The separated components show similar tumour selectivity in athymic mice bearing human pigmented melanomas

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

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Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

2012-02-01

Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

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Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

2017-11-01

To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds

International Nuclear Information System (INIS)

Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

1985-01-01

Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, much attention has been paid to the establishment of selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells. This paper presents 10 B chlorpromazine compounds and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA) as tumor-seeking 10 B compounds which themselves possess selective affinity for the specific metabolic activity of the target cancer cells. An overview of the following studies on the effects of 10 B 1 -BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10 B 1 -BPA; 2) in vivo studies on therapeutic effects of 10 B 1 -BPA using melanoma-bearing hamsters; and 3) preclinical therapeutic experiments using spontaneously occurring malignant melanoma in Duroc pig skin, including experiments in which melanoma was successfully cured. (Namekawa, K.)

A pilot study of SPECT/CT-based mixed-reality navigation towards the sentinel node in patients with melanoma or Merkel cell carcinoma of a lower extremity.

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van den Berg, Nynke S; Engelen, Thijs; Brouwer, Oscar R; Mathéron, Hanna M; Valdés-Olmos, Renato A; Nieweg, Omgo E; van Leeuwen, Fijs W B

2016-08-01

To explore the feasibility of an intraoperative navigation technology based on preoperatively acquired single photon emission computed tomography combined with computed tomography (SPECT/CT) images during sentinel node (SN) biopsy in patients with melanoma or Merkel cell carcinoma. Patients with a melanoma (n=4) or Merkel cell carcinoma (n=1) of a lower extremity scheduled for wide re-excision of the primary lesion site and SN biopsy were studied. Following a Tc-nanocolloid injection and lymphoscintigraphy, SPECT/CT images were acquired with a reference target (ReTp) fixed on the leg or the iliac spine. Intraoperatively, a sterile ReTp was placed at the same site to enable SPECT/CT-based mixed-reality navigation of a gamma ray detection probe also containing a reference target (ReTgp).The accuracy of the navigation procedure was determined in the coronal plane (x, y-axis) by measuring the discrepancy between standard gamma probe-based SN localization and mixed-reality-based navigation to the SN. To determine the depth accuracy (z-axis), the depth estimation provided by the navigation system was compared to the skin surface-to-node distance measured in the computed tomography component of the SPECT/CT images. In four of five patients, it was possible to navigate towards the preoperatively defined SN. The average navigational error was 8.0 mm in the sagittal direction and 8.5 mm in the coronal direction. Intraoperative sterile ReTp positioning and tissue movement during surgery exerted a distinct influence on the accuracy of navigation. Intraoperative navigation during melanoma or Merkel cell carcinoma surgery is feasible and can provide the surgeon with an interactive 3D roadmap towards the SN or SNs in the groin. However, further technical optimization of the modality is required before this technology can become routine practice.

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

Science.gov (United States)

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

2015-02-24

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

Intra-operative lymphatic mapping with Dextran Tc-99m and blue dye for sentinel node detection in patients with primary vulvar malignancies

International Nuclear Information System (INIS)

Morales, R.E.; Aguilar, C.R.; Cano, R.A.; Saavedra, P.; Santos, C.

2004-01-01

Full text: The purpose of this study was to determine the feasibility of sentinel lymph node detection using preoperative lymphoscintigraphy and intra-operative lymphatic mapping in patients with primary vulvar malignancies. Nine patients (29-84 years old) with primary vulvar malignancy were scheduled for sentinel node detection. Two patients had malignant melanoma of the vulva and seven had squamous cell carcinomas. Eight patients did not have a previous surgery of the primary tumour nor of the lymph nodes, one had an aspiration biopsy. Three hours before surgery 1-5 mCi of Tc-99m Dextran was injected intradermally in four points in the skin junction adjacent to the vulvar lesions. Static lymphoscintigraphy was performed using a planar GE gamma camera with a multipurpose low energy collimator, in anterior and lateral views. Images were displayed on a personal computer, through a Portable Imaging Processing software (PIP). In two cases a Siemens ECAM SPECT camera was used, due to necessity of having high-resolution images. Patten blue dye was injected in the junction between the skin and vulvar tumor, in the surgery room, after anaesthesia induction. Agamma probe (Navigator Gamma Guidance System) was used to detect the sentinel node. The activity in the sentinel node was measured in each case, before and after resection. Activity in the remaining tissue was also measured. Nodes were adequately placed in plastic bags and sent to pathology for H-E staining. Non-sentinel nodes were also resected and sent for pathology, except in two cases. Sentinel nodes (SN) were visualised on lymphoscintigraphy 1 to 5 minutes after injection of Tc-99m Dextran. In malignant melanoma drainage to the sentinel node was faster than for other tumours. There were five cases who had bilateral SN in inguinal regions, in other three cases, two SN were located on the same side, two in the inguinal region. In all cases the SN was identified corroborating to the skin mark and with enough

Exploiting Drug Addiction Mechanisms to Select against MAPKi-Resistant Melanoma.

Science.gov (United States)

Hong, Aayoung; Moriceau, Gatien; Sun, Lu; Lomeli, Shirley; Piva, Marco; Damoiseaux, Robert; Holmen, Sheri L; Sharpless, Norman E; Hugo, Willy; Lo, Roger S

2018-01-01

Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal-induced pERK rebound upregulated p38-FRA1-JUNB-CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos-related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death-predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction. Significance: Discontinuing targeted therapy may select against drug-resistant tumor clones, but drug-addiction mechanisms are ill-defined. Using melanoma resistant to but withdrawn from MAPKi, we defined a synthetic lethality between supraphysiologic levels of pERK and DNA damage. Actively promoting this synthetic lethality could rationalize sequential/rotational regimens that address evolving vulnerabilities. Cancer Discov; 8(1); 74-93. ©2017 AACR. See related commentary by Stern, p. 20 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

Metastatic melanoma causing double small intestinal intussusception: diagnosis by computed tomography

International Nuclear Information System (INIS)

Bortolucci, G.; Garcia, M.; Dalcim, L.; Dias, I.; Teshirogi, E.

2011-01-01

Full text: Introduction: Metastases from malignant melanoma to the gastrointestinal tract are uncommon. Often found in jejunum and ileum, they are responsible for up to 7% of complications pre mortem. These metastases manifest with bleeding, perforation, obstruction or intussusception and require immediate surgery. Intussusception is a rare finding in the report described and is presented in a double into distinct segments. History and Physical Examination: M.H.C.S, female, 50 years, presenting 3 cm ulcerated lesion in the calcaneous region of the right foot with two years of evolution, no signs of infection or neoplastic permeation shores. Surgical excision of the lesion was performed and histopathologic analysis showed non-classifiable malignant melanoma. Submitted material to immunohistochemistry showed that markers of antigens Melan A and HMB45 positive, favoring the diagnosis of malignant melanoma. Tumor resection with expanding margins and selective inguinal lymphadenectomy through the technique of sentinel node, with rates equal to V Clark and Breslow thickness of 1.3 cm. Patient presented with acute abdominal obstruction treated surgically. Despite an uneventful post-operative, brain metastases developed, and patient is currently undergoing chemotherapy. Complementary Exams: Contrasted abdominal CT showing distension of the small bowel and an image suggestive of double intussusception. Treatment and Results: Indicated that laparotomy confirmed the presence of double intussusception in small intestine, the first being 110 cm from the angle of Treitz with a palpable tumor mass and dilatation of the upstream and the second character equal to 220 cm of the same, treated with bowel resection followed by end anastomosis. The diagnosis of malignant melanoma was confirmed by immunohistochemical analysis of surgical specimens. Discussion/Conclusion: Metastatic lesions in the gastrointestinal tract are often asymptomatic or nonspecific. The diagnosis should be

Biopsia del ganglio centinela en el melanoma: camino a la desaparición Sentinel lymph node biopsy for melanoma: bound to disappear

OpenAIRE

RE Achenbach; S Monroy

2011-01-01

La biopsia del ganglio centinela continúa siendo utilizada para la terapéutica del melanoma, sin fundamento científico comprobado. Los estudios prospectivos-randomizados han fracasado en demostrar beneficio alguno en el punto clave de los mismos, conocer si aumenta la sobrevida global del paciente con melanoma invasor. Se revisan algunos trabajos que demuestran que el punto de vista contrario a su uso rutinario, es el correcto con el fin de ofrecer al dermatólogo, amplitud de criterio en el m...

A very accurate method for sentinel lymph node investigation: Gamma detecting probe associated with SPECT examination for depth

International Nuclear Information System (INIS)

Ascoli, G.; Cinti, P.; Nonni, M.; Rossi, B.

2002-01-01

Aim: aim of this study is to magnify the lymphoscintigraphy examination by gamma probe with SPECT acquisition for very accurate detection of depth of axilla node in patients affected by melanoma. Methods: according to physiological peculiarities the lymphatic system plays a very important role and represents the most important barrier to neoplastic cells spreading. The 'sentinel node' is the first lymph node draining the affected area. The tendency for surgery is a 'preventive' axillary dissection, even in presence of a clinically negative examination. In fact a high percentage of clinically negative lymph node shows a positive histology (presence of metastatic cells). The nuclear medicine method for researching 'sentinel node' is represented by a regional lymphoscintigraphy with normal gamma camera with a large field of view followed by examination with gamma detecting probe and, in following day, controlled in operating room to confirm the presence of the node early identified. We have completed this protocol with SPECT examination of affected axilla by use of injected laboratory capillary around axilla to perform an exact investigation of node depth. Discussion: Our experience in 150 cases in 18 months shows 100% of axilla 'sentinel node' detection, 25 cases with positive histologic examination and subsequently axillary dissection. Conclusions: In conclusion the scintigraphic examination with lymphoscintigraphy represents a good tool for management of patient with melanoma and the use of ''targeting' with collimated SPECT represent a very aid for the surgeon in reduction time for detection and dissection of lymph node, with high reduction of anesthesia duration

Use of Tc-99m - nanocolloid for sentinel node indentification in cervical cancer

International Nuclear Information System (INIS)

Hubalewska, A.; Sowa-Staszczak, A.; Huszczno, B.; Markocka, A.; Pitynski, K.; Basta, A.; Oplawski, M.; Basta, P.

2003-01-01

The initial draining lymph node for a primary tumor is referred to as the sentinel node. Firstly adopted in the management of patients with cutaneous melanoma and breast cancer, it is now widely tested in cervical cancer. In patients with cervical cancer, lymph node status is the most important prognostic factor for survival. In patients with cervical cancer FIGO stage I and II pelvic lymph node metastases are expected in 0-16 and 24.5-31% and para-aortic lymph node metastases are expected in 0-22 and 11-19% of patients. The removal of pelvic and para-aortic lymph nodes is essential for assessing the biology of the disease. Lymphoscintigraphy enables the visualisation of lymphatic drainage patterns from a great variety of tumour sites prior to surgery. Therefore, the current procedure is to perform the pre-operative mapping of sentinel nodes by static and/or dynamic lymphoscintigraphy, followed by in vivo identification using a gamma detection probe and selective surgical resection. Between 2001-2003, 37 patients with cervical cancer FIGO stage I-IIa were seemed to be qualified to undergo lymphoscintigraphy. The day before surgery 99m Tc-nanocolloid (100 MBq; 0.5-1.0 ml in volume) was applied in each quadrant of the cervix or around the tumor. The static scintigraphic scans were performed after 2 hours p.i. using a dual-head large-field-of-view Siemens gamma-camera equipped with high resolution collimators. SNs were identified intra-operatively using a handheld gamma detection probe (Navigator GPS-Tyco) and intra-operative lymphatic mapping with blue dye. After a resection of the SNs, a standard radical hysterectomy with pelvic and low para-aortic lymph node dissection was performed. Tumor characteristics were compared with sentinel node detection and with the histopathological and immunohistochemical results. The scintigraphy showed a focal uptake in 35 of the 37 patients. In all women one or more sentinel lymph nodes were identified intra-operatively. Of them, 24

Fear of new or recurrent melanoma after treatment for localised melanoma.

Science.gov (United States)

Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

2017-11-01

To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

Science.gov (United States)

Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

2010-07-01

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

Science.gov (United States)

Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

2016-02-01

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, PMerkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

Sentinel node detection in melanomas using contrast-enhanced ultrasound

DEFF Research Database (Denmark)

Nielsen, K. Rue; Klyver, H.; Chakera, A. Hougaard

2009-01-01

in humans. PURPOSE: To investigate the possible use of CEUS in detecting SN in patients with malignant melanomas (MM), and to improve the method by using different concentrations of contrast agent and various positions of the extremity. MATERIAL AND METHODS: Ten patients with MM on an extremity and one...... healthy volunteer were included. One milliliter of a contrast agent (Sonovue; Bracco, Milan, Italy) was injected subcutaneously on both sides of the scar from the excised tumor. Contrast-enhanced lymph channels and lymph nodes (LNs) were searched for using low-mechanical-index CEUS and by stimulated...... tissue damage, as the contrast agent was not registered for subcutaneous administration. RESULTS: In one patient, two contrast-enhanced inguinal LNs were visualized by CEUS, corresponding to two inguinal SNs found by scintigraphic imaging. No contrast-enhanced lymph channels or LNs were visualized in any...

Alpha particles for treatment of disseminated melanoma

International Nuclear Information System (INIS)

Link, E.M.

2010-01-01

Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. 211 At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)

Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

Directory of Open Access Journals (Sweden)

Mara Giavina-Bianchi

2015-01-01

Full Text Available 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.

Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

International Nuclear Information System (INIS)

Martinez-Cadenas, Conrado; Lozoya, Rafael; Boldó, Enrique; Bosch, Nuria; Peñas, Lucas; Flores-Couce, Esther; Ochoa, Enrique; Munárriz, Javier; Aracil, Juan P; Tajahuerce, Marcos; Royo, Ramón

2011-01-01

Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A) mutation was detected in exon 15 of the BRAF gene. Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations

Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

Directory of Open Access Journals (Sweden)

Tajahuerce Marcos

2011-08-01

Full Text Available Abstract Background Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Case Presentation Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A mutation was detected in exon 15 of the BRAF gene. Conclusion Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.

SENTINEL EVENTS

Directory of Open Access Journals (Sweden)

Andrej Robida

2004-09-01

Full Text Available Background. The Objective of the article is a two year statistics on sentinel events in hospitals. Results of a survey on sentinel events and the attitude of hospital leaders and staff are also included. Some recommendations regarding patient safety and the handling of sentinel events are given.Methods. In March 2002 the Ministry of Health introduce a voluntary reporting system on sentinel events in Slovenian hospitals. Sentinel events were analyzed according to the place the event, its content, and root causes. To show results of the first year, a conference for hospital directors and medical directors was organized. A survey was conducted among the participants with the purpose of gathering information about their view on sentinel events. One hundred questionnaires were distributed.Results. Sentinel events. There were 14 reports of sentinel events in the first year and 7 in the second. In 4 cases reports were received only after written reminders were sent to the responsible persons, in one case no reports were obtained. There were 14 deaths, 5 of these were in-hospital suicides, 6 were due to an adverse event, 3 were unexplained. Events not leading to death were a suicide attempt, a wrong side surgery, a paraplegia after spinal anaesthesia, a fall with a femoral neck fracture, a damage of the spleen in the event of pleural space drainage, inadvertent embolization with absolute alcohol into a femoral artery and a physical attack on a physician by a patient. Analysis of root causes of sentinel events showed that in most cases processes were inadequate.Survey. One quarter of those surveyed did not know about the sentinel events reporting system. 16% were having actual problems when reporting events and 47% beleived that there was an attempt to blame individuals. Obstacles in reporting events openly were fear of consequences, moral shame, fear of public disclosure of names of participants in the event and exposure in mass media. The majority of

Sentinel node status prediction by four statistical models: results from a large bi-institutional series (n = 1132).

Science.gov (United States)

Mocellin, Simone; Thompson, John F; Pasquali, Sandro; Montesco, Maria C; Pilati, Pierluigi; Nitti, Donato; Saw, Robyn P; Scolyer, Richard A; Stretch, Jonathan R; Rossi, Carlo R

2009-12-01

To improve selection for sentinel node (SN) biopsy (SNB) in patients with cutaneous melanoma using statistical models predicting SN status. About 80% of patients currently undergoing SNB are node negative. In the absence of conclusive evidence of a SNBassociated survival benefit, these patients may be over-treated. Here, we tested the efficiency of 4 different models in predicting SN status. The clinicopathologic data (age, gender, tumor thickness, Clark level, regression, ulceration, histologic subtype, and mitotic index) of 1132 melanoma patients who had undergone SNB at institutions in Italy and Australia were analyzed. Logistic regression, classification tree, random forest, and support vector machine models were fitted to the data. The predictive models were built with the aim of maximizing the negative predictive value (NPV) and reducing the rate of SNB procedures though minimizing the error rate. After cross-validation logistic regression, classification tree, random forest, and support vector machine predictive models obtained clinically relevant NPV (93.6%, 94.0%, 97.1%, and 93.0%, respectively), SNB reduction (27.5%, 29.8%, 18.2%, and 30.1%, respectively), and error rates (1.8%, 1.8%, 0.5%, and 2.1%, respectively). Using commonly available clinicopathologic variables, predictive models can preoperatively identify a proportion of patients ( approximately 25%) who might be spared SNB, with an acceptable (1%-2%) error. If validated in large prospective series, these models might be implemented in the clinical setting for improved patient selection, which ultimately would lead to better quality of life for patients and optimization of resource allocation for the health care system.

Sentinel lymphnode in breast cancer: an experience with 53 cases

International Nuclear Information System (INIS)

Abreu, Benedita Andrade Leal de; Melo, Nayana Alves de Brito; Abreu, Evandro Leal de; Vieira, Carlos Sabas; Abreu, Everardo Leal de; Universidade Federal do Piaui, Maranhao, PI

2007-01-01

The value of sentinel lymphnode biopsy or selective linfadenectomy in assessing axillary status in breast carcinoma is well established in medical literature. This work presents a brief study from our preliminary experience with 53 patients submitted to pre-surgical lymphoscintigraphy and intraoperatory detection of sentinel lymphnode and compares our records with those of current medical literature. (author)

Sentinel lymphnode in breast cancer: an experience with 53 cases

Energy Technology Data Exchange (ETDEWEB)

Abreu, Benedita Andrade Leal de; Melo, Nayana Alves de Brito; Abreu, Evandro Leal de; Vieira, Carlos Sabas; Abreu, Everardo Leal de [Universidade Estadual do Piaui, Maranhao, PI (Brazil). Centro Bionuclear de Diagnostico; Universidade Federal do Piaui, Maranhao, PI (Brazil). Hospital Sao Marco; E-mail: bionuclear@uol.com.br

2007-09-15

The value of sentinel lymphnode biopsy or selective linfadenectomy in assessing axillary status in breast carcinoma is well established in medical literature. This work presents a brief study from our preliminary experience with 53 patients submitted to pre-surgical lymphoscintigraphy and intraoperatory detection of sentinel lymphnode and compares our records with those of current medical literature. (author)

Sentinel Mining

DEFF Research Database (Denmark)

Middelfart, Morten

business users about potential changes to Key Performance Indicators (KPIs) and thereby facilitate corrective action before such a change becomes a reality. Specifically, sentinels are rule relationships at the schema level in a multidimensional data cube. These relationships represent changes over time...... in certain measures that are followed by a change in a user defined critical measure, typically a KPI. An important property of a sentinel is bi-directionality, which means that the change relationship holds in the complement direction, since a sentinel with the bi-directional property has a higher chance...

Immunolymphoscintigraphy for metastatic sentinel nodes: test of a model

DEFF Research Database (Denmark)

Chakera, A H; Nielsen, B S; Madsen, J

2011-01-01

Aim. To develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. Methods. We selected one of four tumour-specific antibodies against human breast cancer and investigated (1), in immune-deficient (nude) mice with xenograft human b...... in healthy rabbits. Results and Conclusion. Our paper suggests the theoretical possibility of a model of dual isotope immuno-lymphoscintigraphy for noninvasive, preoperative, malignant sentinel node imaging....

Do melanoma patients from Southern climates have a worse outcome than those from Northern climates?

Science.gov (United States)

Woodall, Charles E; Martin, Robert C G; Stromberg, Arnold J; Ginter, Brooke; Burton, Alison; Ross, Merrick I; Edwards, Michael J; McMasters, Kelly M; Scoggins, Charles R

2009-08-01

Sun exposure is known to cause melanoma; what is not known is whether patients from the Southern United States have a different profile of clinicopathologic factors and outcomes than those from the Northern United States. Data from a prospective, randomized trial on surgery for cutaneous melanoma were analyzed. All patients underwent wide excision and sentinel lymph node biopsy. Patients were categorized into two groups: Northern or Southern according to their state of residence. Clinicopathologic factors and outcomes were compared between groups. A total of 2025 patients were included in the analysis; 1214 (60%) were from Southern states. The median follow-up was 52 months. Despite significant differences in clinicopathologic features between groups on both univariate and multivariate analysis, two important factors, namely primary tumor thickness and ulceration were not different, nor was the rate of lymph node metastasis. Additionally, there were no differences in disease-free survival or overall survival between the two groups. Significant differences exist between primary melanomas based on geographic regions; however there are no differences in survival. Cumulative versus episodic sun exposure may play some role in these differences.

Sentinel node concept in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Kiricuta, I.C. [St. Vincenz-Hospital, Limburg (Germany). Inst. for Radiation Oncology

2000-07-01

Background/purpose: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. Material and methods: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin and Eosin (H and E) stained sections and immunohistochemistry. Results: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2-procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a 'pN0' patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or

Land science with Sentinel-2 and Sentinel-3 data series synergy

Science.gov (United States)

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

Towards new therapeutic approaches for malignant melanoma.

Science.gov (United States)

Pacheco, Ivan; Buzea, Cristina; Tron, Victor

2011-11-01

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

Melanoma genetics

DEFF Research Database (Denmark)

Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

2015-01-01

Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

The clinical impact of PET scanning in patients with melanoma: A prospective study

International Nuclear Information System (INIS)

Kalff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A.

1998-01-01

Full text: Small series have shown that PET scanning using F-18 fluorodeoxyglucose (FDG), can quite accurately stage patients melanoma. At this Institute these patients are only sent for PET imaging if they have high risk melanomas ( >3 Clarke's grade primaries) or there remains any significant doubt as to their clinical staging or management after the completion of conventional screening. This prospective study examines how PET scan findings influenced the clinical management decisions in 53 patients (29 males, mean age 54±13 yrs: range 31-81 yrs) Referring doctors were asked to indicate reason for the PET scan, stage their patients on the basis of all their current investigations, and to indicate their management plans prior to PET scanning. Follow-up of subsequent patient management at 2-4 weeks post PET scan was then obtained and compared to pre PET plans. PET was used to stage 26 patients, restage 17, follow-up 5, assess recurrence in 3, and other in 2 patients. To date follow-up has shown that in 32/49 (65%) patients PET was used to triage patients to locoregional surgery (10 patients), radical radiotherapy (5 patients), or to continuing follow-up only (17 patients). Three further high risk patients with negative PET scans had sentinel mode biopsy. In only 13 patients was management already determined, with planned treatment being changed in 6. Four patients have not had their post PET scan review yet. To date proven false negative PET scans have occurred in 3 cases, 2 sentinel node biopsies showed microscopic disease, and one scan incorrectly labelled gall-bladder melanoma as hydro-nephrotic kidney. Interestingly in 3 cases, PET discovered other unsuspected tumours (rectum x 2, plasmacytoma). PET scanning has been incorporated into routine management to triage most high risk patients, but it still alters interventions in half of those patients where management has already been planned. PET clearly misses small volume disease, the importance of which is

Sentinel node concept in breast cancer

International Nuclear Information System (INIS)

Kiricuta, I.C.

2000-01-01

Background/purpose: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. Material and methods: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin and Eosin (H and E) stained sections and immunohistochemistry. Results: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2-procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a 'pN0' patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or lymphatic basins

Clinical relevance of positron emission tomography for initial staging and follow-up of malignant melanoma

International Nuclear Information System (INIS)

Baum, R.P.; Rinne, D.; Kaufmann, R.

2000-01-01

The incidence of melanoma is rapidly increasing (at a rate of 5 percent per year) throughout the world. In Europe, the incidence is approximately 10-12 new cases of invasive melanoma per 100,000 inhabitants. The most important prognostic factor is the stage of disease (Clark Level and vertical tumor depth (TD) according to BRESLOW) at the time of presentation. Ten year survival is 90 percent with a TD of 1.5 mm; 5-year survival is 15-50 percent when there is regional lymph node involvement, and 5 percent when there is disseminated disease. Conventional diagnostic tests for staging include a chest X-ray, lymph node sonography and laboratory tests. Sentinel node biopsy is becoming an increasingly common procedure since melanoma usually metastasizes to regional lymph nodes before dissemination. CT scan of the thorax or abdomen, MRI of the brain and other tests are used only when signs or symptoms warrant. The results of a prospective study which we performed in 100 patients for staging of high risk melanoma (n=48) or for re-staging patients with suspected recurrence demonstrated that FDG whole-body PET is superior to conventional imaging techniques (X-ray, sonography, CT scan) except for the detection of brain metastases. The diagnostic accuracy of PET for the detection of metastases was 92.1% versus 55.7% for conventional imaging (p 1.5 mm); and 2) detection of occult metastases in patients with recurrent disease who are being considered for surgery. PET often changes the diagnostic evaluation and therapeutic management of patients with melanoma. PET has also shown to be cost effective in diagnosis and evaluation of patients with melanoma in the USA. (orig.) [de

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

Directory of Open Access Journals (Sweden)

Metcalfe Chris

2010-05-01

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

Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.

Directory of Open Access Journals (Sweden)

Malgorzata Sztiller-Sikorska

Full Text Available BACKGROUND: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. METHODS: We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. FINDINGS: Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF and proto-oncogene c-MYC. CONCLUSION: Selected anti-clonogenic compounds might be further investigated as potential adjuvants

Seven Non-melanoma Features to Rule Out Facial Melanoma

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Philipp Tschandl

2017-08-01

Full Text Available Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p < 0.001. Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8% and seborrhoeic keratosis (74.3% and lower for actinic keratosis (61.4% and lichenoid keratosis (25.6%. Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

HIV prevalence in South Sudan: data from the ANC sentinel ...

African Journals Online (AJOL)

data, triangulated with data from other sources that will achieve informed consensus about population prevalence. Methodology selection of sample. Sentinel surveillance was conducted among pregnant women aged 15-49 attending ANC. Pregnant women were selected as a proxy for the general population and because ...

VERIFICATION OF THE SENTINEL-4 FOCAL PLANE SUBSYSTEM

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C. Williges

2017-05-01

Full Text Available The Sentinel-4 payload is a multi-spectral camera system which is designed to monitor atmospheric conditions over Europe. The German Aerospace Center (DLR in Berlin, Germany conducted the verification campaign of the Focal Plane Subsystem (FPS on behalf of Airbus Defense and Space GmbH, Ottobrunn, Germany. The FPS consists, inter alia, of two Focal Plane Assemblies (FPAs, one for the UV-VIS spectral range (305 nm … 500 nm, the second for NIR (750 nm … 775 nm. In this publication, we will present in detail the opto-mechanical laboratory set-up of the verification campaign of the Sentinel-4 Qualification Model (QM which will also be used for the upcoming Flight Model (FM verification. The test campaign consists mainly of radiometric tests performed with an integrating sphere as homogenous light source. The FPAs have mainly to be operated at 215 K ± 5 K, making it necessary to exploit a thermal vacuum chamber (TVC for the test accomplishment. This publication focuses on the challenge to remotely illuminate both Sentinel-4 detectors as well as a reference detector homogeneously over a distance of approximately 1 m from outside the TVC. Furthermore selected test analyses and results will be presented, showing that the Sentinel-4 FPS meets specifications.

Neutron capture therapy for melanoma

Energy Technology Data Exchange (ETDEWEB)

Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

1988-01-01

The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

Neutron capture therapy for melanoma

International Nuclear Information System (INIS)

Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

1988-01-01

The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs

Sentinel-3 For Land Applications

Science.gov (United States)

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

Atypical fibroxanthoma-like amelanotic malignant melanoma: A case report and literature review

Directory of Open Access Journals (Sweden)

Chao-Kai Hsu

2013-09-01

Full Text Available Atypical fibroxanthoma (AFX-like malignant melanoma is very rare. Here, we report a case of amelanotic AFX-like melanoma in a 72-year-old Taiwanese woman presenting with two separate, asymptomatic, enlarging erythematous nodules within a large hypopigmented patch on her left cheek. Histologically, both lesions showed cellular nodules in the reticular dermis separated from the overlying flattened epidermis by a zone of solar elastosis or fibrosis. The tumor consisted of sheets of atypical epithelioid cells arranged in a vague nesting pattern, as well as many atypical large or gigantic cells with one or more, large hyperchromatic, vesicular, or pleomorphic nuclei with prominent nucleoli, and moderate-to-abundant eosinophilic or foamy cytoplasm. Focal intraepidermal proliferation of atypical melanocytes with a pagetoid pattern was found only in the periphery of the main tumor. The tumor cells were moderately to strongly positive for S-100, Melan-A, and HMB-45. The pleomorphic giant cells were focally CD68-positive but CD163-negative. The patient underwent tumor excision followed by radiotherapy due to the narrow surgical margins. A sentinel lymph node biopsy revealed no metastasis of the melanoma. This case illustrates the importance of scrutinizing any subtle proliferation of atypical melanocytes in the epidermis in an AFX-like tumor in order to avoid misdiagnosis.

Learning from mistakes: errors in approaches to melanoma and the urgent need for updated national guidelines.

Science.gov (United States)

Simionescu, Olga; Blum, Andreas; Grigore, Mariana; Costache, Mariana; Avram, Alina; Testori, Alessandro

2016-09-01

The tracking and identification of errors in the detection and follow-up of melanoma are important because there is huge potential to increase awareness about the most vulnerable aspects of diagnosis and treatment, and to improve both from the perspective of healthcare economics. The present study was designed to identify where errors occur and to propose a minimum set of rules for the routine guidance of any specialist in melanoma management. This report describes the evaluation of a unique series of 33 cases in which errors applying to many steps in the diagnosis and treatment of melanoma were detected. Cases were collected at two centers in Romania, one public and one private, as part of a process of obtaining patient-requested second opinions. A total of 166 errors were identified across the 33 patients, most of which were treatment errors. The errors fell into six categories: clinical diagnostic errors (36 errors among 30 patients); primary surgical errors (31 errors among 16 patients); pathology errors (24 errors among 17 patients); sentinel lymph node biopsy errors (13 errors among 13 patients); staging errors (17 errors among 13 patients); and treatment or management errors (45 errors among 33 patients). Based on the present results, we propose that in countries lacking national guidelines, clinicians should adhere to international evidence-based guidelines for the diagnosis and treatment of melanoma. © 2015 The International Society of Dermatology.

Primary Dermal Melanoma in a Patient with a History of Multiple Malignancies: A Case Report with Molecular Characterization

Directory of Open Access Journals (Sweden)

Germana Sini

2013-07-01

Full Text Available Introduction: Primary dermal melanoma (PDM is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachronous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis, came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80-100 vs. 5-20%, respectively.

Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

Science.gov (United States)

2014-01-01

Background Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. Conclusions KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma. PMID:25022346

Examine Your Skin

Medline Plus

Full Text Available ... Suggestions Examine Your Skin Newly Diagnosed? Understanding Your Pathology Biopsy: The First Step Sentinel Node Biopsy Melanoma ... Suggestions Examine Your Skin Newly Diagnosed? Understanding Your Pathology Biopsy: The First Step Sentinel Node Biopsy Melanoma ...

Sinclair swine melanoma

International Nuclear Information System (INIS)

Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

1986-01-01

Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

Management of uveal tract melanoma: A comprehensive review

International Nuclear Information System (INIS)

Kapoor, A.; Kumar, H.S.; Beniwal, V.; Beniwal, S.; Mathur, H.

2016-01-01

Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient

High accuracy of family history of melanoma in Danish melanoma cases.

Science.gov (United States)

Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

2015-12-01

The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

Preclinical study of selective thermal neutron capture treatment of pigs having spontaneous melanoma using melanin productive activity

International Nuclear Information System (INIS)

Miyashita, Ichiro; Sawaya, Hiroshi; Nomura, Toyoichiro

1980-01-01

Four pigs having spontaneous melanoma were irradiated with 0.5 - 2 x 10 13 n/cm 2 of thermal neutron under remote anesthesia. Compounds of 10 B used in this experiment were 10 B 12 -chlorpromazine ( 10 B 12 -CPZ), 10 B-dopa, and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA), and they were injected into melanoma or regions around melanoma. After irradiation of thermal neutron, melanoma tended to reduce in four pigs, and melanoma cells in white fur and hair bulb disappeared in 3 of 4 pigs. Hematological examinations and blood chemistry tests did not show any changes in blood findings both before and after the irradiation, and white blood cell counts were within a normal range. Dermatitis following the irradiation disappeared one week later. Histological changes one month after the irradiation indicated that many melanophages feeding melanosome replaced melanoma cells, which suggested disintegration of melanoma cells. Marked effectiveness of this treatment was recognized in each pig. 10 B-BPA.HCI was injected into one pig twice, and its accumulation in melanoma and normal regions around melanoma was expressed as boron concentrations. As a result, the accumulation in melanoma (6.6 μg/g wet tissue) was 3.1 times as much as that in normal regions around melanoma (2.1 μg/g wet tissue). (Tsunoda, M.)

Automated quantification of proliferation with automated hot-spot selection in phosphohistone H3/MART1 dual-stained stage I/II melanoma.

Science.gov (United States)

Nielsen, Patricia Switten; Riber-Hansen, Rikke; Schmidt, Henrik; Steiniche, Torben

2016-04-09

Staging of melanoma includes quantification of a proliferation index, i.e., presumed melanocytic mitoses of H&E stains are counted manually in hot spots. Yet, its reproducibility and prognostic impact increases by immunohistochemical dual staining for phosphohistone H3 (PHH3) and MART1, which also may enable fully automated quantification by image analysis. To ensure manageable workloads and repeatable measurements in modern pathology, the study aimed to present an automated quantification of proliferation with automated hot-spot selection in PHH3/MART1-stained melanomas. Formalin-fixed, paraffin-embedded tissue from 153 consecutive stage I/II melanoma patients was immunohistochemically dual-stained for PHH3 and MART1. Whole slide images were captured, and the number of PHH3/MART1-positive cells was manually and automatically counted in the global tumor area and in a manually and automatically selected hot spot, i.e., a fixed 1-mm(2) square. Bland-Altman plots and hypothesis tests compared manual and automated procedures, and the Cox proportional hazards model established their prognostic impact. The mean difference between manual and automated global counts was 2.9 cells/mm(2) (P = 0.0071) and 0.23 cells per hot spot (P = 0.96) for automated counts in manually and automatically selected hot spots. In 77 % of cases, manual and automated hot spots overlapped. Fully manual hot-spot counts yielded the highest prognostic performance with an adjusted hazard ratio of 5.5 (95 % CI, 1.3-24, P = 0.024) as opposed to 1.3 (95 % CI, 0.61-2.9, P = 0.47) for automated counts with automated hot spots. The automated index and automated hot-spot selection were highly correlated to their manual counterpart, but altogether their prognostic impact was noticeably reduced. Because correct recognition of only one PHH3/MART1-positive cell seems important, extremely high sensitivity and specificity of the algorithm is required for prognostic purposes. Thus, automated

Management of uveal tract melanoma: A comprehensive review

Directory of Open Access Journals (Sweden)

Akhil Kapoor

2016-06-01

Full Text Available Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient.

Sentinel-2B image quality commissioning phase results and Sentinel2 constellation performances

Science.gov (United States)

Languille, F.; Gaudel, A.; Vidal, B.; Binet, R.; Poulain, V.; Trémas, T.

2017-09-01

In the frame of the Copernicus program of the European Commission, Sentinel-2 is a constellation of 2 satellites on a polar sun-synchronous orbit with a revisit time of 5 days (with both satellites), a high field of view - 290km, 13 spectral bands in visible and shortwave infrared, and high spatial resolution - 10m, 20m and 60m. The Sentinel-2 mission offers a global coverage over terrestrial surfaces. The satellites acquire systematically terrestrial surfaces under the same viewing conditions in order to have temporal images stacks. The first satellite was launched in June 2015 and the second in March 2017. In cooperation with the European Space Agency (ESA), the French space agency (CNES) is in charge of the image quality of the project, and so ensured the CAL/VAL commissioning phase during the months following the launch. This cooperation is also extended to routine phase as CNES supports European Space Research Institute (ESRIN) and the Sentinel-2 Mission performance Centre (MPC) for validation in geometric and radiometric image quality aspects, and in Sentinel-2 Global Reference Image (GRI) geolocation performance assessment. This paper points on geometric image quality on Sentinel-2B commissioning phase. It relates to the methods and the performances obtained, as well as the comparison between S2A and S2B. This deals with geolocation and multispectral registration. A small focus is also done on the Sentinel-2 GRI which is a set of S2A images at 10m resolution covering the whole world with a good and consistent geolocation. This ground reference leads to ensure an accurate multi-temporal registration -on refined Sentinel-2 products over GRI- which is also presented in this paper.

Copernicus POD Service: Ready for Sentinel-3

Science.gov (United States)

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

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

International Nuclear Information System (INIS)

Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

2010-01-01

Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → 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-γ and TGF-β 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.

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

Energy Technology Data Exchange (ETDEWEB)

Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

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.

Ocular Melanoma

Science.gov (United States)

... is Ocular Melanoma? Leer en Español: ¿Qué es el melanoma ocular? Written By: Daniel Porter Reviewed By: Robert H Janigian Jr MD Sep. 01, 2017 Ocular melanoma (melanoma in or around the eye) is a type of cancer that develops in the cells that produce pigment. ...

Communication about melanoma and risk reduction after melanoma diagnosis.

Science.gov (United States)

Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

2017-12-01

Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

High accuracy of family history of melanoma in Danish melanoma cases

DEFF Research Database (Denmark)

Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

2015-01-01

The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...

The Sentinel 4 focal plane subsystem

Science.gov (United States)

Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

2017-09-01

The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

Directory of Open Access Journals (Sweden)

Dursun Polat

2008-05-01

Full Text Available Abstract 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.

Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

International Nuclear Information System (INIS)

Wadabayashi, Nobutoshi; Ichihashi, Masamitsu; Honda, Chihiro; Mishima, Yutaka.

1994-01-01

Malignant melanoma occurs not only in the skin but also in ocular tissues. Ocular melanoma located superficially as in conjunctiva can be treated successfully by BNCT. In the present study, we investigated 10 B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10 B concentration in melanoma after administration of 10 B-BPA by oral or drip infusion ranged from 10.4 to 21.5 ppm. The boron concentrations in lens and vitreous body were lower than blood level, whereas higher than blood in sclera and palpebral skin. These results suggest that we can treat such a superficial melanoma lesions as conjunctival melanoma by BNCT using 10 B 1 -BPA. (author)

WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

Science.gov (United States)

Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

2018-02-07

Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

Examine Your Skin

Medline Plus

Full Text Available ... Store In Memory Melanoma Info Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ... Biopsy: The First Step Sentinel Node Biopsy Melanoma Treatment: Stages I & II Melanoma Treatment: Stage III Melanoma ...

Sentinels for snow science

Science.gov (United States)

Gascoin, S.; Grizonnet, M.; Baba, W. M.; Hagolle, O.; Fayad, A.; Mermoz, S.; Kinnard, C.; Fatima, K.; Jarlan, L.; Hanich, L.

2017-12-01

Current spaceborne sensors do not allow retrieving the snow water equivalent in mountain regions, "the most important unsolved problem in snow hydrology" (Dozier, 2016). While the NASA is operating an airborne mission to survey the SWE in the western USA, elsewhere, however, snow scientists and water managers do not have access to routine SWE measurements at the scale of a mountain range. In this presentation we suggest that the advent of the Copernicus Earth Observation programme opens new perspectives to address this issue in mountain regions worldwide. The Sentinel-2 mission will provide global-scale multispectral observations at 20 m resolution every 5-days (cloud permitting). The Sentinel-1 mission is already imaging the global land surface with a C-band radar at 10 m resolution every 6 days. These observations are unprecedented in terms of spatial and temporal resolution. However, the nature of the observation (radiometry, wavelength) is in the continuity of previous and ongoing missions. As a result, it is relatively straightforward to re-use algorithms that were developed by the remote sensing community over the last decades. For instance, Sentinel-2 data can be used to derive maps of the snow cover extent from the normalized difference snow index, which was initially proposed for Landsat. In addition, the 5-days repeat cycle allows the application of gap-filling algorithms, which were developed for MODIS based on the temporal dimension. The Sentinel-1 data can be used to detect the wet snow cover and track melting areas as proposed for ERS in the early 1990's. Eventually, we show an example where Sentinel-2-like data improved the simulation of the SWE in the data-scarce region of the High Atlas in Morocco through assimilation in a distributed snowpack model. We encourage snow scientists to embrace Sentinel-1 and Sentinel-2 data to enhance our knowledge on the snow cover dynamics in mountain regions.

PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells.

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Eastham, Linda L; Mills, Caroline N; Niles, Richard M

2008-06-01

We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.

Variants at the 9p21 locus and melanoma risk

International Nuclear Information System (INIS)

Maccioni, Livia; Rachakonda, Panduranga Sivaramakrishna; Bermejo, Justo Lorenzo; Planelles, Dolores; Requena, Celia; Hemminki, Kari; Nagore, Eduardo; Kumar, Rajiv

2013-01-01

The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS). In the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region. All the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3’ UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A–allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54). Our data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes

Role of sentinel lymph node biopsy in oral cancer.

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Calabrese, L; Bruschini, R; Ansarin, M; Giugliano, G; De Cicco, C; Ionna, F; Paganelli, G; Maffini, F; Werner, J A; Soutar, D

2006-12-01

Squamous cell carcinoma of the oral cavity represents about 2% of all malignant neoplasms and 47% of those developing in the head and neck area. The tongue is the most common site involved, and this incidence is increasing mainly in young people, possibly related to human papilloma virus infections. Prognosis depends on the stage: the 5-year survival rate of tongue squamous cell carcinoma, whatever the T stage, is 73% in pN0 cases, 40% in patients with positive nodes without extracapsular spread (pNl ECS-), and 29% when nodes are metastatic with extracapsular spread (pNl ECS+: p > or = 0.0001). Nodal micrometastases (cN0 pN1) are found in up to 50% of cN0 tongue squamous cell carcinoma patients operated on the neck. At present, no clinical, imaging staging modalities or biological markers are available to diagnose nodal micrometastases. The sentinel node biopsy has been tested since 1996 in order to find a solution to this problem. The sentinel node is the first node reached by the lymphatic stream, assuming an orderly and sequential drainage from the tumour site, and should be predictive of the nodal stage. According to the literature, sentinel node biopsy is a reliable technique in selected cN0 cases, but the procedure is still experimental and should not be performed outside validation trials. Successful application of sentinel node biopsy in the head and neck region requires surgical experience and specific technical devices, including pre-operative lymphoscintigraphy and intra-operative gamma-probe. Moreover, dynamic lymphoscintigraphy seems to be able to show the lymphatic stream from the primary tumour and could allow a selective neck dissection to be tailored thus reducing the related morbidity.

Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

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Jinah Kim

Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

Discovering Sentinel Rules for Business Intelligence

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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.

Independent System Calibration of Sentinel-1B

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Marco Schwerdt

2017-05-01

Full Text Available Sentinel-1B is the second of two C-Band Synthetic Aperture Radar (SAR satellites of the Sentinel-1 mission, launched in April 2016—two years after the launch of the first satellite, Sentinel-1A. In addition to the commissioning of Sentinel-1B executed by the European Space Agency (ESA, an independent system calibration was performed by the German Aerospace Center (DLR on behalf of ESA. Based on an efficient calibration strategy and the different calibration procedures already developed and applied for Sentinel-1A, extensive measurement campaigns were executed by initializing and aligning DLR’s reference targets deployed on the ground. This paper describes the different activities performed by DLR during the Sentinel-1B commissioning phase and presents the results derived from the analysis and the evaluation of a multitude of data takes and measurements.

SENTINEL-1 and SENTINEL-2 Data Fusion for Wetlands Mapping: Balikdami, Turkey

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Kaplan, G.; Avdan, U.

2018-04-01

Wetlands provide a number of environmental and socio-economic benefits such as their ability to store floodwaters and improve water quality, providing habitats for wildlife and supporting biodiversity, as well as aesthetic values. Remote sensing technology has proven to be a useful and frequent application in monitoring and mapping wetlands. Combining optical and microwave satellite data can help with mapping and monitoring the biophysical characteristics of wetlands and wetlands` vegetation. Also, fusing radar and optical remote sensing data can increase the wetland classification accuracy. In this paper, data from the fine spatial resolution optical satellite, Sentinel-2 and the Synthetic Aperture Radar Satellite, Sentinel-1, were fused for mapping wetlands. Both Sentinel-1 and Sentinel-2 images were pre-processed. After the pre-processing, vegetation indices were calculated using the Sentinel-2 bands and the results were included in the fusion data set. For the classification of the fused data, three different classification approaches were used and compared. The results showed significant improvement in the wetland classification using both multispectral and microwave data. Also, the presence of the red edge bands and the vegetation indices used in the data set showed significant improvement in the discrimination between wetlands and other vegetated areas. The statistical results of the fusion of the optical and radar data showed high wetland mapping accuracy, showing an overall classification accuracy of approximately 90 % in the object-based classification method. For future research, we recommend multi-temporal image use, terrain data collection, as well as a comparison of the used method with the traditional image fusion techniques.

The hidden sentinel node in breast cancer

International Nuclear Information System (INIS)

Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R.; Valdes Olmos, R.A.; Hoefnagel, C.A.

2002-01-01

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% (χ 2 , P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

The hidden sentinel node in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R. [Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Valdes Olmos, R.A.; Hoefnagel, C.A. [Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands)

2002-03-01

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% ({chi}{sup 2}, P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

[Role of sentinel lymph nodes and lymphatic mapping of colorectal cancer].

Science.gov (United States)

Ivanov, K; Kolev, N; Ignatov, V; Temelkov, T; Madzhov, R

2005-01-01

The accuracy of staging of colorectal cancer is dependable of number of lymph nodes, colected and investegated from the pathologist. Moreover 50% of newfounded cases with colorectal cancer are diagnosed as I or II stage of the desease. Between 15% and 20% of these patients develop regional or distant metastases around 5 years after the examination, despite of the radical surgery. This may be due to pathological "understaging" (decrease of the stage), becouse of missed micrometastases, which size often is smaller than 5 mm. High accurate and specific pathologoanatomical methods for "ultrastaging" are cost-expensive, therefore their selective application to labeled sentinel lymph nodes has a economical benefit and saves a time. Moreover it is decreasing the understaging effect, assosiated with convectional pathologoanatomical investigaton. In the future, the technical progress will develop the intensive competiton between the sentinel lymph node mapping and the improved imaging diagnostic techniques as flurodeoxyglucose (18FDG), positron emision tomography (PET), or the other molecular imaging techniques. Unfortunately, the limited spatial resolution of these techniques, do not allow to be used for tumor staging as sentinel lymph node techniques. Therefore the sentinel lymphnode mapping become the choice of the lymphnode staging technique.

Management of advanced melanoma

International Nuclear Information System (INIS)

Nathanson, L.

1986-01-01

This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma

Optimizing the Targeting of Mouse Parvovirus 1 to Murine Melanoma Selects for Recombinant Genomes and Novel Mutations in the Viral Capsid Gene

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Matthew Marr

2018-01-01

Full Text Available Combining virus-enhanced immunogenicity with direct delivery of immunomodulatory molecules would represent a novel treatment modality for melanoma, and would require development of new viral vectors capable of targeting melanoma cells preferentially. Here we explore the use of rodent protoparvoviruses targeting cells of the murine melanoma model B16F10. An uncloned stock of mouse parvovirus 1 (MPV1 showed some efficacy, which was substantially enhanced following serial passage in the target cell. Molecular cloning of the genes of both starter and selected virus pools revealed considerable sequence diversity. Chimera analysis mapped the majority of the improved infectivity to the product of the major coat protein gene, VP2, in which linked blocks of amino acid changes and one or other of two apparently spontaneous mutations were selected. Intragenic chimeras showed that these represented separable components, both contributing to enhanced infection. Comparison of biochemical parameters of infection by clonal viruses indicated that the enhancement due to changes in VP2 operates after the virus has bound to the cell surface and penetrated into the cell. Construction of an in silico homology model for MPV1 allowed placement of these changes within the capsid shell, and revealed aspects of the capsid involved in infection initiation that had not been previously recognized.

Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

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Guillaume Sarrabayrouse

Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

Pregnancy and melanoma.

Science.gov (United States)

Driscoll, Marcia S; Martires, Kathryn; Bieber, Amy Kalowitz; Pomeranz, Miriam Keltz; Grant-Kels, Jane M; Stein, Jennifer A

2016-10-01

Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Implementing Sentinels in the TARGIT BI Suite

DEFF Research Database (Denmark)

Middelfart, Morten; Pedersen, Torben Bach

2011-01-01

This paper describes the implementation of socalled sentinels in the TARGIT BI Suite. Sentinels are a novel type of rules that can warn a user if one or more measure changes in a multi-dimensional data cube are expected to cause a change to another measure critical to the user. Sentinels notify u...... pattern mining or correlation techniques. We demonstrate, through extensive experiments, that mining and usage of sentinels is feasible with good performance for the typical users on a real, operational data warehouse....

Sentinel lymph node biopsy in oral cancer

DEFF Research Database (Denmark)

Thomsen, Jørn Bo; Sørensen, Jens Ahm; Grupe, Peter

2005-01-01

PURPOSE: To validate lymphatic mapping combined with sentinel lymph node biopsy as a staging procedure, and to evaluate the possible clinical implications of added oblique lymphoscintigraphy and/or tomography and test the intra- and interobserver reproducibility of lymphoscintigraphy. MATERIAL......: Eleven (28%) patients were upstaged. The sentinel lymph node identification rate was 97.5%. Sentinel lymph node biopsy significantly differentiated between patients with or without lymph node metastasis (P = 0.001). Lymphatic mapping revealed 124 hotspots and 144 hot lymph nodes were removed by sentinel...

Is intra-operative gamma probe detection really necessary for inguinal sentinel lymph node biopsy?

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Oliveira Filho, Renato Santos de; Santos, Ivan Dunshe Abranches Oliveira; Ferreira, Lydia Massako; Almeida, Fernando Augusto de; Simoes, Milvia Maria; Enokihara, Silvia; Barbieri, Antonio; Tovo Filho, Reinaldo [Universidade Federal de Sao Paulo (UNIFESP - EPM), SP (Brazil). Disciplina de Cirurgia Plastica

2000-11-01

Sentinel node (SN) biopsy has changed the surgical treatment of malignant melanoma. The literature has emphasized the importance of gamma probe detection (GPD) of the SN. Our objective was to evaluate the efficacy of patent blue dye (PBD) and GPD for SN biopsy in different lymphatic basins. Patients with cutaneous malignant melanoma in stages I and II were submitted to biopsy of the SN, identified by PBD and GPD, as part of a research project. Patients were seen at Hospital Sao Paulo by a multidisciplinary group (Plastic Surgery Tumor Branch, Nuclear Medicine and Pathology). 64 patients with localized malignant melanoma were studied. The median age was 46.5 years. The primary tumor was located in the neck, trunk or extremities. Preoperative lymphoscintigraphy, lymphatic mapping with PBD and intraoperative GPD were performed on all patients. The SN was examined by conventional and immuno-histological staining. If the SN was not found or contained micrometastases, only complete lymphadenectomy was performed. The SN was identified by PBD if it was blue-stained, and by GPD if demonstrated activity five times greater than the adipose tissue of the neighborhood. Seventy lymphatic basins were explored. Lymphoscintigraphy showed ambiguous drainage em 7 patients. GPD identified the SN in 68 basins (97%) and PBD in 53 (76%). PBD and GPD identified SN in 100% of the inguinal basins. For the remaining basins both techniques were complementary. A metastatic SN was found in 10 basins. Three patients with negative SN had recurrence (median follow-up=11 months). Although both GPD and PBD are useful and complementary, PBD alone identified the SN in 100% of the inguinal lymphatic basins. (author)

Is intra-operative gamma probe detection really necessary for inguinal sentinel lymph node biopsy?

International Nuclear Information System (INIS)

Oliveira Filho, Renato Santos de; Santos, Ivan Dunshe Abranches Oliveira; Ferreira, Lydia Massako; Almeida, Fernando Augusto de; Simoes, Milvia Maria; Enokihara, Silvia; Barbieri, Antonio; Tovo Filho, Reinaldo

2000-01-01

Sentinel node (SN) biopsy has changed the surgical treatment of malignant melanoma. The literature has emphasized the importance of gamma probe detection (GPD) of the SN. Our objective was to evaluate the efficacy of patent blue dye (PBD) and GPD for SN biopsy in different lymphatic basins. Patients with cutaneous malignant melanoma in stages I and II were submitted to biopsy of the SN, identified by PBD and GPD, as part of a research project. Patients were seen at Hospital Sao Paulo by a multidisciplinary group (Plastic Surgery Tumor Branch, Nuclear Medicine and Pathology). 64 patients with localized malignant melanoma were studied. The median age was 46.5 years. The primary tumor was located in the neck, trunk or extremities. Preoperative lymphoscintigraphy, lymphatic mapping with PBD and intraoperative GPD were performed on all patients. The SN was examined by conventional and immuno-histological staining. If the SN was not found or contained micrometastases, only complete lymphadenectomy was performed. The SN was identified by PBD if it was blue-stained, and by GPD if demonstrated activity five times greater than the adipose tissue of the neighborhood. Seventy lymphatic basins were explored. Lymphoscintigraphy showed ambiguous drainage em 7 patients. GPD identified the SN in 68 basins (97%) and PBD in 53 (76%). PBD and GPD identified SN in 100% of the inguinal basins. For the remaining basins both techniques were complementary. A metastatic SN was found in 10 basins. Three patients with negative SN had recurrence (median follow-up=11 months). Although both GPD and PBD are useful and complementary, PBD alone identified the SN in 100% of the inguinal lymphatic basins. (author)

Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma--Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3.

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Jennifer M Atkinson

Full Text Available It has previously been observed that a loss of β-catenin expression occurs with melanoma progression and that nuclear β-catenin levels are inversely proportional to cellular proliferation, suggesting that activation of the Wnt/β-catenin pathway may provide benefit for melanoma patients. In order to further probe this concept we tested LY2090314, a potent and selective small-molecule inhibitor with activity against GSK3α and GSK3β isoforms. In a panel of melanoma cell lines, nM concentrations of LY2090314 stimulated TCF/LEF TOPFlash reporter activity, stabilized β-catenin and elevated the expression of Axin2, a Wnt responsive gene and marker of pathway activation. Cytotoxicity assays revealed that melanoma cell lines are very sensitive to LY2090314 in vitro (IC50 ~10 nM after 72hr of treatment in contrast to other solid tumor cell lines (IC50 >10 uM as evidenced by caspase activation and PARP cleavage. Cell lines harboring mutant B-RAF or N-RAS were equally sensitive to LY2090314 as were those with acquired resistance to the BRAF inhibitor Vemurafenib. shRNA studies demonstrated that β-catenin stabilization is required for apoptosis following treatment with the GSK3 inhibitor since the sensitivity of melanoma cell lines to LY290314 could be overcome by β-catenin knockdown. We further demonstrate that in vivo, LY2090314 elevates Axin2 gene expression after a single dose and produces tumor growth delay in A375 melanoma xenografts with repeat dosing. The activity of LY2090314 in preclinical models suggests that the role of Wnt activators for the treatment of melanoma should be further explored.

Early melanoma diagnosis with mobile imaging.

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Do, Thanh-Toan; Zhou, Yiren; Zheng, Haitian; Cheung, Ngai-Man; Koh, Dawn

2014-01-01

We research a mobile imaging system for early diagnosis of melanoma. Different from previous work, we focus on smartphone-captured images, and propose a detection system that runs entirely on the smartphone. Smartphone-captured images taken under loosely-controlled conditions introduce new challenges for melanoma detection, while processing performed on the smartphone is subject to computation and memory constraints. To address these challenges, we propose to localize the skin lesion by combining fast skin detection and fusion of two fast segmentation results. We propose new features to capture color variation and border irregularity which are useful for smartphone-captured images. We also propose a new feature selection criterion to select a small set of good features used in the final lightweight system. Our evaluation confirms the effectiveness of proposed algorithms and features. In addition, we present our system prototype which computes selected visual features from a user-captured skin lesion image, and analyzes them to estimate the likelihood of malignance, all on an off-the-shelf smartphone.

Detection of sentinel nodes with radiopharmaceuticals

International Nuclear Information System (INIS)

Yokoyama, Kunihiko; Michigishi, Takatoshi; Kinuya, Seigo; Konishi, Shota; Nakajima, Kenichi; Tonami, Norihisa

2000-01-01

Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer ( 99m Tc-labeled albumin, 99m Tc-labeled tin colloid, and 99m Tc-labeled phytic acid) and founded that the detection rate was lowest with

The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?

Science.gov (United States)

Nissan, Moriah H; Solit, David B

2011-12-01

Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.

Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

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Kutushov, M; Gorelik, O

2013-01-01

Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

Examine Your Skin

Medline Plus

Full Text Available ... Biopsy: The First Step Sentinel Node Biopsy Melanoma Treatment: Stages I & II Melanoma Treatment: Stage III Melanoma Treatment: Stage IV Finding the Right Doctor Glossary of ...

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): Novel gene therapeutic for metastatic melanoma

International Nuclear Information System (INIS)

Fisher, Paul B.; Sarkar, Devanand; Lebedeva, Irina V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su Zaozhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

2007-01-01

A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed 'differentiation therapy of cancer' with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display elevated expression in normal melanocytes and nevi with progressive loss of expression as a consequence of melanoma development and progression to metastasis. Based on structure, biochemical properties and chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a member of the expanding IL-10 family of cytokines. In vitro cell culture and in vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell death (apoptosis) in multiple human cancers (including melanomas), without harming normal cells, and promotes profound anti-tumor activity in nude mice containing human tumor xenografts. Based on these remarkable properties, a Phase I clinical trial was conducted to test the safety of administration of mda-7/IL-24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and to promote significant clinical activity, particularly in the context of patients with metastatic melanoma. These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the 'bench to the bedside.'

Verification of the Sentinel-4 focal plane subsystem

Science.gov (United States)

Williges, Christian; Uhlig, Mathias; Hilbert, Stefan; Rossmann, Hannes; Buchwinkler, Kevin; Babben, Steffen; Sebastian, Ilse; Hohn, Rüdiger; Reulke, Ralf

2017-09-01

The Sentinel-4 payload is a multi-spectral camera system, designed to monitor atmospheric conditions over Europe from a geostationary orbit. The German Aerospace Center, DLR Berlin, conducted the verification campaign of the Focal Plane Subsystem (FPS) during the second half of 2016. The FPS consists, of two Focal Plane Assemblies (FPAs), two Front End Electronics (FEEs), one Front End Support Electronic (FSE) and one Instrument Control Unit (ICU). The FPAs are designed for two spectral ranges: UV-VIS (305 nm - 500 nm) and NIR (750 nm - 775 nm). In this publication, we will present in detail the set-up of the verification campaign of the Sentinel-4 Qualification Model (QM). This set up will also be used for the upcoming Flight Model (FM) verification, planned for early 2018. The FPAs have to be operated at 215 K +/- 5 K, making it necessary to exploit a thermal vacuum chamber (TVC) for the test accomplishment. The test campaign consists mainly of radiometric tests. This publication focuses on the challenge to remotely illuminate both Sentinel-4 detectors as well as a reference detector homogeneously over a distance of approximately 1 m from outside the TVC. Selected test analyses and results will be presented.

BioSentinel

Data.gov (United States)

National Aeronautics and Space Administration — The Advanced Exploration Systems' (AES) BioSentinel project will develop, prototype, integrate, test, and prepare for the first spaceflight mission of a broadly...

Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

Directory of Open Access Journals (Sweden)

Sivan Sapoznik

2012-01-01

Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

Canonical analysis of sentinel-1 radar and sentinel-2 optical data

DEFF Research Database (Denmark)

Nielsen, Allan Aasbjerg; Larsen, Rasmus

2017-01-01

This paper gives results from joint analyses of dual polarimety synthetic aperture radar data from the Sentinel-1 mission and optical data from the Sentinel-2 mission. The analyses are carried out by means of traditional canonical correlation analysis (CCA) and canonical information analysis (CIA......). Where CCA is based on maximising correlation between linear combinations of the two data sets, CIA maximises mutual information between the two. CIA is a conceptually more pleasing method for the analysis of data with very different modalities such as radar and optical data. Although a little...

Sentinel Network

Science.gov (United States)

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.

High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node

DEFF Research Database (Denmark)

Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie

2012-01-01

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ...

Sentinel node biopsy in penile cancer

DEFF Research Database (Denmark)

Jakobsen, J. K.; Krarup, K. P.; Sommer, P.

2015-01-01

INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow-up. In th......INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow...... died from complications. CONCLUSIONS: To our knowledge, this is the first complete national study on sentinel node biopsy. Penile cancer sentinel node biopsy with a close follow-up is a reliable lymph node staging and has few complications in a national multicentre setting. Inguinal lymph node...

A word of caution: do not wake sleeping dogs; micrometastases of melanoma suddenly grew after progesterone treatment

International Nuclear Information System (INIS)

Mordoh, Jose; Tapia, Ivana Jaqueline; Barrio, Maria Marcela

2013-01-01

Hormonal treatment might affect the immune response to tumor antigens induced in cancer patients who are being vaccinated. A 33 years-old woman was diagnosed with cutaneous melanoma in May 2009. Her melanoma was located in the intermammary sulcus, had a Breslow thickness of 4 mm, a Clark’s level IV, it was ulcerated and highly melanotic. The bilateral sentinel node biopsy was negative. She entered into a randomized Phase II/III clinical study comparing a vaccine composed of irradiated melanoma cells plus BCG plus GM-CSF versus IFN-alpha 2b and she was assigned to the vaccine arm. During the two years treatment she remained disease-free; the final CAT scan being performed in August 2011. Between November and December 2011, her gynecologist treated her with three cycles of 200 mg progesterone/day for ten days, every two weeks, for ovary dysfunction. In November 2011 the patient returned to the Hospital for clinical and imaging evaluation and no evidence of disease was found. At the next visit in March 2012 an ultrasound revealed multiple, large metastases in the liver. A CAT scan confirmed the presence of liver, adrenal glands and spleen metastases. A needle biopsy of a liver lesion revealed metastatic melanoma of similar characteristics to the original tumor. We suggest that progesterone treatment triggered proliferation of so far dormant micrometastases that were controlled during CSF470 vaccine treatment. The use of progesterone in patients with melanoma that are under immunological treatments should be carefully considered, since progesterone could modify the balance of pro-inflammatory and Th1 functions to a regulatory and anti-inflammatory profile of the immune system that could have an impact in tumor progression

Primary malignant melanoma

Directory of Open Access Journals (Sweden)

A. Ferhat Mısır

2016-04-01

Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival

DEFF Research Database (Denmark)

Riber-Hansen, Rikke; Nyengaard, Jens R; Hamilton-Dutoit, Stephen J

2011-01-01

statistics (categorical data). In addition, disease-free and melanoma-specific survivals were calculated. Mean metastatic volume per patient was 10.6 mm(3) (median 0.05 mm(3); range 0.0001-621.3 mm(3)) and 9.62 mm(3) (median 0.05 mm(3); range 0.00001-564.3 mm(3)) with manual and digital measurement......, respectively. The Bland-Altman plot showed an even distribution of the differences, and the kappa statistic was 0.84. In multivariate analysis, both manual and digital metastasis volume measurements were independent progression markers when corrected for primary tumour thickness [manual: hazard ratio (HR): 1...

Selective thermal neutron capture therapy of malignant melanoma using melanogenesis-seeking 10B-compounds

International Nuclear Information System (INIS)

Mishima, Yutaka

1991-11-01

This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

Sentinel surveillance of soil-transmitted helminthiasis in preschool-aged and school-aged children in selected local government units in the Philippines: follow-up assessment.

Science.gov (United States)

Belizario, Vicente Y; Totañes, Francis Isidore G; de Leon, Winifreda U; Ciro, Raezelle Nadine T; Lumampao, Yvonne F

2015-03-01

This study was a follow-up to the baseline nationwide survey of soil-transmitted helminth (STH) infections in preschool-aged children in the Philippines and in school-aged children in selected sentinel sites to assess the Integrated Helminth Control Program of the Department of Health. The objective of the study was to describe the current prevalence and intensity of STH infections in preschool-aged and school-aged children in 6 sentinel provinces and to compare these data with baseline findings. A cross-sectional study design was used to determine the prevalence and intensity of STH infections. Parasitological assessment involved the examination of stool samples by the Kato-Katz method. Although parasitological parameters in the 2 age groups at follow-up showed significant reductions from the baseline, these parameters remained high despite 3 years of mass drug administration (MDA). Efforts toward achieving high MDA coverage rates, provision of clean water, environmental sanitation, and promotion of hygiene practices must be prioritized. © 2013 APJPH.

Primary ovarian malignant melanoma

Directory of Open Access Journals (Sweden)

Kostov Miloš

2010-01-01

Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

Burden of Melanoma

NARCIS (Netherlands)

C. Holterhues (Cynthia)

2011-01-01

markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

Lymphatic mapping inguinal and sentinel lymph node biopsy in anal canal cancers to avoid prophylactic inguinal irradiation; Le marquage lymphatique et la biopsie du ganglion sentinelle inguinal dans les cancers du canal anal pour eviter l'irradiation inguinale prophylactique

Energy Technology Data Exchange (ETDEWEB)

Bobin, J.Y. [Centre Hospitalier Universitaire Lyon-Sud, Service de Chirurgie Oncoloque, 69 - Pierre-Benite (France); Gerard, J.P.; Chapet, O.; Romestaing, P. [Centre Hospitalier Universitaire Lyon-Sud, Dept. de Radiotherapie et Oncologie, 69 - Pierre-Benite (France); Isaac, S. [Centre Hospitalier Universitaire Lyon-Sud, Dept. d' Anatomopathologie, 69 - Pierre-Benite (France)

2003-11-01

Thirty-five patients with clinically N0 cancers of the canal anal, 33 epidermoid carcinomas et 2 melanomas were histologically staged with inguinal sentinel lymphode biopsy (ISN). With the combined technique, blue dye and radiocolloid the ISN was identified in 100 % of the cases. The ISN was invaded in 7 cases/33 for epidermoid tumors and 2/2 for melanomas. After 18 months of follow-up, no inguinal recurrence could be seen in ISN pN0 cases. In conclusion, ISN biopsy is a reliable procedure to stage anal,, canal cancers. It should prevent unnecessary prophylactic inguinal irradiation for pN0 ISN. Inguinal irradiation is only indicated in pN1 ISN. (author)

Umbilical melanoma: case report and review of anatomical and therapeutic aspects

International Nuclear Information System (INIS)

Brandao, Eduardo Miranda; Gomes, Alexandre Santos de Almeida; Ribeiro, Edilana Sa; Vilaca, Thiago Guimaraes; Macedo, Francisco Igor Bulcao de; Santos, Rogerio Luiz dos; Pernambuco Univ., Recife, PE

2005-01-01

, skin, subcutaneous cellular tissue and peritoneum. Continuity with the round ligament and the urachus allows dissemination through those structures. Such facts justify the difficulty faced while establishing vertical or horizontal growth of Melanomas, as well as using Breslow measurements in that area. In addition to that, the lymphatic drainage, as a function of the classical definition of the Sappey Line, can be directed towards the axillary or inguinal areas, thus making it essential to carry out lymphoscintillography and lymphatic mapping. Conclusion: Umbilical melanoma is a rare occurrence. Due to its embryological and anatomical peculiarities, its clinical histopathological evaluation entails difficulties and demands knowledge of local lymphatic drainage aspects in order to determine its pattern of dissemination. Lymphoscintillography and lymphatic mapping are imposed with sentinel lymph node research as exclusive means for identifying the routes of lymphatic drainage. In this case, we were able to define the drainage for the left axilla and to recover the corresponding lymph nodes, so that histopathological and immunohistochemical exams could be carried out. (author)

[Japanese sentinel project and contribution of laboratory medicine].

Science.gov (United States)

Nakashima, Naoki

2013-06-01

Ordinary passive surveillance (generally spontaneous reporting) of adverse effects of medical products is not enough to manage medical risks/safety. The Japanese government, following the "sentinel initiative" by the US government, started the "Japanese sentinel project" as an active surveillance of medical products with the Pharmaceuticals and Medical Devices Agency(PMDA). Using entire prescription data in the hospital information system, data on laboratory examinations, diagnosis, and therapy specific to an adverse effect are checked by detecting differences between before and after prescription of a specific medical product to extract adverse effects and calculate their correct frequency in the surveillance. The project uses standard masters and protocols to analyze data among medial institutes by installation of the SS-MIX standard storage system. Ten hospitals were selected in 2011 to join the project, and the entire system and network will be implemented in those hospitals and PMDA until 2013 fiscal year. JLAC10 is used in the project as the laboratory examination code of the Japanese Society of Laboratory Medicine. Many incorrect coding and ambiguous coding rules were found by voluntary surveillance of 6 of the 10 hospitals in the project. Thus, the Council on Standardized Master Operation of Clinical Laboratory Examinations will launch in 2013 to improve and maintain JLAC10, which is essential not only for the Japanese sentinel project but also for data utilization by many other projects.

Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.

Directory of Open Access Journals (Sweden)

Charlotte Welinder

Full Text Available Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

Science.gov (United States)

Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

2014-01-01

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Surgery and radiotherapy in the treatment of cutaneous melanoma

DEFF Research Database (Denmark)

Testori, A; Rutkowski, P; Marsden, J

2009-01-01

on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases....

Canine oral melanoma.

Science.gov (United States)

Bergman, Philip J

2007-05-01

Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

Regional control of melanoma neck node metastasis after selective neck dissection with or without adjuvant radiotherapy

NARCIS (Netherlands)

Hamming-Vrieze, Olga; Balm, Alfons J. M.; Heemsbergen, Wilma D.; Hooft van Huysduynen, Thijs; Rasch, Coen R. N.

2009-01-01

OBJECTIVE: To examine the effect of adjuvant radiotherapy on regional control of melanoma neck node metastasis. DESIGN: A single-institution retrospective study. SETTING: Tertiary care cancer center. PATIENTS: The study included 64 patients with melanoma neck node metastasis who were treated with

Influence of previous breast surgery in sentinel lymph node biopsy in patients with breast cancer.

Science.gov (United States)

López-Prior, V; Díaz-Expósito, R; Casáns Tormo, I

The aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection. A retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables. The overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II). Sentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Value of sonomammography utilizing color Doppler technique in qualification of breast cancer patients for sentinel node identification

International Nuclear Information System (INIS)

Basta, P.; Wadowska-Jaszczynska, K.; Krysztopowicz, W.; Przybylska, P.; Wisniowski, Z.

2007-01-01

Sentinel node identification has become a standard procedure in the management of breast cancer. This procedure requires involvement of a multidisciplinary team and is rather costly. Ultrasonography (USG) of axillary lymph nodes is a method that gives hope for improving the quality of qualification of patients for the procedure. Eighty patients with grade I and II breast cancers underwent sentinel node identification followed by axillary lymphadenectomy. Pre-operative ultrasonography was employed to assess axillary lymph nodes, using the morphological and vascular characteristics as predictors of the presence of lymph node metastases. Sensitivity of sentinel node identification reached 89.3%, specificity - 100%, positive predictive value - 100%, negative predictive value - 93.5%, percentage of false negative results - 10.7%. Sensitivity of USG reached 68.75 %, and specificity - 70.31%. In the group of patients in whom the sentinel node was identified, the sensitivity of the method was 69.23 %, and specificity - 72.41%. Preoperative axillary lymph node ultrasonography in breast cancer patients, utilizing color Doppler technique, allows better selection of patients for sentinel node identification procedure. (author)

Clinical value of sentinel lymph node diagnostics in head and neck cancer; Klinische Wertigkeit der Sentinel-Lymph-Node-Diagnostik bei Kopf-Hals-Tumoren

Energy Technology Data Exchange (ETDEWEB)

Kampen, W.U. [Klinik fuer Nuklearmedizin am Universitaetsklinikum Schleswig-Holstein, Campus Kiel (Germany); Hoeft, S. [Klinik fuer Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie am Universitaetsklinikum Schleswig-Holstein, Campus Kiel (Germany); Maune, S. [Praxis fuer Hals-Nasen-Ohrenheilkunde, Kiel (Germany)

2006-06-15

The concept of the so-called sentinel lymph node (SLN), being the first node draining a malignant tumor and thus carrying the highest risk of metastatic disease, is already frequently applied in patients suffering from malignant melanoma and breast cancer. It is the aim of this concept, to reduce postoperative morbidity by omitting a conventional lymph node dissection if the SLN is proven to be free of any tumor cells. First clinical studies showed promising results also in patients with head and neck cancer. However, both the anatomical localization of the primary tumor and the very complex lymphatic, frequently bilateral drainage pattern may lead to significant methodological problems. Besides a skilful intraoperative usage of the gamma probe, the precise preoperative staging of the respective patient for determination of the N0 status and the assiduous histopathological analysis of the excised SLN are extremely important to reach a maximum of sensitivity in this clinical setting. This paper summarizes the data published on the SLN concept in patients with head and neck cancer, describes the several methodological aspects of labeling the SLN with radiocolloides and reviews the today's impact of the SLN method in clinical routine. (orig.)

Discovering Sentinel Rules for Business Intelligence

DEFF Research Database (Denmark)

Middelfart, Morten; Pedersen, Torben Bach

2009-01-01

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 month...

Melanoma during pregnancy

DEFF Research Database (Denmark)

de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

2017-01-01

The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

Microculture-based chemosensitivity testing: a feasibility study comparing freshly explanted human melanoma cells with human melanoma cell lines.

Science.gov (United States)

Marshall, E S; Finlay, G J; Matthews, J H; Shaw, J H; Nixon, J; Baguley, B C

1992-03-04

The culture of cancer cells has many applications in chemosensitivity testing and new drug development. Our goal was to adapt simple semiautomated microculture methods for testing the chemosensitivity of melanoma cells freshly recovered from patients' tumors. Cells were cultured on a substrate of agarose and exposed continuously to cytotoxic drugs, the effects of which were measured by determining the uptake of [3H]thymidine 4-7 days later. Immunocytochemical staining of cells cultured with 5-bromo-2'-deoxyuridine demonstrated that tumor cells were responsible for the measured thymidine incorporation. The effects of cytotoxic drugs were calculated as logarithmic 50% inhibitory concentrations and expressed as divergences from the mean in a log-mean graph. The inhibitory effects of amsacrine, etoposide, doxorubicin, cisplatin, mitomycin C, and fluorouracil were tested. Tumors differed widely in their sensitivity to these drugs, although sensitivity to the three topoisomerase-II-directed agents was highly correlated. Cells from two non-neoplastic hematopoietic progenitor cell lines (FT and 32D) showed chemosensitivity patterns distinct from those in the melanoma cells, indicating tissue selectivity. Two established melanoma cell lines, MM-96 and FME, were tested under the same conditions and showed sensitivity typical of at least some fresh specimens. These results support the validity of melanoma cell lines as models of freshly resected melanoma cells. If successfully applied to other tumor types, such semiautomated approaches could find wide application in routine hospital laboratories for the chemosensitivity testing of patients' tumor cells.

Land use classification from Sentinel-2 imagery

OpenAIRE

Borràs, J.; Delegido, J.; Pezzola, A.; Pereira, M.; Morassi, G.; Camps-Valls, G.

2017-01-01

[EN] Sentinel-2 (S2), a new ESA satellite for Earth observation, accounts with 13 bands which provide high-quality radiometric images with an excellent spatial resolution (10 and 20 m) ideal for classification purposes. In this paper, two objectives have been addressed: to determine the best classification method for S2, and to quantify its improve-ment with respect to the SPOT operational mission. To do so, four classifiers (LDA, RF, Decision Trees, K-NN) have been selected and applied to tw...

High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node.

Science.gov (United States)

Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie; Ejlertsen, Bent; Balslev, Eva; Kroman, Niels

2012-11-15

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases. Copyright © 2012 UICC.

Sentinel-3 SAR Altimetry Toolbox

Science.gov (United States)

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

Advances in Immunotherapy for Melanoma: A Comprehensive Review

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Carmen Rodríguez-Cerdeira

2017-01-01

Full Text Available Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

AKT1 as the PageRank hub gene is associated with melanoma and its functional annotation is highly related to the estrogen signaling pathway that may regulate the growth of melanoma.

Science.gov (United States)

Zhao, Jingjing; Zeng, Xue; Song, Ping; Wu, Xiaohong; Shi, Hongbo

2016-10-01

In order to detect the disease-associated genes and their gene interaction function and association with melanoma mechanisms, we identified a total of 1,310 differentially expressed genes (DEGs) from the Gene Expression Omnibus database GSE3189 with FDR 2 using the R package. After constructing the gene interaction network by STRING with the selected DEGs, we applied a statistical approach to identify the topological hub genes with PageRank score. Forty-four genes were identified in this network and AKT1 was selected as the most important hub gene. The AKT1 gene encodes a serine‑threonine protein kinase (AKT). High expression of AKT is involved in the resistance of cell apoptosis as well as adaptive resistance to treatment in melanoma. Our results indicated that AKT1 with a higher expression in melanoma showed enriched binding sites in the negative regulation of response to external stimulus, which enables cells to adapt to changes in external stimulation for survival. Another finding was that AKT regulated the lipid metabolic process and may be involved in melanoma progression and promotion of tumor growth through gene enrichment function analysis. Two highlighted pathways were detected in our study: i) the estrogen signaling pathway modulates the immune tolerance and resistance to cell apoptosis, which contributes to the growth of melanoma and ii) the RAP1 signaling pathway which regulates focal adhesion (FA) negative feedback to cell migration and invasion in melanoma. Our studies highlighted the top differentially expressed gene AKT1 and its correlation with the estrogen signaling and RAP1 signaling pathways to alter the proliferation and apoptosis of melanoma cells. Analysis of the enrichment functions of genes associated with melanoma will help us find the exact mechanism of melanoma and advance the full potential of newly targeted cancer therapy.

Diagnosis the metastatic sentinel node with Tc-99m-MIBI

International Nuclear Information System (INIS)

Georgiev-Predic, M.; Predic, P.; Karner, I.; Dodig, D.

2002-01-01

Aim: The purpose of this study was to analyse the occurrence of visualisation malignancy of sentinel node during preoperative lymphoscintigraphy in breast cancer. To precisely diagnose the metastatic sentinel node is very difficult. Material and Methods:Preoperative lymphoscintigraphy was performed in 47 patients with breast cancer after injection of Tc-99m-MIBI. We injected 20-40 MBq Tc-99m-MIBI peritumoral. Anterior and prone lateral planar images were obtained 2h, 4h, 6h and 20h after injection. The uptake were in region of sentinel node calculed. The sentinel node was intraoperatively identified and histologically analysed. Results: In 27 patients with intraoperatively detected metastatic sentinel node was in 25 patients increased uptake in sentinel node on scintigrams after 20h detected. In 20 patients with intraoperatively non detected metastatic sentinel node was in 19 patients increased uptake on scintigrams ower 2h-6h detected. Conclusion: The results indicated that is lymphoscintigraphy with Tc-99m-MIBI is a new method for detection the preoperatively metastatic sentinel node

Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

Science.gov (United States)

Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David

2018-05-01

The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

Hepatic angiographic findings of ruptured hepatocellular carcinoma: 'Sentinel signs' versus extravasation

International Nuclear Information System (INIS)

Yun, Seong Jong; Nam, Deok Ho

2014-01-01

This study retrospectively compared the accuracy of angiographic sentinel signs (sentinel vessels, hypovascular areas, and delayed dots) with extravasation in the diagnosis of ruptured hepatocellular carcinoma (HCC). Sixteen patients diagnosed with HCC between March 2007 and November 2011 were evaluated. Among the patients, we identified 32 HCCs (19 ruptured, 13 unruptured), and assessed all HCCs by hepatic angiography with regard to extravasation, sentinel vessels, hypovascular areas, and delayed dots. We compared the sensitivity and specificity of the sentinel signs with those of the extravasation for the diagnosis of a ruptured HCC. For the angiographic diagnosis of a ruptured HCC, the sensitivity of the sentinel signs (sentinel vessel, 63.2%; hypovascular area, 89.5%; delayed dot, 72.7%) was higher than the sensitivity of extravasation (15.8%). The difference in sensitivity between each sentinel sign and extravasation was statistically significant (sentinel vessel, p = 0.012; hypovascular area, p < 0.001; delayed dot, p 0.039). The specificity of sentinel signs for the diagnosis of ruptured HCC was not statistically different from the specificity of extravasation. Sentinel signs are more accurate than extravasation for the angiographic diagnosis of a ruptured HCC.

Human and animal sentinels for shared health risks

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Peter Rabinowitz, MD, MPH

2009-03-01

Full Text Available The tracking of sentinel health events in humans in order to detect and manage disease risks facing a larger population is a well accepted technique applied to influenza, occupational conditions and emerging infectious diseases. Similarly, animal health professionals routinely track disease events in sentinel animal colonies and sentinel herds. The use of animals as sentinels for human health threats, or of humans as sentinels for animal disease risk, dates back at least to the era when coal miners brought caged canaries into mines to provide early warning of toxic gases. Yet the full potential of linking animal and human health information to provide warning of such ‘shared risks’ from environmental hazards has not been realised. Reasons appear to include the professional segregation of human and animal health communities, the separation of human and animal surveillance data and evidence gaps in the linkages between human and animal responses to environmental health hazards. The ‘One Health initiative’ and growing international collaboration in response to pandemic threats, coupled with development in the fields of informatics and genomics, hold promise for improved sentinel event coordination in order to detect and reduce environmental health threats shared between species.

Plasma 25-Hydroxyvitamin D and Risk of Non-Melanoma and Melanoma Skin Cancer

DEFF Research Database (Denmark)

Afzal, Shoaib; Nordestgaard, Børge G; Bojesen, Stig E

2013-01-01

Sun exposure is a major risk factor for skin cancer and is also an important source of vitamin D. We tested the hypothesis that elevated plasma 25-hydroxyvitamin D (25-OH-vitD) associates with increased risk of non-melanoma and melanoma skin cancer in the general population. We measured plasma 25......-OH-vitD in 10,060 white individuals from the Danish general population. During 28 years of follow-up, 590 individuals developed non-melanoma skin cancer and 78 developed melanoma skin cancer. Increasing 25-OH-vitD levels, by clinical categories or by seasonally adjusted tertiles, were associated...... with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD 50 vs. 60 years, 25-OH...

Primary Anorectal Melanoma: An Update

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P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

2012-01-01

Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

Sentinel node detection in pre-operative axillary staging.

Science.gov (United States)

Trifirò, Giuseppe; Viale, Giuseppe; Gentilini, Oreste; Travaini, Laura Lavinia; Paganelli, Giovanni

2004-06-01

The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would 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. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

The SENTINEL-3 Mission: Overview and Status

Science.gov (United States)

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.

Malignant melanoma - a warning

International Nuclear Information System (INIS)

Volden, G.; Rajka, G.; Thune, P.; Falk, E.S.; Krogh, H.K.

1990-01-01

Incidence of malignant melonoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. The intension of the authors is to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education. 15 refs., 2 tabs

The hidden sentinel node in breast cancer

NARCIS (Netherlands)

Tanis, P. J.; van Sandick, J. W.; Nieweg, O. E.; Valdés Olmos, R. A.; Rutgers, E. J. T.; Hoefnagel, C. A.; Kroon, B. B. R.

2002-01-01

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures)

Sentinel-3 for Science

Science.gov (United States)

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).

Future perspectives in melanoma research

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Paolo A. Ascierto

2016-11-01

Full Text Available Abstract The sixth “Melanoma Bridge Meeting” took place in Naples, Italy, December 1st–4th, 2015. The four sessions at this meeting were focused on: (1 molecular and immune advances; (2 combination therapies; (3 news in immunotherapy; and 4 tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS and overall survival (OS of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC, renal cell carcinoma (RCC, bladder cancer, and Hodgkin’s disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4 and the programmed cell death-1 (PD-1 and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.; adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs, chimeric

Aldehyde dehydrogenase (ALDH activity does not select for cells with enhanced aggressive properties in malignant melanoma.

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Lina Prasmickaite

Full Text Available BACKGROUND: Malignant melanoma is an exceptionally aggressive, drug-resistant and heterogeneous cancer. Recently it has been shown that melanoma cells with high clonogenic and tumourigenic abilities are common, but markers distinguishing such cells from cells lacking these abilities have not been identified. There is therefore no definite evidence that an exclusive cell subpopulation, i.e. cancer stem cells (CSC, exists in malignant melanoma. Rather, it is suggested that multiple cell populations are implicated in initiation and progression of the disease, making it of importance to identify subpopulations with elevated aggressive properties. METHODS AND FINDINGS: In several other cancer forms, Aldehyde Dehydrogenase (ALDH, which plays a role in stem cell biology and resistance, is a valuable functional marker for identification of cells that show enhanced aggressiveness and drug-resistance. Furthermore, the presence of ALDH(+ cells is linked to poor clinical prognosis in these cancers. By analyzing cell cultures, xenografts and patient biopsies, we showed that aggressive melanoma harboured a large, distinguishable ALDH(+ subpopulation. In vivo, ALDH(+ cells gave rise to ALDH(- cells, while the opposite conversion was rare, indicating a higher abilities of ALDH(+ cells to reestablish tumour heterogeneity with respect to the ALDH phenotype. However, both ALDH(+ and ALDH(- cells demonstrated similarly high abilities for clone formation in vitro and tumour initiation in vivo. Furthermore, both subpopulations showed similar sensitivity to the anti-melanoma drugs, dacarbazine and lexatumumab. CONCLUSIONS: These findings suggest that ALDH does not distinguish tumour-initiating and/or therapy-resistant cells, implying that the ALDH phenotype is not associated with more-aggressive subpopulations in malignant melanoma, and arguing against ALDH as a "universal" marker. Besides, it was shown that the ability to reestablish tumour heterogeneity is not

[Melanoma in organ transplant patients].

Science.gov (United States)

Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D

2000-02-01

The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean

Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

Directory of Open Access Journals (Sweden)

Goldenberg A

2015-08-01

Full Text Available Alina Goldenberg,1 Igor Vujic,2,3 Martina Sanlorenzo,2,4 Susana Ortiz-Urda2 1Department of Internal Medicine/Dermatology, University of California, San Diego, 2Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA; 3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; 4Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair. Whites have a 27-fold higher incidence of melanoma than African-Americans (AA, but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective: To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods: Qualitative review of the literature. Results: Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion: Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. Keywords: acral, advanced, African-American, disparity, melanoma, survival

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

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Martyna Śniegocka

2018-04-01

Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

Immunohistochemical detection of XIAP in melanoma.

Science.gov (United States)

Emanuel, Patrick O M; Phelps, Robert G; Mudgil, Adarsh; Shafir, Michail; Burstein, David E

2008-03-01

The X-linked inhibitor of apoptosis protein (XIAP) is the most potent of the inhibitor of apoptosis family of eight proteins. High levels of XIAP have been found in melanoma cell lines and are believed to play a role in therapeutic resistance in a number of malignancies. XIAP expression has not been investigated in clinically obtained melanoma tissue samples, nor have studies attempted to correlate XIAP expression with prognostic variables or clinical aggressiveness of melanomas. Sixty-seven patients with primary cutaneous malignant melanoma for whom clinical follow up was available were identified from the records of the Mount Sinai Hospital, comprising 37 thin melanomas (Breslow thickness 1.0 mm). Archival paraffin sections from primary lesions and corresponding metastases were stained with monoclonal anti-XIAP antibody using routine immunohistochemical methods. Six benign intradermal nevi and four in situ melanomas were XIAP negative. 9 of 37 thin melanomas (24%) were XIAP positive. In contrast, 21 of 30 (73%) thick melanomas were XIAP positive, including 3 of 4 ulcerated melanomas that were strongly positive. Over a follow-up period ranging from 6 months to 6 years, 23 melanomas metastasized (22 thick, 1 thin). In total, XIAP was immunohistochemically detected in 17 of 23 metastases (74%). Metastasis occurred in 1 of 9 XIAP-positive thin melanomas; 0 of 28 XIAP-negative thin melanomas; 17 of 22 XIAP-positive thick melanomas, and 5 of 8 XIAP-negative thick melanomas (63%). XIAP is immunohistochemically detectable nearly three times more frequently in thick compared with thin melanomas. These results suggest that XIAP elevation may be correlated with increasing melanoma thickness and tumor progression.

Genetics of familial melanoma

DEFF Research Database (Denmark)

Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

2015-01-01

Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

Methods to Improve Adoptive T-Cell Therapy for Melanoma

DEFF Research Database (Denmark)

Donia, Marco; Hansen, Morten; Sendrup, Sarah L

2013-01-01

desirable. In this study, we demonstrated that a high in vitro tumor reactivity of infusion products was associated with clinical responses upon adoptive transfer. In addition, we systematically characterized the responses of a series of TIL products to relevant autologous short term-cultured melanoma cell...... lines from 12 patients. We provide evidence that antitumor reactivity of both CD8(+) and CD4(+) T cells could be enhanced in most TIL products by autologous melanoma sensitization by pretreatment with low-dose IFN-γ. IFN-γ selectively enhanced responses to tumor-associated antigens other than melanoma...... differentiation antigens. In addition, IFN-γ treatment was invariably associated with restored/increased cancer immunogenicity as demonstrated by upregulation of major histocompatibility complex molecules. These findings suggest a potential synergism between IFN-γ and ACT, and have important implications...

Sunburn, suntan and the risk of cutaneous malignant melanoma--The Western Canada Melanoma Study.

Science.gov (United States)

Elwood, J. M.; Gallagher, R. P.; Davison, J.; Hill, G. B.

1985-01-01

A comparison of interview data on 595 patients with newly incident cutaneous melanoma, excluding lentigo maligna melanoma and acral lentiginous melanoma, with data from comparison subjects drawn from the general population, showed that melanoma risk increased in association with the frequency and severity of past episodes of sunburn, and also that melanoma risk was higher in subjects who usually had a relatively mild degree of suntan compared to those with moderate or deep suntan in both winter and summer. The associations with sunburn and with suntan were independent. Melanoma risk is also increased in association with a tendency to burn easily and tan poorly and with pigmentation characteristics of light hair and skin colour, and history freckles; the associations with sunburn and suntan are no longer significant when these other factors are taken into account. This shows that pigmentation characteristics, and the usual skin reaction to sun, are more closely associated with melanoma risk than are sunburn and suntan histories. PMID:3978032

Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

Science.gov (United States)

Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine

2014-01-01

Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fisetin induces apoptosis through mitochondrial apoptosis pathway in human uveal melanoma cells.

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Wang, Kai; Hu, Dan-Ning; Lin, Hui-Wen; Yang, Wei-En; Hsieh, Yi-Hsien; Chien, Hsiang-Wen; Yang, Shun-Fa

2018-05-01

Fisetin, a diatery flavonoid, been reported that possess anticancer effects in various cancers. The purpose of the study was to investigate the antitumor effects of fisetin in cultured uveal melanoma cell lines and compared with normal retinal pigment epithelial (RPE) cells. MTT assay was used for evaluating cytotoxic effects of fisetin. Flow cytometry study was used for the determination of apoptosis. JC-1 fluorescent reader was used to determine mitochondrial transmembrane potential changes. The results shown that fisetin dose-dependently decreased the cell viability of uveal melanoma cells but not influenced the cell viability of RPE cells. Apoptosis of uveal melanoma cells was induced by fisetin efficiently. Fisetin inhibited antiapoptotic Bcl-2 family proteins and damaged the mitochondrial transmembrane potential. The levels of proapoptotic Bcl-2 proteins, cytochrome c, and various caspase activities were increased by fisetin. In conclusion, fisetin induces apoptosis of uveal melanoma cells selectively and may be a promising agent to be explored for the treatment of uveal melanoma. © 2018 Wiley Periodicals, Inc.

Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

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Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

2014-01-01

Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts

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Michael Ngo

2016-08-01

Full Text Available The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271+ melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2+/VEGFR1+, and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271+ melanoma cells represents a powerful therapeutic approach against metastatic melanoma.

Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma

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Bald, Tobias; Quast, Thomas; Landsberg, Jennifer; Rogava, Meri; Glodde, Nicole; Lopez-Ramos, Dorys; Kohlmeyer, Judith; Riesenberg, Stefanie; van den Boorn-Konijnenberg, Debby; Hömig-Hölzel, Cornelia; Reuten, Raphael; Schadow, Benjamin; Weighardt, Heike; Wenzel, Daniela; Helfrich, Iris; Schadendorf, Dirk; Bloch, Wilhelm; Bianchi, Marco E.; Lugassy, Claire; Barnhill, Raymond L.; Koch, Manuel; Fleischmann, Bernd K.; Förster, Irmgard; Kastenmüller, Wolfgang; Kolanus, Waldemar; Hölzel, Michael; Gaffal, Evelyn; Tüting, Thomas

2014-03-01

Intermittent intense ultraviolet (UV) exposure represents an important aetiological factor in the development of malignant melanoma. The ability of UV radiation to cause tumour-initiating DNA mutations in melanocytes is now firmly established, but how the microenvironmental effects of UV radiation influence melanoma pathogenesis is not fully understood. Here we report that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model promotes metastatic progression, independent of its tumour-initiating effects. UV irradiation enhanced the expansion of tumour cells along abluminal blood vessel surfaces and increased the number of lung metastases. This effect depended on the recruitment and activation of neutrophils, initiated by the release of high mobility group box 1 (HMGB1) from UV-damaged epidermal keratinocytes and driven by Toll-like receptor 4 (TLR4). The UV-induced neutrophilic inflammatory response stimulated angiogenesis and promoted the ability of melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces. Our results not only reveal how UV irradiation of epidermal keratinocytes is sensed by the innate immune system, but also show that the resulting inflammatory response catalyses reciprocal melanoma-endothelial cell interactions leading to perivascular invasion, a phenomenon originally described as angiotropism in human melanomas by histopathologists. Angiotropism represents a hitherto underappreciated mechanism of metastasis that also increases the likelihood of intravasation and haematogenous dissemination. Consistent with our findings, ulcerated primary human melanomas with abundant neutrophils and reactive angiogenesis frequently show angiotropism and a high risk for metastases. Our work indicates that targeting the inflammation-induced phenotypic plasticity of melanoma cells and their association with endothelial cells represent rational strategies to specifically interfere

Antitumor potential induction and free radicals production in melanoma cells by Boron Neutron Capture Therapy

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Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P.; Muniz, R.O.R.; Souza, G.S. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.com.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

2011-12-15

Antiproliferative and oxidative damage effects occurring in Boron Neutron Capture Therapy (BNCT) in normal fibroblasts and melanoma cell lines were analyzed. Melanoma cells and normal fibroblasts were treated with different concentrations of Boronophenylalanine and irradiated with thermal neutron flux. The cellular viability and the oxidative stress were determined. BNCT induced free radicals production and proliferative potential inhibition in melanoma cells. Therefore, this therapeutic technique could be considered efficient to inhibit growth of melanoma with minimal effects on normal tissues. - Highlights: Black-Right-Pointing-Pointer Boron Neutron Capture Therapy (BNCT) induces melanoma cell death. Black-Right-Pointing-Pointer BNCT stimulates free radicals production and proliferative inhibition in melanoma cells. Black-Right-Pointing-Pointer It produces tumor membrane degeneration and destruction with apoptotic bodies formation. Black-Right-Pointing-Pointer This therapy damages tumor cells selectively, with minimum effects on normal adjacent tissue.

The risk of melanoma associated with ambient summer ultraviolet radiation.

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Pinault, Lauren; Bushnik, Tracey; Fioletov, Vitali; Peters, Cheryl E; King, Will D; Tjepkema, Michael

2017-05-17

Depletion of the ozone layer has meant that ambient ultraviolet radiation (UVR) has increased in recent decades. At the same time, the incidence of skin cancers, including melanoma, has risen. The relatively few large-scale studies that linked ambient UVR to melanoma found a trend toward rising incidence closer to the equator, where UVR estimates are highest. Similar research has not been conducted in Canada, where ambient UVR is generally lower than in countries further south. Modelled UVR data for the months of June through August during the 1980-to-1990 period were spatially linked in Geographic Information Systems to 2.4 million white members of the 1991 Canadian Census Health and Environment Cohort and tracked for melanoma diagnosis over an 18-year period (1992 to 2009). Standard Cox proportional hazards models were used to estimate melanoma risk associated with increases of ambient summer UVR, assigned by residence at baseline. Models were adjusted for age, sex and socioeconomic (SES) characteristics. Separate analyses by body site of melanoma were conducted. Effect modification of the association between ambient UVR and melanoma by sex, age, outdoor occupation and selected SES characteristics was evaluated. Differences of one standard deviation (446 J/m², or 7% of the mean) in average ambient summer UVR were associated with an increased hazard ratio (HR) for melanoma of 1.22 (95% CI: 1.19 to 1.25) when adjusting for sex, age and SES characteristics. The HR for melanoma in relative UVR (per 1 standard deviation) was larger for men (HR = 1.26; 95% CI: 1.21 to 1.30) than for women (HR = 1.17; 95% CI: 1.13 to 1.22). Ambient summer UVR is associated with a greater risk of melanoma among the white population, even in a country where most people live within a narrow latitudinal belt. A stronger association between melanoma and ambient UVR was evident among men and among people of lower SES.

Synergy between Sentinel-1 radar time series and Sentinel-2 optical for the mapping of restored areas in Danube delta

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Niculescu, Simona; Lardeux, Cédric; Hanganu, Jenica

2018-05-01

Wetlands are important and valuable ecosystems, yet, since 1900, more than 50 % of wetlands have been lost worldwide. An example of altered and partially restored coastal wetlands is the Danube Delta in Romania. Over time, human intervention has manifested itself in more than a quarter of the entire Danube surface. This intervention was brutal and has rendered ecosystem restoration very difficult. Studies for the rehabilitation / re-vegetation were started immediately after the Danube Delta was declared as a Biosphere Reservation in 1990. Remote sensing offers accurate methods for detecting and mapping change in restored wetlands. Vegetation change detection is a powerful indicator of restoration success. The restoration projects use vegetative cover as an important indicator of restoration success. To follow the evolution of the vegetation cover of the restored areas, satellite images radar and optical of last generation have been used, such as Sentinel-1 and Sentinel-2. Indeed the sensor sensitivity to the landscape depends on the wavelength what- ever radar or optical data and their polarization for radar data. Combining this kind of data is particularly relevant for the classification of wetland vegetation, which are associated with the density and size of the vegetation. In addition, the high temporal acquisition frequency of Sentinel-1 which are not sensitive to cloud cover al- low to use temporal signature of the different land cover. Thus we analyse the polarimetric and temporal signature of Sentinel-1 data in order to better understand the signature of the different study classes. In a second phase, we performed classifications based on the Random Forest supervised classification algorithm involving the entire Sentinel-1 time series, then starting from a Sentinel-2 collection and finally involving combinations of Sentinel-1 and -2 data.

Uveal melanoma: Estimating prognosis

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Swathi Kaliki

2015-01-01

Full Text Available 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.

Italian Euromelanoma Day Screening Campaign (2005-2007) and the planning of melanoma screening strategies.

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Seidenari, Stefania; Benati, Elisa; Ponti, Giovanni; Borsari, Stefania; Ferrari, Chiara; Albertini, Giuseppe; Altomare, Gianfranco; Arcangeli, Fabio; Aste, Nicola; Bernengo, Maria Grazia; Bongiorno, Maria Rita; Borroni, Giovanni; Calvieri, Stefano; Chimenti, Sergio; Cusano, Francesco; Fracchiolla, Claudio; Gaddoni, Giuseppe; Girolomoni, Giampiero; Guarneri, Biagio; Lanzoni, Anna; Lombardi, Mara; Lotti, Torello; Mariotti, Antonio; Marsili, Franco; Micali, Giuseppe; Parodi, Aurora; Peris, Ketty; Peserico, Andrea; Quaglino, Pietro; Santini, Marcello; Schiavon, Sergio; Tonino, Camillo; Trevisan, Giusto; Tribuzi, Paola; Valentini, Paolo; Vena, Gino A; Virgili, Annarosa

2012-01-01

Although no study has definitively shown that unfocused screening of skin cancer is effective, many campaigns have been organized with the aim of increasing awareness on melanoma risk factors. The objective of this study was to analyse the results of the Skin Cancer Screening Day in Italy during the period 2005-2007, to determine the priorities for melanoma control plans in a Mediterranean country. A total of 5002 patients were screened by dermatologists in 31 cities. Individuals who considered themselves to have many naevi and those with a family history of melanoma showed a higher number of common and atypical naevi. Ten melanomas, 20 basal cell carcinomas and two squamous cell carcinomas were histopathologically confirmed. Our observations provide the following suggestions for melanoma prevention strategies: (a) an unfocused campaign is suitable to inform the public about the importance of self-examination of the skin, but is not useful to identify a larger number of melanomas; and (b) melanoma screening campaigns should focus on a selected population, which meets rigorous risk criteria to maintain higher cost-effectiveness. The financial support to effective melanoma screening programmes could be increased, especially in southern populations where lower levels of self-surveillance and socioeconomic conditions represent risk factors for late identification of melanoma.

Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle.

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Gutman, Haim; Ben-Ami, Eytan; Shapira-Frommer, Roni; Schachter, Jacob

2012-08-01

Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this

Evaluation of variants of melanoma-associated antigen genes and mRNA transcripts in melanomas of dogs.

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Stell, Anneliese J; Dobson, Jane M; Scase, Timothy J; Catchpole, Brian

2009-12-01

OBJECTIVE-To characterize variability in melanoma-associated antigen (MAA) genes and gene expression in melanomas of dogs. ANIMALS-18 dogs with malignant melanomas and 8 healthy control dogs. PROCEDURES-cDNA was prepared from malignant melanoma biopsy specimens and from pigmented oral mucocutaneous tissues of healthy control dogs. Genomic DNA was extracted from poorly pigmented melanomas. A PCR assay was performed by use of Melan-A, SILV, or tyrosinase-specific primers. RESULTS-Splice variants of Melan-A and SILV were identified in malignant melanomas and also in healthy pigmented tissues, whereas a tyrosinase splice variant was detected in melanoma tissues only. A short interspersed nuclear element (SINE) insertion mutation was identified in the SILV gene in 1 of 10 poorly pigmented melanomas. Six novel exonic single nucleotide polymorphisms (SNPs; 3 synonymous and 3 nonsynonymous) were detected in the tyrosinase gene, and 1 nonsynonymous exonic SNP was detected in the SILV gene. CONCLUSIONS AND CLINICAL RELEVANCE-Variants of MAA mRNA were detected in malignant melanoma tissues of dogs. The importance of MAA alternative transcripts expressed in melanomas and normal pigmented tissues was unclear, but they may have represented a means of regulating melanin synthesis. The tyrosinase splice variant was detected only in melanomas and could potentially be a tumor-specific target for immunotherapy. A SILV SINE insertion mutation was identified in a melanoma from a Great Dane, a breed known to carry this mutation (associated with merle coat color). The nonsynonymous SNPs detected in tyrosinase and SILV transcripts did not appear to affect tumor pigmentation.

Uveal melanoma in relation to ultraviolet light exposure and host factors.

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Holly, E A; Aston, D A; Char, D H; Kristiansen, J J; Ahn, D K

1990-09-15

We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

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Monica Marzagalli

2016-10-01

Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

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Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

2016-01-01

Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

Thick melanoma in Tuscany.

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Chiarugi, Alessandra; Nardini, Paolo; Borgognoni, Lorenzo; Brandani, Paola; Gerlini, Gianni; Rubegni, Pietro; Lamberti, Arianna; Salvini, Camilla; Lo Scocco, Giovanni; Cecchi, Roberto; Sirna, Riccardo; Lorenzi, Stefano; Gattai, Riccardo; Battistini, Silvio; Crocetti, Emanuele

2017-03-14

The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type life style, where there is a progressive increasing incidence and a low but not decreasing mor- tality, or somewhere an increase too, especially in the older age groups. Also in Tuscany there is a steady rise in incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case- case study, thin and thick melanoma cases, trying to find out those personal and tumour characteristics which may help to customize preventive interventions. RESULTS The results confirmed the age and the lower edu- cation level are associated with a later detection. The habit to perform skin self-examination is resulted protec- tive forward thick melanoma and also the diagnosis by a doctor. The elements emerging from the survey allow to hypothesize a group of subjects resulting at higher risk for a late diagnosis, aged over 50 and carrier of a fewer constitutional and environmental risk factors: few total and few atypical nevi, and lower sun exposure and burning. It is assumable that a part of people did not be reached from messages of prevention because does not recognize oneself in the categories of people at risk for skin cancers described in educational cam- paigns. If we want to obtain better results on diagnosis of skin melanoma we have to think a new strategy. At least to think over the educational messages discriminating people more at risk of incidence of melanoma from people more at risk to die from melanoma, and to renewed active involvement of the Gen- eral Practitioners .

RARE METASTASES OF MALIGNANT MELANOMA

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Marija Trenkić-Božinović

2014-09-01

Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

Cutaneous melanoma in women

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Mi Ryung Roh, MD

2015-02-01

Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

Animal type melanoma: a report of two cases

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Mariângela Esther Alencar Marques

2010-08-01

Full Text Available Dificuldade potencial no diagnóstico histológico de melanomas é a dificuldade em reconhecer variantes pouco frequentes de melanoma. Entre elas, as mais desafiantes incluem exemplos de melanoma desmoplásico, melanoma nevoide, o chamado "melanoma de desvio mínimo", melanomas com proeminente síntese de pigmento ou "melanoma tipo animal" e o nevo azul maligno. Os autores descrevem dois casos de melanoma tipo animal e discute-se a importância do diagnóstico diferencial clinico-histopatológico nesses casos.A potential diagnostic pitfall in the histological assessment of melanomas is the difficulty in recognizing unusual melanoma variants. Among them, the most challenging examples comprise desmoplastic melanomas, nevoid melanomas, the so-called minimal-deviation melanoma, melanomas with prominent pigment synthesis or animal-type melanoma, and the malignant blue nevus. Two cases of animal type melanoma are reported and the importance of clinical-histopathological differential diagnosis is discussed.

Metastases in patients with malignant melanoma despite of negative sentinel lymph node: has the concept to be changed?

International Nuclear Information System (INIS)

Weiss, M.; Dresel, S.; Tatsch, K.; Hahn, K.; Konz, B.; Schmid-Wendtner, M.H.; Sander, C.; Volkenandt, M.

2000-01-01

The aim of the present study was to prove the prognostic value of the SLN-concept in these patients. Methods: So far the clinical follow-up of 162 patients with histologically proven malignant melanoma and metastatically uninvolved (negative) SLN was investigated. Histological examination included standard methods (HE-Test) and special histochemical techniques (S-100, HMB-45). All patients underwent clinical examination, ultrasonic diagnosis of the regional lymph nodes, and X-ray of the chest every 3 months. Results: Despite of negative SLN-findings in 8/162 patients metastases of the malignant melanoma were found after a time period of 5-27 months. Three patients presented with recurrence in the previously mapped (negative) SLN-basin. In another case the scintigraphically visualized SLN could not be identified intraoperatively by means of the hand-held gamma probe. One patient showed intransit-metastases or skin-metastases, respectively; another patient recurred in the scar area. One patient showed hematogenic dissemination (liver) which is not detectable by lymphoscintigraphy; in another patient metastases were found outside the primary lymphatic basin (cervical). Conclusion: In our patient group 4,9% presented with metastases despite negative SLN while published data report up to 11% (observation period 35 months), among them only 3 patients (1,9%) being real concept failures. Our results underline that there is no evidence to change this concept in patients with clinically early stage. (orig.) [de

Matrix Metalloproteinase-9 (MMP-9 polymorphisms in patients with cutaneous malignant melanoma

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Busam Klaus

2007-03-01

Full Text Available Abstract Background Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. Methods We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. Results We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. Conclusion This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

Directory of Open Access Journals (Sweden)

L. Vermeeren

2009-01-01

Full Text Available Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described.

Estimation of dose and exposure at sentinel node study

International Nuclear Information System (INIS)

Skopljak, A.; Kucukalic-Selimovic, E.; Beslic, N.; Begic, A.; Begovic-Hadzimuratovic, S.; Drazeta, Z.; Beganovic, A.

2005-01-01

The purpose of this study was to estimate the dose end exposure in staff involved in sentinel node procedure for breast cancer patients. The Institute of Nuclear Medicine in Sarajevo uses a protocol for lymphoscintigraphy of the sentinel node whereby 13 MBq of 9 9mT c nanocoll are used. In this study, we measured radiation doses and exposure of a nuclear medicine physician and a technologist, as well as a surgeon performing sentinel node lymphoscintigraphy and biopsy. Dose and exposure were calculated using the equation in which we have gamma constant for 9 9mT c. Calculations were made for different times of exposure and distance. In Table 1. we estimated the dose and exposure during sentinel node study. Radiation levels were very low and the most exposed hospital staff performing sentinel node study were nuclear medicine physicians. The doses on the hands of surgeons were negligible 8 hours after exposure.(author)

Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

DEFF Research Database (Denmark)

Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

2002-01-01

of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented...... neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45...

Positron emission tomography of experimental melanoma with [{sup 76}Br]5-bromo-2-thiouracil

Energy Technology Data Exchange (ETDEWEB)

Maars, Ulla E-mail: Ulla.Mars@tox.uu.se; Tolmachev, Vladimir; Sundin, Anders

2000-11-01

Positron emission tomography (PET) has evolved as a new diagnostic modality in cancer patients. Thioureylenes, such as thiouracil and methimazole, are known to be incorporated into growing melanin and selectively retained in melanotic melanoma. In the present study we used [{sup 76}Br]5-bromo-2-thiouracil as tracer for PET imaging of human and murine melanotic melanoma transplanted subcutaneously into rats. The melanomas were clearly depicted 1 day after the injection, when [{sup 76}Br]5-bromo-2-thiouracil was retained in the tumors though the overall radioactivity concentration in the body had declined. Accumulation of {sup 76}Br was also seen in bladder, liver, and kidney. In addition, the rats were simultaneously injected with [{sup 125}I]5-iodo-2-thiouracil and the tissue distribution of radioactivity was mapped by whole-body autoradiography. The results confirmed the selective uptake of thiouracil in the melanoma where the concentration of {sup 125}I-radioactivity was about three-fold higher than that in the liver and lungs. These results show the possibility of using [{sup 76}Br]5-bromo-2-thiouracil for PET diagnostics of melanoma, including dosimetry, prior to targeted therapy using [{sup 131}I]5-iodo-2-thiouracil or [{sup 211}At]5-astato-2-thiouracil.

Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

Science.gov (United States)

Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

2010-06-01

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

Feasibility of sentinel node lymphoscintigraphy in stage I testicular cancer

Energy Technology Data Exchange (ETDEWEB)

Tanis, Pieter J.; Nieweg, Omgo E. [Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Horenblas, Simon [Department of Urology, Netherlands Cancer Institute, Amsterdam (Netherlands); Olmos, Renato Valdes A.; Hoefnagel, Cornelis A. [Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands)

2002-05-01

The aim of this study was to investigate the feasibility of lymphoscintigraphy for sentinel node identification in testicular cancer. Five patients with clinical stage I testicular cancer were prospectively included. A single dose of technetium-99m nanocolloid (mean dose 99 MBq, volume 0.2 ml) was injected into the funiculus in the first patient and into the testicular parenchyma in the following four patients. Dynamic lymphoscintigraphy was performed over 10 min, followed by early and late static images after 15 min and 2 to 24 h, respectively. Lymphoscintigraphy was followed by laparoscopic sentinel node biopsy on the same day in the last two patients using patent blue dye and an endoscopic gamma probe. The funicular administration route showed five hot spots in the right inguinal region after 2 h. Intratesticular administration resulted in sentinel node visualisation in three of the four patients. Dynamic images showed afferent lymphatic vessels to one sentinel node in the left para-aortic region in two patients and two sentinel nodes in the left para-aortic region in another patient. Sentinel nodes were intraoperatively identified in one of two patients who underwent laparoscopic exploration. It is concluded that lymphoscintigraphy for sentinel node identification is feasible in stage I testicular cancer using intratesticular radiocolloid administration. (orig.)

A Harmonized Landsat-Sentinel-2 Surface Reflectance product: a resource for Agricultural Monitoring

Science.gov (United States)

Masek, J. G.; Claverie, M.; Ju, J.; Vermote, E.; Justice, C. O.

2015-12-01

The combination of Landsat and Sentinel-2 data offers a unique opportunity to observe globally the land every 2-3 days at medium (reflectance data from Landsat and Sentinel-2 missions and to deliver them to the community in a combined, seamless form. The HLS will be beneficial for global agricultural monitoring applications that require medium spatial resolution and weekly or more frequent observations. In particular, the provided opportunity to track crop phenology at the scale of individual fields will support detailed mapping of crop type and type-specific vegetation conditions. To create a compatible set of radiometric measurements, the HLS product relies on rigorous pre- and post-launch cross-calibration (Landsat-8 OLI and Sentinel-2 MSI) activities. The processing chain includes the following components: atmospheric correction, cloud/shadow masking, nadir BRDF-adjustment, spectral-adjustment, regridding, and temporal composite. The atmospheric correction and cloud masking is based on the OLI atmospheric correction developed at NASA-GSFC and has been adapted to the MSI data. The BRDF-adjustment is based on a disaggregation technique using MODIS-based BRDF coefficients. The technique has been evaluated using the multi-angular acquisition from the SPOT 4 and 5 (Take5) experiments. The spectral-adjustment relies on a linear regression that has been calibrated and evaluated using synthetic data and surface reflectance processed from a large number of hyperspectral EO-1 Hyperion scenes. Finally, significant effort is placed on product validation and evaluation. The delivered data set will include surface reflectance products at different levels: Using the native gridding, i.e. UTM, 30m for Landsat-8, and UTM, 10-20m for Sentinel-2 Using a common global gridding (Sinusoidal, 30m) Temporal composite (Sinusoidal, 30m, 5-day) During the first year of operation of Sentinel-2A, the HLS will be prototyped over a selection of 30 sites that includes some of the JECAM sites

A new O6-alkylguanine-DNA alkyltransferase inhibitor associated with a nitrosourea (cystemustine) validates a strategy of melanoma-targeted therapy in murine B16 and human-resistant M4Beu melanoma xenograft models.

Science.gov (United States)

Rapp, Maryse; Maurizis, Jean C; Papon, Janine; Labarre, Pierre; Wu, Ting-Di; Croisy, Alain; Guerquin-Kern, Jean L; Madelmont, Jean C; Mounetou, Emmanuelle

2008-07-01

Chemoresistance to O(6)-alkylating agents is a major barrier to successful treatment of melanoma. It is mainly due to a DNA repair suicide protein, O(6)-alkylguanine-DNA alkyltransferase (AGT). Although AGT inactivation is a powerful clinical strategy for restoring tumor chemosensitivity, it was limited by increased toxicity to nontumoral cells resulting from a lack of tumor selectivity. Achieving enhanced chemosensitization via AGT inhibition preferably in the tumor should protect normal tissue. To this end, we have developed a strategy to target AGT inhibitors. In this study, we tested a new potential melanoma-directed AGT inhibitor [2-amino-6-(4-iodobenzyloxy)-9-[4-(diethylamino) ethylcarbamoylbenzyl] purine; IBgBZ] designed as a conjugate of O(6)-(4-iododbenzyl)guanine (IBg) as the AGT inactivator and a N,N-diethylaminoethylenebenzamido (BZ) moiety as the carrier to the malignant melanocytes. IBgBZ demonstrated AGT inactivation ability and potentiation of O(6)-alkylating agents (cystemustine, a chloroethylnitrosourea) in M4Beu highly chemoresistant human melanoma cells both in vitro and in tumor models. The biodisposition study on mice bearing B16 melanoma, the standard model for the evaluation of melanoma-directed agents, and the secondary ion mass spectrometry imaging confirmed the concentration of IBgBZ in the tumor and in particular in the intracytoplasmic melanosomes. These results validate the potential of IBgBZ as a new, more tumor-selective, AGT inhibitor in a strategy of melanoma-targeted therapy.

Getting ready for the arrival of Sentinel data

Science.gov (United States)

Aschbacher, Josef; Milagro Perez, Maria Pilar

2013-04-01

The European Union (EU) and the European Space Agency (ESA) have developed the Global Monitoring for Environment and Security (GMES), being renamed to Copernicus, programme as Europe's answer to the vital need for joined-up data about our climate, environment and security. Through a unique combination of satellite, atmospheric and Earth-based monitoring systems, the initiative will provide new insight into the state of the land, sea and air, providing policymakers, scientists, businesses and the public with accurate and timely information. GMES capabilities include monitoring and forecasting of climatic change, flood risks, soil and coastal erosion, crop and fish resources, air pollution, greenhouse gases, iceberg distribution and snow cover, among others. To accomplish this, GMES has been divided into three main components: Space, In-situ and Services. The Space Component, led by ESA, comprises five types of new dedicated satellites called Sentinels. These missions carry a range of technologies, such as radar and multi-spectral imaging instruments for land, ocean and atmospheric monitoring. While the Sentinel satellites are currently being developed by ESA specifically to meet the needs of GMES, the Contributing Missions, operated by national agencies or commercial entities, are already providing a wealth of data for GMES services, and will continue to deliver complementary data after the Sentinels are in orbit. An integrated Ground Segment ensures access to Sentinels and Contributing Missions data. Access to Sentinel data is governed by the Sentinel data policy, which is part of a wider GMES data and information access policy. The Sentinel data policy envisages free and open access, subject to restrictions only if security or other European interests need to be preserved. As regards the Contributing Missions, the data policy of the mission owners will be respected for the purpose of providing data to GMES service users. The first in the fleet of dedicated

Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

International Nuclear Information System (INIS)

Hay, J. L.; Baguer, C.; Li, Y.; Orlow, I.; Berwick, M.

2012-01-01

Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening) in melanoma first-degree relatives (FDRs) after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic) and risk level (positive versus negative findings) were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

Characterising and improving the performance of the Sentinel-3 SRAL altimeter: A Report from SCOOP, SHAPE & SPICE Projects

Science.gov (United States)

Restano, Marco; Ambrózio, Américo; Cotton, David; Scoop Team; Fabry, Pierre; Shape Team; McMillan, Malcolm; Spice Team; Benveniste, Jérôme

2017-04-01

Under the ESA Scientific Exploitation of Operational Missions (SEOM) Programme, 3 Projects are currently underway to accurately characterise and improve the performance of the Sentinel-3 SRAL SAR mode altimeter. They are: 1) SCOOP (SAR Altimetry Coastal & Open Ocean Performance Exploitation and Roadmap Study) for Coastal and Open Ocean; 2) SHAPE (Sentinel-3 Hydrologic Altimetry PrototypE) for Inland Water; 3) SPICE (Sentinel-3 Performance improvement for ICE sheets) for Ice Sheets. As projects started before the launch of Sentinel-3 (a full SAR mission), calibrated Cryosat-2 data have been used as input to a processor replicating the Sentinel-3 baseline processing. For the SCOOP project, a first test dataset has been released to end users including data from 10 regions of interest. The successful SAMOSA retracker, adopted in the previous CP4O Project (CryoSat Plus for Oceans), has been readapted to re-track Sentinel-3 waveforms. An improved version of SAMOSA will be released at the end of the project. The SHAPE project is working towards the design and assessment of alternative/innovative techniques not implemented in the Sentinel-3 ground segment (performing no Inland Water dedicated processing). Both rivers and lakes will be studied. Amazon, Brahmaputra and Danube have been selected as rivers, whereas Titicaca and Vanern have been chosen as lakes. The study will include the assimilation of output products into hydrological models for all regions of interest. A final dataset will be provided to end users. The SPICE project is addressing four high level objectives: 1) Assess and improve the Delay-Doppler altimeter processing for ice sheets. 2) Assess and develop SAR waveform retrackers for ice sheets. 3) Evaluate the performance of SAR altimetry relative to conventional pulse limited altimetry. 4) Assess the impact on SAR altimeter measurements of radar wave interaction with the snowpack. Dataset used for validation include ICESat and IceBridge products. Vostok

Radiation biology of malignant melanoma

International Nuclear Information System (INIS)

Rofstad, E.K.; Norwegian Cancer Society, Oslo)

1986-01-01

The survival curves for melanoma cells exposed to single radiation doses in vitro and the specific growth delays for melanoma xenografts irradiated with single doses in vivo were found to differ considerably among individual cell lines and tumours. In fact, the differences could be almost as large as the largest differences observed among cell lines and xenografts from tumours of different histology with very different clinical radiocurability. Moreover, radiobiologic parameters that may have significant influence on tumour response to fractionated irradiation, e.g. growth rate, hypoxic fraction, reoxygenation ability, PLD-repair capacity and contact repair capacity, were found to differ greatly in magnitude among individual melanomas. This review therefore concludes that malignant melanoma is a tumour type that is very heterogeneous in radioresponsiveness, i.e. malignant melanomas should no longer be considered to be radiation resistant in general. The values of the α/β ratio derived from cell survival curves for melanoma cells irradiated in vitro and melanoma xenografts irradiated in vivo were found to cover a wide range relative to those for acutely and late responding normal tissues. Although these α/β ratios are no more than estimates of the effective α/β ratios in a clinical situation, they still indicated that hyperfractionation may be beneficial in the treatment of some melanomas, whereas others may be more efficiently treated by use of conventional fractionation regimes, either based on 2 Gy or higher doses per fraction. Consequently, optimum radiation therapy of malignant melanoma will probably require an individualized treatment strategy. In vitro assays for prediction of radiocurability and choice of treatment strategy for individual melanoma patients seem therefore highly warranted. (orig.)

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

Science.gov (United States)

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P model based on the results of multivariate analysis was established to predict the risk of non-sentinel

Evaluation of antitumor effects of folate-conjugated methyl-β-cyclodextrin in melanoma.

Science.gov (United States)

Motoyama, Keiichi; Onodera, Risako; Tanaka, Nao; Kameyama, Kazuhisa; Higashi, Taishi; Kariya, Ryusho; Okada, Seiji; Arima, Hidetoshi

2015-01-01

Melanoma is a life-threatening disorder and its incidence is increasing gradually. Despite the numerous treatment approaches, conventional systemic chemotherapy has not reduced the mortality rate among melanoma patients, probably due to the induction of toxicity to normal tissues. Recently, we have developed folate-conjugated methyl-β-cyclodextrin (FA-M-β-CyD) and clarified its potential as a new antitumor agent involved in autophagic cell death. However, it remains uncertain whether FA-M-β-CyD exerts anticancer effects against melanomas. Therefore, in this study, we investigated the effects of FA-M-β-CyD on the folate receptor-α (FR-α)-expressing melanoma cell-selective cytotoxic effect. FA-M-β-CyD showed cytotoxic effects in Ihara cells, a human melanoma cell line expressing FR-α. In sharp contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered Ihara cells [FR-α(+)] through FR-α-mediated endocytosis. Additionally, FA-M-β-CyD elicited the formation of autophagosomes in Ihara cells. Notably, FA-M-β-CyD suppressed melanoma growth in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double deficient mice bearing Ihara cells. Therefore, these results suggest that FA-M-β-CyD could be utilized as a potent anticancer agent for melanoma chemotherapy by regulating autophagy.

SENTINEL-2 LEVEL 1 PRODUCTS AND IMAGE PROCESSING PERFORMANCES

OpenAIRE

S. J. Baillarin; A. Meygret; C. Dechoz; B. Petrucci; S. Lacherade; T. Tremas; C. Isola; P. Martimort; F. Spoto

2012-01-01

In partnership with the European Commission and in the frame of the Global Monitoring for Environment and Security (GMES) program, the European Space Agency (ESA) is developing the Sentinel-2 optical imaging mission devoted to the operational monitoring of land and coastal areas. The Sentinel-2 mission is based on a satellites constellation deployed in polar sun-synchronous orbit. While ensuring data continuity of former SPOT and LANDSAT multi-spectral missions, Sentinel-2 wil...

ESA's Multi-mission Sentinel-1 Toolbox

Science.gov (United States)

Veci, Luis; Lu, Jun; Foumelis, Michael; Engdahl, Marcus

2017-04-01

The Sentinel-1 Toolbox is a new open source software for scientific learning, research and exploitation of the large archives of Sentinel and heritage missions. The Toolbox is based on the proven BEAM/NEST architecture inheriting all current NEST functionality including multi-mission support for most civilian satellite SAR missions. The project is funded through ESA's Scientific Exploitation of Operational Missions (SEOM). The Sentinel-1 Toolbox will strive to serve the SEOM mandate by providing leading-edge software to the science and application users in support of ESA's operational SAR mission as well as by educating and growing a SAR user community. The Toolbox consists of a collection of processing tools, data product readers and writers and a display and analysis application. A common architecture for all Sentinel Toolboxes is being jointly developed by Brockmann Consult, Array Systems Computing and C-S called the Sentinel Application Platform (SNAP). The SNAP architecture is ideal for Earth Observation processing and analysis due the following technological innovations: Extensibility, Portability, Modular Rich Client Platform, Generic EO Data Abstraction, Tiled Memory Management, and a Graph Processing Framework. The project has developed new tools for working with Sentinel-1 data in particular for working with the new Interferometric TOPSAR mode. TOPSAR Complex Coregistration and a complete Interferometric processing chain has been implemented for Sentinel-1 TOPSAR data. To accomplish this, a coregistration following the Spectral Diversity[4] method has been developed as well as special azimuth handling in the coherence, interferogram and spectral filter operators. The Toolbox includes reading of L0, L1 and L2 products in SAFE format, calibration and de-noising, slice product assembling, TOPSAR deburst and sub-swath merging, terrain flattening radiometric normalization, and visualization for L2 OCN products. The Toolbox also provides several new tools for

Prognosis of patients with transected melanomas.

Science.gov (United States)

Martires, Kathryn J; Nandi, Tina; Honda, Kord; Cooper, Kevin D; Bordeaux, Jeremy S

2013-04-01

The management of melanoma is directly related to Breslow's depth. Biopsying melanomas in a fashion that transects the deep margin precludes an accurate measurement of the true depth. To examine the prognosis of melanomas transected along the deep margins, as well as cases where no residual melanoma was seen on re-excision after transection. Records from a cohort of patients at one institution were examined from 1996 through 2007. Patients were considered to have "transected" melanomas if tumor cells were present on the deep margin of the biopsy. Overall survival was determined. Seven hundred fourteen patients were examined. 171 (24%) of all melanomas were transected. 101(59%) of those lacked tumor cells on re-excision. Patients with transected melanomas were older (OR = 1.03, p < .001), and had higher Breslow's depths (OR = 1.21, p < .001) than those without transected tumors. Those with no residual melanoma after transection were younger (OR = 0.98, p = .010) and more likely to have no lymph node involvement (OR = 2.23, p = .037). Neither transection (p = .760), nor lack of residual melanoma on re-excision after transection (p = .793) influenced survival. A high number of melanomas are transected at diagnosis, many of which lack visible tumor. The original Breslow's depth of transected melanomas without residual tumor on re-excision accurately predicts survival and prognosis. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Lifetime prevalence of non-melanoma and melanoma skin cancer in Australian recreational and competitive surfers.

Science.gov (United States)

Climstein, Mike; Furness, James; Hing, Wayne; Walsh, Joe

2016-07-01

Surfing is one of the most popular outdoor aquatic activities in Australia with an estimated 2.7 million recreational surfers; however, Australia has long been recognized as having the highest incidence of melanoma in the world, and it is the most common type of cancer in young Australians. The aim of this study was to investigate the lifetime prevalence of non-melanoma [basal cell carcinoma (BCC), squamous cell carcinoma (SCC)] and melanoma skin cancers in Australian recreational and competitive surfers. Australian surfers were invited to complete an online surveillance survey to determine the lifetime prevalence of non-melanoma and melanoma skin cancers. A total of 1348 surfers (56.9% recreational) participated in this study, of which 184 surfers reported a skin cancer (competitive n = 96, recreational n = 87). Of non-melanoma and melanoma cancers reported, BCC was the most common (6.8%), followed by melanoma (1.4%) and SCC (0.6%). The relative risk was higher (P well as significantly (P surf are advised to regularly utilize sun protection strategies (avoid peak ultraviolet radiation (10 am-3 pm), rashvest, hat and sunscreen) and primary care physicians are recommended to regularly screen their patients who surf. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sentinel lymph node detection in canine oncological patients

International Nuclear Information System (INIS)

Balogh, L.; Andocs, G.; Mathe, D.

2002-01-01

Sentinel lymph node detection was investigated in dogs with spontaneously occurring tumours. In this pilot study, 24 client-owned spontaneously tumorous dogs presented for sentinel lymph node detection. A multiple method was used with a nuclear medicine technique (injection of 99mT c human serum albumin colloid) with scintigraphy and intraoperative guidance, and blue dye injection. Of the 35 lymph nodes histologically demonstrated to contain metastases, 34 (97%) were found by radioguided surgery, which means that one would have been missed in the intraoperative localisation process; 31 nodes (89%) were clearly visualised in the gamma camera images; only 27 (77%) were blue-stained by vital dye; a mere 8 lymph nodes (23%) were enlarged and therefore easily detectable by palpation. Data obtained from the harmless application of the sentinel node concept are useful for the radiopharmaceutist. The sentinel lymph node concept is well applicable in the veterinary clinic. (author)

Genetics of uveal melanoma and cutaneous melanoma: two of a kind?

NARCIS (Netherlands)

T. van den Bosch (Thomas); E. Kiliç (Emine); A.D.A. Paridaens (Dion); J.E.M.M. de Klein (Annelies)

2010-01-01

textabstractCutaneous melanoma and uveal melanoma both derive from melanocytes but show remarkable differences in tumorigenesis, mode of metastatic spread, genetic alterations, and therapeutic response. In this review we discuss the differences and similarities along with the genetic research

The Surveillance and On-demand Sentinel-1 SBAS Services on the Geohazards Exploitation Platforms

Science.gov (United States)

Casu, F.; de Luca, C.; Zinno, I.; Manunta, M.; Lanari, R.

2017-12-01

The Geohazards Exploitation Platform (GEP) is an ESA R&D activity of the EO ground segment to demonstrate the benefit of new technologies for large scale processing of EO data. GEP aims at providing on-demand processing services for specific user needs, as well as systematic processing services to address the need of the geohazards community for common information layers and, finally, to integrate newly developed processors for scientists and other expert users. In this context, a crucial role is played by the recently launched Sentinel-1 (S1) constellation that, with its global acquisition policy, has flooded the scientific community with a huge amount of data acquired over large part of the Earth on a regular basis (down to 6-days with both Sentinel-1A and 1B passes). The Sentinel-1 data, as part of the European Copernicus program, are openly and freely accessible, thus fostering their use for the development of automated and systematic tools for Earth surface monitoring. In particular, due to their specific SAR Interferometry (InSAR) design, Sentinel-1 satellites can be exploited to build up operational services for the easy and rapid generation of advanced InSAR products useful for risk management and natural hazard monitoring. In this work we present the activities carried out for the development, integration, and deployment of two SBAS Sentinel-1 services of CNR-IREA within the GEP framework, namely the Surveillance and On-demand services. The Surveillance service consists on the systematic and automatic processing of Sentinel-1 data over selected Areas of Interest (AoI) to generate updated surface displacement time series via the SBAS-InSAR algorithm. We built up a system that is automatically triggered by every new Sentinel-1 acquisition over the AoI, once it is available on the S1 catalogue. Then, the system processes the new acquisitions only, thus saving storage space and computing time. The processing, which relies on the Parallel version of the SBAS (P

Metastatic melanoma masquerading as a furuncle

Directory of Open Access Journals (Sweden)

Imran Aslam

2017-10-01

Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

Gray-scale contrast-enhanced utrasonography in detecting sentinel lymph nodes: An animal study

International Nuclear Information System (INIS)

Wang Yuexiang; Cheng Zhigang; Li Junlai; Tang Jie

2010-01-01

Objective: To investigate the usefulness of gray-scale contrast-enhanced ultrasonography for detecting sentinel lymph nodes. Methods: Contrast-enhanced ultrasonography was performed in five normal dogs (four female and one male) after subcutaneous administration of a sonographic contrast agent (Sonovue, Bracco, Milan, Italy). Four distinct regions in each animal were examined. After contrast-enhanced ultrasonography, 0.8 ml of blue dye was injected into the same location as Sonovue and the sentinel lymph nodes were detected by surgical dissection. The findings of contrast-enhanced ultrasonography were compared with those of the blue dye. Results: Twenty-one sentinel lymph nodes were detected by contrast-enhanced ultrasonography while 23 were identified by blue dye with surgical dissection. Compared with the blue dye, the detection rate of enhanced ultrasonography for the sentinel lymph nodes is 91.3% (21/23). Two patterns of enhancement in the sentinel lymph nodes were observed: complete enhancement (5 sentinel lymph nodes) and partial enhancement (16 sentinel lymph nodes). The lymphatic channels were demonstrated as hyperechoic linear structures leading from the injection site and could be readily followed to their sentinel lymph nodes. Histopathologic examination showed proliferation of lymphatic follicles or lymphatic sinus in partial enhanced sentinel lymph nodes while normal lymphatic tissue was demonstrated in completely enhanced sentinel lymph nodes. Conclusions: Sonovue combined with gray-scale contrast-enhanced ultrasonography may provide a feasible method for detecting sentinel lymph nodes.

Pediatric Melanoma and Drug Development

Directory of Open Access Journals (Sweden)

Klaus Rose

2018-03-01

Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

Melanoma survivorship: research opportunities.

Science.gov (United States)

Oliveria, Susan A; Hay, Jennifer L; Geller, Alan C; Heneghan, Maureen K; McCabe, Mary S; Halpern, Allan C

2007-03-01

The rising incidence and mortality rates of melanoma, the most fatal form of skin cancer, are among the greatest increases of all preventable cancers over the past decade. However, because of recent advances in early detection, secondary prevention efforts, and treatment, the number of melanoma survivors is increasing. Little research has been conducted on melanoma survivors and important opportunities exist for research in this understudied population. Here, we outline the important research opportunities related to the study of melanoma survivorship and summarize the paucity of literature currently available. A computerized literature search was performed of the MEDLINE database of the National Library of Medicine from 1966-2005. The scope of the search was limited to those studies published in English. The search was conducted using the following MeSH headings: melanoma, neoplasms, skin neoplasms, survival, and survival rate. The reference lists of relevant book chapters and review articles were further reviewed, and printed materials from recent scientific meetings addressing this topic were obtained. Several factors that affect melanoma survivors warrant further study, including: physiologic long-term effects; psychosocial, behavioral, and cognitive factors; demographic characteristics; surveillance practices; recurrences, secondary primaries, and other cancers; family members of survivors; and economic issues, access to health care/life insurance. Understanding recurrence and second primary cancer risk, psychosocial and cognitive characteristics, behaviors, surveillance patterns, economic sequelae, and family issues of melanoma survivors is important from a public health standpoint to promote the health and well-being of this cohort. Melanoma is an understudied cancer, and the incidence and mortality of this disease are increasing. Describing the long term burden of this cancer and identifying factors that contribute to them will facilitate efforts to develop

Melanoma Surveillance in the US: The Economic Burden of Melanoma

Centers for Disease Control (CDC) Podcasts

This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.

Sentinel lymph node biopsy: An audit of intraoperative assessment ...

African Journals Online (AJOL)

2015-07-02

Jul 2, 2015 ... Sentinel lymph node biopsy: An audit of ... cytotechnology service ... To audit results from intraoperative assessment of sentinel lymph node ..... out, and turnaround time in gynecologic cytology quality assurance: Findings.

Nail apparatus melanoma: a diagnostic opportunity Melanoma do aparelho ungueal: uma oportunidade diagnóstica

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Ana Maria Carreño

2013-04-01

Full Text Available Malignant Melanoma is a high mortality neoplasm. The involvement of the nail apparatus is rare, with only 2 out of 3 patients seeking medical attention as the result of recent nail melanocytic lesions. This results in late diagnosis and a prognosis worse than cutaneous melanoma. We report a female, presenting with ulcerative lesions with clinical and laboratory features compatible with leishmaniasis. On return after treatment initiation a longitudinal melanonychia was observed on her first right finger. Biopsy of the nail matrix was performed. Histopathology was compatible with melanoma in situ. Longitudinal melanonychia is not a specific sign for melanoma and it is important that the dermatologist should identify the suspect lesions correctly. The incidental diagnosis of nail melanoma in situ in our case significantly impacted the patient's survival.Melanoma Maligno é uma neoplasia de alta mortalidade, sendo raro o acometimento do aparelho ungueal. Apenas 2/3 dos pacientes procuram atendimento médico devido lesão melanocítica ungueal recente, tornando o diagnóstico tardio e com prognóstico pior que do melanoma cutâneo. Descreve-se um caso de paciente sexo feminino, apresentando lesões ulceradas com características clínico-laboratoriais compatíveis com leishmaniose tegumentar americana. No retorno após início do tratamento foi observada melanoníquia longitudinal no primeiro quirodáctilo direito. Realizada biópsia da matriz ungueal com histopatológico compatível com melanoma in situ. Melanoníquia longitudinal não é sinal específico de melanoma. A identificação das lesões suspeitas é importante tarefa dos dermatologistas. O diagnóstico incidental de melanoma ungueal in situ do caso relatado resultou em grande impacto na sobrevida da paciente.

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

International Nuclear Information System (INIS)

Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

2013-01-01

Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

A challenging case of ocular melanoma.

Science.gov (United States)

Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

2015-01-01

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Sentinel Lymph Node Biopsy in Breast Cancer: Predictors of Axillary and Non-Sentinel Lymph Node Involvement

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Hakan Postacı

2013-12-01

Full Text Available Background: Sentinel lymph node biopsy is a standard method for the evaluation of axillary status in patients with T1-2N0M0 breast cancers. Aims: To determine the prognostic significance of primary tumour-related clinico-histopathological factors on axillary and non-sentinel lymph node involvement of patients who underwent sentinel lymph node biopsy. Study design: Retrospective clinical study. Methods: In the present study, 157 sentinel lymph node biopsies were performed in 151 consecutive patients with early stage breast cancer between June 2008 and December 2011. Results: Successful lymphatic mapping was obtained in 157 of 158 procedures (99.4%. The incidence of larger tumour size (2.543±1.21 vs. 1.974±1.04, lymphatic vessel invasion (70.6% vs. 29.4%, blood vessel invasion (84.2% vs. 15.8%, and invasive lobular carcinoma subtype (72.7% vs. 27.3% were statistically significantly higher in patients with positive SLNs. Logistic stepwise regression analysis disclosed tumour size (odds ratio: 1.51, p=0.0021 and lymphatic vessel invasion (odds ratio: 4.68, p=0.001 as significant primary tumour-related prognostic determinants of SLN metastasis. Conclusion: A close relationship was identified between tumour size and lymphatic vessel invasion of the primary tumour and axillary lymph node involvement. However, the positive predictive value of these two independent variables is low and there is no compelling evidence to recommend their use in routine clinical practice.

FOREST AREA DERIVATION FROM SENTINEL-1 DATA

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A. Dostálová

2016-06-01

Full Text Available The recently launched Sentinel-1A provides the high resolution Synthetic Aperture Radar (SAR data with very high temporal coverage over large parts of European continent. Short revisit time and dual polarization availability supports its usability for forestry applications. The following study presents an analysis of the potential of the multi-temporal dual-polarization Sentinel-1A data for the forest area derivation using the standard methods based on Otsu thresholding and K-means clustering. Sentinel-1 data collected in winter season 2014-2015 over a test area in eastern Austria were used to derive forest area mask with spatial resolution of 10m and minimum mapping unit of 500 m2. The validation with reference forest mask derived from airborne full-waveform laser scanning data revealed overall accuracy of 92 % and kappa statistics of 0.81. Even better results can be achieved when using external mask for urban areas, which might be misclassified as forests when using the introduced approach based on SAR data only. The Sentinel-1 data and the described methods are well suited for forest change detection between consecutive years.

Radiopharmaceuticals targeting melanoma

Energy Technology Data Exchange (ETDEWEB)

Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

2008-02-15

Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

Intraoperative examination of sentinel lymph nodes using scrape ...

African Journals Online (AJOL)

Background. In breast cancer, sentinel lymph node biopsy (SLNB) is widely used to assess the axilla when the nodes appear normal on palpation and ultrasonography. When the sentinel lymph nodes (SLNs) are negative, no further dissection is required. Surgical dissection or radiotherapy of the axilla is indicated for ...

Pediatric melanoma: incidence, treatment, and prognosis

Directory of Open Access Journals (Sweden)

Saiyed FK

2017-04-01

Full Text Available Faiez K Saiyed,1 Emma C Hamilton,1 Mary T Austin,1,2 1Department of Pediatric Surgery, McGovern Medical School, 2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole. Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. Keywords: melanoma, pediatric, adolescent, childhood

Contribution of the sentinel lymph node detection in oral cavity and oropharynx cancer

International Nuclear Information System (INIS)

Comte, F.; Barge, M.L.; Chevalier, J.; Rossi, M.; Zanca, M.; Alovisetti, C.; Garrel, R.; Guerrier, B.; Costes, V.

2004-01-01

The histopathological features of lymph nodes removal in head and neck cancer bring major prognostic information. Molecular biology or immuno histological techniques allow a far better detection sensitivity while underlining micrometastases. However, due to the great number of removed lymph nodes, an exhaustive histological analysis is impossible and an efficient targeting is desirable. The aim of this study was to establish the feasibility of the gamma probe directed biopsy of the sentinel lymph node in oral and oropharyngeal carcinoma. Up to date, 13 patients with oral and oropharyngeal cancers (T1pNO) were included. The sentinel lymph node was detected during surgery and selectively resected before traditional neck lymph dissection. The sentinel lymph node (SLN) was detected in 92 % of patients. In one case, the immunohistochemical analysis of the SLN showed a micro-metastatic involvement while the classical histological analysis remained negative.The preliminary analysis of our study attests the SLN radio-localization efficiency in head and neck cancers and allows the systematic detection of micro-metastatic involvement. The pursuit of this study will continue to confirm these results from a larger population and to precise the prognostic value of the micro-metastatic stage. (author)

Clinical value of sentinel lymph node diagnostics in head and neck cancer

International Nuclear Information System (INIS)

Kampen, W.U.; Hoeft, S.; Maune, S.

2006-01-01

The concept of the so-called sentinel lymph node (SLN), being the first node draining a malignant tumor and thus carrying the highest risk of metastatic disease, is already frequently applied in patients suffering from malignant melanoma and breast cancer. It is the aim of this concept, to reduce postoperative morbidity by omitting a conventional lymph node dissection if the SLN is proven to be free of any tumor cells. First clinical studies showed promising results also in patients with head and neck cancer. However, both the anatomical localization of the primary tumor and the very complex lymphatic, frequently bilateral drainage pattern may lead to significant methodological problems. Besides a skilful intraoperative usage of the gamma probe, the precise preoperative staging of the respective patient for determination of the N0 status and the assiduous histopathological analysis of the excised SLN are extremely important to reach a maximum of sensitivity in this clinical setting. This paper summarizes the data published on the SLN concept in patients with head and neck cancer, describes the several methodological aspects of labeling the SLN with radiocolloides and reviews the today's impact of the SLN method in clinical routine. (orig.)

Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous Melanoma Regression in the Melanoma-Bearing Libechov Minipig

International Nuclear Information System (INIS)

Planska, Daniela; Burocziova, Monika; Strnadel, Jan; Horak, Vratislav

2015-01-01

Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma

Intraoperative examination of sentinel lymph nodes using scrape ...

African Journals Online (AJOL)

2014-08-03

Aug 3, 2014 ... Background. In breast cancer, sentinel lymph node biopsy (SLNB) is widely used to assess the axilla when the nodes appear normal on palpation and ultrasonography. When the sentinel lymph nodes (SLNs) are negative, no further dissection is required. Surgical dissection or radiotherapy of the axilla is ...

Molecular Classification of Melanoma

Science.gov (United States)

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.

The evolution of the sentinel node procedure in the treatment of breast cancer.

Science.gov (United States)

Tvedskov, Tove Filtenborg

2017-10-01

patients with micrometastases that might still benefit from an ALND. Efforts should continue to improve the model. As a part of the PhD thesis, new molecular markers were tested for prediction of non-sentinel node metastases. In addition, method of detection of the breast cancer could be a possible predictor of non-sentinel node metastases. It has been hypothesized that breast cancers detected by screening represent a clinical indolent group of cancers with lower risk of non-sentinel node metastases compared to symptomatic cancers. This hypothesis was tested in this thesis in a large Danish dataset. No significant difference in the risk of non-sentinel node metastases was found between patients with screen-detected and symptomatic breast cancers, and a less aggressive treatment of the axilla in patients with screen-detected breast cancers cannot be supported. Likewise, the method of detection is not expected to be able to improve the predictive models. Until 2012, the standard treatment of Danish patients with micrometastases or ITC in the sentinel node was ALND. Still, in selected patients ALND was not performed. This thesis includes a comparison of the risk of axillary recurrence and survival between patients with and without ALND. The overall axillary recurrence rate was only 1.6% after 6 years of follow-up, despite between 9 - 18 % of these patients are expected to have non-sentinel node metastases. No significant difference was seen in axillary recurrence and overall survival between patients with and without ALND. These results support the safety of omitting ALND in patients with only micrometastases or ITC in the sentinel node and since 2012 Danish breast cancer patients with ITC or up to two micrometastatic sentinel nodes are no longer offered an ALND. In Denmark the standard surgical treatment of the axilla in locally recurrent breast cancer is no further treatment of the axilla in case of previous ALND, and ALND in case of previous SLND.  To investigate whether

Emerging biomarkers for cancer immunotherapy in melanoma.

Science.gov (United States)

Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

2017-09-14

The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells.

Science.gov (United States)

Rossi, Ursula A; Finocchiaro, Liliana M E; Glikin, Gerardo C

2017-01-01

Malignant melanoma is a fast growing form of skin cancer with increasing global incidence. Clinically, canine malignant melanoma and human melanoma share comparable treatment-resistances, metastatic phenotypes and site selectivity. Both interferon-β (IFNβ) and bortezomib (BTZ) display inhibitory activities on melanoma cells. Here, we evaluated the cytotoxic effects of the combination of BTZ and IFNβ gene lipofection on cultured melanoma cell lines. Cell viability determined by the acid phosphatase method, cell migration mesasured by the wound healing assay, DNA fragmentation and cell cycle by flow cytometry after propidium iodide staining and reactive oxygen species (ROS) production by H2DCF-DA fluorescence. Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNβ transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration. The combined treatment produced a significant raise of apoptosis evidenced by DNA fragmentation as compared to either BTZ or IFNβ gene lipofection single treatments. Furthermore, BTZ significantly increased the intracellular ROS generation induced by IFNβ gene transfer in melanoma cells, an effect that was reversed by the addition of the ROS inhibitor N-acetyl-L-cystein. The present work encourages further studies about the potential of the combination of interferon gene transfer with proteasome inhibitors as a new combined therapy for malignant melanoma, both in veterinary and/or human clinical settings. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study

Energy Technology Data Exchange (ETDEWEB)

Klein, M.; Freedman, N.; Marciano, R.; Moshe, S.; Chisin, R. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Medical Biophysics and Nuclear Medicine; Lotem, M. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Oncology; Gimon, Z. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Surgery

2000-05-01

Aim: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. Methods: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy of clinical follow-up. Results: Group I: Out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. (orig.) [German] Ziel: Diese Pilot-Studie beschreibt die Anwendung der Ganzkoerper-PET (WB PET) zum Staging beim Melanom. Bei primaerem Melanom wurde WB PET in Verbindung mit der Lymphszintigraphie (LS) angewandt und mit der Histopathologie verglichen, um den Status des Sentinel Lymph Node (SLN) zu untersuchen. Zusaetzlich wurde WB PET fuer primaere und metastatische Melanome zum Screening auf Fernmetastasen, zum Restaging und zum Follow-up benutzt. Methoden: Gruppe I: 17 Patienten mit primaerem kutanem Melanom erhielten LS, WB PET und eine operative SLN-Entfernung. Die WB PET-Ergebnisse wurden mit den SLN-Biopsien verglichen und zum Screening fuer Fernmetastasen benutzt. Gruppe

Nivolumab-induced vitiligo in a metastatic melanoma patient: A case report.

Science.gov (United States)

Edmondson, Lindsay A; Smith, Leticia V; Mallik, Alka

2017-12-01

The programmed-death-1 inhibitors selectively block programmed-death-1 interaction with its receptor, which restores active T-cell response directed at tumor cells, inducing an anti-tumor effect. This nonspecific activation of the immune system can also lead to a wide spectrum of side effects. Nivolumab has been used effectively to prolong survival in patients with metastatic melanoma and is recommended as a category 1 agent for systemic therapy in metastatic or unresectable melanoma per the National Comprehensive Cancer Network guidelines. We present a case of a 64-year-old woman who began nivolumab therapy for metastatic melanoma. After six doses of nivolumab therapy, the patient experienced generalized hypopigmentation on her face, chest, back, arms, and lower extremities. Although vitiligo has been reported in as many as 10.7% of patients undergoing nivolumab therapy in some clinical trials, we believe this is the first case to describe the progression of nivolumab-induced vitiligo in a metastatic melanoma patient. This case provides significant insight into the onset, symptoms, development, and treatment options for patients experiencing vitiligo as a result of nivolumab therapy.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

Science.gov (United States)

Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

Science.gov (United States)

Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

2017-02-01

Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

Malignant melanoma at a scientific laboratory

International Nuclear Information System (INIS)

Shy, C.M.; Checkoway, H.; Marshall, E.G.

1985-01-01

The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

Science.gov (United States)

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

2018-03-01

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort.

Science.gov (United States)

Cho, Hyunje G; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Assimes, Themistocles; Han, Jiali; Stefanick, Marcia; Tang, Jean Y; Sarin, Kavita Y

2018-07-01

Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk. We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women. Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset. Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma. Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort. Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea

KAUST Repository

Tsangaris, Catherine; Moschino, Vanessa; Strogyloudi, Evangelia; Coatu, Valentina; Ramšak, Andreja; Abu Alhaija, Rana; Carvalho, Susana; Felline, Serena; Kosyan, Alisa; Lazarou, Yiota; Hatzianestis, Ioannis; Oros, Andra; Tiganus, Daniela

2015-01-01

Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the “Integrated Biological Responses version 2” index was useful for the interpretation of overall biomarker responses.

Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea

KAUST Repository

Tsangaris, Catherine

2015-09-23

Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the “Integrated Biological Responses version 2” index was useful for the interpretation of overall biomarker responses.

Biochemical biomarker responses to pollution in selected sentinel organisms across the Eastern Mediterranean and the Black Sea.

Science.gov (United States)

Tsangaris, Catherine; Moschino, Vanessa; Strogyloudi, Evangelia; Coatu, Valentina; Ramšak, Andreja; Alhaija, Rana Abu; Carvalho, Susana; Felline, Serena; Kosyan, Alisa; Lazarou, Yiota; Hatzianestis, Ioannis; Oros, Andra; Tiganus, Daniela

2016-01-01

Pollution effects were assessed by means of biochemical biomarkers (catalase, glutathione S-transferase and acetylcholinesterase activities, and metallothioneins content) in five species at selected coastal sites across the Eastern Mediterranean and the Black Sea. The mussel Mytilus galloprovincialis, a well-established sentinel species, was investigated in the Adriatic Sea, Aegean Sea, and Black Sea. The mussel Brachidontes pharaonis and the striped red mullet Mullus surmuletus were used in the Levantine Sea where M. galloprovincialis is not present. The white seabream Diplodus sargus sargus and the gastropod Rapana venosa were additionally sampled in the Adriatic and the Black Sea, respectively. Mussels showed catalase, glutathione S-transferase, and acetylcholinesterase responses to pollution in most geographical areas while the response of metallothioneins was restricted to a few sites. R. venosa showed marked responses of catalase and metallothioneins whereas both fish species did not generally exhibit variations in biomarker values among sites. The approach based on the reference deviation concept using the "Integrated Biological Responses version 2" index was useful for the interpretation of overall biomarker responses.

SENTINEL-1 RESULTS: SEA ICE OPERATIONAL MONITORING

DEFF Research Database (Denmark)

Toudal Pedersen, Leif; Saldo, Roberto; Fenger-Nielsen, Rasmus

2015-01-01

In the present paper we demonstrate the capabilities of the Sentinel-1 SAR data for operational sea-ice and iceberg monitoring. Most of the examples are drawn from the Copernicus Marine Environmental Monitoring Service (CMEMS) production.......In the present paper we demonstrate the capabilities of the Sentinel-1 SAR data for operational sea-ice and iceberg monitoring. Most of the examples are drawn from the Copernicus Marine Environmental Monitoring Service (CMEMS) production....

Breast Conserving Surgery and Sentinel Lymph Node Biopsy in Locally Advanced Breast Cancer: Single Center Experience

Directory of Open Access Journals (Sweden)

Atakan Sezer

2011-06-01

Full Text Available Objective: Patients with locally advanced breast cancer may undergo breast conserving surgery after neoadjuvant chemotherapy. The aim of the study is to evaluate the results of locally advanced breast cancer patients who underwent breast conserving surgery, axillary dissection and sentinel lymph node biopsy in a single center. Material and Methods: 12 patients with locally advanced breast cancer stage IIIA/IIIB were included in the study between 2002-2009. The patients were given anthracycline-based regimen before surgery. Patients underwent breast conserving surgery, axillary dissection, and sentinel lymph node biopsy followed by radiotherapy. Results: There were five patients in stage IIIA, six in stage IIIB, and one in stage IIIC. Patients had received 3-6 regimen of FAC/FEC. Eight had partial and four had complete response. Five positive axilla were detected. The median value of the lymph nodes was 12 (n:8-19. Five patients underwent sentinel lymph node biopsy. The biopsy has failed in one patient and the median value of dissected sentinel node was 3.5 (n:3-4. Locoregional recurrence was not observed in any patients. The mean follow-up of the patients was 29.8 months and median time was 16 (n:2-80 months.Of the 12 patients 10 are alive and 2 were deceased. Conclusion: In selected locally advanced patients, breast conserving surgery and sentinel lymph node biopsy may be applied by a multidisciplinary approach, and excellent success may be achieved in those patients as in early breast cancer patients.

The role of sentinel node detection techniques in vulvar and cervival cancer

International Nuclear Information System (INIS)

Wydra, D.; Sawicki, S.; Emerich, J.; Romanowicz, G.

2002-01-01

The sentinel node is the first lymph node that receives the lymph drainage from the primary tumour. The pathological status of the sentinel node should reflect the histopathology of the entire regional lymph drainage area - both vulvar and cervical cancer spread through the lymphatic system. In gynaecological oncology recent studies have confirmed the utility of the sentinel node concept in vulvar and cervical cancer. Three techniques for sentinel node localisation are available. The preoperative lymphoscintigraphy and intraoperative handheld gamma probe detection require the administration of the technetium-99m-labelled colloid around the tumour. The other method is based on the injection of the patent blue dye - during the surgery of the sentinel node because of the dye uptake becomes visible. Following detection, the sentinel lymph node can be removed separately and assessed with ultrastaging and immunohistochemical staining. In the early stages of vulvar and cervical cancer the lymph nodes metastases rate is relatively low - in most cases lymphadenectomy is not necessary. The determination of the regional lymph nodes' pathological status may limit the extent of the surgical treatment. The sentinel node detection rate is relatively high and depends on the applied technique. This technique may play an important role in the treatment of vulvar and cervical cancer. This paper describes the details of sentinel node identification and reviews the literature. (author)

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

NARCIS (Netherlands)

Weide, Benjamin; Martens, Alexander; Hassel, Jessica C.; Berking, Carola; Postow, Michael A.; Bisschop, Kees; Simeone, Ester; Mangana, Johanna; Schilling, Bastian; Di Giacomo, Anna Maria; Brenner, Nicole; Kaehler, Katharina; Heinzerling, Lucie; Gutzmer, Ralf; Bender, Armin; Gebhardt, Christoffer; Romano, Emanuela; Meier, Friedegund; Martus, Peter; Maio, Michele; Blank, Christian; Schadendorf, Dirk; Dummer, Reinhard; Ascierto, Paolo A.; Hospers, Geke; Garbe, Claus; Wolchok, Jedd D.

2016-01-01

Purpose: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients. Experimental Design:

Imidazopyridine-fused [1,3]-diazepinones part 2: Structure-activity relationships and antiproliferative activity against melanoma cells.

Science.gov (United States)

Bellet, Virginie; Lichon, Laure; Arama, Dominique P; Gallud, Audrey; Lisowski, Vincent; Maillard, Ludovic T; Garcia, Marcel; Martinez, Jean; Masurier, Nicolas

2017-01-05

We recently described a pyrido-imidazodiazepinone derivative which could be a promising hit compound for the development of new drugs acting against melanoma cells. In this study, a series of 28 novel pyrido-imidazodiazepinones were synthesized and screened for their in vitro cytotoxic activities against the melanoma MDA-MB-435 cell line. Among the derivatives, seven of them showed 50% growth inhibitory activity at 1 μM concentration, and high selectivity against the melanoma cell line MDA-MB-435. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In vitro and in vivo studies in boron neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

Allen, B.J.

1982-01-01

A multidisciplinary research project in boron neutron capture therapy of malignant melanoma is under consideration by the Australian Atomic Energy Commission. This paper reviews the biochemistry of melanoma and the properties of some melanoma-affined radiopharmaceuticals and their boron analogues. Human cell lines are being used for in vitro tests of uptake and incorporation of some of these compounds, and selected lines will then be implanted in nude mice for in vivo distribution studies. The fidelity of human melanoma xenografts in nude mice has been well studied, and results are reviewed in this paper. Boron concentration will be measured directly by plasma arc emission spectroscopy or liquid scintillation counting with 14 C-labelled boron analogues. Track-etch techniques will be used for the microscopic determination of boron in tumor sections. Neutron irradiation and radiobiology experiments are outlined

Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

Directory of Open Access Journals (Sweden)

Amy E Gilbert

Full Text Available Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10 to primary and metastatic melanoma cells compared to healthy volunteers (n = 10 (P<0.0001. Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21 (P<0.0001. Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800 compared to 2% of cultures from healthy controls (n = 600 produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

Science.gov (United States)

Gilbert, Amy E.; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H.; Takhar, Pooja; Geh, Jenny L. C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Rudman, Sarah M.; Beavil, Rebecca L.; Blower, Philip J.; Beavil, Andrew J.; Gould, Hannah J.; Spicer, James; Nestle, Frank O.; Karagiannis, Sophia N.

2011-01-01

Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer. PMID:21559411

Metastatic melanoma after 23 years of primary ocular melanoma.

LENUS (Irish Health Repository)

Karde, Supriya Ramesh

2016-11-23

We describe a case of 52-year-old man who presented with an episode of tonic-clonic seizures. He had right ocular melanoma 23 years ago with subsequent enucleation which was the standard treatment at that time. CT scans of the brain and of the thorax-abdomen-pelvis revealed widespread metastatic lesions in the brain, lung and liver. Further investigations including bronchoscopy with cytopathology uncovered that the metastatic disease was a recurrence of ocular melanoma. He received palliative radiotherapy and died 6 months later. Ocular melanoma is often associated with fulminant metastatic disease after a period of dormancy. Thus, despite successful treatment of the localised disease at initial presentation, an effort is needed for optimal long-term follow-up plan in order to improve survival in case of recurrence.

Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine

International Nuclear Information System (INIS)

Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S.; Packer, S.

1990-01-01

During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of 10 B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

Science.gov (United States)

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

SENTINEL-2 Services Library - efficient way for exploration and exploitation of EO data

Science.gov (United States)

Milcinski, Grega; Batic, Matej; Kadunc, Miha; Kolaric, Primoz; Mocnik, Rok; Repse, marko

2017-04-01

With more than 1.5 million scenes available covering over 11 billion sq. kilometers of area and containing half a quadrillion of pixels, Sentinel-2 is becoming one of the most important MSI datasets in the world. However, the vast amount of data makes it difficult to work with. This is certainly an important reason, why the number of Sentinel based applications is not as high as it could be at this point. We will present a Copernicus Award [1] winning service for archiving, processing and distribution of Sentinel data, Sentinel Hub [2]. It makes it easy for anyone to tap into global Sentinel archive and exploit its rich multi-sensor data to observe changes in the land. We will demonstrate, how one is able not just to observe imagery all over the world but also to create its own statistical analysis in a matter of seconds, performing comparison of different sensors through various time segments. The result can be immediately observed in any GIS tool or exported as a raster file for post-processing. All of these actions can be performed on a full, worldwide, S-2 archive (multi-temporal and multi-spectral). To demonstrate the technology, we created a publicly accessible web application, called "Sentinel Playground" [3], which makes it possible to query Sentinel-2 data anywhere in the world, and experts-oriented tool "EO Browser" [4], where it is also possible to observe land changes through longer period by using historical Landsat data as well. [1] http://www.copernicus-masters.com/index.php?anzeige=press-2016-03.html [2] http://www.sentinel-hub.com [3] http://apps.sentinel-hub.com/sentinel-playground/ [4] http://apps.eocloud.sentinel-hub.com/eo-browser/

Combined endoscopic and laparoscopic approach for palliative resection of metastatic melanoma of the stomach

Directory of Open Access Journals (Sweden)

Pritchard SA

2006-03-01

Full Text Available Abstract Background Metastatic tumours of the stomach present a clinical dilemma for the surgeon. Palliative surgical resection can alleviate symptoms and prolong survival in selected patients. However, previous studies have used open methods of surgical resection with potentially high morbidity and mortality. We describe the use of laparoscopic wedge resection of the stomach for palliative resection of metastatic melanoma to highlight the benefits of this technique. Case presentation A 58 year old male was investigated for iron deficiency anaemia while under treatment for pulmonary metastatic malignant melanoma. An upper gastrointestinal endoscopy revealed a 5 cm diameter ulcer on the anterior wall of the stomach, biopsies from the ulcer confirmed metastatic melanoma. Laparoscopic wedge resection of the stomach lesion was performed without complication. Conclusion Laparoscopic approach has many benefits and is useful for the palliative resection of rare tumours of the stomach in order to preserve the quality of life. Its use should be considered in selected patients.

Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

Science.gov (United States)

Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S

2016-05-01

Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.

Sentinel nodes identified by computed tomography-lymphography accurately stage the axilla in patients with breast cancer

International Nuclear Information System (INIS)

Motomura, Kazuyoshi; Sumino, Hiroshi; Noguchi, Atsushi; Horinouchi, Takashi; Nakanishi, Katsuyuki

2013-01-01

Sentinel node biopsy often results in the identification and removal of multiple nodes as sentinel nodes, although most of these nodes could be non-sentinel nodes. This study investigated whether computed tomography-lymphography (CT-LG) can distinguish sentinel nodes from non-sentinel nodes and whether sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. This study included 184 patients with breast cancer and clinically negative nodes. Contrast agent was injected interstitially. The location of sentinel nodes was marked on the skin surface using a CT laser light navigator system. Lymph nodes located just under the marks were first removed as sentinel nodes. Then, all dyed nodes or all hot nodes were removed. The mean number of sentinel nodes identified by CT-LG was significantly lower than that of dyed and/or hot nodes removed (1.1 vs 1.8, p <0.0001). Twenty-three (12.5%) patients had ≥2 sentinel nodes identified by CT-LG removed, whereas 94 (51.1%) of patients had ≥2 dyed and/or hot nodes removed (p <0.0001). Pathological evaluation demonstrated that 47 (25.5%) of 184 patients had metastasis to at least one node. All 47 patients demonstrated metastases to at least one of the sentinel nodes identified by CT-LG. CT-LG can distinguish sentinel nodes from non-sentinel nodes, and sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. Successful identification of sentinel nodes using CT-LG may facilitate image-based diagnosis of metastasis, possibly leading to the omission of sentinel node biopsy

Joint Sentinel-1 and SMAP data assimilation to improve soil moisture estimates

Science.gov (United States)

Lievens, H.; Reichle, R. H.; Liu, Q.; De Lannoy, G.; Dunbar, R. S.; Kim, S.; Das, N. N.; Cosh, M. H.; Walker, J. P.; Wagner, W.

2017-12-01

SMAP (Soil Moisture Active and Passive) radiometer observations at 40 km resolution are routinely assimilated into the NASA Catchment Land Surface Model (CLSM) to generate the SMAP Level 4 Soil Moisture product. The use of C-band radar backscatter observations from Sentinel-1 has the potential to add value to the radiance assimilation by increasing the level of spatial detail. The specifications of Sentinel-1 are appealing, particularly its high spatial resolution (5 by 20 m in interferometric wide swath mode) and frequent revisit time (6 day repeat cycle for the Sentinel-1A and Sentinel-1B constellation). However, the shorter wavelength of Sentinel-1 observations implies less sensitivity to soil moisture. This study investigates the value of Sentinel-1 data for hydrologic simulations by assimilating the radar observations into CLSM, either separately from or simultaneously with SMAP radiometer observations. To facilitate the assimilation of the radar observations, CLSM is coupled to the water cloud model, simulating the radar backscatter as observed by Sentinel-1. The innovations, i.e. differences between observations and simulations, are converted into increments to the model soil moisture state through an Ensemble Kalman Filter. The assimilation impact is assessed by comparing 3-hourly, 9 km surface and root-zone soil moisture simulations with in situ measurements from 9 km SMAP core validation sites and sparse networks, from May 2015 to 2017. The Sentinel-1 assimilation consistently improves surface soil moisture, whereas root-zone impacts are mostly neutral. Relatively larger improvements are obtained from SMAP assimilation. The joint assimilation of SMAP and Sentinel-1 observations performs best, demonstrating the complementary value of radar and radiometer observations.

Xeroderma pigmentosum genes and melanoma risk.

Science.gov (United States)

Paszkowska-Szczur, K; Scott, R J; Serrano-Fernandez, P; Mirecka, A; Gapska, P; Górski, B; Cybulski, C; Maleszka, R; Sulikowski, M; Nagay, L; Lubinski, J; Dębniak, T

2013-09-01

Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. Copyright © 2013 UICC.

The Sentinel-4 detectors: architecture and performance

Science.gov (United States)

Skegg, Michael P.; Hermsen, Markus; Hohn, Rüdiger; Williges, Christian; Woffinden, Charles; Levillain, Yves; Reulke, Ralf

2017-09-01

The Sentinel-4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program. SENTINEL-4 will provide accurate measurements of trace gases from geostationary orbit, including key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Key to achieving these atmospheric measurements are the two CCD detectors, covering the wavelengths in the ranges 305 nm to 500 nm (UVVIS) and 750 to 775 nm (NIR) respectively. The paper describes the architecture, and operation of these two CCD detectors, which have an unusually high full-well capacity and a very specific architecture and read-out sequence to match the requirements of the Sentinel- 4 instrument. The key performance aspects and their verification through measurement are presented, with a focus on an unusual, bi-modal dark signal generation rate observed during test.

The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

Science.gov (United States)

Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

1991-08-01

We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

Metastatic melanoma of mesentery

International Nuclear Information System (INIS)

Shamim, M. S.; Ali, S.A.; Shirazi, B.; Shamim, M.

2004-01-01

A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively. (author)

U.S. Geological Survey distribution of European Space Agency's Sentinel-2 data

Science.gov (United States)

Pieschke, Renee L.

2017-03-31

A partnership established between the European Space Agency (ESA) and the U.S. Geological Survey (USGS) allows for USGS storage and redistribution of images acquired by the MultiSpectral Instrument (MSI) on the European Union's Sentinel-2 satellite mission. The MSI data are acquired from a pair of satellites, Sentinel-2A and Sentinel-2B, which are part of a larger set of ESA missions focusing on different aspects of Earth observation. The primary purpose of the Sentinel-2 series is to collect multispectral imagery over the Earth’s land surfaces, large islands, and inland and coastal waters. Sentinel-2A was launched in 2015 and Sentinel-2B launched in 2017.The collaborative effort between ESA and USGS provides for public access and redistribution of global acquisitions of Sentinel-2 data at no cost, which allows users to download the MSI imagery from USGS access systems such as Earth- Explorer, in addition to the ESA Sentinels Scientific Data Hub. The MSI sensor acquires 13 spectral bands that are highly complementary to data acquired by the USGS Landsat 8 Operational Land Imager (OLI) and Landsat 7 Enhanced Thematic Mapper Plus (ETM+). The product options from USGS include a Full-Resolution Browse (FRB) image product generated by USGS, along with a 100-kilometer (km) by 100-km tile-based Level-1C top-of-atmosphere (TOA) reflectance product that is very similar (but not identical) to the currently (2017) distributed ESA Level 1C product.

Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

Science.gov (United States)

Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

2012-01-01

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-γ were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

Long-term Survival after Metastatic Childhood Melanoma

DEFF Research Database (Denmark)

Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

2014-01-01

SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant...... of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

Directory of Open Access Journals (Sweden)

Alexander Joseph Trevarton

2013-07-01

Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

Tidal Creek Sentinel Habitat Database

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Ecological Research, Assessment and Prediction's Tidal Creeks: Sentinel Habitat Database was developed to support the National Oceanic and Atmospheric...

Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines

Directory of Open Access Journals (Sweden)

Joanna Jaworek-Korjakowska

2016-01-01

Full Text Available Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.

Assessing Vegetation Response to Soil Moisture Fluctuation under Extreme Drought Using Sentinel-2

Directory of Open Access Journals (Sweden)

Harry West

2018-06-01

Full Text Available The aim of this study was to determine the extent to which Sentinel-2 Normalised Difference Vegetation Index (NDVI reflects soil moisture conditions, and whether this product offers an improvement over Landsat-8. Based on drought exposure, cloud-free imagery availability, and measured soil moisture, five sites in the Southwestern United States were selected. These sites, normally dry to arid, were in various states of drought. A secondary focus was therefore the performance of the NDVI under extreme conditions. Following supervised classification, the NDVI values for one-kilometre radius areas were calculated. Sentinel-2 NDVI variants using Spectral Bands 8 (10 m spatial resolution, 5, 6, 7, and 8A (20 m spatial resolution were calculated. Landsat-8 NDVI was calculated at 30 m spatial resolution. Pearson correlation analysis was undertaken for NDVI against moisture at various depths. To assess the difference in correlation strength, a principal component analysis was performed on the combination of all bands and the combination of the new red-edge bands. Performance of the red-edge NDVI against the standard near infrared (NIR was then evaluated using a Steiger comparison. No significant correlations between Landsat-8 NDVI and soil moisture were found. Significant correlations at depths of less than 30 cm were present between Sentinel-2 NDVI and soil moisture at three sites. The remaining two sites were characterised by low vegetation cover, suggesting a cover threshold of approximately 30–40% is required for a correlation to be present. At all sites of significant positive moisture to NDVI correlation, the linear combination of the red-edge bands produced stronger correlations than the poorer spectral but higher spatial resolution band. NDVI calculated using the higher spectral resolution bands may therefore be of greater use in this context than the higher spatial resolution option. Results suggest potential for the application of Sentinel-2

Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

Centers for Disease Control (CDC) Podcasts

This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.

Roles of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer patients

International Nuclear Information System (INIS)

Sun Xiao; Liu Juanjuan; Wang Yongsheng; Wang Lei; Yang Guoren; Zhou Zhengbo; Li Yongqing; Liu Yanbing; Li Taiyu

2010-01-01

The objective of this study was to evaluate roles of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer patients. Five hundred and sixty-five consecutive breast cancer patients were prospectively randomized into groups with or without preoperative lymphoscintigraphy. In a group with lymphoscintigraphy, 238 patients had sentinel lymph nodes spotted in lymphoscintigram. The visualization of sentinel lymph nodes in lymphoscintigram was not associated with patients' age, primary tumor size and location, histopathologic type and time interval from injection of radiocolloid to lymphoscintigraphy. However, patients with axillary metastasis had a lower identification rate of sentinel lymph nodes by lymphoscintigraphy than those without metastasis (P=0.003). The identification rate of axillary sentinel lymph nodes was 99.3% in the group and the rate was similar whether there was sentinel lymph nodes spotted in axillary in lymphoscintigram or not (99.6% vs. 98.1%, P=0.327). The false-negative rate in this group was 4.2%. While in a group without lymphoscintigraphy, the identification rate and the false-negative rate were 99.6% and 4.8%, respectively. There was no significant difference between the two groups in the identification rate of axillary sentinel lymph nodes (P=0.594) and in the false-negative rate (P=1.00). Preoperative lymphoscintigraphy could neither improve the identification rate nor reduce the false-negative rate of breast cancer sentinel lymph node biopsy, and it is not necessary for sentinel lymph node biopsy in breast cancer patients. (author)

Systematic genomic and translational efficiency studies of uveal melanoma.

Directory of Open Access Journals (Sweden)

Chelsea Place Johnson

Full Text Available To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.

Podoplanin Expression in Canine Melanoma.

Science.gov (United States)

Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

2016-12-01

A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

Sentinel-5: the new generation European operational atmospheric chemistry mission in polar orbit

Science.gov (United States)

Pérez Albiñana, Abelardo; Erdmann, Matthias; Wright, Norrie; Martin, Didier; Melf, Markus; Bartsch, Peter; Seefelder, Wolfgang

2017-08-01

Sentinel-5 is an Earth Observation instrument to be flown on the Metop Second Generation (Metop-SG) satellites with the fundamental objective of monitoring atmospheric composition from polar orbit. The Sentinel-5 instrument consists of five spectrometers to measure the solar spectral radiance backscattered by the earth atmosphere in five bands within the UV (270nm) to SWIR (2385nm) spectral range. Data provided by Sentinel-5 will allow obtaining the distribution of important atmospheric constituents such as ozone, on a global daily basis and at a finer spatial resolution than its precursor instruments on the first generation of Metop satellites. The launch of the first Metop-SG satellite is foreseen for 2021. The Sentinel-5 instrument is being developed by Airbus DS under contract to the European Space Agency. The Sentinel-5 mission is part of the Space Component of the Copernicus programme, a joint initiative by ESA, EUMETSAT and the European Commission. The Preliminary Design Review (PDR) for the Sentinel-5 development was successfully completed in 2015. This paper provides a description of the Sentinel-5 instrument design and data calibration.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

Science.gov (United States)

Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

2017-01-01

Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

Peptides in melanoma therapy.

Science.gov (United States)

Mocellin, Simone

2012-01-01

Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

Electron Paramagnetic Resonance Spectrometry and Imaging in Melanomas: Comparison between Pigmented and Nonpigmented Human Malignant Melanomas

Directory of Open Access Journals (Sweden)

Quentin Godechal

2013-06-01

Full Text Available It has been known for a long time that the melanin pigments present in normal skin, hair, and most of malignant melanomas can be detected by electron paramagnetic resonance (EPR spectrometry. In this study, we used EPR imaging as a tool to map the concentration of melanin inside ex vivo human pigmented and nonpigmented melanomas and correlated this cartography with anatomopathology. We obtained accurate mappings of the melanin inside pigmented human melanoma samples. The signal intensity observed on the EPR images correlated with the concentration of melanin within the tumors, visible on the histologic sections. In contrast, no EPR signal coming from melanin was observed from nonpigmented melanomas, therefore demonstrating the absence of EPR-detectable pigments inside these particular cases of skin cancer and the importance of pigmentation for further EPR imaging studies on melanoma.

Choroidal melanoma

International Nuclear Information System (INIS)

Hernandez Quesada, Flora

2013-01-01

A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

The Sentinel-1 Mission: New Opportunities for Ice Sheet Observations

Directory of Open Access Journals (Sweden)

Thomas Nagler

2015-07-01

Full Text Available The Sentinel satellite constellation series, developed by the European Space Agency, represents the dedicated space component of the European Copernicus program, committed to long-term operational services in a wide range of application domains. Here, we address the potential of the Sentinel-1 mission for mapping and monitoring the surface velocity of glaciers and ice sheets. We present an ice velocity map of Greenland, derived from synthetic aperture radar (SAR data acquired in winter 2015 by Sentinel-1A, the first satellite of the Copernicus program in orbit. The map is assembled from about 900 SAR scenes acquired in Interferometric Wide swath (IW mode, applying the offset tracking technique. We discuss special features of IW mode data, describe the procedures for producing ice velocity maps, and assess the uncertainty of the ice motion product. We compare the Sentinel-1 ice motion product with velocity maps derived from high resolution SAR data of the TerraSAR-X mission and from PALSAR data. Beyond supporting operational services, the Sentinel-1 mission offers enhanced capabilities for comprehensive and long-term observation of key climate variables, such as the motion of ice masses.

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

Science.gov (United States)

Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

Proteomics in uveal melanoma.

LENUS (Irish Health Repository)

Ramasamy, Pathma

2014-01-01

Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

Mistletoe in the treatment of malignant melanoma

Directory of Open Access Journals (Sweden)

Esin Sakallı Çetin

2014-03-01

Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

Citrullus lanatus 'sentinel' (watermelon) extract reduces atherosclerosis in LDL receptor-deficient mice.

Science.gov (United States)

Poduri, Aruna; Rateri, Debra L; Saha, Shubin K; Saha, Sibu; Daugherty, Alan

2013-05-01

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar 'sentinel,' on hypercholesterolemia-induced atherosclerosis in mice. Male low-density lipoprotein receptor-deficient mice at 8 weeks old were given either C. lanatus 'sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water while being fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus 'sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus 'sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake and in urine output between the two groups. C. lanatus 'sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate-/low-density lipoprotein cholesterol. Plasma concentrations of monocyte chemoattractant protein-1 and interferon-gamma were decreased and those of interleukin-10 were increased in mice consuming C. lanatus 'sentinel' extract. Intake of C. lanatus 'sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus 'sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Sentinel lymph nodes in cancer of the oral cavity

DEFF Research Database (Denmark)

Thomsen, Jørn Bo; Christensen, Rikke Kølby; Sørensen, Jens Ahm

2007-01-01

when compared with (B) step-sectioning and immunostaining of the entire sentinel lymph node at 250 microM levels. METHODS: Forty patients with T1/T2 cN0 oral cancer were enrolled. Three patients were excluded. In one patient no sentinel lymph node was identified. The remaining two had unidentified...

Melanoma Surveillance in the US: The Economic Burden of Melanoma

Centers for Disease Control (CDC) Podcasts

2011-10-19

This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

Clinical significance of the molecular detection of melanoma cells circulating in the peripheral blood in melanoma patients.

Science.gov (United States)

Konstantopoulos, K; Psatha, M; Kalotychou, V; Frangia, N; Ioannovits, I; Meletis, I; Loukopoulos, D

2001-06-01

Blood circulating melanoma cells may be important for the spread of the disease. The current methods are not sensitive in detecting micro metastases. Tyrosinase mRNA can be detected in peripheral blood by a molecular test. As tyrosinase is expressed only in melanocytes and melanocytes normally do not circulate in the blood, the test may prove reliable in detecting circulating melanoma cells. we used a reverse-transcription polymerase chain reaction (RT-PCR) detecting tyrosinase mRNA in the blood. A prospective investigation in melanoma patients undergoing surgery was conducted; follow-up duration was 12 months. University Department Laboratory and Melanoma Clinic of a Tertiary Hospital. a total of 27 Greek patients with a diagnosis of malignant melanoma at different stages of the disease; 12 months follow-up after surgery. Samples form 12 healthy volunteers and 13 patients with chronic myelogenous leukemia served as controls. none. none. We detected mRNA tyrosinase in the peripheral blood in 16 out of 27 melanoma patients studied. No tyrosinase mRNA was detected in any of the 25 samples from the controls. Two of the 16 positive cases developed a metastasis within the next 12 months following testing. The other 14 positive cases remain metastasis free for this period, as also did the test negative cases. Detection of blood circulating melanoma cells by a RT-PCR technique, may be helpful in defining melanoma patients who are at risk for the spread of the disease.

PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

African Journals Online (AJOL)

2015-12-01

Dec 1, 2015 ... commonly in larynx, tongue, and tonsil.2 Primary mel- anoma of the larynx and trachea are very rare among the group of non-cutaneous melanomas. In primary melanoma of the larynx, the least common site is the subglottic mucosa.3 Here we present a case of primary malignant melanoma of aryepiglottic ...

Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.

Science.gov (United States)

Mar, Victoria J; Chamberlain, Alex J; Kelly, John W; Murray, William K; Thompson, John F

2017-10-16

A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

Targeted Therapy for Melanoma

International Nuclear Information System (INIS)

Quinn, Thomas; Moore, Herbert

2016-01-01

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 "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)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 "2"1"2Pb labeled DOTA-Re(Arg"1"1)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 "2"1"2Pb. 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.

Targeted Therapy for Melanoma

Energy Technology Data Exchange (ETDEWEB)

Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

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.

Laser radiation therapy of skin melanoma

Energy Technology Data Exchange (ETDEWEB)

Wagner, R.I.; Kozlov, A.P.; Moskalik, K.G.

1981-10-01

Pulsed neodymium laser radiation was used for the treatment of 79 patients with cutaneous melanomas and 19 patients with melanoma metastases to the skin. The patients were followed up from 3 months up to 8 years. During this period local recurrences were detected in 2 cases. Out of 70 patients with cutaneous melanomas, who by the start of the treatment had no metastases in the regional lymph nodes or distant organs, metastases developed in 15 patients (21.4%). There are all reasons to consider pulsed laser radiation an effective means of treatment of some forms of skin melanoma.

[Selective biopsy of the sentinel lymph node in patients with breast cancer and previous excisional biopsy: is there a change in the reliability of the technique according to time from surgery?].

Science.gov (United States)

Sabaté-Llobera, A; Notta, P C; Benítez-Segura, A; López-Ojeda, A; Pernas-Simon, S; Boya-Román, M P; Bajén, M T

2015-01-01

To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection were 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24-75). Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Sentinel Asia step 2 utilization for disaster management in Malaysia

International Nuclear Information System (INIS)

Moslin, S I; Wahap, N A; Han, O W

2014-01-01

With the installation of Wideband InterNetworking engineering test and Demonstration Satellite (WINDS) communication system in the National Space Centre, Banting; officially Malaysia is one of the twelve Sentinel Asia Step2 System Regional Servers in the Asia Pacific region. The system will be dedicated to receive and deliver images of disaster struck areas observed by Asia Pacific earth observation satellites by request of the Sentinel Asia members via WINDS satellite or 'Kizuna'. Sentinel Asia is an initiative of collaboration between space agencies and disaster management agencies, applying remote sensing and web-GIS technologies to assist disaster management in Asia Pacific. When a disaster occurred, participating members will make an Emergency Observation Request (EOR) to the Asian Disaster Reduction Centre (ADRC). Subsequently, the Data Provider Node (DPN) will execute the emergency observation using the participating earth observation satellites. The requested images then will be processed and analysed and later it will be uploaded on the Sentinel Asia website to be utilised for disaster management and mitigation by the requestor and any other international agencies related to the disaster. Although the occurrences of large scale natural disasters are statistically seldom in Malaysia, but we can never be sure with the unpredictable earth climate nowadays. This paper will demonstrate the advantage of using Sentinel Asia Step2 for local disaster management. Case study will be from the recent local disaster occurrences. In addition, this paper also will recommend a local disaster management support system by using the Sentinel Asia Step2 facilities in ANGKASA

Acral melanoma detection using a convolutional neural network for dermoscopy images.

Science.gov (United States)

Yu, Chanki; Yang, Sejung; Kim, Wonoh; Jung, Jinwoong; Chung, Kee-Yang; Lee, Sang Wook; Oh, Byungho

2018-01-01

Acral melanoma is the most common type of melanoma in Asians, and usually results in a poor prognosis due to late diagnosis. We applied a convolutional neural network to dermoscopy images of acral melanoma and benign nevi on the hands and feet and evaluated its usefulness for the early diagnosis of these conditions. A total of 724 dermoscopy images comprising acral melanoma (350 images from 81 patients) and benign nevi (374 images from 194 patients), and confirmed by histopathological examination, were analyzed in this study. To perform the 2-fold cross validation, we split them into two mutually exclusive subsets: half of the total image dataset was selected for training and the rest for testing, and we calculated the accuracy of diagnosis comparing it with the dermatologist's and non-expert's evaluation. The accuracy (percentage of true positive and true negative from all images) of the convolutional neural network was 83.51% and 80.23%, which was higher than the non-expert's evaluation (67.84%, 62.71%) and close to that of the expert (81.08%, 81.64%). Moreover, the convolutional neural network showed area-under-the-curve values like 0.8, 0.84 and Youden's index like 0.6795, 0.6073, which were similar score with the expert. Although further data analysis is necessary to improve their accuracy, convolutional neural networks would be helpful to detect acral melanoma from dermoscopy images of the hands and feet.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

Science.gov (United States)

Mahmood, Muhammad N; Lee, Min W; Linden, Michael D; Nathanson, S D; Hornyak, Thomas J; Zarbo, Richard J

2002-12-01

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Validation of sentinel data.

NARCIS (Netherlands)

Bartelds, A.I.M.

1993-01-01

The Dutch Sentinel Practice Network, "de Peilstations" started in 1970. The purpose of this network is to gain a better insight into the epidemiology of a number of illnesses and conditions as they are presented to the general practitioner. The network is sponsored by the Ministry of Welfare, Public

The Phosphoinositide 3-Kinaseα Selective Inhibitor, BYL719, Enhances the Effect of the Protein Kinase C Inhibitor, AEB071, in GNAQ/GNA11 Mutant Uveal Melanoma Cells

Science.gov (United States)

Musi, Elgilda; Ambrosini, Grazia; de Stanchina, Elisa; Schwartz, Gary K.

2014-01-01

G-protein mutations are one of the most common mutations occurring in uveal melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-Kinase (PI3K)/AKT pathways. In this study, we described the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11 mutations via PKC inhibition with AEB071 (Sotrastaurin) and PI3k/AKT inhibition with BYL719, a selective PI3Kα inhibitor. Growth inhibition was observed in GNAQ/GNA11 mutant cells with AEB071 versus no activity in WT cells. In the GNAQ-mutant cells, AEB071 decreased phosphorylation of MARCKS, a substrate of PKC, along with ERK1/2 and ribosomal S6, but persistent AKT activation was present. BYL719 had minimal anti-proliferative activity in all uveal melanoma cell lines, and inhibited phosphorylation of AKT in most cell lines. In the GNA11 mutant cell line, similar effects were observed with ERK1/2 inhibition, mostly inhibited by BYL719. With the combination treatment, both GNAQ and GNA11 mutant cell lines showed synergistic inhibition of cell proliferation and apoptotic cell death. In vivo studies correlated with in vitro findings showing reduced xenograft tumor growth with the combination therapy in a GNAQ mutant model. These findings suggest a new therapy treatment option for G-protein mutant uveal melanoma with a focus on specific targeting of multiple downstream pathways as part of combination therapy. PMID:24563540

The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells.

Science.gov (United States)

Musi, Elgilda; Ambrosini, Grazia; de Stanchina, Elisa; Schwartz, Gary K

2014-05-01

G-protein mutations are one of the most common mutations occurring in uveal melanoma activating the protein kinase C (PKC)/mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K)/AKT pathways. In this study, we described the effect of dual pathway inhibition in uveal melanoma harboring GNAQ and GNA11 mutations via PKC inhibition with AEB071 (sotrastaurin) and PI3K/AKT inhibition with BYL719, a selective PI3Kα inhibitor. Growth inhibition was observed in GNAQ/GNA11-mutant cells with AEB071 versus no activity in wild-type cells. In the GNAQ-mutant cells, AEB071 decreased phosphorylation of myristoylated alanine-rich C-kinase substrate, a substrate of PKC, along with ERK1/2 and ribosomal S6, but persistent AKT activation was present. BYL719 had minimal antiproliferative activity in all uveal melanoma cell lines, and inhibited phosphorylation of AKT in most cell lines. In the GNA11-mutant cell line, similar effects were observed with ERK1/2 inhibition, mostly inhibited by BYL719. With the combination treatment, both GNAQ- and GNA11-mutant cell lines showed synergistic inhibition of cell proliferation and apoptotic cell death. In vivo studies correlated with in vitro findings showing reduced xenograft tumor growth with the combination therapy in a GNAQ-mutant model. These findings suggest a new therapy treatment option for G-protein-mutant uveal melanoma with a focus on specific targeting of multiple downstream pathways as part of combination therapy.

Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

Directory of Open Access Journals (Sweden)

Daryoush Shahbazi-Gahrouei

2006-11-01

Full Text Available BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI contrast agents, Gd-hematoporphyrin (Gd-H and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP were synthesized and tested in nude mice with human melanoma (MM-138 xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138 were studied in 30 (five groups of six nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA on proton relaxation times was measured in tumors and other organs. T1 values, signal enhancement and the Gd concentration for different contrast agent solutions were also investigated. RESULTS: The porphyrin agents showed higher relaxivity compared to the clincal agent, Gd-DTPA. A significant 16% and 21% modification in T1 relaxation time of the water in human melanoma tumors grafted in the nude mice was revealed 24 hours after injection of Gd-TCP and Gd-H, respectively. The percentage of injected Gd localized to the tumor measured by inductively coupled plasma atomic emission spectrometry (ICP-AES was approximately 21% for Gd-TCP and 28% for Gd-H which were higher than that of Gd-DTPA (10%. CONCLUSIONS: The high concentration of Gd in the tumor is indicative of a selective retention of the compounds and indicates that Gd-TCP and Gd-H are promising MR imaging contrast agents for melanoma detection. Gd-porphyrins have considerable promise for further diagnostic applications in magnetic resonance imaging. KEY WORDS: MRI, porphyrin-based contrast agent, hematoporphyrin, melanoma.

Lymphatic drainage and sentinel node location in breast cancer

International Nuclear Information System (INIS)

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

1999-01-01

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

Melanoma

Science.gov (United States)

... cancers in females aged 15 to 29 years old. Tanning-bed use contributes to this. Melanoma: Who ... Publications Connect With Us Contact Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal ...

Marine mammals as sentinel species for oceans and human health.

Science.gov (United States)

Bossart, G D

2011-05-01

The long-term consequences of climate change and potential environmental degradation are likely to include aspects of disease emergence in marine plants and animals. In turn, these emerging diseases may have epizootic potential, zoonotic implications, and a complex pathogenesis involving other cofactors such as anthropogenic contaminant burden, genetics, and immunologic dysfunction. The concept of marine sentinel organisms provides one approach to evaluating aquatic ecosystem health. Such sentinels are barometers for current or potential negative impacts on individual- and population-level animal health. In turn, using marine sentinels permits better characterization and management of impacts that ultimately affect animal and human health associated with the oceans. Marine mammals are prime sentinel species because many species have long life spans, are long-term coastal residents, feed at a high trophic level, and have unique fat stores that can serve as depots for anthropogenic toxins. Marine mammals may be exposed to environmental stressors such as chemical pollutants, harmful algal biotoxins, and emerging or resurging pathogens. Since many marine mammal species share the coastal environment with humans and consume the same food, they also may serve as effective sentinels for public health problems. Finally, marine mammals are charismatic megafauna that typically stimulate an exaggerated human behavioral response and are thus more likely to be observed.

Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo-Thermo-Immunotherapy

Directory of Open Access Journals (Sweden)

Tomoaki Takada

2009-01-01

Full Text Available Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP, is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP upon exposure to an alternating magnetic field (AMF. This study tested if a chemo-thermo-immunotherapy (CTI therapy strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M. We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43∘C than either 41∘C or 46∘C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43∘C compared to that with 41∘C or 46∘C. CD+T cells were infiltrated at the site of the re-challenge melanoma transplant.

Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

Science.gov (United States)

Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, pcancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Advanced Melanoma Facebook Live Event

Science.gov (United States)

In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

The Copernicus Sentinel 4 mission: a geostationary imaging UVN spectrometer for air quality monitoring

Science.gov (United States)

Bazalgette Courrèges-Lacoste, G.; Sallusti, M.; Bulsa, G.; Bagnasco, G.; Veihelmann, Ben; Riedl, S.; Smith, D. J.; Maurer, R.

2017-09-01

Sentinel-4 is an imaging UVN (UV-VIS-NIR) spectrometer, developed by Airbus Defence and Space under ESA contract in the frame of the joint EU/ESA COPERNICUS program. The mission objective is the operational monitoring of trace gas concentrations for atmospheric chemistry and climate applications - hence the motto of Sentinel-4 "Knowing what we breathe". Sentinel-4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, methane, and aerosol properties over Europe and adjacent regions from a geostationary orbit (see Fig. 1). In the family of already flown UVN spectrometers (SCIAMACHY, OMI, GOME and GOME 2) and of those spectrometers currently under development (Sentinel-5p and Sentinel-5), Sentinel-4 is unique in being the first geostationary UVN mission. Furthermore, thanks to its 60-minutes repeat cycle measurements and high spatial resolution (8x8 km2), Sentinel-4 will increase the frequency of cloud-free observations, which is necessary to assess troposphere variability. Two identical Sentinel-4 instruments (PFM and FM-2) will be embarked, as Customer Furnished Item (CFI), fully verified, qualified and calibrated respectively onto two EUMETSAT satellites: Meteosat Third Generation-Sounder 1 and 2 (MTG-S1 and MTG-S2), whose Flight Acceptance Reviews are presently planned respectively in Q4 2021 and Q1 2030. This paper gives an overview of the Sentinel-4 system1 architecture, its design and development status, current performances and the key technological challenges.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

Science.gov (United States)

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Current management and novel agents for malignant melanoma

Directory of Open Access Journals (Sweden)

Lee Byung

2012-02-01

Full Text Available Abstract Advanced malignant melanoma remains a challenging cancer. Over the past year, there have been 3 agents approved for treatment of melanoma by Food and Drug Administration. These include pegylated interferon alpha-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for treatment of unresectable or metastatic melanoma. This review will also update on the development of novel agents, including tyrosine kinase inhibitors and adoptive cellular therapy.

Solar Sentinels: Report of the Science and Technology Definition Team

Science.gov (United States)

2006-01-01

The goal of NASA s Living With a Star (LWS) program is to develop the scientific understanding necessary to effectively address those aspects of the connected Sun Earth system that directly affect life and society. Along with the other elements of LWS, Solar Sentinels aims to discover, understand, and model the heliospheric initiation, propagation, and solar connection of those energetic phenomena that adversely affect space exploration and life and society here on Earth. The Solar Sentinels mission will address the following questions: (1) How, where, and under what circumstances are solar energetic particles (SEPs) accelerated to high energies and how do they propagate through the heliosphere? And (2) How are solar wind structures associated with these SEPs, like CMEs, shocks, and high-speed streams, initiated, propagate, evolve, and interact in the inner heliosphere? The Sentinels STDT recommends implementing this mission in two portions, one optimized for inner heliospheric in-situ measurements and the other for solar remote observations. Sentinels will greatly enhance the overall LWS science return.

A texture based pattern recognition approach to distinguish melanoma from non-melanoma cells in histopathological tissue microarray sections.

Directory of Open Access Journals (Sweden)

Elton Rexhepaj

Full Text Available AIMS: Immunohistochemistry is a routine practice in clinical cancer diagnostics and also an established technology for tissue-based research regarding biomarker discovery efforts. Tedious manual assessment of immunohistochemically stained tissue needs to be fully automated to take full advantage of the potential for high throughput analyses enabled by tissue microarrays and digital pathology. Such automated tools also need to be reproducible for different experimental conditions and biomarker targets. In this study we present a novel supervised melanoma specific pattern recognition approach that is fully automated and quantitative. METHODS AND RESULTS: Melanoma samples were immunostained for the melanocyte specific target, Melan-A. Images representing immunostained melanoma tissue were then digitally processed to segment regions of interest, highlighting Melan-A positive and negative areas. Color deconvolution was applied to each region of interest to separate the channel containing the immunohistochemistry signal from the hematoxylin counterstaining channel. A support vector machine melanoma classification model was learned from a discovery melanoma patient cohort (n = 264 and subsequently validated on an independent cohort of melanoma patient tissue sample images (n = 157. CONCLUSION: Here we propose a novel method that takes advantage of utilizing an immuhistochemical marker highlighting melanocytes to fully automate the learning of a general melanoma cell classification model. The presented method can be applied on any protein of interest and thus provides a tool for quantification of immunohistochemistry-based protein expression in melanoma.

Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database

DEFF Research Database (Denmark)

Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri

2018-01-01

estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics...

The patterns of melanoma presentation in Rijeka region.

Science.gov (United States)

Pavlović-Ružić, Ira; Jonjić, Nives; Zamolo, Gordana; Zuvić-Butorac, Marta; Katunarić, Miljenko; Pečanić, Sanja

2013-01-01

There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.

[Telomerase activity in uveal melanomas].

Science.gov (United States)

Rohrbach, J M; Riedinger, C; Wild, M; Partsch, M

2000-05-01

The maximum number of cell divisions of a certain cell population is genetically fixed so that aging cells become non-dividing (senescent) at least. This replicative life span, also known as "Hayflick limit", is probably defined by a "critical" length of the telomeres. Telomeres are special DNA-sequences located at the four ends of the chromosomes which are shortened with each cell cycle. Cells of most, but not all malignant tumours have been shown to reactivate the enzyme telomerase so that telomeres can be reconstructed, "Hayflick limit" can be overcome, and unlimited cell division can be established. This study was undertaken to elucidate whether telomerase reactivation is used by uveal melanoma cells. Fresh tumour tissue was removed from 10 untreated uveal melanomas after enucleation. Telomerase activity was determined using a PCR ELISA according to the Telomeric Repeat Amplification Protocol (TRAP). Normal tissue of the skin and the conjunctiva served as control. Telomerase activity was detectable in 90% of the investigated uveal melanomas. All control specimens were telomerase negative. Uveal melanoma growth seems to depend on telomerase reactivation. Thus, telomerase inhibition could offer a new principle for uveal melanoma therapy in the future.

Oral Amelanotic Melanoma | Adisa | Annals of Ibadan Postgraduate ...

African Journals Online (AJOL)

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 ...

SPICE: Sentinel-3 Performance Improvement for Ice Sheets

Science.gov (United States)

McMillan, M.; Escola, R.; Roca, M.; Thibaut, P.; Aublanc, J.; Shepherd, A.; Remy, F.; Benveniste, J.; Ambrózio, A.; Restano, M.

2017-12-01

For the past 25 years, polar-orbiting satellite radar altimeters have provided a valuable record of ice sheet elevation change and mass balance. One of the principle challenges associated with radar altimetry comes from the relatively large ground footprint of conventional pulse-limited radars, which reduces their capacity to make measurements in areas of complex topographic terrain. In recent years, progress has been made towards improving ground resolution, through the implementation of Synthetic Aperture Radar (SAR), or Delay-Doppler, techniques. In 2010, the launch of CryoSat-2 heralded the start of a new era of SAR Interferometric (SARIn) altimetry. However, because the satellite operated in SARIn and LRM mode over the ice sheets, many of the non-interferometric SAR altimeter processing techniques have been optimized for water and sea ice surfaces only. The launch of Sentinel-3, which provides full non-interferometric SAR coverage of the ice sheets, therefore presents the opportunity to further develop these SAR processing methodologies over ice sheets. Here we present results from SPICE, a 2 year study that focuses on (1) developing and evaluating Sentinel-3 SAR altimetry processing methodologies over the Polar ice sheets, and (2) investigating radar wave penetration through comparisons of Ku- and Ka-band satellite measurements. The project, which is funded by ESA's SEOM (Scientific Exploitation of Operational Missions) programme, has worked in advance of the operational phase of Sentinel-3, to emulate Sentinel-3 SAR and pseudo-LRM data from dedicated CryoSat-2 SAR acquisitions made at the Lake Vostok, Dome C and Spirit sites in East Antarctica, and from reprocessed SARIn data in Greenland. In Phase 1 of the project we have evaluated existing processing methodologies, and in Phase 2 we are investigating new evolutions to the Delay-Doppler Processing (DDP) and retracking chains. In this presentation we (1) evaluate the existing Sentinel-3 processing chain by

Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models

Czech Academy of Sciences Publication Activity Database

Tavares, M. T.; Shen, S.; Knox, T.; Hadley, M.; Kutil, Zsofia; Bařinka, Cyril; Villagra, A.; Kozikowski, A. P.

2017-01-01

Roč. 8, č. 10 (2017), s. 1031-1036 ISSN 1948-5875 R&D Projects: GA ČR GA15-19640S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : HDAC6 inhibitors * nexturastat A * melanoma Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.746, year: 2016

Lack of GNAQ and GNA11 germ-line mutations in familial melanoma pedigrees with uveal melanoma or blue nevi

Directory of Open Access Journals (Sweden)

Jason Ezra Hawkes

2013-06-01

Full Text Available Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q subunit alpha (GNAQ, Guanine nucleotide-binding protein G(q subunit alpha-11 (GNA11 and BRCA1 associated protein-1 (BAP1. Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.

Identification of the sentinel lymph node using hemosiderin in locally advanced breast cancer

Directory of Open Access Journals (Sweden)

PAULO HENRIQUE WALTER DE AGUIAR

Full Text Available ABSTRACT Objective: to verify the agreement rate in the identification of sentinel lymph node using an autologous marker rich in hemosiderin and 99 Technetium (Tc99 in patients with locally advanced breast cancer. Methods: clinical trial phase 1, prospective, non-randomized, of 18 patients with breast cancer and clinically negative axilla stages T2=4cm, T3 and T4. Patients were submitted to sub-areolar injection of hemosiderin 48 hours prior to sentinel biopsy surgery, and the identification rate was compared at intraoperative period to the gold standard marker Tc99. Agreement between methods was determined by Kappa index. Results: identification rate of sentinel lymph node was 88.9%, with a medium of two sentinel lymph nodes per patients. The study identified sentinel lymph nodes stained by hemosiderin in 83.3% patients (n=15, and, compared to Tc99 identification, the agreement rate was 94.4%. Conclusion: autologous marker rich in hemosiderin was effective to identify sentinel lymph nodes in locally advanced breast cancer patients.

Development of radiolabeled mannose-dextran conjugates for sentinel lymph node detection

International Nuclear Information System (INIS)

Fernandez Nunez, Eutimio Gustavo

2011-01-01

Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [ 99m Tc(CO)3] + . Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99m Tc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa ( 99m Tc - DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radio complex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99m Tc - DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile. (author)

Examples of Sentinel-2A Mission Exploitation Results

Science.gov (United States)

Koetz, Benjamin; Hoersch, Bianca; Gascon, Ferran; Desnos, Yves-Louis; Seifert, Frank Martin; Paganini, Marc; Ramoino, Fabrizio; Arino, Olivier

2017-04-01

The Sentinel-2 Copernicus mission will bring significant breakthrough in the exploitation of space borne optical data. Sentinel-2 time series will transform land cover, agriculture, forestry, in-land water and costal EO applications from mapping to monitoring, from snapshot to time series data analysis, from image-based to pixel-based processing. The 5-days temporal revisiting of the Sentinel-2 satellites, when both units will be operated together, will usher us in a new era for time series analysis at high spatial resolutions (HR) of 10-20 meters. The monitoring of seasonal variations and processes in phenology and hydrology are examples of the many R&D areas to be studied. The mission's large swath and systematic acquisitions will further support unprecedented coverage at the national scale addressing information requirements of national to regional policies. Within ESA programs, such as the Data User Element (DUE), Scientific Exploitation of Operational Missions (SEOM) and Climate Change Initiative (CCI), several R&D activities are preparing the exploitation of the Sentinel-2 mission towards reliable measurements and monitoring of e.g. Essential Climate Variables and indicators for the Sustainable Development Goals. Early Sentinel-2 results will be presented related to a range of applications and scientific domains such as agricultural monitoring at national scale (DUE Sen2Agri), wetland extent and condition over African Ramsar sites (DUE GlobWetland-Africa), land cover mapping for climate change (CCI Land Cover), national land monitoring (Cadaster-Env), forest degradation (DUE ForMoSa), urban mapping (DUE EO4Urban), in-land water quality (DUE SPONGE), map of Mediterranean aquaculture (DUE SMART) and coral reef habitat mapping (SEOM S2-4Sci Coral). The above-mentioned activities are only a few examples from the very active international land imaging community building on the long-term Landsat and Spot heritage and knowledge.

Hydrothermal Alteration Mineral Mapping Using Sentinel-2A MSI and ASTER Data in the Duolong Ore Concentrating Area,Tibetau Plateau,China

Science.gov (United States)

Hu, B.; Wan, B.

2017-12-01

The porphyry copper deposits are characterized by alteration zones. Hydrothermal alteration minerals have diagnostic spectral absorption properties in the visible and near-infrared (VNIR) through the shortwave infrared (SWIR) regions. In order to identify the alteration zones in the study area, the Sentinel-2A Multi-Spectral Instrument(MSI) * Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and field inspection were combined. The Sentinel-2A MSI has ten bands in the visible and near-infrared (VNIR) regions, which has advantages of detecting ferric iron alteration minerals. Six ASTER bands in the shortwave infrared(SWIR) regions have been demonstrated to be effective in the mapping of Al-OH * Mg-OH group minerals. Integrating ASTER and Sentinel-2A MSI (AM) for mineral mapping can compensate each other's defect. The methods of minimum noise fraction(MNF) * band combination * matched filtering were applied to get Al-OH and Mg-OH group minerals information from AM data. The anomaly-overlaying selection method was used to process three temporal Sentinel-2A MSI data for extracting iron oxides minerals. The ground inspection has confirmed the validity of AM and Sentinel-2A MSI data in mineral mapping. The methodology proved effective in an arid area of Duolong ore concentrating area,Tibet and hereby suggested for application in similar geological settings.

TAPIOCA MELANOMA OF THE IRIS

NARCIS (Netherlands)

DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

Sentinel-5 instrument: status of design, performance, and development

Science.gov (United States)

Gühne, T.; Keim, C.; Bartsch, P.; Weiß, S.; Melf, M.; Seefelder, W.

2017-09-01

The Sentinel-5 instrument is currently under development by a consortium led by Airbus Defence and Space in the frame of the European Union Copernicus program. It is a customer furnished item to the MetOp Second Generation satellite platform, which will provide operational meteorological data for the coming decades. Mission objective of the Sentinel-5 is to monitor the composition of the Earth atmosphere for Copernicus Atmosphere Services by taking measurements of trace gases and aerosols impacting air quality and climate with high resolution and daily global coverage. Therefore the Sentinel-5 provides five dispersive spectrometers covering the UV-VIS (270…500 nm), NIR (685 …773 nm) and SWIR (1590…1675 and 2305…2385 nm) spectral bands with resolutions <=1nm. Spatially the Sentinel-5 provides a 108° field of view with a ground sampling of 7.5 x 7 km2 at Nadir. The development program is post PDR and the build-up of the industrial team is finalised. We report on the instrument architecture and design derived from the driving requirements, the predicted instrument performance, and the general status of the program.

Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

Directory of Open Access Journals (Sweden)

Yuchun Luo

Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

Melanomas: radiobiology and role of radiation therapy

International Nuclear Information System (INIS)

Peschel, Richard E.

1995-01-01

Purpose/Objective: This course will review the radiobiology of malignant melanoma (MM) and the clinical use of radiation therapy for metastatic melanoma and selected primary sites. The course will emphasize the scientific principles underlying the clinical treatment of MM. Introduction: The incidence of malignant melanoma has one of the fastest growth rates in the world. In 1991, there were 32,000 cases and 7,000 deaths from MM in the United States. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for Stage I-II cutaneous MM. Five-year survival rates depend on (a) sex: female-63%, male-40%; (b) tumor thickness: t 4 mm-25%; (c) location: extremity-60%, trunk-41%; and (d) regional lymph node status: negative-77%, positive-31%. Despite adequate surgery, 45-50% of all MM patients will develop metastatic disease. Radiobiology: Both the multi-target model: S = 1-(1-e-D/Do)n and the linear quadratic mode: -In(S) = alpha x D + beta x D2 predict a possible benefit for high dose per fraction (> 400 cGy) radiation therapy for some MM cell lines. The extrapolation number (n) varies from 1-100 for MM compared to other mammalian cells with n=2-4. The alpha/beta ratios for a variety of MM cell lines vary from 1 to 33. Other radiobiologic factors (repair of potentially lethal damage, hypoxia, reoxygenation, and repopulation) predict a wide variety of clinical responses to different time-dose prescriptions including high dose per fraction (> 400 cGy), low dose per fraction (200-300 cGy), or b.i.d. therapy. Based on a review of the radiobiology of MM, no single therapeutic strategy emerges which could be expected to be successful for all tumors. Time-Dose Prescriptions: A review of the retrospective and prospective clinical trials evaluating various time-dose prescriptions for MM reveals: (1) MM is a radiosensitive tumor over a wide range of diverse time-dose prescriptions; and (2) The high clinical response rates to a

In vitro radiobiological evaluation of selective killing effects of 10B1-paraboronophenylalanine.HCl in the thermal neutron capture therapy of malignant melanoma cells

International Nuclear Information System (INIS)

Ichihashi, M.; Ueda, M.; Hayashibe, K.; Hatta, S.; Tsuji, M.; Mishima, Y.; Fukuda, H.; Kobayashi, T.; Kanda, K.

1985-01-01

In order to clarify the specific affinity of 10 B 1 -p-boronophenylalanine.HCl ( 10 B 1 -BPA) to melanoma cells, the killing effects of 10 B 1 -BPA in the thermal neutron capture treatment on both cultured melanotic and amelanotic melanoma cells were compared with those on non-melanoma cells, such as Alexander cells, HeLa cells and normal human fibroblasts. Cells in the plateau phase cultured in the usual medium for 4-7 days were incubated with the medium containing 50 μg/ml 10 B 1 -BPA for 20 hours until 2 hours before thermal neutron irradiation. After thermal neutron irradiation, the number of colonies consisting of more than 50 cells was counted to obtain the dose-survival curves. The melanotic cells pre-incubated with 10 B 1 -BPA had more enhanced killing sensitivity to thermal neutron irradiation than amelanotic melanoma cells pre-incubated similarly with 10 B 1 -BPA. 10 B 1 -BPA pre-incubation had no enhanced killing effects on Alexander cells, but had slightly enhanced killing effects on HeLa cells. These results indicate that 10 B 1 -BPA could be incorporated by a specific uptake mechanism of melanoma cells and accumulated within melanotic melanoma cells and that 10 B 1 -BPA at present could be the best chemical for the thermal neutron capture therapy of human malignant melanoma. (Namekawa, K.)

[Multiple conjunctival malignant melanomas (author's transl)].

Science.gov (United States)

Haddad, R

1979-04-01

5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.

BioSentinel: Developing a Space Radiation Biosensor

Science.gov (United States)

Santa Maria, Sergio R.

2015-01-01

BioSentinel is an autonomous fully self-contained science mission that will conduct the first study of the biological response to space radiation outside low Earth orbit (LEO) in over 40 years. The 4-unit (4U) BioSentinel biosensor system, is housed within a 6-Unit (6U) spacecraft, and uses yeast cells in multiple independent microfluidic cards to detect and measure DNA damage that occurs in response to ambient space radiation. Cell growth and metabolic activity will be measured using a 3-color LED detection system and a metabolic indicator dye with a dedicated thermal control system per fluidic card.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

Science.gov (United States)

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Metastatic breast disease from cutaneous malignant melanoma.

Science.gov (United States)

Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

2014-01-01

Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sarcoidosis in Melanoma Patients: Case Report and Literature Review

Energy Technology Data Exchange (ETDEWEB)

Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

2015-06-15

Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

Science.gov (United States)

Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

2014-01-01

Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

GAB2 amplifications refine molecular classification of melanoma.

Science.gov (United States)

Chernoff, Karen A; Bordone, Lindsey; Horst, Basil; Simon, Katherine; Twadell, William; Lee, Keagan; Cohen, Jason A; Wang, Shuang; Silvers, David N; Brunner, Georg; Celebi, Julide Tok

2009-07-01

Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.

Solitary Secondary Malignant Melanoma of Clavicle Two Years after Enuclation for Ocular Melanoma

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Halil Tozum

2013-01-01

Full Text Available Solitary metastasis of uveal melanoma to bone is extremely rare and usually associated with other organ involvement. We present a rare case of an ocular melanoma patient presenting with solitary metastasis to the clavicle two years after enucleation, without any other organ involvement. In this report, we tried to present our treatment strategy for the solitary metastasis of bone.

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

International Nuclear Information System (INIS)

Ghislin, Stephanie; Obino, Dorian; Middendorp, Sandrine; Boggetto, Nicole; Alcaide-Loridan, Catherine; Deshayes, Frederique

2012-01-01

Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

Directory of Open Access Journals (Sweden)

Ghislin Stephanie

2012-10-01

Full Text Available Abstract Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18 expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

Linear Malignant Melanoma In Situ: Reports and Review of Cutaneous Malignancies Presenting as Linear Skin Cancer.

Science.gov (United States)

Cohen, Philip R

2017-09-18

Melanomas usually present as oval lesions in which the borders may be irregular. Other morphological features of melanoma include clinical asymmetry, variable color, diameter greater than 6 mm and evolving lesions. Two males whose melanoma in situ presented as linear skin lesions are described and cutaneous malignancies that may appear linear in morphology are summarized in this report. A medical literature search engine, PubMed, was used to search the following terms: cancer, cutaneous, in situ, linear, malignant, malignant melanoma, melanoma in situ, neoplasm, and skin. The 25 papers that were generated by the search and their references, were reviewed; 10 papers were selected for inclusion. The cancer of the skin typically presents as round lesions. However, basal cell carcinoma and squamous cell carcinoma may arise from primary skin conditions or benign skin neoplasms such as linear epidermal nevus and linear porokeratosis. In addition, linear tumors such as basal cell carcinoma can occur. The development of linear cutaneous neoplasms may occur secondary to skin tension line or embryonal growth patterns (as reflected by the lines of Langer and lines of Blaschko) or exogenous factors such as prior radiation therapy. Cutaneous neoplasms and specifically melanoma in situ can be added to the list of linear skin lesions.

BAP1 has a survival role in cutaneous melanoma.

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Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Jönsson, Göran; Frederick, Dennie T; Tsao, Hensin

2015-04-01

Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability, induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent.

Skin protection behaviour and sex differences in melanoma location in patients with multiple primary melanomas.

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Warren, Matthew; McMeniman, Erin; Adams, Agnieszka; De'Ambrosis, Brian

2017-02-01

Previous studies have shown that sunscreen usage, sun-protection measures and self-examination rates in patients with single primary melanomas (SPM) are similar to that in the general population. This study hypothesises that these rates would be different in a population with multiple primary melanomas (MPM). We further hypothesise that there would be a sex difference in melanoma location in patients with MPM. The objectives of this study were to determine skin protection measures, self-examinations and melanoma location in a cohort of patients with MPM. A survey was conducted on 137 patients with MPM examining their sun-protection measures, skin self-examination rates and medical and phenotypic characteristics. These data were combined with a review of their medical records to examine the patients' skin cancer history. Patients with MPM had higher rates of skin self-evaluation (74% vs 22%), sunscreen usage (70% vs 45%) and other sun-protection measures (95% vs 46%) than has been published for patients with a history of a SPM. We have also shown that women have a higher risk of developing melanomas on their arms (p skin self-examination, sunscreen usage and other sun-protection methods in patients with MPM is higher than in studies of patients with SPM. It also highlighted sex differences in terms of melanoma location for patients with MPM. Further studies to examine the cause of the differences in these forms of protective behaviour could help improve the utilisation of these important preventative measures in all patients. © 2015 The Australasian College of Dermatologists.

Intraoperative Sentinel Lymph Node Evaluation

DEFF Research Database (Denmark)

Shaw, Richard; Christensen, Anders; Java, Kapil

2016-01-01

BACKGROUND: Intraoperative analysis of sentinel lymph nodes would enhance the care of early-stage oral squamous cell carcinoma (OSCC). We determined the frequency and extent of cytokeratin 19 (CK19) expression in OSCC primary tumours and surrounding tissues to explore the feasibility of a "clinic......-ready" intraoperative diagnostic test (one step nucleic acid amplification-OSNA, sysmex). METHODS: Two cohorts were assembled: cohort 1, OSCC with stage and site that closely match cases suitable for sentinel lymph node biopsy (SLNB); cohort 2, HNSCC with sufficient fresh tumour tissue available for the OSNA assay (>50......% of tumours. Discordance between different techniques indicated that OSNA was more sensitive than qRT-PCR or RNA-ISH, which in turn were more sensitive than IHC. OSNA results showed CK19 expression in 80% of primary cases, so if used for diagnosis of lymph node metastasis would lead to a false-negative result...

EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma.

Science.gov (United States)

Miao, Benchun; Ji, Zhenyu; Tan, Li; Taylor, Michael; Zhang, Jianming; Choi, Hwan Geun; Frederick, Dennie T; Kumar, Raj; Wargo, Jennifer A; Flaherty, Keith T; Gray, Nathanael S; Tsao, Hensin

2015-03-01

BRAF(V600E) is the most common oncogenic lesion in melanoma and results in constitutive activation of the MAPK pathway and uncontrolled cell growth. Selective BRAF inhibitors such as vemurafenib have been shown to neutralize oncogenic signaling, restrain cellular growth, and improve patient outcome. Although several mechanisms of vemurafenib resistance have been described, directed solutions to overcome these resistance lesions are still lacking. Herein, we found that vemurafenib resistance can be (i) mediated by EPHA2, a member of the largest receptor tyrosine kinases (RTK) subfamily erythropoietin-producing hepatocellular (EPH) receptors, and (ii) associated with a greater phenotypic dependence on EPHA2. Furthermore, we developed a series of first-in-class EPHA2 inhibitors and show that these new compounds potently induce apoptosis, suppress viability, and abrogate tumorigenic growth of melanoma cells, including those that are resistant to vemurafenib. These results provide proof of concept that RTK-guided growth, and therapeutic resistance, can be prospectively defined and selectively targeted. In this study, we show that resistance to selective BRAF inhibitors can be mediated by the RTK EPHA2. Furthermore, direct targeting of EPHA2 can successfully suppress melanoma growth and mitigate therapeutic resistance. ©2014 American Association for Cancer Research.

Monosomy 3 by FISH in uveal melanoma: variability in techniques and results.

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Aronow, Mary; Sun, Yang; Saunthararajah, Yogen; Biscotti, Charles; Tubbs, Raymond; Triozzi, Pierre; Singh, Arun D

2012-09-01

Tumor monosomy 3 confers a poor prognosis in patients with uveal melanoma. We critically review the techniques used for fluorescence in situ hybridization (FISH) detection of monosomy 3 in order to assess variability in practice patterns and to explain differences in results. Significant variability that has likely affected reported results was found in tissue sampling methods, selection of FISH probes, number of cells counted, and the cut-off point used to determine monosomy 3 status. Clinical parameters and specific techniques employed to report FISH results should be specified so as to allow meta-analysis of published studies. FISH-based detection of monosomy 3 in uveal melanoma has not been performed in a standardized manner, which limits conclusions regarding its clinical utility. FISH is a widely available, versatile technology, and when performed optimally has the potential to be a valuable tool for determining the prognosis of uveal melanoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Meningeal Melanomas Associated With Transforming Ota Nevus to Malignant Melanoma: A Case Report

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Seyed-Mohammad Fereshtehnejad

2010-11-01

Full Text Available Intracranial invasion of cellular blue nevus (CBN from the skin is extremely rare and such a condition with malignant transformation is even rarer.A case of meningeal melanoma with malignant transformation which was derived from an Ota   nevus is presented in this report.   A21-year-old man with a neurocutaneous syndrome since childhood was referred with headache and mild left hemiparesia. CT scan and MRI demonstrated intracranial lesions and conjunctival biopsy leads to the pathologic diagnosis of blue nevus.Thereafter his parietal lesion was operated by craniotomy with total gross excision.On histopathological examination, diagnosis of malignant melanoma was confirmed.Approximately 2 months after radiotherapy and chemotherapy, he afflicted to diplopia and blurred vision on the leftside due to enlargement of orbital and cavernous sinus lesion. Following one year follow-up,he was survived and thrived with diffuse leptomeningeal nodular enhancement in favor of melanoma dissemination.Primary intracranial melanomas are though rare, but it should be suspected especially in the presence of periorbital blue nevus or nevus of Ota. Moreover, although CBN is considered benign, scalp or periorbital CBN has the potential for intracranial invasion and malignant ransformation.

Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

Centers for Disease Control (CDC) Podcasts

2011-10-19

This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

RTS effect detection in Sentinel-4 data

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Candeias, Henrique; Gnata, Xavier; Harlander, Maximilian; Hermsen, Markus; Hohn, Rüdiger; Riedl, Stefan; Skegg, Michael; Williges, Christian; Reulke, Ralf

2017-09-01

The future ESA Earth Observation Sentinel-4/UVN is a high resolution spectrometer intended to fly on board a Meteosat Third Generation Sounder (MTG-S) platform, placed in a geostationary orbit. The main objective of this optical mission is to continuously monitor the air quality over Europe in near-real time. The Sentinel-4/UVN instrument operates in three wavelength bands: Ultraviolet (UV: 305-400 nm), Visible (VIS: 400- 500 nm) and Near-infrared (NIR: 750-775 nm). Two dedicated CCD detector have been developed to be used in the Focal Plane Subsystems (FPS), one for the combined UV and VIS band, the other covering the NIR band. Being a high resolution spectrometer with challenging radiometric accuracy requirements, both on spectral and spatial dimensions, an effect such the Random Telegraph Signal (RTS) can represent a relevant contribution for the complete system accuracy. In this work we analyze the RTS effect on data acquired during the FPS testing campaign with qualification models for the Sentinel-4/UVN detectors. This test campaign has been performed in late 2016. The strategy for the impact assessment of RTS is to measure the effect at room temperature and then to extrapolate the results to the at instrument operational temperature. This way, very-long lasting data acquisitions could be avoided since the RTS frequency is much lower at cryogenic temperatures. A reliable technique for RTS effect detection has been developed in order to characterize the signal levels amplitude and occurrence frequencies (flipping rate). We demonstrate the residual impact of the RTS on the global In-Orbit Sentinel-4/UVN instrument performance and products accuracy.

Implications of a positive sentinel node in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Gurney, Benjamin A S; Schilling, Clare; Putcha, Venkata

2012-01-01

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients ...

Persistent Scatterer Interferometry using Sentinel-1 Data

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Monserrat, Oriol; Crosetto, Michele; Devanthery, Nuria; Cuevas-Gonzalez, Maria; Qihuan, Huang; Barra, Anna; Crippa, Bruno

2016-04-01

This work will be focused on the deformation measurement and monitoring using SAR imagery from the C-band Sentinel-1, a space mission funded by the European Union and carried out by the European Space Agency (ESA) within the Copernicus Programme. The work will firstly address the data processing and analysis procedure implemented by the authors. This includes both Persistent Scatterer Interferometry (PSI) tools to analyse large stacks of SAR images (say, typically more than 20 images), and Differential SAR Interferometry (DInSAR) tools to analyse short SAR image stacks. The work will discuss the characteristics of the main products derived by using Sentinel-1 DInSAR and PSI: deformation maps, deformation velocity maps, deformation time series, residual topographic error, etc. The analysis will be carried out over different types of land use area, e.g. urban, peri-urban and rural areas. The deformation monitoring based on Sentinel-1 data will be compared with the monitoring based on data from pre-existing missions, e.g. C-band ERS and Envisat, X-band TerraSAR-X and CosmoSkyMed, etc. The comparison will concern different study areas, mainly located in Italy and Spain.

[Molecular and immunohistochemical diagnostics in melanoma].

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Schilling, B; Griewank, K G

2016-07-01

To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

Integrative Genome Comparison of Primary and Metastatic Melanomas

Science.gov (United States)

Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

2010-01-01

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

Reflectance confocal microscopy features of thin versus thick melanomas.

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Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia

2018-01-24

In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

Ambulatory Melanoma Care Patterns in the United States

International Nuclear Information System (INIS)

Ji, A. L.; Davis, S. A.; Feldman, S. R.; Fleischer, A. B.; Baze, M. R.; Feldman, S. R.; Feldman, S. R.; Fleischer, A. B.

2013-01-01

To examine trends in melanoma visits in the ambulatory care setting. Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979 to 2010 were used to analyze melanoma visit characteristics including number of visits, age and gender of patients, and physician specialty. These data were compared to US Census population estimates during the same time period. Results. The overall rate of melanoma visits increased (ρ< 0.0001) at an apparently higher rate than the increase in population over this time. The age of patients with melanoma visits increased at approximately double the rate (0.47 year per interval year, ρ< 0.0001) of the population increase in age (0.23 year per interval year). There was a nonsignificant(ρ=0.19) decline in the proportion of female patients seen over the study interval. Lastly, ambulatory care has shifted towards dermatologists and other specialties managing melanoma patients and away from family/internal medicine physicians and general/plastic surgeons. Conclusions. The number and age of melanoma visits has increased over time with respect to the overall population, mirroring the increase in melanoma incidence over the past three decades. These trends highlight the need for further studies regarding melanoma management efficiency

Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

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M. McComiskey

2015-01-01

Full Text Available Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

International Nuclear Information System (INIS)

Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

1981-01-01

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

The 'Sentinel Node' Concept: More Questions Raised than Answers Provided?

Science.gov (United States)

Schlag

1998-01-01

preoperative lymph node staging. However, there is none. General criteria like size, shape, structure, or texture in variable imaging modalities are unreliable. While it is still too early to definitely evaluate in this context new diagnostic modalities like PET, immunoscintigraphy, or contrast-enhanced MRI, the initial results do not provoke clear enthusiasm toward the development of a sensitive and specific staging tool with regard to the nodal status. Adequate specificity may be obtained by external or endoluminal ultrasound-guided fine needle biopsies. However, uncertainty arises from eventually unrepresentative tissue sampling. The sentinel lymphonodectomy technique may remedy the dilemma, enabling a risk-adapted, individual indication for regional lymphatic dissection. This concept, first introduced in 1977 by Cabanas into the treatment of penis carcinoma, is based on the evidence of orderly and predictable lymphatic drainage pathways. Tumor cell progression within the lymphatic system seems to follow a sequential pattern. Primary draining lymph nodes possess the structural and functional capability to retain and to fight tumor cells efficiently. The 'sentinel node' is defined as the first tumor draining filter, and, if uninvolved, should thus adequately predict the nodal status of the disease. Skip metastases beyond an uninvolved sentinel node are supposed to be a very rare event. The reliability of the 'Cabanas approach', however, was limited by its relatively poor localization technique, and therefore failed to gain widespread acceptance. Unfortunately, the significance of the concept was not fully appreciated at the time. It is to Morton's credit that the procedure was reinstituted in malignant melanoma through a dye injection technique at the primary tumor site. This led to a rapid development and refinement of intraoperative lymphatic mapping. One major step in this process was to use radiolabeled colloids in conjunction with gamma-camera imaging or gamma probe

Long term survival with the combination of interferon and chemotherapy in metastatic melanoma

International Nuclear Information System (INIS)

Karagoz, B.; Bilgi, O.; Ozgun, A.; Emirzeoglu, L.; Celika, S.; Ozet, A.

2015-01-01

The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-α (IF-α) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-α plus chemotherapy and IF-α maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-α plus chemotherapy and IF-α maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of auto immunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-α treatment with concurrent chemotherapy and maintenance. IF-α plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs

Shared care in the follow-up of early-stage melanoma: a qualitative study of Australian melanoma clinicians’ perspectives and models of care

Directory of Open Access Journals (Sweden)

Rychetnik Lucie

2012-12-01

Full Text Available Abstract Background Patients with early stage melanoma have high survival rates but require long-term follow-up to detect recurrences and/or new primary tumours. Shared care between melanoma specialists and general practitioners is an increasingly important approach to meeting the needs of a growing population of melanoma survivors. Methods In-depth qualitative study based on semi-structured interviews with 16 clinicians (surgical oncologists, dermatologists and melanoma unit GPs who conduct post-treatment follow-up at two of Australia’s largest specialist referral melanoma treatment and diagnosis units. Interviews were recorded, transcribed and analysed to identify approaches to shared care in follow-up, variations in practice, and explanations of these. Results Melanoma unit clinicians utilised shared care in the follow-up of patients with early stage melanoma. Schedules were determined by patients’ clinical risk profiles. Final arrangements for delivery of those schedules (by whom and where were influenced by additional psychosocial, professional and organizational considerations. Four models of shared care were described: (a surgical oncologist alternating with dermatologist (in-house or local to patient; (b melanoma unit dermatologist and other local doctor (e.g. family physician; (c surgical oncologist and local doctor; or (d melanoma physician and local doctor. Conclusions These models of shared care offer alternative solutions to managing the requirements for long-term follow-up of a growing number of patients with stage I/II melanoma, and warrant further comparative evaluation of outcomes in clinical trials, with detailed cost/benefit analyses.

SENTINEL LYMPH NODE CONCEPT IN DIFFERENTIATED THYROID CANCER

Directory of Open Access Journals (Sweden)

Markovic Ivan

2014-12-01

Full Text Available Introduction: Differentiated thyroid carcinoma (DTC account up to 90% of all thyroid malignacies, and represents the most common malignant tumors of endocrine system. The incidence of papillary thyroid carcinoma (PTC, especially small tumors is rapidly increasing during past three decades. At the time of diagnosis, the incidence of lymph node metastases (LNM ranges from 80 to 90%. During the last 15 years, LNM were recognized as bad prognostic factor for both local-regional relapse (LRR and cancer specific survival. There is general agreement that neck dissections are indicated in cases of clinically apparent LNM. The subject of the current controversy is the surgical treatment of occult LNM that remain unrecognized on preoperative diagnosis (cN0. The extent of operations of the lymph nodes ranges from “wait and see” so-called “Western school” principle substantiated the role of applying ablative I131therapy and frequency peroperative complications (recurrent laryngeal nerve injury and hypoparathyroidism, especially for less experienced teams to mutual prophylactic dissection of the central and lateral compartments so-called “Japanese school” due to the limited use of radioactive iodine therapy and significantly lower operating morbidity if dissetion was done during primary operation. Despite high prevalence of occult LNM, existing controversies regarding diagnosis, longterm prognostic impact and extent of lymph node surgery, motivated some authors to apply consept of sentinel lymph node biopsy (SLNb in DTC, taking into account excellent results of SLN concept in breast cancer and skin melanoma. This review presents the summarized results of relevant studies and three meta-analysis of accuracy and applicability of SLN concept in patients with differentiated thyroid carcinoma.

Differentiating regressed melanoma from regressed lichenoid keratosis.

Science.gov (United States)

Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

2017-04-01

Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

Science.gov (United States)

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

primary malignant amelanotic melanoma arising from a vitiligo patch

African Journals Online (AJOL)

2014-05-05

May 5, 2014 ... Malignant melanoma is a rare tumour in people of. African descent including those affected by albinism. (1). The incidence of malignant melanoma in Africans is estimated to ranging from 0.5 to 1.5 per 100,000 people (2). Acrolentiginous melanoma is the most common type of melanoma in this population.

Sentinel Node in Oral Cancer

DEFF Research Database (Denmark)

Tartaglione, Girolamo; Stoeckli, Sandro J; de Bree, Remco

2016-01-01

/static scan and/or SPECT/CT. RESULTS: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical......PURPOSE: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer...... localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately...

Organized nation-wide implementation of sentinel lymph node biopsy in Denmark

DEFF Research Database (Denmark)

Friis, E.; Galatius, H.; Garne, J.P.

2008-01-01

they could include patients into the study. As a result of this strategy the sentinel lymph node staging was fully implemented in all Danish surgical breast cancer centres within three years and all sentinel node biopsies in the period were recorded in the DBCG data centre. Furthermore, the strategy...